摘要:

Russian Chemical Reviews 69 (5) 367 ± 408 (2000) Sulfones and sulfoxides in the total synthesis of biologically active natural compounds E N Prilezhaeva Contents I. Introduction II. Brief characterisation of reactions applicable in the synthesis of natural compounds based on the use of sulfones and sulfoxides III. Syntheses based on a-sulfonyl or a-sulfinyl carbanions IV. Formation of C=C bonds by thermolysis of sulfoxides V. Syntheses based on reactions of unsaturated sulfones and sulfoxides VI. Conclusion Abstract. total in sulfoxides and sulfones of use the on Data Data on the use of sulfones and sulfoxides in total stereo-, natural of syntheses enantioselective and regio- stereo-, regio- and enantioselective syntheses of natural com- com- pounds published over the last 15 ± 20 years are discussed and pounds published over the last 15 ± 20 years are discussed and classified The reactions.of types important most the into classified into the most important types of reactions. The biblio- biblio- graphy references 420 includes graphy includes 420 references. I. Introduction Sulfonyl- and sulfinyl-containing intermediates and their precur- sors are finding increasing use in the synthesis of natural com- pounds because these groups satisfy the requirements of sophisticated multistage transformations. In this review, the most important requirements are stated based on the concepts proposed by the eminent chemist and populariser of science, E Block.1 These functional groups should be: (1) readily accessible; (2) highly reactive; (3) able to effect asymmetric induction; (4) readily removable at a particular stage of the synthesis.Sulfoxides and sulfones are rather readily available com- pounds. Methods for their synthesis both from the corresponding sulfides and other precursors have been well developed.2±5 Owing to their high reactivity, sulfoxides and sulfones can induce the stereo-, regio- and enantioselective formation of new C7X bonds and, what is particularly important, of C7C bonds. Enantiomerically pure sulfoxides are excellent mediators in the asymmetric synthesis. The fact that the sulfur atom in sulfoxides containing different substituents is an ideal asymmetry center (Montanari 6 was the first to note this fact back in the 1970s) is not the only reason.The ability of the sulfinyl group to form chelates due to complexation with other polar groups in the molecule as well as with catalysts is used in enantioselective syntheses resulting in 1?2, 1?3 and more distant asymmetry E N Prilezhaeva N D Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 117913 Moscow, Russian Federation. Fax (7-095) 135 53 28. Tel. (7-095) 939 36 21 Received 24 November 1999 Uspekhi Khimii 69 (5) 403 ± 446 (2000); translated by T N Safonova #2000 Russian Academy of Sciences and Turpion Ltd DOI 10.1070/RC2000v069n05ABEH000561 367 368 369 390 392 403 transfer.5, 7 ± 13 The wide application of chiral sulfoxides is also favoured by the availability of convenient methods for their preparation in enantiomerically pure S- or R-forms.5, 12 Sulfonyl groups do not possess inherent asymmetry and are substantially less active complex-forming agents.However, due to their specific bulk and electronic properties, these compounds can perform regio- and stereocontrol. Reactions of sulfones proceed under rather mild conditions, which makes it possible to retain chiral carbon centres (even those located in the vicinity of the sulfonyl group) throughout the process. A wide variety of chemoselective procedures for the removal of sulfonyl and sulfinyl groups are available (see, for example, Ref. 14). Classical heterogeneous reduction with Raney nickel (Ra/Ni) continues to be used.Mild heterogeneous desulfonation (desulfination) with metal amalgams (primarily with Na/Hg) is also often employed. However, the majority of modern proce- dures involve homogeneous processes, viz., reactions of transition metal salts, palladium(0) complexes or solutions of alkali metals in ammonia. Since the use of lanthanides have attracted growing interest in recent years,15, 16 mild desulfonation with SmI2 is rather often used (see, for example, Refs 16 ± 19). Reductive desulfurisa- tion, elimination of sulfenic and sulfinic acids to formC=Cbonds and double elimination of hydroxy and sulfonyl groups from substituted sulfones can readily be performed. Although the sulfonyl fragment is a poor leaving group (see, for example, Ref.20), conditions were found under which this group in some compounds can be replaced by the attacking reagents. In spite of the fact that synthetic applications of sulfones have been surveyed (see, for example, Refs 21 and 22), the data on the use of these compounds in the synthesis of natural products remain to be systematised. Applications of particular types of sulfones, such as g-hydroxyvinyl sulfones 23, 24 and sulfolenes,25, 26 for these purposes have been described. Examples of the use of sulfones were cited in reviews devoted to syntheses of selected groups of natural compounds (juvenile hormones 27 and linear polyprenols 28, 29). Recently, Carreno 12 has reported a compre- hensive analysis of the uses of chiral sulfoxides in asymmetric syntheses of biologically active compounds.Therefore, in the present review the attention is focused on sulfonyl-containing and racemic sulfinyl-containing precursors and intermediates without special reference to asymmetric synthesis, all the more so since the stereochemistry of all chiral centres has not always been reported in the original studies. Yet another aim of this review is to368 demonstrate how successfully sulfones and sulfoxides comple- ment each other in syntheses of natural compounds. II. Brief characterisation of reactions applicable in the synthesis of natural compounds based on the use of sulfones and sulfoxides Even a brief analysis of reactions of sulfoxides and sulfones gives an idea of their wide synthetic potential.These compounds can provide the basis for the erection of the building for the synthesis of natural compounds. Fuchs and coworkers 24 compared this building to a majestic pyramid. Reactions of carbanions stabilised by a-sulfonyl or (to a lesser extent) a-sulfinyl groups are often used in the synthesis of natural compounds. Among various reagents used for a-deprotona- tion,30, 31 lithium bases (for example, alkyllithium compounds or lithium diisopropylamide LDA) predominate. In this review, these species will be sometimes described as C-lithiated species in accordance with the original reports although this is not quite correct. It has been rigorously proved 32 that in the crystalline state of sulfur-containing alkyllithium compounds, the metal atom is bound to the oxygen atom of the sulfonyl (sulfinyl) group rather than to the a-carbon atom.However, this fact is not reflected in their reactions in solution. Electrophilic reagents attack exclu- sively the carbon atom unlike their reactions with carbanions stabilised by the carbonyl group. Alkylation with alkyl or cyclo- alkyl halides, tosylates or mesylates (Scheme 1, path a) affords Scheme 1 a CHR3 bc 7 R1S(O)nCHCH2R2 R1S(O)nCH(R3)CH2R2 A R2CH2CH R1S(O)n OH B R1S(O)n CHCOR3 C R2H2C R3CHCH(R4)CHCH2R2 d OH R1S(O)n D R1S(O)nCHCH2CH2EWG e E CH2R2 n=1, 2; (a) R3X, X=Hal, OTs, OMs (Ms=MeSO2); (b) R3CHO; O EWG, EWG is an electron- R4 ; (e) (c) R3CO2R4; (d ) R3 withdrawing group.sulfones or sulfoxides A and their reductive desulfurisation leads to the elongation of a saturated chain. Elimination of fragments of acids RSOnH (n=1 or 2) from derivatives A results in the formation of the C=C bond. For most sulfones, this process occurs under rather drastic conditions. Many sulfoxides eliminate sulfenic acid upon mild thermolysis, which provided the basis for a method of introduction of C=C bonds with E configuration into complex molecules proposed by Trost .33 ± 35 [H] R2(CH2)2R3 A R3 a or b R2 (a) n=2, B ; (b) n=1, D. Reactions with carbonyl compounds or oxiranes lead to the 1,2-addition at the carbonyl group (Scheme 1, paths b and c) or to the oxirane-ring opening (path d ). Reactions of a-sulfonyl carb- anions with aldehydes are of particular importance because the E N Prilezhaeva resulting epimeric mixtures of 2-hydroxy sulfones B (n=2) serve as an inexhaustible source for the construction of new functional groups, viz., vinylsulfonyl, oxosulfonyl, saturated hydroxy or oxo groups.Of prime importance is the Julia olefination resulting in stereoselective construction of the C=C bond with either the E (Ref. 36) or Z (Ref. 37) configuration following acylation of the hydroxy group (Scheme 2, paths a and b). Scheme 2 a, b R3 CH2R2 R1S(O)n c CHCH2R3 R2H2C B R1S(O)n d R3 R2H2C R1S(O)n f f e CHC(O)R3 R2CH2CH2C(O)R3 R2H2CR2(CH2)2CH(OH)R3 (a) n=2, Ac2O; (b) Na/Hg; (c) n=1, 2; (d ) n=2, B ; (e) n=2, [O]; ( f ) [H]. The most important precursors in the asymmetric synthesis, viz., 2-hydroxy sulfoxides (B, n=1),12 must be used only in enantiomerically pure form.Therefore, these compounds are generally prepared by selective reduction according to Solla- die 38, 39 starting from 2-oxo sulfoxides C. The most convenient procedure for the synthesis of the latter involves the reaction of a-sulfinyl carbanions with the carbonyl groups of esters (Scheme 1, path c). a-Sulfonyl(sulfinyl) carbanions, being active C-nucleophiles, readily react with various electron-deficient multiple bonds (Scheme 1, path e). Either aryl or (more rarely) tert-butyl groups generally serve as substituents R1 in sulfonyl(sulfinyl) fragments. This is dictated not only by the necessity of providing conditions for regiospecific deprotonation but also for kinetic reasons. For example, benze- nesulfenic acid is eliminated upon thermolysis of sulfoxides at substantially lower temperatures than methanesulfenic acid.40 Among unsaturated precursors, vinyl sulfones are worthy of particular attention. Fuchs and coworkers 23, 24 believed that these sulfones are ideal starting compounds (superior even to enones) for sophisticated syntheses.New C7C bonds are formed upon addition of C-nucleophiles (predominantly metal alkyls) at the activatedC=Cbonds of vinyl sulfones followed by the reaction of electrophiles with the resulting a-sulfonyl carbanionic centre (Scheme 3, path a). Reactions of theC=Cbonds of ene sulfoxides with C-nucleophiles occur successfully, if additional acceptors, for example, carbonyl groups, are introduced into the sulfoxide molecules.Reactions of heteronucleophiles with ene sulfoxides Scheme 3 R1S(O)nCH(R4)CHR2R3 R4X 7 a R1S(O)nCHCHR2R3 S(O)nR1 b R3 R1S(O)nCH CHR2 R2 c, d R2CH CHR3 ; (c) n=2, R3MgX, n=1, 2; (a) R3M(M=Li, MgX); (b) R3 Ni(II) or Fe(III); (d ) B .Sulfones and sulfoxides in the total synthesis of biologically active natural compounds and ene sulfones (see Section V.1.b) as well as the Diels ± Alder [4+2] cycloaddition (Scheme 3, path b) are also widely used. Cross-coupling of vinyl sulfones with Grignard reagents in the presence of transition metal salts makes it possible to replace the sulfonyl group according to Julia,41 the C=C bonds being unaffected (Scheme 3, paths c and d ).Linear and cyclic polyunsaturated structures are successfully constructed with the use of various 1,3-dienes generated from substituted 3-sulfolenes by cheletropic elimination of SO2.26 Allyl sulfoxides and, particularly, allyl sulfones are very reactive compounds. Due to abstraction of the labile allylic hydrogen, these compounds readily form ambident carbanions, which can undergo alkylation both at the a- and (more rarely) g-positions. In the presence of palladium catalysts or Lewis acids, the sulfonyl group in allyl sulfones is replaced by various nucle- ophiles.42, 43 Because of the wide diversity of their transforma- tions, Trost 44 has named allylic sulfones `organic chameleons'.Of rearrangements of sulfoxides and sulfones, the Mis- low ± Evans sulfenyl ± sulfenate rearrangement 45, 46 (which is used for the formation of hydroxy allylic fragments), the Pum- merer reaction 47, 48 (which has many applications, but is predom- inantly used for the construction of cyclic molecules) and the Ramberg ± BaÈ cklund reaction 49, 50 (which is used for the intro- duction of C=C bonds) are most commonly used in the synthesis of natural compounds. Because of a great body of information on syntheses involving rearrangements of sulfoxides and sulfones, these processes cannot be considered in this review in detail. III. Syntheses based on a-sulfonyl or a-sulfinyl carbanions 1. Alkylation a. Alkylation followed by reductive removal of sulfur-containing groups The simplest procedure for the formation of new C7C bonds involves alkylation of a-sulfonyl or a-sulfinyl carbanions followed by reductive removal of sulfur-containing groups.This strategy was used for the first time in the syntheses of components of essential oils, viz., racemic a-santalene [()-1] and a-santalol [()-2],51 as well as for the preparation of a pure trans-isomer of Br SO2Ph a b, c, d ()-1 e, f SO2Ph OH Cl g, d ()-2 (a) PhSO2Na, DMF; (b) BunLi, THF, hexamethylphosphorous triamide (HMPT); (c) Cl ; (d ) Na/Hg, EtOH; (e) BunLi; ( f ) Cl ; Cl (g) AcO7. a b, c, d Br CH2SO2Tol 5 4 3 (a) TolSO2Na (Tol=4-MeC6H4) (97%); (b) BunLi; (c) 3; (d) Et2NLi,778 8C.369 squalene (3) 52 by alkylation of the anion of farnesyl phenyl sulfone (4) with farnesyl bromide (5). This procedure is often used for the coupling of complex polyfunctional fragments con- taining numerous chiral centres. Recently, this method has been used for the preparation of intermediates 6 ± 8 in the synthesis of ambrein (the intermediate 6 53), polysubstituted biologically active furan compounds, viz., calicogorgins A and C (the intermediates 7a and 7b, respectively 54), and the antibiotic mycotrienin (the intermediate 8 55) (the sites of coupling are indicated by arrows). OTHP 6 THP is tetrahydropyran-2-yl. R O O O OAc 6 n NHAc 7a,b n=1,R=Me (a); n=2, R = H (b). OMe NH MeO OR3 OMe O OR2 MeO OR1 8 OMe R1±R3 are protective groups.This procedure can also be used for the construction of linear enantiomerically pure pheromones, both saturated and contain- ing isolated C=C bonds. Mori and coworkers 56 ± 64 performed convergent syntheses of pheromones (ee 97%± 98%) starting from two or more enantiomerically pure building blocks. If the absolute configuration of the natural pheromone was unknown, all possible enantiomers were synthesised in amounts sufficient for biological assays. Below are presented the syntheses of four possible enantiomers of 3,7-dimethylnonadecane (9), which is a pheromone of tortricid Agromyza frontella (an alfalfa pest).56 11 (3S,7S )-9 c SO2Ph a, b 11 SO2Ph 11 a, d, c (R) 11 (3R,7S )-9 a, b, c 11 (3S,7R)-9 SO2Ph 11 (S ) a, d, c 11 (3R,7R)-9 (a) BunLi; (b) I.I ; (c) Na/Hg, EtOH; (d ) Other pheromones synthesised by Mori and coworkers with the use of alkylation ± desulfonylation methodology are listed in Table 1 (the coupling sites are indicated by arrows).370 Table 1. Pheromones synthesised by alkylation ± desulfurisation. Structure Name 13,17-Dimethyl- nonatriacontane Me(CH2)11 3,13-Dimethyl- heptadecane 6,10,14-Trimethyl- pentadecan-2-ol 6,10,13-Trimethyl- tetradecan-1-ol 6,12-Dimethyl- pentadecan-2-one 4,8-Dimethyldecanal Methyl 2,6,10-tri- methyltridecanoate a Preliminary data of biological studies. b In the study,61 enantiomers inactive with respect to Tribolium castaneum, but active with respect to other species Tribolium were prepared.Pheromones whose molecules contain double bonds were constructed by alkylation ± desulfonylation starting from allylic sulfones and (or) allyllic halides. This procedure was used for the preparation of enantiomerically pure faranal (10), which is the pheromone of Pharaoh's ant.64 a, b, c SO2Ph(+)-(3S,4R)-10 H (a) BunLi; (b) Br OTHP H The synthesis of the pheromone of California scale ()-11 in the racemic form required the use of a threefold excess of allyl bromide because deprotonation and, correspondingly, alkylation of the initial methyl sulfone occurred non-regiospecifically.65 OH a, b SO2Me OH SO2CH(All)2 ()-11 All=CH2CH=CH2; (a) BunLi; (b) 3 equiv. of BrAll; (c) Na/NH3 . Absolute configuration of natural pheromone unknown (CH2)21Me " OH (2R,6R,10R) a unknown OH O "(4R,8R) CHO unknown CO2Me In the synthesis of the sex pheromone of Douglas fir tussock moth 12, a-thiylation followed by hydrolysis was used for the simultaneous formation of the oxo group and removal of the sulfonyl group; the C=C bond was formed by stereospecific hydrogenation of the triple bond.66 Me(CH2)9CH2SO2Tol H ...CH2OTHP H H CHO H ; (c) Na/Hg, EtOH. (a) BunLi; (b) 2 equiv. of Me(CH2)4C:C(CH2)3I; (c) (MeS)2; (d ) CuCl2 , SiO2; (e) H2 , 5%Pd/BaSO4 . OH c An elegant method for stepwise alkylation developed by Moiseenkov and coworkers 28, 67 ± 70 makes it possible to synthe- sise polyunsaturated natural molecules by C5-homologation.Lithiated d-hydroxyallylic or saturated sulfones (including those containing a chiral centre) and the corresponding unsaturated terpenoid halides served as the starting compounds. This method- ology was used for the preparation not only of relatively small molecules [for example, the pheromone components of San-Jose scale, viz., a-neryl and a-geranyl propionates (13a,b)67], but also of long-chain natural regulators, such as polyprenol- and dolichol- like alcohols 14 68 or 15.69 The addition of a crown ether, viz., dibenzo-18-crown-6 (DB-18-C-6), to a solution of sodium in liquid ammonia in the stage of reductive desulfonation made it E N Prilezhaeva Ref. Biological characteristic Number of pos- sible enantiomers (the number of enantiomers synthesised) 57 4 (4) kairomone for wasp Trichogramma nubiale 63 4 (4) sex pheromone of western false hemlock looper Nepytia freemani 58 8 (8) pheromone of rice moth Corcyra cephalonica 59 4 (4) aggregation pheromone of predatory stink bug Stiretrus anchorago 60 female-produced sex pheromone 4 (4) of banded cucumber beetle Diabrotica balteata Le Conte 61 4 (2)b aggregation pheromone of red-flour beetle Tribolium castaneum 62 8 (8) sex pheromone of stink bug Euschistus heros/E.obscurus a, b, a, c SO2Tol d, e C(CH2)4Me Me(CH2)9C(CH2)3C SMe H H (CH2)4Me Me(CH2)9C(CH2)3 O ()-12371 Sulfones and sulfoxides in the total synthesis of biologically active natural compounds BnOCH2 OBOM possible to suppress the undesirable allylic isomerisation of the adjacent C=C bond.70 H PhSO2CH2 a Me a b, c Cl I OH SO2R CHO H BnOCH2 PhSO2 OBOM H O + OCOEt 13a ...13b OCOEt Me O (a) (Mor is morpholinyl); (b) Na/NH3 , MorSO2CHLi CH2OLi 18 DB-18-C-6; (c) EtCOCl. BOM�BnOCH2; (a) potassium bis(trimethylsilyl)amide (potassium hexamethyldisilazanide, KHMDS), THF. a, b, c, a, d H CH2Br CH2OBn BnOCH2 3 SO2Ph BnO b, c a BnO OH 3 n 14a,b SO2Ph Me I ; (b) Na/NH3; (c) PBr3, Py; n = 1 (a), 2 (b); (a) PhSO2CHLi CH2OLi CH2OH (d ) Na/NH3 , DB-18-C-6. HO a, b, c 2 OH m 19 H (a) KHMDS; (b) Na2HPO4, Na/Hg, MeOH, 0 8C; (c) CF3CO2H, CH2Cl2 ,770 8C. OH m 2 15a,b Me HCH2CH2OLi; (c) Na/NH3.m = 2 (a), 3 (b); (a) PBr3; (b) PhSO2CHLi the enantiomerically pure form starting from (S,S )-(7)-diethyl tartrate,72 phomactin D (18), which is a 12-membered PAF antagonist,73 and the 14-membered carbocycle 7(8)-deoxyasper- diol (19), which is a synthetic precursor of the widespread cembranoid antitumor agent asperdiol.74 However, attempts to perform macrocyclisation of the halo- genosulfone in the synthesis of an analogue of terpenoid 19 failed.75 Intramolecular alkylation ± reductive desulfonylation leads to ring closure. This procedure was used for the synthesis of racemic pumiliotoxin C (16), which is contained in excretions of arrow- poison frog ,71 the bicyclic pheromone (+)-exo-brevicomin (17) in OTs Intramolecular alkylation was used in the total synthesis of 21-membered heterocyclic antibiotics (+)-trienomycins A and F 76 and for the construction of the AB ring system of taxol.77 PhSO2 2 steps a O O PhSO2 Prn Prn NBoc NBoc a, b, c O O O O O SO2Ph O O Prn 21 20 O HN O ()-16 Boc is tert-butoxycarbonyl; (a) BunLi, HMPT,778?20 8C.PhSO2 (a) BunLi, DMSO, KI; (b) Cl O ; (c) Al/Hg, EtOH. CO2Et CH2OTs HO H O a O O ... OH H H BocN H BocN HNCO2Me a, b, c O CH2OTs O R2 R1 R1 SO2Ph CO2Et (S,S ) SO2Ph 22a ± c O O b, c O (b) Br R1=Me (a), Pri (b), 4-MeOC6H4CH2OC6H4CH2O (PMBO) (c); R2=D-Pri, L-Pri, D-Bn, L-4-HOC6H4CH2; (a) K2CO3 , DMF; CO2Me; (c) SmI2 , THF,MeOH,778 8C, NHEt CH2OTs O (+)-17 R2 O 20 min (50% ± 98%).(a) BunLi, THF,778 8C; (b) Me2CuLi, Et2O,Me2S; (c) Na, EtOH,THF.372 Unlike the above-mentioned studies in which alkylation was generally performed with the use of bromides or iodides, the enantiomerically controlled construction of the C(1)7C(17) frag- ment in the total synthesis of ionophoric boromycin was carried out using the mild reaction of a chloride with an anion generated from the 2-oxosulfonyl group.78 Oxo sulfone 20 serves as an example of additional activation of the a-sulfonyl carbanionic centre in alkylation. The sulfone 20 was used as the starting material in the synthesis of compound 21, which is the key intermediate for the preparation of the antibiotic ()-aplasmomycin.79 Amino-acid-derived oxo sulfones 22a ± c were successfully used in the peptide synthesis.80 Cyclic ketones containing the sulfonyl group at the a-position undergo three-carbon ring expansion when a fluoride anion acts on the products of alkylation of enolates of these ketones with silicon-containing allylic iodides or mesylates [Me3SiCH2(XCH2)C=CH2], which generate trimethyleneme- thane.81 Trost and coworkers 82 used this procedure for the preparation of muscone 23 from 2-sulfonylcyclododecanone 24 in high yield.O O SO2Ph SO2Ph SiMe3 a b 24 O O SO2Ph c, d ()-23 X (X=I, OSO2Me), NaH, NaI, DME; (a) Me3Si (b) Bun4 NF, THF; (c) H2 , 5% Pd/BaSO4; (d ) Na/Hg, Na2HPO4, H2O. The application of more complex oxosulfonyl precursors made it possible to construct sterically hindered systems of the 11,11-dimethylbicyclo[5.3.1]undecane series, such as compound 25, which is the key intermediate in the synthesis of taxane derivatives,83 as well as to prepare fused cyclopentanoids of the type 26, which serve as the starting compounds for the preparation of hirsutene, hirsutic acid and coriolin.84 O O HO O SO2Me SO2Me 26 25 SO2Me The formal total synthesis of carba-prostacyclin (27), which is an analogue of prostacyclin, was reported.85 The compound 27 is more stable, but exhibits no lesser activity in the inhibition of blood coagulation.The allylic sulfone dianion 28 was alkylated with enantiomerically pure mesylate of substituted hydroxycyclo- pentane. The necessary side chains were introduced into com- pound 29 by reactions with the corresponding lithium cuprates.The reactions were accompanied by the replacement of the CH2OMs MsOCH2 SO2CH(Li)CH CH2 + CH2OR1 28 Li OR1 E N Prilezhaeva H R2O(CH2)4 PhSO2 a + CH2OR1 CH2OR1 29 OR1 (E )-30 OR1 H H HO2C(CH2)3 (CH2)4R2 + (CH2)4Me CH2OR1 OH 27 (Z)-30 OH OR1 R1=SiMe2But; (a) LiCu[(CH2)3OR2]2; R2=CH(Me)OEt. sulfonyl group and migration of theC=Cbond to form a mixture of (Z)- and (E )-isomers of compound 30. The latter is the key intermediate in the synthesis of carba-prostacyclin (27). As to a-sulfinyl carbanions, the simplest alkylation ± reductive desulfinylation procedure is rather rarely used in the synthesis of natural compounds. However, the racemic juvenile hormone 31 was synthesised by two-step reduction of the compound 32, which is an alkylation product of disulfoxide 33, via intermediate dithioether 34.86 SO SO a, b Et 33 SO SO c CO2Me Et 32 S S d CO2Me Et 34 Et Et e CO2Me Et Et Et CO2Me Et O ()-31 (a) LDA; (b) Br CO2Me; (c) SnCl2 , AcCl, DMF; (d ) Ra/Ni, DMSO; (e) m-chloroperbenzoic acid (MCPBA).In the total synthesis of racemic biotin 35,87 an intermediate obtained by alkylation of a sulfoxide was reduced to sulfide. O O NR RN NR RN c, d a, b (CH2)4CO2But S S O O O O NH HN NR RN (CH2)4CO2But (CH2)4CO2H S S 35 R=Bn, All; (a) MeLi; (b) I(CH2)4CO2But; (c) TiCl3; (d ) HBr.Sulfones and sulfoxides in the total synthesis of biologically active natural compounds Deprotection of the amino and carboxy groups was performed in two steps to produce ()-biotin 35.The reactions given below exemplify the use of alkylation of the anions derived from oxo sulfoxides upon deprotonation at the a-position with respect tohe carbonyl group. Due to the induction exerted by the sulfinyl group, alkylation of an enantio- merically pure derivative of 1,3-dithiane 1-oxide (36) proceeded selectively to form compound 37. Its hydrolysis afforded natural (7)-(R)-2,6-dimethylheptanoic acid [(7)-(R)-38].88 O O Et S Et S a, b c S S (SR,2R)-37 O O (SR,2R)-36 HO2C (7)-(R)-38I ; (c) NaOH (39%). (a) (Me3Si)2NLi; (b) The total synthesis of an antimalarial drug, viz., sesquiterpe- noid (+)-artemisinin (39), was carried out starting from sulfoxide 40,89 which had been prepared from pulegone.The sulfinyl group acts as an activating agent that promotes alkylation of enolate. c a, b O O O O SOPh 40 SOPh H OO 5 steps O O OH H O O 39 O H O (a) 2 equiv. of LDA, HMPT, THF,735 8C; (b) O ; (c) Al/Hg. Br b. Alkylation of a-sulfonyl carbanions followed by elimination of sulfinic acid Homoallylic sulfones are promising starting compounds for the introduction of C=C bonds by alkylation of a-sulfonyl carban- ions followed by elimination of sulfinic acid. Julia and Arnould 90 were the first to use this approach in the synthesis of natural compounds. These authors performed a convergent (C15+C5)- synthesis of methyl retinoate (41) related to vitamin A starting from b-ionone.The key step of this scheme involves dehydrosulfi- nylation of homoallylic sulfone 42 prepared by alkylation of SO2Ph a, b 43 PhSO2 CO2Me c 42 373 CO2Me 41 (a) BunLi; (b) Br CO2Me; (c) K2CO3 , MeOH (73%). sulfone 43. However, the E-configurations of all C=C bonds of the final reaction product 41 have not been established reliably. 90 This study 90 gave impetus to intensive investigations aimed at developing a sulfonyl procedure for the preparation of vitamin A as retinol acetate (44) (the results were surveyed in Ref. 91). This approach seemed to be promising owing to a small number of steps and the possibility of recycling of the sulfinate eliminated. The most essential results were obtained by researchers of Rhone ± Poulenc 92, 93 and of Hoffman ± LaRoche.94, 95 Two versions of the convergent (C15+C5) schemes (Scheme 4, paths I Scheme 4 Path I a 43+ OAc Cl PhSO2 OAc (b or c), d H 46 15 13 11 9 7 6 1 OAc 8 10 12 14 23 5 4 44 (a) ButOK, THF; (b) PriONa, C6H14 , 30 8C, 1 h (82% ± 86%); (c) EtONa, EtOH, D, 13 h (83%), (d) Ac2O, Py.Path II a OH Br + TolSO2 TolSO2 OH b c OH 44 (a ) LDA, THF; (b) NaNH2, NH3 (liquid),730 8C, 50 min (85%); (c) Ac2O, Et3N. Path III a OH SO2Ph+ X OH b, c SO2Ph OAc d 44 44+ 45 X=Cl, Br; (a) ButOK; (b) NaOH, Me2NH, 20 8C, 16 h (75%) (ratio 44 : 45*1 : 2); (c) AcCl, Py; (d ) PdCl2 (70%). OAc 47374 and II ) 92, 93, 95 and the (C13+C7) scheme 4 (path III ) 94 were developed together with several procedures for the elimination of sulfinic acid.The major difficulties were associated with the formation of an admixture of the biologically inactive isomer 45 with the (Z)-C(9)=C(10) bond and the isomer 47. Apparently, the isomer 45 was formed as a result of isomerisation of the intermediate sulfone 46, whereas the isomer 47 was formed upon prolonged action of a base. The best results were obtained with the use of mild heterogeneous elimination of sulfinic acid (PriONa, hexane, path I b). However, isolation of pure retinol acetate (44) requires recrystallisation.92 Other procedures for elimination (path I c, path II e and path III h) call for a number of additional operations. Thus upon desulfonylation with a solution of NaOH in Me2NH, the content of the isomer 45 in the reaction mixture reached 34%.After isomerisation under the action of PdCl2 and recrystallisation, pure retinol acetate was obtained in 70% yield. None of the sulfonyl procedures has been used in industry, at least, before 1984.96 In the case of less complex molecules, for example, in the formation of (E,E)-1,3-dienes, the reactions are not accompanied by isomerisation. Therefore, (E )-homoallylic sulfones of the types 48 and 49 are convenient starting compounds. Elimination of sulfinic acid was used in the synthesis of pheromone components 50 and 51.97 a, b, c HO PhSO2 48 HO 7 50 PhSO2 a, e, c PhSO2 PhSO2 HO PhSO2 49HO 8 51 (a) BunLi; (b) THPO 7I; (c) H3O+; (d) ButOK, ButOH, D; I; ( f ) Na/Hg. (e) THPO 8 In the total convergent synthesis of the ionophore antibiotic indanomycin 52,98 the formation of the (E,E )-diene bridge Br MeO2C O H H Et MeO2C O H H Et 53 O H Et HO2C O H H Et 52 R=SiMe2But; (a) LDA, THF, 778 8C (97%); (b) triton B (BnMe3NOH), MeOH, 40 8C; (c) CH2N2, Et2O, 0 8C.PhSO2 d 7 f, d 8 ORH a PhSO2 + H Et PhSO2 ORH b, c H H Et OR 3 steps O H HN H Et E N Prilezhaeva between two cyclic fragments of the molecule occurred as elimi- nation of sulfinic acid involving only the hydrogen atom of the acyclic part of the intermediate sulfone 53. The synthesis of racemic lavandulol ()-54 involved formal replacement of the sulfonyl group.99 The intermediate sulfone 55 was hydrostannylated simultaneously with the elimination of sulfinic acid.The subsequent reaction of stannane 56 with trioxane in the presence of boron trifluoride etherate was accom- panied by elimination of Bun3 SnH and migration of the double bond. c a, b TolSO2 55 TolSO2 OH d SnBu3 56 ()-54 (a) BunLi; (b) Br (97%); (c) Bun3 SnH, AIBN (azobisisobutyro- nitrile) (97%); (d ) (CH2O)3, Et2O.BF3 (57%). c. Alkylation of a-sulfonyl carbanions with synchronous elimination of sulfinic acid For saturated molecules, alkylation of a-sulfonyl carbanions with elimination of sulfinic acid is exemplified by the reaction of alkylating reagents with a-carbanions derived from 2-sulfonyl- substituted cyclic ethers, viz., tetrahydropyrans or tetrahydro- furans 57a,b.The sulfonyl groups in tetrahydropyrans and tetrahydrofurans facilitate a-deprotonation. However, Ley and coworkers 100 found that an intermediate formed in the course of the subsequent reaction with an electrophile is stabilised due to synchronous elimination of sulfinic acid. Apparently, the driving force for this process is the formation of the endocyclicC=Cbond in the reaction products 58a,b. n a, b R1 R2 O58a,b n n c or a, d R1 R1 R2 SO2Ph O59a,b O 57a,b n a, e, f O R1 O 60a,b n =0 (a), 1 (b); (a) BunLi; (b) R2X; (c) R2MgX, ZnBr2; (d) R2X, C10H8Na; (e) I(CH2)4OTHP; ( f) H3O+.The reactions with Grignard reagents in the presence of zinc salts or with alkyl halides in the presence of sodium naphthalenide afforded tetrahydro derivatives 59a,b, which are the formal replacement products of the sulfonyl group, instead of dihydro- pyrans or dihydrofurans 58a,b. The reactions of the sulfones 57 with electrophiles containing a protected hydroxy group at the o-position are of considerable interest for the synthesis of certain natural compounds. These reactions afford spiroketals 60 because the hydroxy group of the substituent in the intermediate 58 immediately reacts with the nucleophilic double bond after deprotection in an acidic medium. The simplest examples of this approach are the syntheses of 1,7-dioxaspiro[5.5]undecane (61), which is a component of the pheromone of Dacus Olea 101 and of the so-called fruit flies particularly widespread in tropical coun- tries,102 as well as the syntheses of analogous compounds 62 and 63.101Sulfones and sulfoxides in the total synthesis of biologically active natural compounds O O O O O 63 62 O61 The construction of the spiroketal fragment in the total enantioselective synthesis of an ionophore routiennocin (64), which is a carrier of divalent cations, presented a more difficult problem.103 This problem was solved with the use of alkylation of the anions derived from sulfonyltetrahydropyrans 65 or 66.In both cases, spiroketal 67, which is the necessary precursor in this synthesis, was obtained. I + O O OBn O PhSO2 65 ...I O O + OSiPh2But PhSO2 H O 66 OH O H N ... CO2H HO O O (CH2)2OH O O 67 HN O 64 Total syntheses of polyfunctional macrolides of the avermec- tin ± melbemycin family, which were discovered about 20 years OR1 R1O a, b, c + Br O O 71 72 R1O R1O O Me 2 steps O H Et 74 OR2 R1O O R3 Me O H Et ... OR2 HO CH2OR1 O 77 OR1 MeO MeO O R1 and R2 are protective groups; R3=HO O; (a) ButLi; (b) Me3Al; (c) ButMe2SiCl, DMAP (4-dimethylaminopyridine), O O (73); ( f) BF3 . Et2O; (g) Et3N, DMF; (d) BunLi; (e) Me O PhSO2 H Et ago,{ present a major achievement by Ley and coworkers. These compounds exhibit a very broad spectrum of antiparasitic, including antihelminthic, activities, and their use in medical practice is recognised to be an impressive breakthrough.104 Ley and coworkers started their studies in this field with the development of a procedure for the synthesis of substituted spiroketals by reactions of anions generated from 2-sulfonylte- trahydropyrans with new reagents, viz., alkoxy-substituted epox- ides of the type 68.For example, this procedure was used for the synthesis of a minor component (69) of the pheromone of olive moth.105 7 + SO2Ph O OTHP CH2(CH2)2 (a) BunLi,778?20 8C; (b) (7)-camphorsulfonic acid. Syntheses of the most important representatives of this series, viz., avermectin B1a (70) 106 and melbemycin b1 (as the agly- cone),107 are characterised by the elegant and versatile applica- tions of sulfonyl and other building blocks.The key steps of the total synthesis of avermectin (70) containing 30 stereogenic centres, five C=C bonds with a fixed configuration and numerous functional groups are given in Scheme 5. In particular stages of the synthesis, the intermediates were compared with the degradation products of natural aver- mectin. The first step of the synthesis of the macrolide 70 involved { Avermectin was isolated from actinomycete MA-46650 in 1978.104 OR2 R1O d, e, f O O O CHO 75 OR223 22 O 13 17 15 O 25 19 11 10 O O 1 HO 3 7 4 O 70 OH CH2SO2Ph R1OCH2 OH ; (h) Na/Hg. O (76) OR1 CH2CH2OTHP O 68 OH O OR2 OH Me d, g, h H EtMe H Et 375 ab O HO O 69 Scheme 5 Me 4 steps O H Et376 the reaction of enantiomerically pure diepoxide 71 [an important synthon for the C(17) ± C(19) fragment] with a vinylic bromide 72 to form a substituted epoxide.Subsequent reactions with sub- stituted 2-sulfonyltetrahydropyran 73 followed by transforma- tions required for the formation of the C(22)=C(23) bond afforded spiroketal 74, which is the `northern' [C(11)7C(25)] hemispherical fragment of the macrolide 70. The terminal C=C bond in the compound 74 was converted into the aldehyde group in two steps. The reaction of the intermediate 75 with the anion generated from allylsulfonyl synthon 76 resulted in the formation of the (E )-C(10)=C(11) bond (the Julia olefination, Section III.2.a).Compound 77 contained *12% of an admixture of the (Z)-C(10)=C(11) isomer. The completion of the synthesis involved the macrolactonisation of the intermediate 77 following oxidation at C(1) with simultaneous formation of the C(3)=C(4) bond and the attachment of the disaccharide residue R3, which was obtained from oleandrose, at C(13). The synthesis of a somewhat less complex molecule, viz., melbemycin b1 (78), was carried out according to an analogous scheme.107 The major synthons in this scheme are either identical to compounds used for the preparation of avermectin (70) (for example, diepoxide 71) or differ only in the functional groups (synthons 79, 80 and 81 correspond to compounds 72, 73 and 76, respectively).The formation of spiroketal is also a fundamental step in the construction of the `northern' fragment. The coupling of the `northern' and `southern' fragments to form the (E )-C(10)=C(11) bond was performed by the reaction of the aldehyde group of the `northern' fragment with the a-sulfonyl carbanion of the `southern' fragment. This reaction is not the standard olefination procedure according to Julia because the C(9)=C(10) double bond is converted into the required C(10)=C(11) bond.107O O I 71 79 OSiPh2But O 15 O 25 19 11 PhSO2 10 O80 O O 1 HO PhSO2 3 80 10 OSiPh2But 5 OH 7 78 OMe O 5 O Ph 81 OH The common feature in the syntheses of the macrolides 70 and 78 is the method of formation of the trisubstituted C(14)=C(15) bond.This bond is introduced upon reactions with the halide synthons 72 or 79. This makes it possible to circumvent the difficulties encountered in earlier studies (see Section III.2.a) in attempting to construct this bond with the use of sulfonyl or sulfinyl precursors. 2. Addition to oxygen-containing electrophiles a. Addition of a-sulfonyl carbanions to carbonyl groups of aldehydes and ketones Lythgoe 108 and Kocienski 109 ± 111 have shown that an important problem of olefination (coupling of synthons with the stereo- specific formation of the C=C bond) can be solved by reductive elimination of 2-hydroxy sulfones, which are prepared by the reactions of aldehydes with a-sulfonyl carbanions, proposed by E N Prilezhaeva Julia and Paris.36 This procedure is an excellent alternative to the phosphonate Wittig method. The optimum conditions for olefi- nation were found, viz., acetylation or benzoylation of the hydroxy group and reductive elimination with sodium amalgam in a mixture of methanol with tetrahydrofuran or ethyl acetate.112 In studies of the scope and limitations of this reaction, it was demonstrated that E-disubstituted double bonds can be formed with a stereoselectivity of *80%± 100%.The stereoselectivity is enhanced in the case of chain branching at the b-position with respect to the double bond, whereas a substituent at the a-position hinders the reaction.113 Trisubstituted C=C bonds are formed with difficulty and the stereoselectivity of this process is low, whereas attempts to obtain tetrasubstitutedC=Cbonds failed.109 Since the stereochemistry of the initial acyloxy sulfone (threo-, erythro- or a mixture of both forms) has no effect on the stereo- selectivity of the formation of the C=C bond, it was suggested that this process occurs via a common intermediate 82 formed upon reductive elimination of the sulfinate anion or from the diastereomers 83a or 83b.109, 113 The intermediate 82 is long-lived enough to assume the conformation favourable for elimination of the acyloxy anion.This may not be the case with ketones exerting steric hindrances, which explains the fact that olefination with the use of acyloxysulfonyl derivatives prepared from ketones is not always successful.Recently, a more intricate mechanism of the olefination has been proposed.114 However, none of the suggested reaction schemes was confirmed by quantitative methods, for example, by kinetic methods. AcO AcO e7 R1 H 7PhSO¡2 H H R2 83a,b 82 R1=H, R2=SO2Ph (a); R1=SO2Ph, R2=H(b). Below are summarised the results of the use of this method- ology in the syntheses of natural compounds performed by Kocienski and Lythgoe with their coworkers. This procedure was used for the formation of the (E )-C=C bond in the alcohol 84, which is the key intermediate in the synthesis of calciferol,115 and for the preparation of different modifications of vitamin D, a, b, c PhSO2 AcO d PhSO2 BzO H 84 HO H CHO (a) BunLi; (b) ; (c) Ac2O; (d ) Na/Hg, MeOH, AcOMe.BzO H OH OH 86 85Sulfones and sulfoxides in the total synthesis of biologically active natural compounds including a-hydroxy vitaminD3 (see Ref. 116) and vitaminD4 .117 (More recently,118 25-hydroxy vitamin D2 was prepared accord- ing to an analogous procedure with the use of ethylmagnesium bromide instead of BuLi for deprotonation). This scheme was applied to the synthesis of the major C25 segments (85 and 86) for the preparation of the antibiotics moenocinol119 and diumyci- nol,120 respectively. Later, the Julia olefination (which is sometimes called the Julia ± Kocienski or the Julia ± Lythgoe olefination) has found wide application in the synthesis. Thus this procedure was used in the synthesis of botryococcene 87 (Scheme 6), which is an algae hydrocarbon. The compound 87 has a specific branched structure.The product of its exhaustive hydrogenation (88) is a promising biological marker in petroleum production.121 SO2Ph HO PhSO2 (a) BunLi; (b) CHO Olefination is the major stage in the total syntheses of a number of biologically active long-chain compounds. This reac- tion has been used in the formation of the (E)-C(10)=C(11) bond in the antibiotic pseudomonic acid C (89),122, 123 the C(16)=C(17) bond in the antibiotic ionomycin (90) responsible for the transport of Ca2+ ions 124, 125 and the C(7)=C(8) bond in the diene frag- ment of curacin (91) exhibiting antitumor activity.126 To construct the double bond between the piperidine and decahyd- OH5 HO 10 HO O 11 23 H O 21 O HOH OH 17 H 16 O O 9 11 90 8 7 OMe 91 NR H H O H H O 92a,b [R=Me (a), H (b)].Scheme 6 a, b c, d 87 88 ; (c) Ac2O; (d) Na/Hg; (e) Pd/C. O 7 CO2H O 8931 OH (CH2)2CO2H S N H H 16 14 O 13 17 15 12 O 18 19 11 10 O 9 1 O 8 7 2 3 6 5 4 93 377 e ronaphthalene fragments in the synthesis of alkaloids (+)-himba- cine (92a) and (+)-himbeline (92b), the aldehyde and sulfonyl groups should be bound to the pyrimidine and decahydronaph- thalene synthons, respectively,127 otherwise steric hindrance to olefination occurs. One of the double bonds of the 1,3-diene system of indanomycin was also formed according to this proce- dure.128 The Julia olefination is often used for the introduction of C=C bonds into the starting compounds which are subsequently employed in total syntheses.For example, double bonds in the following fragments were formed according to this procedure: in the C(1)7C(22) fragment for the construction of immunodepres- sant FK,129 in the C(22)7C(31) fragment of an intermediate for the macrolide antibiotic roxaticin 130 and in the triene group of the C(10)7C(27) fragment used in the synthesis of the immunode- pressant rapamycin.131, 132 In the total synthesis of the antitumor macrolide aplyronine, coupling by the reaction of the a-sulfonyl anion with the aldehyde group was employed twice.133 When the C(3)7C(17) fragment was constructed in the synthesis of boro- mycin, the intermediate 2-hydroxysulfonyl unit was used for the stereoselective formation of the hydroxy group rather than for the introduction of the double bond.134 The Julia olefination was also used in the total syntheses of the majority of macrolides of the avermectin � melbemycin group, for example, of avermectin B1a (Ley et al.,106 Hanessian et al.135 and White et al.136), as well as of the simplest compound of this group, viz., melbemycin b3 (93), which served as the favourite subject in earlier synthetic studies performed by Kocienski,137 Baker 138 and Barrett 139 with their coworkers.The Julia procedure was used for the coupling of large frag- ments which have been synthesised beforehand and already contained the required chiral centres.Macrolactonisation was performed in the final stage of the synthesis. In the synthesis of these very complex systems, the previously established regularities hold on the whole. The formation of the disubstituted C(10)=C(11) bond occurs most readily and with a high stereo- selectivity, particularly, when the aldehyde group is bound to the C(11) atom of the `northern' fragment, while the sulfonyl group is bound to the C(10) atom of the `southern' fragment.106, 137 When the functional groups are located in the reverse order, the results are somewhat worse.135, 138 When the ketone was used in place of the aldehyde for the formation of the C(8)=C(9) bond of avermectin B1a [the carbonyl group at the C(8) atom of the `southern' fragment and the sulfonyl group at the C(9) atom of the `northern' fragment],136 the reaction was complicated by lactonisation of the intermediate. The formation of the trisubsti- tuted C(14)=C(15) bond with the use both of the ketone 136 and aldehyde 139 versions of olefination occurs in low yield and affords an admixture of an undesirable regioisomer.With the aim of constructing this bond, more sophisticated approaches, though also based on reactions of sulfoxides and sulfones, were applied.136, 139 Kocienski was the first to note 109 that the use of olefination for the preparation of large amounts of compounds is hampered by the necessity of consuming a considerable amount of amalgam for desulfonation. Presently, a number of procedures free of this drawback are available.Thus it is believed 140 that reduction with magnesium in ethanol upon catalysis with mercuric chloride occurs due to in situ formation of magnesium amalgam. It was also recommended to use SmI2 in THF141 or HMPA.141, 142 In the latter case, a trisubstituted double bond is successfully formed from ketones and primary sulfones, though only in low-molec- ular-weight model compounds. Reactions of a-sulfonyl anions with aldehyde groups have also been used for the coupling of bulky, e.g., cycloaliphatic, segments. This coupling not necessarily involved the formation of the C=C bond, but sometimes occurs through hydroxy- or oxo-functional- ised saturated units. The key steps in a multistep (more than 100 steps) enantio- and stereospecific total synthesis of okadaic acid 94 , which is a378 potential antitumor drug,{ involved couplings of the segments A, B and C, which have been prepared according to the retro- synthetic approach, in the order (B+C)+A (the atomic num- bering scheme corresponds to that used for okadaic acid).144 ± 147 OH O H O O 13 14 HO O O 27 29 O 15 OH H O O HO H H H 94 H OHOMOM OR PhSO2 O O H O 13 15 14 O 14 27 O H OBn CHO H O BnO O A B (R=But, Ph) O 28 29 O PhSO2 H C MOM is methoxymethyl.D-Glucose derivatives served as chiral pools for the construc- tion of the segments A, B and C. The OH group at C(27) was obtained by transformation of the 2-hydroxysulfonyl grouping formed by the reaction of the aldehyde group of the segment B with the anion from the sulfone C, and the C(14)=C(15) double bond was formed according to Julia with the participation of the sulfonyl centre of the segment A.The stereoselective introduction of the methyl groups at C(13) in the segment A145 and at C(29) in the segment C147 was performed according to `heteroconjugate addition' to a-silyl vinyl sulfones developed by Isobe and co- workers (this procedure will be considered in more detail in Section V.1). The final steps in the total synthesis of acid 94 with the construction of all its 17 chiral centres involve deprotection of the functional groups and conversion of 1,2-acetonide into the hydroxy acid. The use of intramolecular reactions of a-sulfonyl carbanions with aldehydes 148 ± 151 is exemplified by the synthesis of tetrono- lide 95, which is the aglycone of the antitumor antibiotic tetro- carcin,148, 149 as well as by the construction of a bicyclo- [13.3.0]octadecane core 96 for the synthesis of terpestacin and of a 14-membered core 97 for the preparation of sarcophytol A.150 Syntheses of the compounds 96 and 97 involved oxidation of hydroxy groups to carbonyl groups followed by reductive removal of the sulfonyl group (Scheme 7), while the synthesis of the compound 95 additionally involved stereospecific reduction of the carbonyl group to the hydroxy group.Attempts to use this approach in the synthesis of the antitumour antibiotic lankacidin were unsuccessful.Apparently, this is associated with the use of the imidazolesulfonyl group.152 CHO HO HO MeO O O O H H H 95 OH { It was believed 143 that acid 94 and its esters isolated from marine algae are toxins, which cause mortality of the gastroenteritis type as a result of diarrhetic shellfish poisoning. E N Prilezhaeva Scheme 7 O OHC PhSO2(CH2)2 a, b, c O O O O 96 Pri Pri d, b, e O CH2SO2Ph CHO 97 (a) LiHMDS, PhH, 25 8C; (b) oxidation; (c) Al/Hg; (d ) LiHMDS, PhH, 22 8C, 5 min; (e) SmI2 , THF. The Z-olefination method, which has also been developed by Julia,37 is applied more rarely than the E-version. In this case, a mixture of diastereomeric acyloxy sulfones generated originally was treated with a strong base followed by desulfonylation of an intermediate (Z)-vinyl sulfone to form (Z)-alkene.This proce- dure was used for the preparation of components of the pher- omones 98a ± c [98% of the (Z)-isomers],37 dehydro-(Z)-12- squalene (99a) and (Z)-16-phytoene (99b) (in both cases, the selectivity was*87%).153 In the latter case, the aldehyde compo- nent was generated in situ by oxidation of a portion of the a-sulfonyl carbanions 100. SO2Ph AcO a 7 b SO2Ph OAc +CH O n m n OLi m c, a SO2Ph OH OAc n m n m 98a ± c n=2, m = 7 (a); n=1, m = 8 (b); n=3, m=8(c). SO2Ph R2 R2 e, f d 7 CHO CH R1 R1 100 R2 R2 SO2Ph R1 g, h R1 R1 R1 R2 99a,b AcO R2CH2 , R2=Me; 99a: R1= CH2 , R2=Me; 99b: R1= 2 (a) Ac2O; (b) NaOH; (c) Na2S4O6; () MoO5 , Py, HMPT; (e) 100; ( f) Ac2O, Et3N; (g) NaH, THF; (h) BunMgX, Ni(acac)2 .Later on, Moiseenkov and Nefedov with coworkers 154 ± 156 slightly improved the procedure forZ-olefination and applied it to the synthesis of trideca-(4E),(7Z)-dien-1-yl acetate (101) (the potato moth pheromone) 155 and (E,Z)- and (E,E,Z)-acetogenin C5H11 AcO(CH2)3 101 Bun (CH2)3OAc 102 Bun (CH2)8 (CH2)2OR 103a ± b R=Ac (a), H (b).Sulfones and sulfoxides in the total synthesis of biologically active natural compounds Bun (CH2)8 (CH2)3 Bun 105 104 O O pheromones 102 and 103a,b.155 The previously unknown cyclo- propane ketones 104 and 105 served as the key compounds in the syntheses of the latter compounds (in the schemes, the double bonds formed with the use of the a-sulfonyl carbanions are indicated by arrows).Otera and coworkers 157 ± 160 elaborated a procedure for the transformation of ethers of 2-hydroxy sulfones through double elimination. This procedure extends the possibilities of applica- tion of reactions of sulfonyl carbanions with aldehydes. Initially, acyloxy or alkoxy groups in esters and ethers of 2-hydroxy sulfones are eliminated under the action of a strong base (gen- erally, ButOK) followed by dehydrosulfinylation of vinyl sulfone to form the acetylene bond. If allylic isomerisation can occur in the stage of generation of unsaturated sulfone, an E,E-diene system is formed. The latter procedure has been used 159 for the preparation of piperine 106, which is one of the components of black pepper, starting from the aldehyde 107.Yet another natural dienamide, viz., trichonine (108), was also prepared according to this proce- dure [85%, 10% and 5% of the (2E,4E )-, (2E,4Z)- and (2Z,4E)- isomers, respectively].160 O PhSO2 CH2SO2Ph O a, b, c d N O OAc O O N O 106 O PhSO2 7 d e, f Me(CH2)14CHLiSO2Ph N Me(CH2)14 OAc O N Me(CH2)14 108 (82%) O N (a) BunLi; (b) OHC (107); (c) Ac2O; (d) ButOK, ButOH; (e) 107; ( f) Ac2O, Py. An ingenious convergent (C10+C10) scheme for the synthesis of vitamin A was also developed.161, 162 Tetrahydropyran-2-yl ethers of 2-hydroxy sulfones proved to be the starting compounds of choice for this sequence of reactions.In the first step, the second allylic bond was established with respect to the sulfonyl group. Elimination of sulfinic acid from the intermediate A occurred with the participation of the remote allylic hydrogen atom at C(12). The resulting vitamin A contained>85% of the all-trans isomer; PhSO2 CH2SO2Ph a, b, c OAc d OTHP H PhSO2 OH H A , H+; (a) BunLi; (b) OHC OAc; (c) O (d ) MeOK, cyclo-C6H12 , 35 8C. this amount is substantially greater than those obtained with the use of other sulfonyl methods (see Section III.1.b). b. Addition of a-sulfinyl carbanions to carbonyl groups of aldehydes and ketones As mentioned above (Section II), epimeric mixtures of 2-hydroxy sulfoxides formed in the reactions of aldehydes with a-sulfinyl carbanions are rather rarely used in the synthesis of natural products. The synthesis of the enantiomerically pure pheromone (+)-(7R,8S )-disparlure (109) by the reaction of the correspond- ing aldehydes with enantiomerically pure (S )-tert-butyl 6-meth- ylheptyl sulfoxide (110) 163 or (S )-a-chlorododecyl tolyl sulfoxide (111) is one of a few examples.164 O a, b S But (CH2)5Pri (S)-110 O (CH2)4Pri (CH2)9Me SH But112 OH H O g, h S Tol CH(CH2)9Me (S)-111 Cl O k S Ph CH2CO(CH2)4Pri 115 OH O S Ph (CH2)4Pri C10H21 (a) ButLi; (b) Me(CH2)9CHO (45%); (c) SnCl2 , AcCl; (d ) LiAlH4 ; (e) Me3OBF4 ; ( f ) NaOH; (g) LDA; (h) Pri(CH2)4CHO (39%); (i) ButOK, ButOH; ( j) BunLi, THF,7100 8C; (k) Bun2 AlH; (l ) MeLi; (m) C10H21I; (n) Zn, Me3SiCl.The total yield of the compound 109 was low because hydroxy sulfoxides 112 and 113 were obtained as mixtures of diastereo- mers. The procedure with the use of enantiomerically pure 2-hydroxy sulfoxide 114, which is prepared by stereoselective reduction of oxo sulfoxide 115, is approximately twice as effi- cient.165 The ratio of the diastereomers in a mixture of 2-hydroxy sulfoxides depends on the nature of substituents in the initial sulfoxide and aldehyde. Stork and coworkers 166 reported that the reaction of sulfoxide 117 with ketone 118, which was used in a rather simple synthesis of protected chiral polyol 116 containing all 10 asymmetric centres of the secoacid of the aglycone of erythromycin, afforded a mixture of 2-hydroxy sulfoxides con- taining 80% of the target epimer.Compound 119 was obtained [the C(1)7C(12) fragment with the required configuration; the HO SOPh EtCO a, b O O 117HO HO EtCO O O PhSO O 379 O H H c, d, e, f (CH2)4Pri Me(CH2)9 109 O (CH2)9Me i, j OH 109 Tol H (CH2)4Pri S C Cl 113 OH O l, m S Ph (CH2)4Pri 114 n, e, f 109 CH2OSiPh2But O 3 steps380 HO HO Et CH2OH O OH O O O 116 MeCO CH2OSiPh2But (a) 3 equiv. of LDA; (b) (118). O O BnO(CH2)2 a, b, c SOTol O O OH BnO(CH2)2 CH2OSiMe2But O O O O 119 OHC OSiMe2But (a) BunLi, THF; (b) ; (c) Ra/Ni, Me2CO. O O admixture of another isomer was <7%] in the course of con- struction of the aglycone of amphotericin B.167 The formation of the benzyl ether of (S )-chroman-2-carb- aldehyde [(+)-(S )-120], which is the key intermediate in the synthesis of vitamin E,168 proceeded exclusively stereo- and enantioselectively due apparently to the influence of the adjacent C=C bond on the carbanionic centre of lithiated sulfoxide 121.O OH Tol O Tol S R1O CHO R1O S Li a, b + OR1 R2 R2 OR1 121 O Tol HO S BnO c, d, e R2 O O CHO (+)-(S )-120 R1=SiMe2But; R2=(MeO)2CH; (a) Bun4 NF; (b) MeONa, MeOH; (c) Ra/Ni; (d ) BnBr, K2CO3; (e) CF3CO2H, H2O. The stereo- and enantioselectivity of the reactions of a-sulfinyl carbanions with aldehydes increases in the presence of alkoxycar- bonyl groups adjacent to the carbanionic centre.12 This can be demonstrated by syntheses of enantiomerically pure pheromone lactams 169 and maytansin 170 exhibiting antitumour activity.Macrocyclic lactones of the type 122, in particular, 16-mem- bered (7)-pyrenophorin (123), were synthesised 171 using intra- molecular ring closure based on the reaction of the a-sulfinyl R (CH2)n71 R a S O (CH2)nCHOAr O O OH O 122 (30% ± 81%) O NH, MeCN, Ar=4-ClC6H4; R=H, Me; n=8, 10; (a) 20 8C, 2 ± 6 days. O O O O O O (7)-123 E N Prilezhaeva carbanion with the aldehyde group. This reaction proceeds under very mild conditions and occurs according to a more complex mechanism rather than the ordinary 1,2-addition at the carbonyl group; this is typical of sulfoxides containing an electron-with- drawing group at the a-position.It is believed that this reaction proceeds via a,b-unsaturated sulfoxide A, which undergoes allylic isomerisation to sulfoxide B followed by the sulfoxide ± sulfenate rearrangement to sulfenate C. In the presence of bases, the latter gave the reaction product D.172 ± 174a R2R3CHCH C(Z)SR1 R1S(O)CH2Z+R2R3CHCHO O A R2R3CCH CHZ R2R3C CHCH(Z)SR1 C B OSR1 O R2R3C(OH)CH CHZ D Z=CO2R, CN, COR; (a) NH, 20 8C. Since a-sulfinyl-substituted carbonyl compounds are most commonly used as the starting materials in this reaction, the latter is abbreviated to SPAC (Sulfoxide Piperidine and Carbonyl). c. Reactions of a-sulfonyl carbanions with esters If a molecule contains both the aldehyde and ester groups, the former is the first to react with the a-sulfonyl carbanion, as is the case, for example, in the synthesis of alternaric acid 175 or the antibiotic A-8558G.176 In the absence of such competition, the reactions involving ester groups, including lactone groupings, proceed readily.Reac- tions of a-sulfonyl carbanions with esters were used for the construction of the intermediates 124a,b in the syntheses of components of pheromones of peach moth, viz., of (Z)-eicos-13- en-10-one (125a) and (Z)-nonadec-12-en-9-one (125b).177 Julia and coworkers 178 prepared the pheromone of yellow scale (127) starting from enantiomerically pure lactone (R)-126. In this syn- thesis, advantages were taken of yet another interesting reaction, which has been discovered in the same laboratory,41 viz., the replacement of the sulfonyl group in the intermediate 128 under the action of isopropylmagnesium chloride in the presence of FeCl3 .c, d a, b RCHC(O)(CH2)2CH(OMe)2 RCH2SO2Tol SO2Tol e C6H13 RCH2C(O)(CH2)2CHO 124a,b RCH2C(O)(CH2)2 125a,b R=C8H17 (a), C7H15 (b); (a) LDA; (b) MeO2C(CH2)2CH(OMe)2 ; (c) Al/Hg; (d ) 3%HCl, H2O; (e) C6H13C=PPh3 . SO2Ph a, b O H 3 steps OH PhSO2 H c OAc 128 PhSO2 H OAc Pri (+)-(R)-127 O H O[(R)-126]; (c) PriMgCl, FeCl3 . (a) BunLi; (b)Sulfones and sulfoxides in the total synthesis of biologically active natural compounds The reaction of the sulfonyl anion with the ester group served as the key step 179 in the stereocontrolled synthesis of pseudoan- nonacin A.The oxo sulfone 22a, which is the reaction product of lithiated methyl phenyl sulfoxide with protected alanine methyl ester 129,180 was used in the synthesis of isosteres of peptides.80 O O H BocN PhSO2CH2Li H BocN OMe THF, 778 8C SO2Ph 22a 129 The reaction of a-sulfonyl anions with esters was used as the key step in the construction of the macrolide brefeldin A (130) (which is related to prostaglandin and is a highly active fungicidal and antitumour drug,181, 182) and of the corresponding secoacid 131.183 The compound 130 was prepared both in racemic and optically active forms, whereas the acid 131 was obtained only in the optically active form. In all three cases, the lower branch was constructed via substituted oxo sulfones 132 ± 134 using similar procedures (Scheme 8).The phosphonate method was used for the construction of the (E )-C(10)=C(11) bond in brefeldin (130),181, 182 while Trost et al. 183 made use of the Julia methodology to form this bond in compound 131 } following reduction of the oxo group in the intermediate 134 to the hydroxy group. The C(2)=C(3) bond and the chiral centre at C(4) were generated with the use of various procedures for the introduction of the sulfinyl group 181, 183 followed by thermolysis. This methodology is described in more detail in Section IV. The intramolecular reactions under consideration have also been used for the synthesis of polycyclic terpenoids, for example, trinoranastreptene 185 or precursors for guaiane terpenoids.186, 187 A general procedure for the synthesis of terpenoids with fused } An analogous procedure was used for the construction of the lower branch in more recent syntheses of brefeldin.184 CO2R2 CO2R2 CO2H R1O 2 steps a, b c, d, e O O 3 O OH OBn 132 3 PhSO2 CH2OCOPh f 10 steps R3O R3O O 3 OR3 O 133 O PhSO2 O O H H O O h, i, j g R4O R4O O OR5 CO2Me H H 3 134 PhSO2 SOPh OR6 H 3 steps CO2MeOR5 R4O R4O H 7 7 7 R1±R5 are protective groups; (a) PhSO2CH(CH2)3CH(OBn)Me; (b) R2Cl, EtPri2N; (c) Me2SO, NaOH; (d ) BrCH2CO2Me; (e ) D; ( f) PhSO2CH(CH2)3CH(OR3)Me; (g) PhSO2CH(CH2)3CH(OR5)Me (90%± 96%); (h) NaBH4; (i) Ac2O; ( j ) Na/Hg, Na2HPO4 (65%).381 medium-sized rings involving intramolecular reactions of a-sul- fonyl carbanions with esters was also proposed.188 d. Reactions of a-sulfinyl carbanions with esters Owing to the development of enantioselective procedures for the reduction of oxo sulfoxides,12, 27 which can be readily prepared by reactions of a-sulfinyl carbanions with esters, enantiomerically pure chiral 2-hydroxy sulfoxides became readily accessible com- pounds and found wide use in asymmetric synthesis, including the preparation of biologically active compounds.12 Thus 4-substituted butenolides 135a,b both with the R- and S-configurations of the asymmetric centre were prepared from the same oxo sulfoxide 136a or 136b.189 The high enantioselectivity in the synthesis of 2-hydroxy sulfoxides 137a,b, which are required for the preparation of R-enantiomers of butenolides 135a,b, was achieved by the addi- tion of ZnCl2 in the course of hydride reduction of the oxo sulfoxides 136a,b. In this case, a rigid chelate complex of zinc O O a b Tol SCH2COR RCO2Et+ MeS 136a,b Tol O OH S 4 steps R Tol O RH O (R)-135a,b 137a,b O OH 4 steps S c Tol R 136a,b O HR O (S )-135a,b 138a (de 86%), 138b (de 90%) R=But (a), C8H17 (b); (a) LDA; (b) Bui2AlH, ZnCl2; (c) Bui2AlH. involving both functional groups of the oxo sulfoxide was formed as a result of which the hydride attack occurred from the required side.Reduction of the oxo sulfoxides 136a,b without addition of Scheme 8 OH O O H 2 O 4 CO2R2 3 steps 3 15 HO H 11 OH 3 10 H ()-130 (+)-130 O H O 5 steps R4O OR5 H 3 OH H CO2HOH H 131382 ZnCl2 afforded hydroxy sulfones 138a,b with a high diasteroese- lectivity.The latter were transformed into the S-enantiomers of the butenolides 135a,b. An analogous approach was used in the synthesis of macro- lides for the preparation of enantiomerically pure diethers of lasiodiplodins, (R)- and (S )-139.190 Epimeric 2-hydroxy sulfox- ides 140 were synthesised by the reduction of oxo sulfoxide 141 in the presence or in the absence of ZnCl2. It should be noted that when the compound 141 was prepared from diester 142 and the chiral sulfinyl anion, only the methoxycarbonyl group of the aliphatic chain was involved in the reaction, while the methoxy- carbonyl group in the aromatic ring remained intact and was subsequently used for the construction of the macrolide lactone fragment.OMe OMe CO2Me a b, c O CO2Me O S CO2Me 7 7 MeO MeO Tol 141 142 OMe O OMe O O 3 steps CO2Me OH S MeO 7 MeO Tol (R,S,R)-140 (S )-139 OMe OMe O d 3 steps CO2Me OH O O 141 7 MeO MeO Tol (R)-139 (SS,R)-140 O (a) 2.2 equiv. of LiCH2S , THF,778 8C; (b) ZnCl2; Tol (c) Bui2AlH, 20 8C (de>95%); (d) Bui2AlH, THF,778 8C, (de 86%). Chiral sulfinyl groups of 2-hydroxy sulfoxides served as inductors in diastereospecific syntheses of the protected secoacids 143 and 144 representing degradation products of the macrolides (R,R)-pyrenophorin and (R)-patulolide A, respectively.191 The g-hydroxy-a,b-unsaturated fragment of the secoacid 144 was constructed by the SPAC-type reaction of aldehyde 145 with the ethyl sulfinylacetate anion.172 ± 174 OMEM OEt EtO 3 CO2Et CO2H (R)-144 (R)-143 OH OSiMe2But MEM is (2-methoxyethoxy)methyl.a, b, c d ArS 5 HO2C(CH2)7CO2Et CO2Et O O 4 steps 5 ArS CO2Et OH O e, f CHO 5 (R)-144 OSiMe2But 145 O Me NH; (c) S (a) (COCl)2, PhH; (b) N ; (d) Bui2AlH, Ar NH, MeCN; THF,778 8C; (e) PhS(O)CH2CO2Et, ( f ) MeOCH2CH2OCH2Cl. E N Prilezhaeva In the synthesis of (7)-(R)-yashabushiketol 146, which is a rare representative of natural compounds containing a chiral hydroxy group at the b-position with respect to the carbonyl group, the hydroxysulfonyl intermediate was converted into the target ketol through the formation and cleavage of chiral epoxide 147.192 O O O c, d a, b S S Ph Me Tol Tol O O H OH 2 steps e S Ph (CH2)2Ph Tol (+)-(R)-147 2 steps S S OH Ph Ph OH O Ph Ph (7)-(R)-146 (a) LDA, THF, 778 8C; (b) Ph(CH2)2CO2Me (87%), [(+)-(R)]; S .(c) ZnCl2; (d) Bui2AlH; (e) BunLi, Ph S Syntheses of brefeldin A (130) performed predominantly with the use of sulfinyl-containing intermediates or auxiliary reagents are presented below. Solladie et al.193 prepared a chiral cyclo- pentane precursor 148 with the use of enantiomerically pure 2-hydroxy sulfoxide 149, which had been synthesised from sub- stituted cyclopentane 150 in two steps.The formation of chiral centres at C(4) and C(15) in the brefeldin molecule was completely controlled by the sulfinyl group of the compound 149. The (E )-C(10)=C(11) bond in the fragment 151 was formed using the Julia olefination with the participation of the aldehyde group of the precursor 148.193 O OH S CO2Me Tol 5 steps a, b RO CH2OBn CH2OBn 149 150 O O O O c, d, e 6 steps OSiMe2But CHO 148 151 3 OR CO2Me 5 steps (+)-130 RO OSiMe2But 3 R=MEM; (a) 2 equiv. of LiCH2S(O)Tol; (b) Bui2AlH, ZnCl2; 7 (c) PhSO2 OSiMe2But ; (d) Ac2O, Py; (e) Na/Hg (80%). 3 Two analogous schemes proposed by Corey (R1=MOM, R2=Me) 194 Ar=Tol, (R1=MEM, and Nokami Ar=4-ClC6H4, R2=Et) 195 for the construction of the g-hydroxy-a,b-unsaturated C(4)7C(15) fragment of the brefeldin molecule are based on a simplified approach using the SPAC reaction.These schemes involve the reaction of aldehyde 152 with chiral arylsulfonylacetates in the presence of piperidine as the key step.Sulfones and sulfoxides in the total synthesis of biologically active natural compounds O CH2CO2Me S CHO Ar OSiMe2But R1O 3 NH, MeCN 152 OH CO2R2 ... (+)-130 R1O OSiMe2But 3 A new approach to the synthesis of carbohydrates 196 and to the preparation of (+)-nonactic and 8-epi-nonactic acids, which served as the starting compounds in the synthesis of the macrolide antibiotic nonactin,197 was developed using 2-hydroxy sulfoxides as precursors. A modification of this method involving the reaction of homochiral sulfinyl ketones with Et2AlCN made it possible to prepare alkylglycidic acids with ee 97% and a highly reactive hypoglycemic agent (+)-(R)-palmoxirate.198 e. Reactions of a-sulfonyl carbanions with oxiranes Reactions of a-sulfonyl carbanions with oxiranes give rise to g-hydroxysulfones (see Scheme 1, path d).Both the intermolecu- lar and intramolecular versions of these reactions are applied to the synthesis of natural compounds. These reactions are often used in the initial stages of syntheses of polyfunctional molecules, such as an inhibitor of cholesterol biosynthesis 153,199 compound O a, b PhSO2 3 OCH2OH O 11 steps DPSO O HO PhSO2 HOCH2 CO2H 3 O 153 O CH2OH .DPSO=ButPh2SiO; (a) EtMgBr; (b) BunLi, DPSO O O SO2Ph a, b, c, d O OMPM O C6H4OBOM-3 O OMe OMPM 154 C6H4OBOM-3; O MPM=4-MeOC6H4CH2; (a) 2 equiv. of BunLi; (b) (c) Na/Hg; (d ) MeI, KOH. (CH2)9SO2Ph TBSO(CH2)3 a, b, c, d OMOM MOMO (CH2)3OTBS Me(CH2)9 9 O OMOM O 155 OMOM Me(CH2)9 , TBS=ButMe2Si; (a) BunLi; (b) O O O OH DME, 20 8C; (c) MOMCl, Pri2NEt; (d ) Na/Hg, EtOH. 383 154 (which is a fragment of the tumour promoter debromoaply- siatoxin) 200 and the key fragment 155 for the construction of the antitumour acetogenin (+)-bullatacin.201 In the total synthesis of the amino acid hypoglycine A (156) containing a methylenecyclopropane fragment, epoxide-ring opening was employed twice.202 The intermediate 157 was con- structed by intermolecular reaction with an a-sulfonyl carbanion, whereas the three-membered ring in the key compound 158 was formed by an intramolecular reaction.Me3SiCH2 c a, b OTs Me3Si(CH2)2SO2Ph OH PhSO2 157 Me3SiCH2 d O PhSO2 CH2OH 5 steps H Me3SiCH2 NH + 3 PhSO2 CO¡2158 (2S,4R)-156 CH2OTs; (c) K2CO3 , MeOH, THF; (d ) LDA, THF. (a) BunLi; (b) O The synthesis of the enantiomerically pure piperidine alkaloid (+)-nitramine (159) 203 is yet another example of a ring closure through the intramolecular epoxide-ring opening. Oxirane was used for the preparation of the intermediate 160 in the formal synthesis of (+)-laurencin isolated from red algae.204 The latter compound is the acetogenin with the D4-oxocene skeleton.TolSO2 CH2N(CH2)3SO2Tol Ts a b O NH OH NTs OH 159 (a) 2 equiv. of BunLi (64%); (b) Na/Hg, Na2HPO4 (74%). SO2Tol Et CH2OSiPh2But OH b, c a O (CH2)3SO2Tol Et O O CH2OSiPh2But OSiMe3 O 6 steps Et Et O O CH2OSiPh2But 160 HOCH2 (a) LDA, THF, 765 8C; (b) oxidation; (c) diazabicycloundecene (DBU). 3. Reactions of a-sulfinyl and a-sulfonyl carbanions with C7C multiple bonds a. Addition of a-sulfinyl carbanions to activated multiple bonds The addition of a-sulfinyl carbanions to activated multiple bonds in the synthesis of natural compounds has been primarily studied by Hua and coworkers. The key step of these reactions involves the Michael addition of enantiomerically pure ambident carb- anions, which are prepared from allylic sulfoxides or their nitro- gen analogues, viz., a-sulfinyl ketimines, to double bonds most commonly activated by carbonyl groups.In classical investiga- tions by Haynes and coworkers,205, 206 it was demonstrated with model compounds that the reactions of lithiated allylic sulfoxides with substituted cyclopentenones occur exclusively as the stereo- selective addition to the double bond, while the carbonyl group remains intact.384 The first line of investigations performed by Hua and co- workers 207 ± 211 was devoted to the addition of allylsulfinyl anions to enones. The total enantioselective synthesis of hirsutene (161) (a tricyclic biogenetic precursor of the polyquinanes coriolin and hirsutic acid }) is a typical example of this approach.In the first stage, the (S )-allylsulfinyltolyl carbanion added to 2-methyl- cyclopent-2-enone.207 Reduction of the reaction product 162 to sulfide followed by cyclisation afforded substituted hexahydro- pentalenone 163 containing the rings B and C of hirsutene. The compound 163 was transformed in several steps and then the construction of the ring A was completed on the basis of bicyclic enone 164. Attempts to perform this synthesis starting from the cyclic allylsulfinyl anion 165 failed 208 because the anions of cyclic sulfoxides of this type reacted with 2-methylcyclopent-2-enone to Li+ O 7 a, b S Tol STol O C B H 163 H B A H H (+)-161 O (a) ; (b) AcCl; (c) Zn, AcOH; (d ) TiCl4 , AcOH; (e) (HOCH2)2 , TsOH; ( f ) MCPBA; (g) diazabicyclononene (DBN); (h) pyridinium chlorochromate (PCC).PhSO 7 Li+ A + 165 form only undesirable g-adducts. However, the molecule of equally complicated (+)-12,13-epoxytrichocet-9-ene (166) pos- sessing high biological activity was constructed starting from cyclic allylic sulfoxide 167 according to a procedure which was chosen based on retrosynthetic analysis.209 In this case, cyclo- pentenone 168 additionally activated with the methoxycarbonyl group was used. An analogous, but somewhat more complicated procedure made it possible to perform the total synthesis of (+)-pentalenene related to antitumour pentalenolactone.210 O O (+)-166 PhSO + 167 } Another version of the sulfonyl approach to polyquinanes is shown in Scheme 8.184 OAc O c, d S Tol 162 O e, f, g, h 9 steps O C B 164 O H C O 164 C HO S Ph O O MeO2C 168 E N Prilezhaeva Bulky substituents in the cyclic enone do not hinder the stereoselective addition of the allylsulfinyl carbanion to the double bond.The preparation of compound 169, which is the key intermediate in the synthesis of methyl ester of ()-pentale- nolactone E, from bicyclic enone 170 211 or the construction of the prostaglandin precursor 171 from enone 172 (Pivnitskii and coworkers 212) serve as examples. SOTol CH2OR 7 TolS(O)CHCH CH2 O CH2OSiMe2But HO 170 H 169 (60%) R=SiMe2But. O O 7 PhSOC(C5H11)CH CH2 SOPh Me2PhCO OCMe2Ph 172 C5H11 171 The second line of investigations performed by Hua and coworkers dealt with the construction of molecules of polycyclic alkaloids based on reactions of carbanions from chiral sulfinyl ketimines with a,b-unsaturated esters followed by (sometimes synchronous) cyclisation.Thus the total syntheses of parasympa- thomimetic agents (7)-slaframine (173) and (7)-6-epi-slaframine (174) were performed starting from the sulfoxide (R)-175 anion and N-protected methyl 2-aminoacrylate.213 The diastereomers 176a and 176b were obtained in a ratio of 3 : 2. OSiMe2But OSiMe2But O OSiMe2But O S S O a, b N N + CH2S Tol Tol N O O Tol (R)-175 176b NHBoc 176a NHBoc 4 steps 4 steps OAc OAc H H N N 174 NH2 173 NH2 CO2Me .(a) BunLi; (b) NHBoc An analogous reaction of the anion of tricyclic (R)-a-sulfinyl ketimine 177 with methyl acrylate was used for the preparation of epimers of indolo[2,3-a]quinolizidine, viz., (+)- and (7)-178 (the ratio was 1 : 1.9). The key step in the synthesis of pentacyclic b, c, d a, b O N N O NH O CH2S S Tol (R)-177 Tol N H N H + HN HN (+)-178 (7)-178 (a) LDA, CO2Me; (b) NaCN.BH3; (c) Ra/Ni; (d ) LiAlH4 .Sulfones and sulfoxides in the total synthesis of biologically active natural compounds yohimbane alkaloids 179 ± 181 involves the reaction of (S )-177 with methoxycarbonylcyclohexene.214 H N H H N H H NH HN H H H 181 180 179 A general procedure for the synthesis of esters of racemic a-amino acids 215 is based on the addition of a carbanion gener- ated from methyl methylthiomethyl sulfoxide at theC:Nbond of nitriles.The unstable adducts 182a ± d were isomerised through a prototropic shift to form enamino sulfoxides 183a ± d. The Pum- merer rearrangement under the action of Ac2O yielded com- pounds 184a ± d from which racemic phenylglycine, alanine and valine derivatives (185a ± c, respectively) were prepared. Treat- ment of the compound 184d with substituted phenylhydrazine hydrochloride 186 afforded racemic N-acetyl-5-hydroxytrypto- phan methyl ester (187).215 HN SOMe H2N a, b c MeSCH2SOMe R SOMe CHSMe 182a ± d R SMe 183a ± d RCHCO2Me d, e NHAc O 185a ± c CH2CHCO2Me HO AcHN R MeS NHAc f, g SMe 184a ± d NH 187 R=Ph (a), Me (b), Pri (c), (MeO)2CH(CH2)2 (d); (a) NaH, THF, 20 8C; (b) RCN; (c) Ac2O; (d ) R=Ph, Me, Pri; MeOH, Et3N; (e) Ra/Ni; ( f ) R=(MeO)2CH(CH2)2 , 4-BnOC6H4NHNH2 .HCl (186); (g) Ra/Ni, EtOH. b. Reactions of a-sulfonyl carbanions with activated C=C bonds Specific transformations of anionic intermediates formed as a result of addition of a-sulfonyl anions to activated double bonds have found use in the synthesis of natural products. Martel et al.216 found that the addition of a-sulfonyl carb- anions generated from 3-methylbut-2-en-1-yl sulfones to esters of a,b-unsaturated acids afforded cyclisation products of the initially anionic intermediates rather than the usual adducts.Thus the intermediate 188 formed from sulfone 189 and ethyl 3-methylbut- 2-enoate is stabilised through cyclisation with 1,3-elimination of the sulfonyl anion to produce ethyl trans-chrysanthemate (190),217 PhSO2 189 PhSO2 CO2Et a 7 H 7PhSO¡2 CO CO2Et Et 190 188 CO2Et b, c 190 CO2Et (a) CO2Et, ButOK, THF; (b) EtMgBr, CuCl2 , THF; (c) CO2Et. CO2Et 385 which is a component of natural insecticides, viz., pyrethroids. The optimum conditions for this reaction involve the use of compo- nents taken in a ratio sulfone :THF:ButOK=1 : 2 : 3. A large number of aryl and alkyl chrysanthemates were synthesised according to this procedure.218 Some of these compounds are more active insecticides than natural pyrethroids. Julia and coworkers 219 prepared the ester 190 by the reaction of the sulfone 189 with ethylmagnesium bromide and then with diethyl isopropylidenemalonate. Later on, Campbell et al.220 demonstrated that the reactions of anions generated from E-isomers of polyunsaturated sulfones with esters of polyunsaturated acids under conditions proposed by Martel and coworkers 218 were not accompanied by isomer- isation of double bonds.This procedure was used for the prepa- ration of the key compounds in the biosynthesis of terpenoids, viz., (+)-presqualene alcohol (191) and (+)-prephytoene alcohol (192). In this study, the structure of natural prephytoene alcohol was also established. OH 2 191 2 3192 OH Reactions of a,b-unsaturated carbonyl compounds with a-sulfonyl carbanions generated from 3-oxo-1,3-dihydroiso- benzofuran-1-yl phenyl sulfone (193a) (`phthalide sulfone') and its analogues play an important role in the synthesis of biologically active compounds.Hauser and Rhee 221 studied reactions of the model compounds 193a,b with linear enones or a,b-unsaturated esters and demonstrated that the resulting carbanionic intermedi- ate is stabilised in the course of cyclisation through elimination of the sulfinate anion. The resulting 1,4-dihydroxy-naphthalene is readily oxidised to naphthoquinone, whereas methylation pre- vents oxidation. Apparently, the driving force for this process is the formation of a thermodynamically favourable aromatic struc- ture. SO2Ar SO2ArR2 a, b O O 7ArSO¡27COR3 O O R1 R1 193a,b O R2 OH COR3 R2 O R1 OMe COR3 R2 OH R1 COR3 OMe R1 R1 = H (a), OMe (b); R2=H, Me; R3=OEt, Me; (a) LDA, THF,778 8C; (b) R2CH=CHCOR3.Owing to the possibilities of varying the structures of ana- logues of phthalide sulfone 193a and, especially, of a,b-unsatu- rated carbonyl compounds, a flexible and rather versatile procedure was developed for stereoregular aromatic annelation, which is strictly controlled by the structures of the starting compounds. This method was successfully used by Hauser386 a, b, c PhSO2 d, e O O MeO 193b d, f, cMe MeO PhSO2 d, g O O 193c O (a) LDA, THF; (b) MeCH=CHCO2Me; (c) methylation, (d ) LiOBut; (e) Me (g) (199) (50%). O O et al.222 ± 234 and by other researchers 235 ± 238 and assumed partic- ular importance in the synthesis of aglycones of antitumour antibiotics, for example, compounds 194 ± 198.Selected stages of the total syntheses of these compounds are shown in Scheme 9. The key reactions of the anions prepared from phthalide sulfones 193 with a,b-unsaturated carbonyl compounds generally proceed with high yields. (The exception is the reaction of phthalide sulfone 193c with lactone 199 producing compound 200 in a yield of only 50%.) However, the multistep character of subse- quent transformations impairs the efficiency of the process as a whole. Thus in the total synthesis of the antibiotic of the anthra[1,2-b]pyran series, viz., O-methylkidamycinone 194, start- ing from phthalide sulfone 193b and methyl methacrylate,222 a naphthalene derivative 201 was converted into the final antibiotic 194 in nine steps.The use of cyclic enones (such as compounds 202 or 203) as Michael acceptors is much more efficient. Thus the reaction of phthalide sulfone 193b with 5-acetoxymethylcyclohex- 2-enone (202) afforded the anthraquinone derivative 204 in 81% yield.223, 224 Despite the fact that 11 steps were required to build up the ring A and to obtain the final product, viz., g-citromycinone ()-195, the total yield was*39%. A comparatively low yield of ()-dimethyl-6-deoxydaunomycin ()-196 prepared from the same precursor 204 was attributed to the formation of an admixture of its C(9)-epimer in the final stage.224 The use of the simplest bicyclic enone 203 made it possible to perform a five-step OMe O Me 9 steps CO2Me OMe MeO O MeO 201 194 (*18%) Me 11 steps OH O B C D CH2OAc O MeO 204 9 steps OMe 4 steps A B OMe O MeO MeO O Me OH OMe O 4 steps O OH O OH O 200 Osynthesis of a tetracyclic triketone 197 in good yield.The latter is a versatile precursor for the preparation of daunomycinones.225 An exceptional interest in the synthesis of antibiotics of the anthracyclinone series (see, for example, Ref. 239) arises from their high biological activity. Thus since the 1970s 239 to the present, daunomycin and adrianomycin obtainable by micro- biological methods find use in medicine as antitumour drugs.240 Hauser et al.227, 228 have developed additional ways of improv- ing procedures with the use of monocyclic enones.Thus the con- vergent synthesis of ()-7,9-dideoxydaunomycinone (205) was performed in a rather high yield.227 In the first stage, the anion generated from phthalide sulfone 193b reacted with 5-ethoxy-2,5- dihydrofuran-2-one (206). Then the reaction product 207 was converted into phthalide sulfone 208 in two steps. The subsequent reaction of the anion generated from 208 with 5-acetylcyclohex-2- enone 209 afforded the tetracyclic product 210, which was converted into the target 7,9-dideoxydaunomycinone ()-205. 193b E N Prilezhaeva Scheme 9 MeO O Me OH Et OH A B DOH OH ()-195 (*39%) OMe OCOO Ac 9 OH O MeO OH ()-196 (*18%) O O A BOH O 197 (*46%) OH 198 (*5%) H CH2OAc (203) (84%); (202) (81%); ( f ) H O MeO MeO OEt PhSO2 a, b 2 steps a, c O O O O OMe MeO OMe MeO 208 207Sulfones and sulfoxides in the total synthesis of biologically active natural compounds OMe MeO Ac 9 steps MeO OMe OMe O 210O OH Ac 9 7 MeO O OH ()-205 (38% ± 40%) Ac (a) LDA; (b) (209).O OEt (206); (c) O O Disubstituted cyclohexenone 211 served as the starting com- pound in the synthesis of racemic aklavinone (212) and pyrromy- cinone (213).228 O CO2Me H Et CH2CO2Me OH H O OH OH OH OBn 211 O()-212 OH O CO2MeEt OH OH O OH OH ()-213 Further progress in the application of bicyclic enones to annelation was achieved 229 ± 234 once procedures for the synthesis of compounds 214a,b and 215, which contain substituents corre- sponding to the substituents in the rings A of anthracyclinones, had been developed.H H OH R Et O O H215 H214a,b R=Ac (a), Et (b). Thus a new more efficient procedure was proposed 232 for the preparation of racemic aklavinone [()-212] starting from readily available compounds, viz., phthalide sulfone 193b and enone 214b (the total yield was*17% with respect to 2-ethylacrolein used as the starting compound for the preparation of the enone 214b). The first regio- and enantiospecific synthesis of a compound of the anthracyclinone series, viz., the preparation of (7)-(R)-7,11- dideoxy-13-deoxydaunomycinone (216) from the anion of phtha- lide sulfone 193d and enantiomerically pure enone 215, was performed.233 Compound ()-218 possessing the nonlinear benzo-[a]naph- thacene skeleton was synthesised starting from phthalide sulfone 193b and tricyclic enone 217.234 In this study, yet another problem was solved.Thus the nature and arrangement of the substituents in the A rings of the natural pigments G2N and G2A were established. 387 Me O OH Et OMe OH MeO O 217 O (7)-(R)-216 Me MeO O OMe OH O MeO 218 The procedure for annelation proposed by Hauser has been extended to the preparation of antibiotics containing five-mem- bered rings. This procedure was used for the synthesis of com- pound 219, which is a close analogue of kinafluorenone.235 For this purpose, the anion prepared from 193a was brought into reaction with indenone 220, which had been synthesised in situ by flash pyrolysis of its adduct with cyclopentadiene (221).a b O O 220 221 OH O 219 OH (a) flash pyrolysis (>95%); (b) 193a, LiOBut,760 8C (73%). Syntheses of natural 1,4-dihydroxyanthraquinones 222 using reactions of the anions generated from phthalide sulfones 223 with monoketals of substituted benzoquinones 224 provide other examples of annelation according to Hauser.236 O R1 OH R1 O PhSO2 R3 R3 + O R4 O R2 OMe R2 R4 MeO OMe 224 O222 223 R1±R4=Alk. ()-Daunomycinone was synthesised analogously from the sulfone 193a and analogues of benzoquinone monoketals 224.237 The reaction of the anion of 5,6-methylenedioxyphthalide sulfone with methyl methacrylate afforded functionally substituted naph- thalenes necessary for the synthesis of lignins.238 c.p-Allylic alkylation with a-sulfonyl carbanions Among processes with the use of Pd(0) complexes, p-allylic alkylation occupies a prominent place. In these reactions, soft nucleophiles react with allylic Pd(0) complexes as the cationoid components. These complexes can be prepared from allylic com- pounds containing good leaving groups, such as acyloxy or sulfonyl groups. This procedure became popular due to mild reaction conditions and high stereospecificity. The reaction can be performed either with the use of stoichiometric amounts of a Pd(0) complex in a basic medium or as a catalytic process in neutral or388 weakly basic media.In the latter case, the Pd(0) complex can be prepared in situ from a Pd2+ salt. The introduction of phosphine or other ligands allows one to change the regio- and stereo- chemistry of the reaction (see the reviews 241 ± 243). In these processes, a-sulfonyl carbanions activated with the adjacent oxo, carboxy or sulfonyl groups or (more rarely) with the allylic bond are widely used along with other C-nucleophiles. Trost and Weber 244 were the first to use this procedure for the synthesis of biologically active compounds and they transformed simple terpenoids into more complex compounds. The reaction of an allylic palladium complex prepared from methyl geraniate 225 with the ambident anion, which has been synthesised by the reaction of methyl 4-methlyl-2-phenylsulfonylbut-3-enoate (226) with NaH in THF, followed by transformation of the reaction product 227 afforded farnesol (228).An analogous reaction of the anion 226 with the allylic Pd(0) complex 229 afforded all-trans- geranylgeraniol (230). PhSO2 a 7 + CO2Me CO2Me 226 225 Pd PhSO2 b, c CO2Me 227 CO2Me OH 228 4 steps CO2Me 226+ 229 Pd OH 230 (a) dppe is 1,2-bis(diphenylphosphino)ethane, THF, 25 8C (65%); (b) Bui2AlH, MePh,740 8C; (c) Li, EtNH2778 8C. A p-allylic version of the synthesis of retinol acetate (44, 67% of the trans isomer) was carried out 245 using the reaction of the anion generated from substituted allylic sulfone 231a with the Pd(0) prenylacetate complex in the presence of an excess of triphenylphosphine.Its aromatic analogue 232 exhibiting anti- tumour activity was synthesised analogously. In the case of sulfones containing acyclic substituents R, the reactions stopped at the stage of formation of compounds 233c,d. PhSO2 a + OAc R 231a ± d Pd PhSO2 b OAc R OAc R 44, 232 233a ± d R= (232, 233b); (44, 233a); MeO (233d); (233c); (a) NaH, THF, PPh3; (b) EtONa, EtOH. Tsuji was the first to propose a catalytic version of this reaction 242, 246 and he recommended to employ O-methoxycar- bonyl as the leaving group. This procedure was used for the preparation 247 of ubiquinone-10 (234), which is the coenzyme Q10 exhibiting cardiovascular activity, and its analogues.Compound E N Prilezhaeva 235 containing an allylic O-methoxycarbonyl group was brought into the reaction with the anion of an activated sulfone 236 containing an allylic hydroxy group, which was employed to form a new allylic O-methoxycarbonyl group in the intermediate 237. The iterative reaction with the sulfone 236 and the formation of the MeO2CO group made it possible to build up a polyunsatu- rated chain. The last stage of the process involved oxidation of the aromatic ring to the quinoid one. OMe OH MeO OCO2Me a, b TolSO2 +MeO2C MeO235 OMe 236 OCO2Me CO2Me 8 steps 237 TolSO2 O MeO MeO O 8 234 (a) 5 mol.%of Pd(PPh3)4 , THF; (b) MeOCOCl, Et2NC6H4 , Py, PhH.Natural compounds exibiting analgesic activity, viz., tetrapre- nylquinone 238 and -quinol 239, were prepared analogously.248 The synthesis of trans,trans,trans-geranylgeraniol (230) from a-sulfonyl-substituted ester 240 and oxirane 241 was also per- formed using the catalytic version.249 In this scheme, the metal- complex catalysis was used for the regiospecific opening of the oxirane ring. OH O 3 3 238 239 O OH MeO2C CO2Me PhSO2 PhSO2 OH b, c a (E)-230 240 (a) (241), 5 mol.%of Pd(PPh3)4 , THF, 25 8C (90%); O (b) PhSH, Cs2CO3; (c) LiBHEt3 , THF, 5 mol.%of PdCl2(dppp) [dppp is 1,3-bis(diphenylphosphino)propane] (100% E). The catalytic procedure has assumed utmost importance in intramolecular cyclisations, which offers outstanding possibilities for the construction (including diastereocontrol) of carbo- and heterocycles (see the reviews 250, 251).Thus the diastereoselective introduction of a cyclopropane ring into the steroid molecule was performed by the reaction of the carbanion generated from the sulfonyl(ethoxycarbonyl) fragment of compound 242 with the p-allylic Pd complex generated in the same molecule. The final product, viz., glaucasterol (243), con- tains a three-membered ring at C(24)7C(25).252 2-(Hex-1-en-1- yl)-1-methoxycarbonyl-1-phenylsulfonylcyclopropane was syn- thesised analogously. The latter compound served as the starting material for the synthesis of dictyopterene A (244) containing a three-membered ring and of a seven-membered dictyopterene B (245).253Sulfones and sulfoxides in the total synthesis of biologically active natural compounds OMe HO Bun H RC(O)O Bun R=2,4-Cl2C6H3; (a) DBU, THF, Pd(dppe)2 .Examples of the construction of more complex carbocycles are considered below. Bicyclic ()-punctaporonin B (246) was syn- thesised in 12 steps starting from substituted cyclobutanone.254 The palladium-catalysed reaction of the allyloxirane fragment of compound 247 with the activated a-sulfonyllactone fragment afforded the intermediate 248, which was converted into the target product 246. COBn O O O248 (a) Pd(Ph3P)4 , dppe, THF, 60 8C. In the synthesis of 14-membered ()-isolobophytolide (249), the methoxycarbonyl(phenylsulfonyl) carbanion served as the anionic component of the initial compound 250 and the pivalate OHO MeO2C OC(O)But 250 OC(O)R SO2Tol CO2Et a 242 SO2Tol CO2Et 4 steps H H 243 (90%) SO2Ph a CO2Me Bun 3 steps CO2Me SO2Ph 3 steps HBun 245 O 6 steps O SO2Ph 247 O CH2OH OH H 6 steps SO2Ph OH ()-246 OHO O a, b HSO2Ph H SO2Ph CO2Me 251 389 O H O H O H 249 (a) O,N-bis(trimethylsilyl)acetamide, Pd(Ph3P)4 , dppe, THF; (b) Bun4 NF.anion served as the leaving group. The resulting macrocyclic intermediate 251 was transformed into the target product 249.255 Cyclisation catalysed by palladium complexes is of particular importance for the preparation of medium-size heterocycles, which are widespread in nature, but which have previously been difficultly accessible.256 ± 261 The construction of the key inter- mediates in the synthesis of natural lactones, viz., 10-membered phoracantholide (252),256 12-membered recifeiolide (253) 257 and 16-membered exaltolide (254),258 from acyclic precursors serve as characteristic examples. O O O O O O 254 253 252 H 244 The construction of nine- and eight-membered functionally substituted cyclic ethers 255a,b and 256, which are precursors of oxonins 257 and 258 isolated from the algae Laurencia, presented a substantially more difficult problem.The regio- and stereo- chemical direction of cyclisation of the acyclic precursors 259 and 260 is determined by the site of attack of the anion generated from the sulfone on the allyl palladium fragment and depends on the nature of the leaving group and, especially, on the ligand used.Thus the methoxycarbonyloxy group and triethyl phosphite appeared to be the best leaving group and ligand, respectively, for the ring closure in compound 259 required for the construction of the skeleton of nine-membered brasilenyne (257). The ratio of the cyclisation products, viz., trans ± trans-255a (similar to the natural isomer) and undesirable cis ± trans-255b, was 14 : 1.259 PhSO2 OC(O)OMe PhSO2 SO2Ph a SO2Ph + O O OSiMe3 OSiMe3 Et a Et255a 259 PhSO2SO2Ph Cl + O O OSiMe3 C Et CH 257 OH Et255b (a) 5 mol.%of Pd2(dba)3 (dba is dibenzylideneacetone), 50 mol.%of P(OEt)3 , CHCl3 , THF.A chloride anion and bisphosphite 261 appeared to be the best leaving group and ligand, respectively, in the stereoconvergent synthesis of compound 256, which is a precursor of enantio- merically pure (7)-lauthisan (258).260 Because of the formation of O Cl PhSO2 PhSO2 SO2Ph SO2Ph PhSO2 16 steps SO2Pha + O Et C6H13 C6H13 O O Et Et C6H13 262 256 260390 256 (a) 5 mol. %of Pd2(dba)3, CHCl3, KH, THF± dioxane, 80 8C. the six-membered cyclic products 262, the yield of the eight- membered reaction product 256 was only 70%.260 The construction of more complex heterocycles, viz., macro- lides of the cytochalasin series, which possess high membrane- transport and a broad spectrum of other biological activities, presented a particularly interesting problem. Trost and coworkers performed a 12-step synthesis of the model antibiotic A 22667718 (264) starting from undecynal via the intermediate 263,262 a 9-step synthesis of (7)-aspochalasin [(7)-265] from N-protected leucine ester via the precursor 266 263 and construction of the 26-mem- bered skeleton of tetrin (267).264 EtO 263 O H Z=COOBn.O O R1 R2 R1, R2=H, Me. A precursor of pentacyclic alloyohimbone was synthesised anal- ogously using the Pd(0)-catalysed ring closure in compound 268 with the acetoxy group serving as the leaving group.265 NHTolSO2AcO 268 A 12-step synthesis of the skeleton of the macrocyclic anti- tumour compound roseophillin (269) is yet another example of the high efficiency of palladium-catalysed cyclisation.266 Acyclic C6H13 O 258 Et OAc SO2Ph O CO2Me 6 steps NHZ 267 N O SPh O P , O O OP O O (261) compound 270 was transformed into the cyclic precursor 271 by the reaction of the methoxycarbonylsulfonylfragment with the allylpalladium complex incorporating the oxirane ring.The groups that activate the anionic centre were not removed follow- ing cyclisation and they were employed in subsequent trans- formations. Thus the ester group was used in the construction of tricyclic sulfone 272. The benzenesulfonyl group in compound 272 is homoallylic and hence it was readily eliminated in the presence of ButOK as sulfinic acid. Simultaneously, the isopropyl group was attached to the adjacent carbon atom by the action of dimethylisopropylzincmagnesium chloride on the C=C bond of the enone formed (attempts to use more traditional cuprates have been unsuccessful).O ButMe2SiO MeO2C 270 PhSO2 O O CO2H PhSO2 CO2Me 271 O 264 O H OEt O PhSO2 OCO2Et Bn N O CH2SO2Ph 272 O H BuiH 266 HN (a) [Pd(0)] (85%); (b) an excess of ButOK; (c) Me2PriZnMgCl (51%). ... IV. Formation of C=C bonds by thermolysis of sulfoxides O OH O H BuiH O HN (7)-265 In many cases, thermal elimination of sulfenic acid from sulf- oxides leads to the formation of (E )-C=C bonds. In 1960, Kingsbury and Cram 267 suggested that at moderate temperatures this process occurs according to a concerted mechanism via a transition stateA.More recently,268 this suggestion was confirmed by kinetic studies. O Ar S H D Ar C C Ar 7ArSOH H Me A OSiPh2But H A modification of this reaction proposed by Trost et al.33 ± 35, 40, 269, 270 has been widely used predominantly for the introduction of (E )-C=C bonds at the a,b-position with respect to the carbonyl groups of ketones or esters. This procedure is convenient because a one-pot sulfenylation ± sulfinylation ± dehy- drosulfenylation sequence can be used. Initially, an alkylthio group is introduced at the a-position with respect to the elec- tron-withdrawing group under the action of disulfide in a basic medium. The alkylthio group is readily oxidised to the sulfinyl group, which is removed by thermolysis, most commonly, upon boiling in toluene.All steps are carried out under mild conditions; the presence of functional groups in the molecule does not hinder this process. The temperature required for dehydrosulfenylation depends on the substrate structure. Sometimes, it is necessary to add a thiophilic scavenger. This method for the directed intro- duction of (E)-C=C bonds advantageously supplements the Julia olefination and dehydrosulfinylation of homoallylic sulfones. E N Prilezhaeva a ... OH OSiMe2But Pri b, c Bn N O 269 Ar Ar H MeSulfones and sulfoxides in the total synthesis of biologically active natural compounds The synthesis of components of bee pheromones is the first example of the use of the sulfenylation ± sulfinylation ± dehydro- sulfenylation sequence for the preparation of natural com- pounds.270 Ethyl linoleate served as the starting compound for the preparation of the attractant 273.(E)-9-Oxodec-2-enoic acid (274) (the queen substance, viz., the attractant of the queen bee and simultaneously the pheromone of termites) was prepared from an azelaic acid ester. In both cases, thermolysis was performed by boiling in toluene with the addition of calcium carbonate. SMe c a, b 5 4 CO2Et CO2Et SOMe d 5 4 CO2Et CO2Et 273 (81%) O CO2Me a, b, c d, e CO2Me 2 SOMe O CO2H 2 274 (a) cyclo-C6H11NPriLi; (b) MeSSMe, THF, HMPT,778 8C; (c) oxidation; (d ) PhMe, CaCO3 , 110 8C, 16 h; (e) H3O+.The sulfinyl groups located at the allylic or propargyl posi- tions are also readily eliminated under conditions of thermolysis because the resulting conjugated diene and enyne systems are thermodynamically favourable. This procedure was used for the preparation of dodeca-8,10-dien-1-ol (275) 271 (the major compo- nent of the pheromone of apple fruit moth) and polyunsaturated esters 276, which are the key compounds in the synthesis of natural unsaturated endiandric acids involving mild cascade electrocyclisation.272 PhSO a, b, c d OH SPh 8 OH 6 275 (a) LDA; (b) Br(CH2)8OH; (c) ArCO3H; (d ) PhMe, NEt3, D. SPh a, b, c + C Ph C CO2Me n 2 HC CH C Ph 2 C CO2Me n 2 276 n=0, 1; (a) Cu(OAc)2 , Py, EtOH; (b) MCPBA; (c) PhMe, 50 8C, D.EndocyclicC=Cbonds can also be readily constructed by this procedure. For example, all four possible enantiomers of the natural CoA inhibitor, viz., acaterin (277), with an acetogenin- type skeleton were prepared. The latter is a promising anti- atherosclerosis drug.273 The (4R,10R) absolute configuration was assigned to the natural inhibitor. Both compound (+)-277a and its C(10)-epimer 277b were prepared by thermolysis (after oxida- c a, b O O MeS C7H15 O O O 278 (R) 391 O O + MeS C7H15 MeS C7H15 O O OH OH d,e d, eO O C7H15 C7H15 O O OH (4R,10S )-277b OH (4R,10R)-277a (a) LDA, MeSSO2Me; (b) LDA, C7H15COCl; (c) NaBH4 , THF, H2O; (d ) oxidation; (e) PhMe, CaCO3 , D, 3 h. tion) of substituted valerolactones isolated from a mixture of reduction products of compound 278.The second pair of epimers of the compound 277 was synthesised according to the same procedure starting from (S )-g-valerolactone. An analogous procedure for the introduction of the endocy- clicC=Cbond was used 274 in the synthesis of compounds 279a,b, which were supposed to correspond to stereoisomers of a more complex acetogenin, viz., epoxyrollin A. However, the 13C NMR and mass spectra of both stereoisomers 279a,b differed from those of the natural product. O O 7 7 O O O O C14H29 C14H29 (4S,180R,190S )-279b (4S,180S,190R)-279a A short elegant synthesis of (+)-(R)- and (7)-(S )-muscones 23 involved asymmetric methylation of the C=C bond of the enone 280 in the presence of D- or L-camphor derivatives, respectively.275 The enone 280 was prepared by elimination of benzenesulfenic acid from the oxo sulfoxide 281.O O SOPh b (R)-(7)-23 a c (S )-(+)-23 (CH2)6 280 (CH2)6 281 , PhMe, (a) PhH, CaCO3, D (83%); (b) MeLi, CuI2, NHOH NMe , PhMe, THF (ee 100%); (c) MeLi, CuI2, OH HN THF (ee 100%). NMe 8-Hydroxymenth-3-ene (282), which is a component of mint essential oil, was prepared according to a general procedure for the transformation of saturated ketones to enones proposed by Taber and Gunn. 276 In the first step, a-chloroethylsulfinyl carb- anion was added to the carbonyl group of 4-methylcyclohexanone to form epoxide. When distilled, the latter underwent spontaneous isomerisation to give unstable oxo sulfoxide 283, which readily eliminated sulfenic acid.The addition of MeLi to enone 284 completed the process.392 SOPh O MeCO SOPh O a, b, c d 7PhSOH 283 OH Ac e 282 284 (a) LDA, THF; (b) MeCH(Cl)SOPh; (c) NaOH (90%); (d ) D, CaCO3; (e) MeLi. If the sulfonyl group is located in the aliphatic chain, the direction and the rate of hydrogen abstraction upon thermolysis depend predominantly on its acidity.35, 269 However, thermolysis of steroid sulfoxides is a stereocontrolled process due apparently to the unique features of this system of rigidly fused rings. Thus attempts to introduce the C(15)=C(16) bond into the estrone molecule according to a conventional procedure [starting from C(16)-selenoxide 277] failed, but this bond was constructed upon prolonged heating of the methyl ether of C(16)-(phenylsulfi- nyl)estrone in the presence of triphenyl phosphite, which is an active thiophilic scavenger.40 Elimination of sulfenic acid from the A ring of 5a- or 5b-cholestanes occurred under standard con- ditions.278 The dependence of the direction and rate of thermolysis on the stereochemistry of the sulfur atom was observed for the first time in the case of bulky thermally stable (R)- and (S )-ada- mantylsulfinyl groups, which are not able to undergo stereo- mutation.This made it possible to develop procedures for the selective synthesis of difficultly accessible 5a- or 5b-cholest-2-enes and cholest-3-enes.276 The formation of C=C bonds by thermolysis of sulfoxides was also used in more sophisticated synthetic sequences.For example, this reaction served as a stage in the construction of brefeldin A (130) 181, 183 and in the synthesis of hirsutene 207 (in the latter case, thermolysis was carried out in an alkaline medium according to a procedure reported previously 279). Other examples will be considered below. In the course of the total enantioselective synthesis of indoli- zine alkaloids elaeokanines A and B, Hua et al. 280 used a large number of approaches based on reactions of sulfinyl-containing intermediates. Enamino sulfoxide 285 was prepared by alkylative annelation in the reaction of 1,3-diiodopropane with the anion of (+)-(R)-sulfinyl ketimine 286.Reduction of the reaction product afforded a mixture of all four possible epimeric indolizine sulf- oxides represented in pairs as 287a and 287b. The reaction of each of these epimers with butanal in the presence of lithium diisopro- pylamide proceeded quantitatively, the C(8a) chiral centre, which is essential for the subsequent synthesis, remaining unchanged. Thermolysis of a 2 : 1 mixture of hydroxy sulfoxides 288a and 288b gave the single product, viz., hydroxyindolizine 289a with the O O c a, b S S N Tol Tol N(+)-(R)-286 285 O O H H S S + Tol N Tol N 287a 287b E N Prilezhaeva O OH H H S Prn Tol e a, d Prn 287a O N + N S OH Tol 288b 288a O OH H H f Prn Prn N N 290a 289a O OH H H S Prn Tol e a, d Prn 287b O N + N S OH Tol 288d 288cOH H Prn N 289b (a) LDA; (b) I(CH2)3I; (c) NaBH4 , 287a : 287b (1 : 1); (d) PrnCHO; (e) 110 8C, PhMe (*80%); ( f ) PCC (>90%).C(7)=C(8) bond. Oxidation of the hydroxy group of 289a resulted in (+)-elaeokanine A (290a). (7)-Elaeokanine B (289b), which is (unlike elaeokanine A) a hydroxy derivative, was pre- pared by thermolysis of hydroxy sulfoxides 287c,d obtained by the reaction of butanal with the diastereomers 287b. V. Syntheses based on reactions of unsaturated sulfones and sulfoxides 1. Addition at the C=C bonds a. Addition of C-nucleophiles The synthesis of racemates of alkaloids (291 ± 293) of the Aspido- sperma family from a single pentacyclic precursor provides an example of the use of unsaturated sulfones and sulfoxides as acceptors of C-nucleophiles for the transformation of the basic skeleton, which has been constructed beforehand.281 ± 283 Owing to the high acidity of the hydrogen atom at C(5) of the enone fragment, the carbanion can readily be generated and involved in the Michael addition to methyl vinyl sulfone, methyl 1-methyl- thiovinyl sulfoxide or methyl vinyl sulfoxide.Subsequent mod- ifications of the adducts 294 and 295 involved the formation of additional rings in the alkaloids 4-hydroxyaspidofractinine (291) and 1-acetylaspidoalbidine (293) and the introduction of the ethyl group at position 5 in 1-acetylaspidospermidine 292 (Scheme 10). Vinyl sulfones have found substantially wider application due to the fundamental studies of Fuchs and coworkers, which have been surveyed in detail in their reviews.23, 24 Hence, these studies will be considered in this review only briefly.Fuchs and coworkers have developed convenient procedures for the synthesis of sub- stituted cycloalkenyl sulfones, including enantiomerically pure sulfones, containing a free or substituted hydroxy group at the g-position. In the case of vinyl sulfones, unlike enones, the attack of even hard nucleophiles (for example, alkyllithium) occurs exclusively at the C=C bonds following a Michael addition. Owing to the high nucleophilicity of the resulting a-sulfonyl carbanion compared to enolate, the addition can be combined with a subsequent reaction of the newly formed a-sulfonyl carbanion with an internal or external electrophile resulting in additional functionalisation.The presence of g-hydroxy groups in these vinyl sulfones allows one to control the stereochemistry of the process.Sulfones and sulfoxides in the total synthesis of biologically active natural compounds O N a or b H S(O)nMe O O N 294 5 H H O O NTs N c, d CHO H O 295 (a) CH2=CHSO2Me, ButOK, ButOH, n=2; (b) CH2=CHSOMe, LDA, n=1; (c) CH2=C(SOMe)SMe, LDA; (d ) HClO4, H2O; (e) Ra/Ni, n=1. The scheme given below outlines in general convergent total syntheses of natural or related compounds, viz., (7)-prostaglan- din E2 (296),284 (+)-carbacyclin (27) 285 and ()-morphine (297),286 carried out by Fuchs and coworkers.The key steps of these syntheses involve b-addition ± a-alkylation of cycloalkenyl sulfones 298 ± 300 (in the scheme, the sites of the a- and b-attacks are indicated by arrows). OH NMe2 a SPh SO2Ph a, b 301 (ee 92%) ButMe2SiO b 298 NMe2 5 steps CO2Me SO2Ph C5H11 H ButMe2SiO ButMe2SiO O CO2H C5H11 HO H 296 HO Li (a) . CO2Me C5H11; (b) I H Me2ButSiO CH(CH2)3CO2H SO2Ph 8 steps +NMe3 ButMe2SiO C5H11 299 27 OH NMe OSiButMe2 OH HO 16 steps O 300 PhSO2 297 OH The synthesis of prostaglandin 296 from the vinyl sulfone 298 involves only seven steps (the total yield was 13% with respect to 2-phenylthiocyclopent-3-enol 301 with ee 92%).284 The prepara- NH OH HN ()-291 N e Et H NAc ()-292 NO NAc 293 tion of racemic cephalotaxine 302a 287, 288 is worthy of notice as an example of more complicated syntheses.The scheme under con- sideration is of interest from the viewpoint of the diversity of chemical transformations. The lithiated intermediate 303 pre- pared from vinyl sulfone 304 by consecutive reactions with the lithium derivative 305, allyl bromide and then with BunLi contains the homoallylic sulfonyl group, which is spontaneously eliminated as lithium sulfinate. The exo-1,3-diene group of the reaction product 306 is used in one of the major steps of subsequent transformations to produce cephalotaxine, viz., for the construc- tion of the seven-membered heterocycle.A modification of this procedure afforded 11-hydroxycephalotaxine (302b). However, this method, despite its elegant character, is unsuitable for the preparation of optically active forms of compounds 302a,b.287, 288 PhSO2 O a, b, c O O O O 303 304 CH2OR OO 12 steps O O 306 CH2OR O X = H (a), OH (b); (a) O Li (305), R=O (b) BrCH2CH=CH2; (c) BunLi; (d) 20 8C, 7PhSO2Li. A procedure for the `heteroconjugate addition' developed by Isobe 289 made it possible to solve a very important problem of the efficient stereocontrol in the construction of new acyclic C7C bonds enabling, simultaneously, further carbon-chain elongation. This method was tested using model pyranosides containing a-silylated vinylsulfonyl substituents at C(5).In this case, D-glu- copyranose derivatives serve as chiral pools. Owing to the bulky a-silyl substituent, the substrate molecule adopts a conformation in which the direction of the attack of the nucleophilic reagent [syn or anti with respect to the H atom at C(5)] depends both on the nature of the reagent and the sub- 393 Scheme 10 CH2OR SO2C6H4Li-2 d O X11 O N O HOH 302a,b OMe Me O ; O394 SiR3 O SO2Ph H 307 X SiR3 O HO SO2Ph H X 308 stituents in the pyran ring, which can form chelates with nucleo- philes. In the absence of polar substituents (compound 307), the reaction with alkyllithium proceeds exclusively as syn-alkyla- tion.290 The presence of the hydroxy group at C(4) in compound 308 and the use of a Grignard reagent provide conditions for exclusive anti-alkylation due to the formation of a chelate with the reagent.291 Subsequent chain elongation in the intermediates 309 and 310 was performed predominantly by alkylation of the a-sulfonyl carbanion after desilylation. This method was used for the introduction of the syn-methyl group at position 6 in the total syntheses of maysine and N-methylmaysenine 292 as well as of racemic maytansinol (311) 293 and (7)-maytansinol.294 Vinyl sulfones 312 and 313 were used as the starting compounds for the construction of the C(4)7C(9) fragment.In the total synthesis of okadaic acid (94), vinyl sulfones 314 and 315 were used for the introduction of the anti-C(13)-methyl group and the syn-C(29)- methyl group into the segments A145 and C,147 respectively. Cl Me O N MeO 1 2 Me MeO 311 Me3Si H PhSO2 O O(CH2)2OMe 312 a-Silylated vinylsulfonyl groups at C(6) of the pyran ring were used for `pseudoenantiomeric' addition.295 In the total synthesis of tautomycin (316), compounds 317 and 318 were employed for the spiro-fusion of rings pseudoenantiomeric with respect to okadaic acid as well as for the introduction of the methyl group at position 3 of the segmentC.The segmentsCand B were coupled O Me3Si O PhSO2 314 Pri OH O OH O O O O OMe O A H H O SiR3 RO SO2Ph 317 R=SiMe2But. SiR3 MeLi O SO2Ph Me H 309 X Me SiR3 MeMgBr O SO2Ph HO H X 310 OHO Me 5 3 4 67 8 HO 9 O HNPhSO2 Me3Si O MeO OMe BnO 313 OH SiMe3 PriO O H SO2Ph 315 H OH O 16 18 O 17 O H 316 C B H H O SiR3 RO SO2Ph 318 by the reaction of the C(16)-sulfonyl carbanion of the former with the C(17),C(18)-epoxide of the latter in the presence of BF3 .Et2O. Esterification with the segment A completed the synthesis.296, 297 Studies by Posner et al.11, 298 have played a decisive role in the development of asymmetric synthesis based on reactions of C-nucleophiles with enantiomerically pure vinyl sulfoxides. These reactions made use of enantiomerically pure 2-(sulfinyl)- cycloalkenones 319a,b or 2-(sulfinyl)alkenolides 319c,d as the substrates. Convenient procedures for the synthesis of these compounds were devised.The carbonyl group activates the double bond thus promoting Michael-type addition of C-nucleo- philes. The stereochemistry of addition can be controlled by adding chelating agents. Thus conditions for the Si-attack of the nucleophile are created in the presence of ZnBr2, which binds the sulfinyl and carbonyl groups to form a rigid chelate. In the absence of this additive, Re-attack predominantly occurs. O Tol S X O (CH2)n 319a ± d Posner and coworkers used not only organometallic com- pounds but also lithium enolates as nucleophiles. The high optical purity of the resulting compounds was attained by varying the reaction parameters and using enantiomerically pure precursors. Thus the formal synthesis of the methyl ether of (S,S )-11- oxoequilenin was carried out starting from (S )-(+)-2-(tolylsulfi- nyl)cyclopent-2-enone [(S )-(+)-319a] via the secosteroid 320.299, 300 The reaction of the same vinyl sulfone 319a with lithium enolate 321 gave rise to the Michael addition product 322 with a diastereoselectivity of 91%± 94%.The latter com- pound was converted in six steps into methyl ether of estradiol (323) with ee>97%.301 O O Tol S (S )-(+)-319a TolSO a, bMeO TolSO2 O e, fMeO 322 MgBr, THF,778 8C; (b) MeI, HMPT; (c) Me2CuLi, (a)MeO Et2O, 0 8C; (d ) BrCH2CO2Me, HMPT, 25 8C; (e)MeO ( f ) MCPBA. Vinylation of vinyl sulfone 319a in the presence of ZnBr2 followed by methylation afforded a mixture of diastereomers of trisubstituted cyclopentanones.Reductive desulfinylation of the latter made it possible to obtain enantiomerically pure substituted cyclopentanones 324a,b, which are required for the synthesis of steroids.302 E N Prilezhaeva X=CH2, n = 1 (a), 2 (b); X=O: n = 1 (c), 2 (d). O O MeO2CCH2 c, d 320 MeO O O H 6 steps H H H MeO 323 (ee >97%) OLi Br (321);Sulfones and sulfoxides in the total synthesis of biologically active natural compounds O O H TolSO a, b + TolSO H 319a c, d c, d O O Me H H Me (S )-(+)-324a (S )-(7)-324b (a) ZnBr2; (b) CH2=CHMgBr; (c) MeI; (d ) Al/Hg. Quaternary chiral centres can be generated using 3-alkyl- substituted tolylsulfonylcyclopentenone as the starting com- pound.303 For example, vinyl sulfone 326 was used in the stereo- convergent synthesis of the sesquiterpene (+)-a-cuparenone (325); however, the ee value of the resulting product was only 70%.O O Tol O S a, b, c, d, e 326 Tol 325 (a) Tol2CuLi; (b) MCPBA; (c) ButOK; (d ) MeI; (e) Me2CuLi, MeI. The five-step synthesis of enantiomerically pure (7)-methyl jasmonate with ee>98% was carried out 304 starting from vinyl sulfone (R)-(7)-319a. O O O O Tol Tol a b, c S S C(SiR3)2CO2Me (R)-(7)-319a O O Et STol d, e, f CH2CO2Me CH2CO2Me (a) (R3Si)2C(Li)CO2Me; (b) P2I4; (c) KF; (d ) NaH; (e) BrCH2 Et; ( f ) Ra/Ni. Using enantiomerically pure (S )-(+)-tolylsulfinylbutenolide 319c 305 or -pentenolide 319d 306 as the starting compounds in the reactions with a Grignard reagent in the presence of ZnBr2 or with substituted lithium enolates, enantiomerically pure antitumour (7)-podarhizon and 3-substituted esters of glutaric acids, respec- tively, were prepared.Holton et al.307 used an analogous reaction and vinyl sulfoxide 327 as the starting compound in the formal total synthesis of aphidicolin, which exhibits in vitro activity against the virus Herpes simplex. Tol S O O 327 O b. Addition of heteronucleophiles In the synthesis of natural products, reactions of vinyl sulfones or vinyl sulfoxides with alkoxides or amines resulting in the con- struction of C7Oor C7N bonds were used almost exclusively in 395 the intramolecular versions regardless of the nature of the acceptor.Thus the key step of the 15-step enantioselective total syn- thesis of the pheromone (1R,3S,6R,9S,10S )-9,10-epoxytetra- hydroedulan (+)-328 involved cyclisation of hydroxyvinyl sulfone 329 yielding compounds 330a,b in a ratio of 3.5:1.308 OH NaH 4 steps OH THF CN SO2Ph OAc OH 2 steps OH SO2Ph 329 OAc OAc O O CH2SO2Ph CH2SO2Ph+ 330b 330a OAc O O O Ra/Ni 4 steps 330a H (+)-328 In the synthesis 309 of 2,3-disubstituted pyrrolidines 331a and piperidines 331b (the starting materials in the synthesis of bio- logically active compounds) from acyclic alkoxy- and hydroxy- substituted aminovinyl sulfones 332a,b, cyclisation proceeded also nonstereoselectively. The best cis-stereoselectivity (*80%) was achieved with the use of the hydroxy derivatives 332a.The protection of the hydroxy group (the best results were obtained with R3=Pri3Si) favours trans-stereoselectivity. OR2 Boc CH2SO2Ph R1N SO2Ph a, b n NR1 n OR2 331a,b 332a,b n = 1 (331a), 2 (331b); R1=H, (CH2)2CO2Me; R2 = H (332a), Pri3Si (332b); (a) CF3CO2H, CH2Cl2; (b) Et2NH, THF, 778 8C. In more rigid systems, for example, in the synthesis of the alkaloids clavepictines A and B 333a,b from monocyclic com- H (CH2)3 9 steps a N NR1 O O PhSO2 O O SO2Ph 334 HN R2O Me 333a,b C5H11 R1=Troc (trityloxycarbonyl); R2=Ac (a), H (b); (a) 10% C/Pd, THF, NH4OAc, 20 8C, 48 h (94%).396 pound 334, cyclisation through b-amination of the double bond of the vinylsulfone fragment occurs with a high stereoselectivity.310 In the synthesis of (7)-monomorine 335, 5-endo-trig cyclisa- tion of compound 337 prepared from norleucinol 336 took place also in a highly stereoselective manner.311 The construction of the second ring from the monocyclic intermediate 338 occurred through intramolecular reductive amination.PhSO2 5 steps HO NH2 336 PhSO2 Bun NHBz PhSO2 Bun Bz N 338 (73%) Intramolecular addition of heteronucleophiles at the C=C bonds of vinyl sulfoxides plays a considerable role in the asym- metric synthesis.12 In the series of studies performed by Iwata et al.,312 ± 315 the addition of remote hydroxy groups to the vinyl sulfoxide fragment was used for the construction of enantiomerically pure dioxa- spirodecanes and -undecanes, which are the major components of pheromones of many insects.The enantioselectivity of spirocycli- sation is achieved owing to the asymmetric induction of the chiral sulfinyl group due to which this method has advantages over some others.100, 101 Dioxaspirodecanes (2R)-339a,b, which are phero- mones of the wasp Paravespula vulgaris,312, 313 were prepared by the action of KH on 5-hydroxydihydropyran sulfoxides 340a,b followed by reductive desulfination of the reaction products 341a,b. Two other diastereomers of the pheromone, viz., 342a,b, were synthesised by isomerisation of the cyclisation product in an acidic medium followed by reductive desulfination of isomeric sulfoxides 343a,b.The closure of the six-membered rings by an analogous intramolecular reaction afforded (R)- and (S )-1,7- dioxaspiro[5.5]undecanes 61 313, 314 and more complex molecules of talaromycins A and B, which are metabolites of the toxic mushroom Talaramyces stipitatus.315 Tol O S R1 a R2 (CH2)2C O 340a,b OH O b R1 O (2R)-339a,b R2 O O R1 c R2 SOTol 343a,b R1=H,R2=Me (a); R1=Me, R2=H(b); (a) KH, THF, 778 8C; (b) Ra/Ni, MeOH; (c) TsOH. Bun ButOK ButOH NHBz OAc 337H 4 steps Bun N (7)-335 SOTol O R1 R2 O341a,b O b R1 O(2S )-342a,b R2 E N Prilezhaeva Solladie et al.168 used cyclisation involving a remote hydroxy group and the C=C bond of the chiral vinylsulfinyl fragment of the molecule as one of the steps in the above-considered synthesis of a vitamin E precursor, viz., (+)-(S )-122.Polycyclic alkaloids, such as (+)-carnegine (344) and (+)-canadine (345), can be prepared by intramolecular amination of vinylsulfinyl bonds in spite of the fact that this process is not always stereoselective.316, 317 O N MeO O H OMe NMe MeO H 344 345 OMe Monocyclic (+)- and (7)-sedamines were synthesised 316 from linear precursors, viz., substituted (E )- and (Z)-alkenyl sulfoxides. Thus cyclisation of the sulfoxide (E)-346 followed by chain elongation in the reaction of the a-sulfinyl carbanion of diastereomer 347a with benzaldehyde and reductive desulfinyla- tion of the reaction product afforded (+)-sedamine (348). (7)-Sedamine was prepared according to the same procedure starting from the (Z)-isomer of the sulfoxide 346.Ph (CH2)4CH F3C(O)C S a Me N O (E)-346 Ph H H Ph + S S Me N Me N O 347b (9%) O 347a (91%) b, c, d H OH H Ph Me N 348 (a) PhCH2NEt3OH,740 8C; (b) LDA; (c) PhCHO; (d ) Ra/Ni. An alternative procedure for the preparation of carnegine (344) was developed 318 based on the reaction of enantiomerically pure (R)-2,4-dinitrophenylethynyl sulfoxide (349) containing the highly electrophilic triple bond with 2-(3,4-dimethoxyphenyl)- O O a HC CS +Ar2(CH2)2NH2 S Ar2(CH2)2NH Ar1 349 350a,b Ar1 352a,b MeO b c, d 344 NH MeO O S Ar1 c e NH NH HN HN O 351 S Ar1 (b); (a), Ar1= NO2; Ar2= OMe MeO HN O2N (a) 20 8C; (b) 350a, CF3CO2H, 0 8C, 100%; (c) Ra/Ni; (d) CH2O, NaCNBH3; (e) 350b, TsOH, MeOH,730 8C (70%).Sulfones and sulfoxides in the total synthesis of biologically active natural compounds ethylamine (350a).The tricyclic alkaloid (+)-tetrahydroharman (351) was prepared with a rather high selectivity starting from amine 350b containing the indole substituent via the vinyl sulf- oxide 352b. Intermolecular addition of a nitrogen nucleophile to the vinylsulfinyl bond was used in the synthesis of structurally unique (R,R)- and (S,S )-homalines 353 from epimeric 4-phenyl-1,5- diazacyclooctan-2-ones [(R)-(+)-354) and (S )-(7)-354].319 The reaction of pyrazolidine with enantiomerically pure substituted (R)- or (S )-(E )-vinyl sulfoxides 355 in an excess of ButOK followed by the removal of the sulfinyl group under the action of SmI2 afforded bicyclic compounds.The target products were prepared from these bicyclic compound in two steps after reduc- tive cleavage of the N7N bond under the action of Na/NH3 . O O Tol S N c a, b + NH N Ph CO2But NH Ph (+)-(S )-355 (7)-(R)-355 O O HN Ph N(CH2)3N ... NMe MeN O HN Ph Ph 353 (+)-(R)-354 (7)-(S )-354 (a) ButOK; (b) SmI2; (c) Na/NH3 . 2. The Diels ± Alder reaction a. Sulfonyl- and sulfinyl-containing dienophiles The high reactivity of vinyl sulfones as dienophiles in [4+2] cycloaddition reactions was reported in the 1960s. Ethyl vinyl sulfone readily enters into Diels ± Alder reactions not only with electron-rich dienes (the reaction with cyclopentadiene is exother- mic), but also with electron-deficient dienes (for example, with hexachlorocyclopentadiene 320).More recently, owing to the fact that the adducts of vinyl sulfones can readily undergo reductive desulfonation, the latter have found application as equivalents of nonactivated alkenes and alkynes, which are difficult to introduce into the [4+2] cycloaddition reactions.321, 322 However, the Diels ± Alder reactions are rather rarely used for the preparation of biologically active compounds due apparently to their low stereoselectivity. The first step of the synthesis of sesquiterpenoid sterpuric acid (356) involved cycloaddition of cyclic vinyl sulfone to the highly electrophilic Danishefsky diene (357).323, 324 The ratio between the target isomer 358a and the undesirable isomer 358b was*2 : 1 (the total yield of the final product was 11%).The reaction of 3-silyloxy-2-sulfolene with diene 359, which is the key SO2Ph a, b + MeO2C 357 OSiMe3 H H MeO2C MeO2C + O O PhSO2 358b PhSO2 358a H HO2C ... 358a OH 356 (a)*150 8C, 5 days; (b) oxidation. 397 O O RO Me3SiO H H H H a, b + + RO RO SO2 359 OMe SO2 361b SO2 361a O OHOH H ... H 361a O O HO H HO S 360 R=Pri3Si; (a) 170 ± 180 8C, 48 h; (b) Py. TsOH, D (82% ± 85%). O BnO SO2Ph SO2Ph BnN b, c, d a + O SO2Ph PhSO2 Bn N 362 BnO O N Et BnN Et MeO SO2Ph HN MeO (a) 150 8C, 8 days; (b) 2M HCl, (MeO)3CH; (c) KOH, THF; (d ) EtCuMgI.step in the formal synthesis of breynolide (360), also proceeded nonselectively to form a mixture of adducts 361a,b.325 (E )-1,2- Bis(diphenylsulfonyl)ethene is a more efficient dienophile. Its reaction with 5-benzoyloxy-2-pyridone proceeded with a higher selectivity and was used in the synthesis of racemic ibogamine via the adduct 362 (the total yield was 14%).326, 327 In the absence of catalysts, [4+2] cycloaddition involving vinyl sulfones proceeds at rather high temperature. The use of catalysts makes it possible to use milder reaction conditions and to enhance the selectivity. Thus the selectivity of the Diels ± Alder reaction of tetracyclic vinyl sulfone 363 with diene 364 in the presence of EtAlCl2 at 0 8C was higher than 90%.Such strategy for the ring buildup made it possible to perform the C(15)- and C(20)-enantioselective synthesis of racemic alkaloid 3-epi-allo- yohimbone (365) with a skeleton similar to that of reserpine.328 C A a, b O H ND SO2Ph BNTs ()-363 C A N O N N H BNHD H H SO2Ph Ts 4 steps E H H 365 O O (a) (364), EtAlCl2 , 0 8C; (b) 0.5 M HCl. OSiMe3 An application of intramolecular [4+2] cycloaddition involv- ing a,b-unsaturated sulfonyl fragments has been described. Thus the stereospecific construction of the skeleton of cis ± anti ± cis- estrone was carried out 329 by the reaction of the o-quinodi- methane fragment formed upon pyrolysis of the benzocyclo-398 butane moiety of compound 366 with the vinylsulfonyl group of the same molecule.OBut OBut COCH2 a OH MeO H H 366 TolSO2 MeO (a) 195 8C, 1,2-Cl2C6H4, 6 h (*62%). Based on their experience on intramolecular Diels ± Alder reactions of polyene sulfones,330 Craig et al.331 attempted to use this approach in the synthesis of vitamin D3 and its analogues, which have attracted growing interest because of the discovery of new pharmacological properties of these compounds.332 How- ever, the construction of the block CD for the synthesis of vitamin D3 can be performed 333 only starting from compound 367 containing the highly reactive sulfonylethynyl fragment. Selective hydrogenation of one of the C=C bonds in the major reaction product 368b afforded the key intermediate in the synthesis of vitamin D3, viz., sulfone containing the rings CD.Corey et al.334 ± 336 used ethynylsulfonyl precursors for the construction of the rings AB of forskolin (369) possessing valuable pharmaco- logical properties. Owing to the additional activation of the triple bonds in compounds 370a,b with ester groups, cyclisation H 1158C, 9 h C 367 PhSO2C 3 3 Pri Pri H H + 368a 368b PhSO2 PhSO2 3 Pri H 2 steps D C 368b H H PhSO2 O O C O O CSO2Tol SO2Tol 2 steps a or b B A R R 370a,b O HO O OH OAc H OH 369 R=H(a), OCO2Et (b); (a) R=H, CH2Cl2 , 23 8C, 36 h (64%, ee 97%); Me , 95 8C, 48 h (65%, ee 93%). (b) R=OCO2Et,But But N occurred in the absence of a catalyst under mild conditions with a high enantioselectivity.The introduction of activating groups and the addition of catalysts, which allow one to perform the Diels ± Alder reactions under milder conditions, are particularly necessary if less reactive vinyl sulfoxides are used as dienophiles. The Diels ± Alder synthesis involving polyfunctional racemic vinyl sulfoxides was applied, for example, in the preparation of ()-dehydrogriseofulvin (371)337 starting from the sulfoxide 372 or sodium salts of prephenates 373 via the intermediates 374a,b, which were generated from the sulfoxide 375.338 When surveying his investigations, Danishefsky particularly emphasised these studies.339 The reactions of vinyl sulfoxides even with Danishef- sky's silyloxydienes necessitated prolonged heating and were accompanied by elimination of sulfenic acid.OMe O SOPh + O Me MeO Me3SiO 372 Cl OMe O OMe O O MeO 371 Cl O OMe O CO2Me + OMe Me3SiO SOPh375 CO2Na CO2Na O R1 R2 373a,b R1=OH, R2=H(a); R1=H, R2=OH(b); (a) 100 8C, 20 h; (b) AcOH, AcOEt; (c) BBN (9-borabicyclononane); (d ) NaOH. The development of procedures for efficient asymmetric syn- thesis starting from enantiomerically pure sulfinyl-containing dienophiles presented the major problem. The search for the optimum reaction conditions and for the chiral sulfinyl dienophile of choice for the synthesis of (+)-(1R,4R)- and (7)-(1S,4S )- enantiomers of norborn-4-enone was carried out using the [4+2] cycloaddition of cyclopentadiene to (+)-(R)-tolyl vinyl sulf- oxide 340 and its analogues 341, 342 as examples. The full selectivity was achieved only with the use of a more complex compound, viz., a ketene equivalent 376.The reaction of the latter with cyclo- pentadiene in the presence of BCl3 at 770 8C gave only one adduct, which was transformed into (+)-(1R,4R)-norborn-4- enone.343 The reaction proceeded selectively due to the formation MeO H O a S CO2Me 376 O OMe O 4 steps S O CO2Me (a) , BCl3, CH2Cl2 ,770 8C, 9 h (88%). E N Prilezhaeva OMe OMe ... a, b, c, d O (+)-(1R,4R) (de 100%)Sulfones and sulfoxides in the total synthesis of biologically active natural compounds of a BCl3 chelate with both the sulfinyl and methoxycarbonyl groups of the substrate. It should be noted that the noncatalytic reaction afforded a mixture of all possible enantiomeric adducts.Koizumi and coworkers 344 ± 347 made a major contribution to the development of procedures for the asymmetric synthesis of natural compounds starting from chiral sulfinyl-containing dieno- philes. The synthesis of (+)-epi-b-santalene 377 involved the reaction of cyclopentadiene with ethyl (Z)-(R)S-2-methyl-3-(tolylsulfinyl)- prop-2-enoate (Scheme 11).344, 345 In this synthesis, the reaction CO2Et S Tol O (Z)-(R)S CO2Me HOS CO2Me R1 (R)SCO2R1 R2 SO (Z)-(S)S-380a6 steps HO HO f (Z)-(S)S-380b R1= menthyl: R2=2-pyridyl (380a), R2=3-trifluoromethyl-2- pyridyl (380b); (a) (c) , ZnCl2,720 8C, 3.5 h (94%); (d ) 778 8C (94%); (e) 0 8C, 6 days (*100%).399 Scheme 11 O a 10 steps SOTol CO2Et (+)-377 SOR1 3 steps b O CO2Me CO2Me (7)-378a O O 3 steps O (+)-378b c SOR1 O O CO2Me CO2Me 8 steps O O temperature can be noticeably decreased and the enantioselectiv- ity of the reaction can be enhanced in the presence of an additional (compared to tolyl vinyl sulfoxide) electron-withdrawing substitu- ent at the C=C bond of the vinyl sulfoxide. The influence of the second alkoxycarbonyl group in dimethyl (R)S-(menthylsulfinyl)- maleate makes a reaction with cyclopentadiene at room temper- ature highly enantioselective. This was used for the preparation of the enantiomerically pure bicyclic lactone 378a, which is the starting compound in the synthesis of various natural products.346 The application of zinc salts as catalysts allows one to perform the reactions at low temperatures. However, in this case an isomeric adduct is formed.This adduct can be transformed into either lactone 378b or `the Ono lactone' (379), which is an important precursor in the synthesis of natural compounds, for example, of carbocyclic nucleosides.347 The lactone 379 can also be synthes- ised starting from the adduct of menthyl (S)S-3-(2-pyridylsulfin- yl)acrylate (380a) with cyclopentadiene, which was prepared in high yield in the presence of Et2AlCl.348 Recently,349 this adduct has been used in the total synthesis of the alkaloid cis-trikentrin B.The selectivity of condensation of compound 380a with the less active dienophile furan is lower. However, this reaction was used for the preparation of D-showdomycin 381 and methyl epi- shikimate 382.350 The sulfoxide 380b with a 3-trifluoromethyl-2- pyridyl group is a `champion' among dienophiles of this series. Its adduct with 2-methoxyfuran, viz., compound 383, which was formed in quantitative yield at 0 8C in the absence of a catalyst, was employed in the synthesis of a glyoxylase I inhibitor (384) (Scheme 11).351 Chiral N-substituted sulfinylmaleimides 385a ± d are efficient dienophiles. These compounds react with cyclopentadiene in the presence of ZnCl2 at low temperature to form almost exclusively exo-adducts 386a ± d in quantitative yields.352 The adduct 386d was used 353 for the preparation of the bicyclic alkaloids (+)-indo- lizidine 387 and (+)-laburnine 388.(+)-379 O SOR1 O O S R1 d 6 steps (+)-379 a NR2 CO2R1 NR2 SOR2 385a ± d O 386a ± d O O e R2=(CH2)2C:CH 9 steps 7 steps CO2R1 SOR2 N N 9 steps H H O Me Me HO CO2Me HO (+)-388 (+)-387 NH R1= HO ; R2=Me (a), Ph (b), Bn (c), (CH2)2C:CH (d); OH Et O OH 381 OH (+)-382 (a) , ZnCl2 ,778 8C (95% ± 100%). O O CH2OC HO OMe11 steps O HO CO2R1 SOR2 OH 383 (7)-384 The search for new types of electron-rich dienes holds prom- ise. This will extend the scope of synthetic applications of sulfinyl- containing dienophiles.For example, condensation of `Dane's diene' (389) with the sulfinyl-substituted ester of maleic acid 390 354 or with sulfinyl-substituted cyclopentenone 391 355 afforded the adducts 392 and 393, respectively, which are pre- cursors in the steroid synthesis, with a high diastereoselectivity. , 25 8C, 19 h (87%); , 90 8C, 6 h (87%); (b) CO2Bn a, b , Et2AlCl, CO2Me O O H OMe , , Et2AlCl,778 8C (*70%); ( f ) MeO MeO 389 392400 c 389 MeO 393 O Tol S CO2Bn (a) (390), TiCl4 ,778 8C (ee >98%); CO2Me (b) Al/Hg (ee >98%); (c) O The reaction of the diene 389 with the sulfoxide 390 was accompanied by spontaneous elimination of sulfenic acid. b. Sulfonyl- and sulfinyl-containing dienes As yet, sulfonyl-substituted and, particularly, enantiomerically pure sulfinyl-substituted dienes have received little use in the synthesis of natural products. Evans 356 was the first to propose a tandem [4+2] cyclo- addition of a racemic sulfinyl-containing diene and the sulfonyl- sulfenate rearrangement of the adduct using the synthesis of a derivative of the hasubanan series as an example.More recently, Posner and coworkers (see the review 357) performed systematic studies of the Diels ± Alder reactions of 3-sulfinyl- (394a) and 3-sulfonyl-2-pyrones (394b) with electron- rich dienophiles, such as vinyl ethers or vinyl sulfides. Unlike other substituted pyrones whose Diels ± Alder reactions proceed only at high temperatures (resulting in the degradation of the initially formed adducts), the pyrones 394a,b at low temperatures (some- times at high pressure) give polysubstituted bicyclic lactones, which are excellent starting compounds for the preparation of various natural products.Thus the reaction of the sulfinyl-substituted pyrone 394a with ethyl vinyl sulfide proceeded stereoselectively to form 358 the endo- adduct 395, which was converted into tetrasubstituted cyclo- hexene 396 through the sulfoxide-sulfenate rearrangement under conditions of alkaline methanolysis. Subsequent transformations afforded substituted cyclohexadiene 397, which is the key inter- mediate in the synthesis of ()-chorismic acid (398). A shorter synthetic path for the cyclohexadiene 397 is based on the reaction of sulfonylpyrone 394b with 1,3-dioxole.359 O PhSO O + SPh 394a CO2MeSPh HO396 OH CO2Me HO397 OMEM O TolSO O H H b H MeO Tol O S (391), EtAlCl2 ,725 8C (93%).O a b SOPh O SPh 395 CO2MeSOPh c 2 steps HO OMEMCO2Me O HO2C 398 OH E N Prilezhaeva O SO2Tol TolSO2 O O 2 steps d O O+ O O O 394b MeO2C SO2Tol O e 397 O OMEM (a) 20 8C, 0.8 kbar (73%); (b) MeONa (90%); (c) 85 8C; (d) 25 8C, 11 ±12 kbar (87%); (e) Zn (87%). Posner and coworkers performed asymmetric syntheses of a number of enantiomerically pure natural compounds by introduc- ing sulfonylpyrone 394b into the Diels ± Alder reaction with optically pure vinyl ether (7)-(S )-399 360 ± 362 catalysed by Lewis acid 400.360 The transformation of the endo-adduct 401, which was obtained with a high stereoselectivity, afforded trisubstituted cyclohexene (7)-402.A somewhat lower stereoselectivity was achieved when this reaction was carried out in the absence of a catalyst at 25 8C.361 The cyclohexene 402 served as the starting compound for the preparation of the key intermediate 403 (the total yield was 62%) in the total synthesis of 1a,25a-didehydroxy- vitamin D3 as well as for the synthesis of methyl (7)-tri-O-acetyl- 4-epi-shikimate (404) (the total yield was 23.4%, ee >98%). H H O a b, c SO2Tol OC OC 394b+ Ph Ph Pri O 401 Pri (7)-(S )-399 EtO2C OSiMe3 7 steps CO2Me H OC Ph 403 OSiMe2But Pri CO2Me 402 OH 12 steps OAc AcO But 404 OAc AlMe O (a) Me (400), 745 8C, 12 h; (b) MeONa; (c) Al/Hg.But 2 Readily available racemic 2-(phenylsulfinylmethyl)buta-1,3- diene (405) is an active diene.363 This compound reacted with dimethylcyclopropene to give a mixture of exo- and endo-adducts 406. After reductive desulfinylation, the exo-adduct was con- verted into D3-carene (407). The sulfoxide-sulfenate rearrange- ment of compound 406 under the action of P(OEt)3 afforded the hydroxy derivative 408 from which racemic chaminic acid (409) was prepared. Thermal condensation of the diene 405 with methyl vinyl ketone gave rise to a mixture of 1,4- and 1,3-substituted cyclohexenes in a ratio of 3 : 1. The adduct 410 was converted into racemic D1(7)-menthene-2,8-diol (411) in three steps.Sulfonyl- and sulfinyl-substituted diene units can be involved in intramolecular [4+2] cycloaddition. For example, this proce- dure was used for the preparation of compound 412, which is an401 Sulfones and sulfoxides in the total synthesis of biologically active natural compounds example of an asymmetric synthesis of a natural product with the use of such dienes.368 b a + O O Tol Tol PhSOCH2 PhSOCH2 S S CO2H CO2H 407 406 a, b 405 + HO CO2H CO2H 2 steps c 406 416b 415 416a 6 steps HO2C 409 408 OH O HO Ac 2 steps d Me 405+ O PhSOCH2 417 410 411 (a) , THF, D; (b) Na2CO3, H2O (90%), (416a : 416b=4 : 1). (a) 808C, 5 kbar; (b) Li, NH3 (liquid); (c) P(OEt)3; (d ) PhH, 80 8C. COO CO important fragment in the total synthesis of the macrolide ikarugamycin.364 3.Syntheses based on elimination of SO2 from 2,5-dihydrothiophene 1,1-dioxides (3-sulfolenes) Et CO2Et 135 8C CH2SO2Ph H H CO2Et Et Et 4 steps O H H CH2SO2Ph H 412 (70%) H A short synthesis of sesquiterpenoid (+)-sterpurene (413) was carried out 365 using the cascade intramolecular [4+2] cyclo- addition involving the diene system of sulfinyl-substituted tet- raene 414. PhSO H C 3 steps H 414 413 3-Sulfolenes readily eliminate SO2 to form substituted buta-1,3- dienes. This process is the cheletropic ring-opening reaction which obeys the Woodward ± Hoffmann rule and occurs under condi- tions of pyrolysis, sometimes in the presence of bases. The introduction of substituents into the sulfolene ring, which can be readily performed, for example, by alkylation at the a-position, followed by thermolysis allows one to prepare various buta-1,3- dienes starting from 3-sulfolenes.These butadienes can be used in the synthesis of polyunsaturated linear and carbocyclic natural compounds. Thus the homofarnesene components of the fire-ant trail pheromone 418a,b were prepared 369 from 2,3-dimethyl-4- (phenylthio)-3-sulfolene (Scheme 12). Polysubstituted thiophene 419 was converted into 3-sulfolene 420 by electrolytic reduction followed by oxidation at the sulfur atom.370 The compound 420 was subjected to in situ thermolysis resulting in a mixture of a juvenoid methoprene 421 and its (2Z,4E)-isomer. Sulfolene 422 was used as the starting material 371 for the preparation of tricyclic compound 423 containing the taxane ring system.3-Methyl-3-sulfolene served as the starting compound in many syntheses of natural compounds, for example, of open- chain a-sinensal (424) (an important contributor to the odour of the Chinese orange oil) 372 or bicyclic terpenoids of the eudesmane series 425 ± 427.373 In the latter cases, the intramolecular Diels ± Alder reactions proceeded with extremely high stereoselectivities (Scheme 13). Convenient procedures for the preparation of enantiomeri- cally pure 2-sulfinyl-substituted butadienes have been developed recently.366, 367 The transformation of the endo-adduct (416a) of diene 415 with maleic anhydride in the synthesis of monoterpe- noid (7)-(1S,5R)-karahana ether (417) (ee >93%) is the first The use of nitrogen-containing dienophilic groups (for exam- ple, imine or enamide groups) in the intramolecular Diels ± Alder reactions opens up the way to the construction of racemic alkaloids (Scheme 14).Apparently, the first to be performed was the short synthesis of racemic elaeokanine A (289a) via the Scheme 12 SPh SPh SOPh SPh e, f d c a, b 418a SO2 SO2 418b (a) BunLi; (b) Br; (c) LiAlH4; (d ) oxidation; (e) chromatographic separation; ( f) BunLi, Et2O, NaOH. Me a, b, c d OMe OMe OMe PriO2C PriO2C HO2C SO2 S 420 419 421a,b (a) 2e7; (b) PriOH, H+ (84%); (c) MCPBA; (d ) PhMe, D.402 a SO2 422 O (a) PhMe, D, 50 min; (b) a, b SO2 e SO2 O g SO2 SO2 (CH2)2C(Me) CH2 (a) LiHMDS; (b) CH2Br; (c) oxidation; (d ) D; (e)BrCH2 intermediate 428 starting from the sulfolene 429.374 Elimination of SO2 and cyclisation were carried out by passing compound 429 through a heated column (370 ± 390 8C) filled with glass helices.Martin et al.375 performed the formal total synthesis of penta- cyclic lycorine (a natural plant-growth inhibitor, which is an important alkaloid of the Amaryllidacae family) via the key O OSiMe3 Prn NHCH2OAc SO2 429 RN O C O O 431 R=CH2C6H4OMe-4. CH2NMe2 NaOH 200 8C SO2 (CH2)3CONH2 434 R1=CH2OH, R2 = H (a); R1=H; R2=CH2OH (b). CO2Me ... SO2 R=CH2CH=CH2, X = CH2 (a); R=Bn, X =O (b). H b, c, d, e H H O 423 ; ZnCl2; (c) BF3, Et2O; (d ) PhMe, D; (e) NaOH.CHO SO2 c, d, c 424 f H 425 h O OH H 426 d Ac H i H 427 O O ; (h) MeMgBr; (i) Ph3P=CH2. ; ( f ) 80 8C; (g) CH2I precursor lycorane 430. Sulfolene-containing enamide 431 was used as the starting compound. Short syntheses of racemic lupinine 432a and epilupinine 432b were performed starting from bicyclic compound 433, which has been prepared by pyrolysis and the intramolecular Diels ± Alder reaction of disubstituted sulfo- lene 434.376 Analogous conversions of the precursors 435a,b, O OH Me3SiO D 2 steps O 2 steps N N Prn Prn CH2 428 H H H H O O 3 steps D H H N N O SO2 O O R 430 O CH2NMe2 CH2NMe2 R2 R1 ... N N N H2C 432a,b 433 O O RN X RN XH D Me2NCO SO2 H Me2NCO 435a,b 436a,b E N Prilezhaeva Scheme 13 Scheme 14 289aSulfones and sulfoxides in the total synthesis of biologically active natural compounds which have been prepared from 3-methoxycarbonyl-3-sulfolene, afforded the bicyclic systems 436a,b.The latter served as the starting compounds in the synthesis of heteroyohimboids.377 The sulfolene grouping has also been used as a protective group in modifications of vitamin D3. For the purpose of introducing methyl groups at C(6) and C(19) 378 or the fluorine atom at C(19),379 an adduct of vitaminD3 with SO2 at its 1,3-diene fragment has been initially prepared. After completion of the required transformations, the adduct was decomposed by mild thermolysis. In the total synthesis of racemic estra-1,3,5(10)-trien-17-one (437), a mixture of epimers of substituted 1,3-dihydrobenzo[c]- thiophene 2,2-dioxide 438 was used as the precursor.This mixture gave rise to the quinodimethane intermediate 439 upon thermal elimination of SO2 , which underwent stereospecific cyclisation to the final product.380 O CH2CH2 2 steps SO2 210 8C 8 h SO2 438 O O CH2CH2 H H H 439 437 (85%) VI. Conclusion Among reactions of sulfoxides and sulfones playing an important role in the synthesis of natural compounds, alkylation of carb- anions obtained from these compounds or the Julia olefination became conventional processes. However, the improvement of these procedures is still in progress. Thus the use of dimethoxy- ethane as the solvent in the first stage of the Julia olefination 381 in combination with SmI2 (see Refs 141 and 142) made it possible to O OH O O R2 R2 790 8C R3 7 R3 R1O R1O 440 (62%) PhSO PhSO R1=SiMe2But, R2=CH=CHCH(OR1)(CH2)3Me; R3=(CH2)3CO2But.O O X X CH2Br a 7 SO2Tol SO2Tol 443a,b X = S (a, 92%), O (b, 87%); (a) DMF,778 8C; (b) AlCl3, 0 8C, 10 min. R1 R1 NH R2 a or b + CH2CHO R2 SO2 HN R1=R2=H(a); R1=OMe, R2= H (b); R1=R2=OMe (c); (a) AcOH, 20 8C, R1=H, OMe; R2=OMe; (b) R1=R2=H, CF3CO2H, 20 8C; (c) PhMe, D, 18 h. 403 construct trisubstituted C=C bonds, which previously failed, for example, in the synthesis of macrolides of the avermectin ± melbe- mycin series.136, 139 One would expect that considerable study will be given to the enhancement of the stereoselectivity of catalytic Diels ± Alder reactions, particularly, involving nonracemic sulfinyl dienes and dienophiles, to the use of new asymmetric building blocks, for example, chiral (ee 95%± 99%) allylic sulfones synthesised recently,382 and to the development of p-allylic alkylation cata- lysed by transition metals based on the strategy of the transfer of the reaction centre to the remote functional group (for example, in the synthesis of tetracyclic (7)-dendrobine)383 with the participa- tion of sulfinyl-containing nucleophiles.Convergent syntheses (Fuchs 23 took an active part in po- pularisation of this method) have found a rather wide application in the reactions considered in this review.More modern method- ologies, which allow one to perform one-pot syntheses of complex compounds, are not used so often. These procedures are said to be consecutive or tandem processes,384 ± 386 cascade reactions,387 processes with the use of counterattacking reagents 388 or poly- component condensations.389 The examples of multicomponent reactions considered below demonstrate that this approach to the synthesis of natural compounds is fruitful. Thus three-component cyclisation of an allylsulfinyl anion with a substituted cyclopentenone and an aldehyde afforded compound 440. Modification of the latter made it possible to synthesise the prostaglandin derivative 441.390 Epithio- and epoxyestratetraenones 442a,b 391 were synthesised by three-com- ponent cyclisation involving the allylsulfonyl anion, which made it possible to construct the steroid skeleton with a high stereo- selectivity without isolation of the intermediates 443a,b.The synthesis of the alkaloids apoyohimbines 444a,b 392 was based on the cascade process involving the Pictet ± Spengler reaction of substituted tryptamines with a sulfolene-containing aldehyde, elimination of SO2 from the intermediates 445a,b and the intra- molecular Diels ± Alder reaction. This allows one to perform one- steps introduction of the methoxycarbonyl group at C(22) yield- ing a pentacyclic reaction product with the stereochemistry of the natural compound (Scheme 15). Scheme 15 O 4 steps OH CO2But 441 O X b H 442a,b R1 N N R2 c H H NH NH SO2 H MeO2C MeO2C 445a ± c 444a ± c (30% ± 54%)404 The area of these investigations would be expected to expand in the near future.When this review had been prepared for publication, the results of new studies devoted to the applications of sulfoxides and sulfones to the synthesis of natural compounds appeared. The most interesting of them are briefly considered below. Conventional alkylation ± desulfonylation of a-sulfonyl carbanions 393 ± 397 (including those prepared from oxiranes 398) along with an interesting version of reductive alkylation of 1,1-di(sulfone) with lithium naphthalenide, allyl bromide or sodium amalgam 399 were used for the construction of C7C bonds.Endocyclic C=C bonds were formed by pyrolysis of oxo sulfoxides.400, 401 In addition to the coupling of fragments through the (E )-C=C bonds using the classical olefination according to M Julia in the construction of natural molecules,402 ± 404 the increasing popularity has acquired a modification of this proce- dure developed by S Julia 405 using model compounds (see Refs 406 ± 417 and references cited therein). The procedure elabo- rated by S Julia involves the reactions of aldehydes with anions generated from 2-benzothiazolyl sulfones whose participation makes it possible to perform olefination as a one-pot process. Double bonds between the pyrrole rings in natural compounds are formed by successive treatment of a mixture of a sulfone and an aldehyde with DBU and PBun3 .408 The reactions of a-sulfonyl anions 409, 410 or anions of chiral sulfoxides 411 with carbonyl compounds were used for binding fragments through the CH2CO or CH2CH(OH) groups.Unsaturated sulfones were involved in cyclisation of acyclic g-hydroxyvinyl sulfones,412 ± 414 metallation of vinyl sulfones at the C=C bond followed by the introduction of a substituent 415, 416 and [4+2] cycloaddition of ethynyl sulfones to N-Boc-pyrrole.417, 418 Free-radical Ni(acac)2 - catalysed arylation of optically active sulfoxide with Ph3ZnMgCl was also reported.419 The one-pot diastereoselective synthesis of a complex polycyclic compound by cascade cyclisation involving sulfones or sulfoxides under conditions of radical catalysis was described. 420 References 1.E Block J. Chem. Educ. 48 814 (1971) 2. S Patai, Z Rappoport, C JM Stirling (Eds) The Chemistry of Sulfoxides and Sulfones (New York; London; Chichester: Wiley, 1988) 3. T Durst, in Comprehensive Organic Chemistry Vol. 3 (Eds D Barton, WD Ollis) (Oxford: Pergamon Press, 1979) 4. G Krecze, K Shank, in Methoden der Organischen Chemie (Houben-Weil) Vol. E-11 (Ed. E Klemann) (Stuttgart: Georg Thieme, 1985) p. 669, 1182 5. E N Prilezhaeva, in Poluchenie i Svoistva Organicheskikh Soedinenii Sery (Synthesis and Properties of Organic Compound of Sulfur) (Ed. L I Belen'kii) (Moscow: Khimiya, 1998) p. 115 6. F Montanari, in Organic Sulfur Chemistry (Ed. C J MStirling) (London: Butterworth, 1975) p.181 7. G Solladie Synthesis 185 (1981) 8. G Solladie Chimia 38 233 (1984) 9. G Solladie, in Asymmetric Synthesis Vol. 2 (Ed. J D E Morrison) (New York: Academic Press, 1983) p. 184 10. G H Posner, in Asymmetric Synthesis Vol. 2 (Ed. J D E Morrison) (New York: Academic Press, 1983) p. 225 11. G H Posner, H Mallarmo, K Miura,M Hulce, in Asymmetric Reactions and Processes in Organic Chemistry (Eds E L Eliel, G H Otsuka) (Washington, DC: American Chemical Society, 1982) p. 139 12. M C Carreno Chem. Rev. 95 1717 (1995) 13. G H Solladie, in Comprehensive Organic Synthesis Vol. 6 (Eds BMTrost, J E Fleming) (Oxford: Pergamon, 1991) p. 148 14. L I Belen 'kii, in Khimiya Organicheskikh Soedinenii Sery. Obshchie Voprosy (The Chemistry of Organic Compounds of Sulfur.General Problems) (Ed. L I Belen'kii) (Moscow: Khimiya, 1988) p. 191 15. H B Kagan,M Sasaki, J Collin Pure Appl. Chem. 60 1725 (1988) 16. G A Molander Chem. Rev. 92 29 (1992) E N Prilezhaeva 17. G A Molander, G Hahn J. Org. Chem. 51 1135 (1986) 18. R Pontikis, J Wolf, C Monneret, J-C Florent Tetrahedron Lett. 36 3523 (1995) 19. M Oikawa, W Oikawa, A Ichihara Tetrahedron Lett. 34 4797 (1993) 20. X Creary J. Org. Chem. 50 5080 (1985) 21. N S Simpkins Tetrahedron 46 6951 (1990) 22. N S Simpkins Sulfones in Organic Synthesis (New York: Pergamon Press, 1993) 23. T F Braish, P L Fuchs Chem. Rev. 86 903 (1986) 24. Z Jin, P C Vandort, P L Fuchs Phosphorus Sulfur Silicon Relat. Elem. 95/96 1 (1994) 25. T E Bezmenova Khimiya Tiofen-1,1-dioksidov (The Chemistry of Thiophene-1,1-dioxides) (Kiev: Naukova Dumka, 1981) p.690 26. T E Bezmenova Fiziologicheski Aktivnye Veshchestva (Physiologically Active Compounds) (Kiev: Naukova Dumka, 1985) No. 17, p. 63 27. A V Lozanova, A M Moiseenkov Khim. Prir. Soedin. 133 (1986) a 28. N Ya Grigor'eva, V V Veselovsky, A M Moiseenkov Khim.-Farm. Zh. 21 845 (1987) b 29. N Ya Grigor'eva, O A Pinsker Usp. Khim. 63 177 (1994) [Russ. Chem. Rev. 63 169 (1994)] 30. A Krief Tetrahedron 36 2531 (1980) 31. F M Stoyanovich, in Khimiya Organicheskikh Soedinenii Sery. Obshchie Voprosy (The Chemistry of Organic Compounds of Sulfur. General Problems) (Ed. L I Belen'kii) (Moscow: Khimiya, 1988) p. 128 32. G Boche Angew.Chem., Int. Ed. Engl. 28 277 (1989) 33. B M Trost, T N Salzmann J. Am. Chem. Soc. 95 6840 (1973) 34. B M Trost,W P Conway, P E Stege, T J Dietsche J. Am. Chem. Soc. 96 7165 (1974) 35. B M Trost Chem. Rev. 78 363 (1978) 36. M Julia, J-M Paris Tetrahedron Lett. 4833 (1973) 37. M Julia, J-P Stacino Tetrahedron 42 2469 (1986) 38. G Solladie, C Greck, G Demailly, A Solladie-Cavallo Tetrahedron Lett. 23 5047 (1982) 39. G Solladie, G Demailly, C Greck Tetrahedron Lett. 26 435 (1985) 40. B M Trost, T N Salzmann, K Hiroi J. Am. Chem. Soc. 98 4887 (1976) 41. J L Fabre,M Julia, J N Verpeaux Tetrahedron Lett. 23 2469 (1982) 42. B M Trost,M R Ghadiri J. Am. Chem. Soc. 106 7260 (1984) 43. B M Trost,M R Ghadiri J. Am. Chem. Soc. 108 1098 (1986) 44.B M Trost Bull. Chem. Soc. Jpn. 61 107 (1988) 45. D A Evans, G C Andrews Acc. Chem. Res. 7 147 (1974) 46. R W Hoffmann Angew. Chem., Int. Ed. Engl. 18 563 (1979) 47. A M Moiseenkov, V A Dragan, V V Veselovsky Usp. Khim. 60 1255 (1991) [Russ. Chem. Rev. 60 643 (1991)] 48. O De Lucchi, U Miotti, G Modena Org. React. 40 157 (1991) 49. L A Paquette Org. React. 25 1 (1977) 50. F S Guziec Jr , L J SanFilippo Tetrahedron 44 6241 (1988) 51. M Julia, P Ward Bull. Soc. Chim. Fr. 3065 (1973) 52. P A Grieco, Y Masaki J. Org. Chem. 39 2135 (1974) 53. H Tanimoto, T Oritani Tetrahedron 53 3527 (1997) 54. D I MaGee, J D Leach, T C Mallais Tetrahedron Lett. 38 1289 (1997) 55. J S Panek, C E Masse J. Org. Chem. 62 8290 (1997) 56. K Mori, J Wu Liebigs Ann. Chem.213 (1991) 57. K Mori, J Wu Liebigs Ann. Chem. 83 (1992) 58. K Mori, H Harada, P Zagatti, A Cork, D R Hall Liebigs Ann. Chem. 259 (1991) 59. K Mori, J Wu Liebigs Ann. Chem. 783 (1991) 60. K Mori, Y Igarashi Liebigs Ann. Chem. 717 (1988) 61. K Mori, H Takikawa Liebigs Ann. Chem. 497 (1991) 62. K Mori, N Murata Liebigs Ann. Chem. 1153 (1994) 63. H Takikawa, Y Shirai, M Kobayashi, K Mori Liebigs Ann. Chem. 1965 (1996) 64. K Mori, H Ueda Tetrahedron Lett. 22 461 (1981) 65. V A Dragan, V V Veselovsky, A M Moiseenkov Izv. Akad. Nauk SSSR, Ser. Khim. 1143 (1989) c 66. Y Murata, K Inomata, H Kinoshita, H Kotake Bull. Chem. Soc. Jpn. 56 2535 (1983) 67. A M Moiseenkov, R I Ishchenko, V V Veselovsky, V N Odinokov, E V Polunin, B G Kovalev, B A Cheskis, G A Tolstikov Khim.Prir. Soedin. 422 (1989) aSulfones and sulfoxides in the total synthesis of biologically active natural compounds 112. P J Kocienski, B Lythgoe, S Ruston J. Chem. Soc., Perkin Trans. 1 829 (1978) 113. P J Kocienski, B Lythgoe, I Waterhouse J. Chem. Soc., Perkin Trans. 1 1045 (1980) 114. G E Keck, K A Savin,M A Weglarz J. Org. Chem. 60 3194 (1995) 115. P J Kocienski, B Lythgoe, D A Roberts J. Chem. Soc., Perkin Trans. 1 834 (1978) 116. P J Kocienski, B Lythgoe, I Waterhouse Tetrahedron Lett. 4419 (1979) 117. P J Kocienski, B Lythgoe, S Ruston J. Chem. Soc., Perkin Trans. 1 1290 (1979) 118. J W Morzycki, H K Schnoes, H F De Luca J. Org. Chem. 49 2148 (1984) 119. P J Kocienski,M Todd J. Chem.Soc., Perkin Trans. 1 1777 (1983) 120. P J Kocienski,M Todd J. Chem. Soc., Perkin Trans. 1 1783 (1983) 121. N M Hird, T V Lee, T M Leigh, J R Maxwell, T M Peakman Tetrahedron Lett. 30 4867 (1989) 122. G E Keck, D F Kachensky, E J Enholm J. Org. Chem. 49 1462 (1984); 50 4317 (1985) 123. D R Williams, J L Moore, M Yamada J. Org. Chem. 51 3916 (1986) 124. S Hanessian, N G Cooke, B DeHoff, D Sakito J. Am. Chem. Soc. 112 5276 (1990) 125. D A Evans, R L Dow, T L Shih, J M Takacs, R Zahler J. Am. Chem. Soc. 112 5290 (1990) 126. H Ito, N Imai, K Takao, S Kobayashi Tetrahedron Lett. 37 1799 (1996) 127. D J Hart, W-L Wu, A P Kozikowski J. Am. Chem. Soc. 117 9369 (1995) 128. M P Edwards, S V Ley, S G Lister, B D Palmer, D J Williams J. Org.Chem. 49 3503 (1984) 129. Y Morimoto, A Mikami, S Kuwabe, H Shirahama Tetrahedron Lett. 32 2909 (1991) 130. Y Mori,M Asai, J Kawade, H Furukawa Tetrahedron 51 5315 (1995) 131. S-H Chen, R F Horvath, J Joglar,M J Fisher, S J Danishefsky J. Org. Chem. 56 5834 (1991) 132. R F Horvath, R G Linde II, C M Hayward, J Joglar, D Yohannes, S J Danishefsky Tetrahedron Lett. 34 3993 (1993) 133. H Kigoshi, K Suenaga, T Mutou, T Ishigaki, T Atsumi, H Ishiwata, A Sakakura, T Ogawa, M Ojika, K Yamada J. Org. Chem. 61 5326 (1996) 134. S Hanessian, D Delorme, P C Tyler, G Demailly, Y Chapleur Can. J. Chem. 61 634 (1983) 135. S Hanessian, A Ugolini, P J Hodges, P Beaulieu, D Dube, C Andre Pure Appl. Chem. 59 299 (1987) 136. J D White, G L Bolton, A P Dantanarayana, C M J Fox, R N Hiner, R W Jackson, K Sakuma, U S Warrier J.Am. Chem. Soc. 117 1908 (1995) 137. P J Kocienski, S D A Street, C Yeates, S F Campbell J. Chem. Soc., Perkin Trans. 1 2171 (1987) 138. R Baker,M J O'Mahony, C J Swain J. Chem. Soc., Chem. Commun. 1326 (1985) 139. A G M Barrett, R A E Carr, S V Attwood, G Richardson, N D A Walshe J. Org. Chem. 51 4840 (1986) 140. G H Lee, H K Lee, E B Choi, B T Kim, C S Pak Tetrahedron Lett. 36 5607 (1995) 141. M Ihara, S Suzuki, T Taniguchi, Y Tokunaga, K Fukumoto Synlett 859 (1994) 142. I E Marko, F Murphy, S Dolan Tetrahedron Lett. 37 2089 (1996) 68. V A Koptenkova, V V Veselovsky,M A Novikova, A M Moiseenkov Izv. Akad. Nauk SSSR, Ser. Khim. 817 (1987) c 69. V V Veselovsky, V A Koptenkova, M A Novikova, A M Moiseenkov Izv.Akad. Nauk SSSR, Ser. Khim. 2052 (1989) c 70. E V Polunin, A M Moiseenkov Izv. Akad. Nauk SSSR, Ser. Khim. 1568 (1983) c 71. N A LeBel,N Balasubramanian J. Am. Chem. Soc. 111 3363 (1989) 72. Y Masaki, K Nagata, Y Serizawa, K Kaji Tetrahedron Lett. 23 5553 (1982) 73. H Miyaoka, Y Saka, S Miura, Y Yamada Tetrahedron Lett. 37 7107 (1996) 74. J A Marshall, D G Cleary J. Org. Chem. 51 858 (1986) 75. C P Astles, E J Thomas J. Chem. Soc., Perkin Trans. 1 845 (1997) 76. A B Smith III, J Barbosa,W Wong, J L Wood J. Am. Chem. Soc. 117 10 777 (1995) 77. D Crich, S Natarajan, J Z Crich Tetrahedron 53 7139 (1997) 78. J D White, M A Avery, S C Choudhry, O P Dhingra, M Kang, A J Whittle J. Am.Chem. Soc. 105 6517 (1983) 79. J D White, T R Vedananda,M Kang, S C Choudhry J. Am. Chem. Soc. 108 8105 (1986) 80. B Lygo, C N Rudd Tetrahedron Lett. 36 3577 (1995) 81. B M Trost Chem. Soc. Rev. 11 141 (1982) 82. B M Trost, J E Vincent J. Am. Chem. Soc. 102 5680 (1980) 83. B M Trost, H Hiemstra J. Am. Chem. Soc. 104 886 (1982) 84. B M Trost, D P Curran J. Am. Chem. Soc. 103 7380 (1981) 85. H-J Gais,W A Ball, J Bund Tetrahedron Lett. 29 781 (1988) 86. J-P Demoute, D Hainaut, E Toromanoff C. R. Hebd. Seances Acad. Sci., Ser. C 277 49 (1973) 87. S Lavielle, S Bory, B Moreau,M J Luche, A Marquet J. Am. Chem. Soc. 100 1558 (1978) 88. P C B Page, S M Allin, E W Collington, R A E Carr Tetrahedron Lett. 35 2607 (1994) 89. M A Avery,W K M Chong, C J White J.Am. Chem. Soc. 114 974 (1992) 90. M Julia, D Arnould Bull. Soc. Chim. Fr. II 746 (1973) 91. R S H Liu, A E Asato Tetrahedron 40 1931 (1984) 92. P Chabardes, J P Decor, J Varygnat Tetrahedron 33 2799 (1977) 93. P S Marchand,M Rosenberger, G Saucy, P A Wehrli, H Wong, L Chambers, M P Ferro,W Jackson Helv. Chim. Acta 59 387 (1976) 94. A Fischli,H Mayer,W Simon, H-J Stoller Helv. Chim. Acta 59 397 (1976) 95. G L Olson, H-C Cheung, K D Morgan, C Neukom, G Saucy J. Org. Chem. 41 3287 (1976) 96. O Isler, F Kienzle, in Kirk-Othmer Encyclopedia of Chemical Tech- nology Vol. 24 (New York: Wiley, 1984) p. 146 97. C Herve du Penhoat,M Julia Tetrahedron 42 4807 (1986) 98. K C Nicolau, D P Papahatjis, D A Claremon, R L Magolda, R E Dolle J.Org. Chem. 50 1440 (1985) 99. Y Ueno, S Aoki, M Okawara J. Chem. Soc., Chem. Commun. 683 (1980) 100. D S Brown, M Bruno, R J Davenport, S V Ley Tetrahedron 45 4293 (1989) 101. S V Ley, B Lygo, A Wonnacott Tetrahedron Lett. 26 535 (1985) 102. M T Fletcher, W Kitching Chem. Rev. 95 789 (1995) 103. D Diez-Martin, N R Kotecha, S V Ley, S Mantegani, J C Menendez, H M Organ, A D White, B J Banks Tetrahedron 48 7899 (1992) 104. H G Davies, R H Green Chem. Soc. Rev. 20 211 (1991) 105. C Greck, P Grice, S V Ley, A Wonnacott Tetrahedron Lett. 27 5277 (1986) 106. S V Ley, A Armstrong, D Diez-Martin, M J Ford, P Grice, J G Knight, H C Kolb, A Madin, C A Marby, S Mukherjee, A N Shaw, A M Z Slawin, S Vile, A D White, D J Williams, M Woods J.Chem. Soc., Perkin Trans. 1 667 (1991) 107. S V Ley, N J Anthony, A Armstrong, M Gabriella Brasca, T Clarke, D Culshaw, C Greck, P Grice, A B Jones, B Lygo, A Madin, R N Sheppard, A M Z Slawin, D J Williams Tetrahedron 45 7161 (1989) 108. B Lythgoe Chem. Soc. Rev. 9 449 (1980) 109. P J Kocienski Chem. Ind. 548 (1981) 110. P J Kocienski Phosphorus Sulfur Silicon Relat. Elem. 24 477 (1985) 111. P J Kocienski, in Comprehensive Organic Synthesis Vol. 6 (Eds BMTrost, J E Fleming) (Oxford: Pergamon, 1991) p. 967 143. M Norte, A Padilla, J J Fernandez, M L Souto Tetrahedron 50 9175 (1994) 144. M Isobe, Y Ichikawa, D-L Bai, H Masaki, T Goto Tetrahedron 43 4767 (1987) 145. Y Ichikawa,M Isobe, D-L Bai, T Goto Tetrahedron 43 4737 (1987) 146.Y Ichikawa, M Isobe, T Goto Tetrahedron 43 4749 (1987) 147. Y Ichikawa, M Isobe, H Masaki, T Kawai, T Goto, C Katayama Tetrahedron 43 4759 (1987) 148. K Takeda, M Urahata, E Yoshii, H Takayanagi, H Ogura J. Org. Chem. 51 4735 (1986) 149. K Takeda, E Kawanishi,H Nakamura, E Yoshii Tetrahedron Lett. 32 4925 (1991) 150. K Takeda, A Nakajima, E Yoshii Synlett 249 (1995) 405406 151. D R Williams, P J Coleman, C R Nevill, L A Robinson Tetrahedron Lett. 34 7895 (1993) 152. A S Kende, K Liu, I Kaldor,G Dorey, K Koch J. Am. Chem. Soc. 117 8258 (1995) 153. M Capot, T Cuvigny, C Herve du Penhoat,M Julia, G Loomis Tetrahedron Lett. 28 6273 (1987) 154. N M Ivanova, B A Cheskis, A M Moiseenkov, O M Nefedov Izv. Akad. Nauk, Ser. Khim. 2362 (1992) c 155.N M Ivanova, B A Cheskis, A M Moiseenkov, O M Nefedov Izv. Akad. Nauk SSSR, Ser. Khim. 2521 (1991) c 156. A M Moiseenkov, B A Czeskis, N M Ivanova, O M Nefedov J. Chem. Soc., Perkin Trans. 1 2639 (1991) 157. T Mandai, T Yanagi, K Araki, Y Morisaki, M Kawada, J Otera J. Am. Chem. Soc. 106 3670 (1984) 158. J Otera, H Misawa, K Sugimoto J. Org. Chem. 51 3830 (1986) 159. T Mandai, T Moriyama, K Tsujimoto, M Kawada, J Otera Tetrahedron Lett. 27 603 (1986) 160. T Moriyama, T Mandai,M Kawada, J Otera, B M Trost J. Org. Chem. 51 3896 (1986) 161. J Otera, H Misawa, T Mandai, T Onishi, S Suzuki, Y Fujita Chem. Lett, 1883 (1985) 162. J Otera, H Misawa, T Onishi, S Suzuki, Y Fujita J. Org. Chem. 51 3834 (1986) 163. D G Farnum, T Veysoglu, A M Carde, B Duhl-Emsviller, A Taylor, T A Pancoast, T J Reitz, R T Carde Tetrahedron Lett.4009 (1977) 164. T Satoh, T Oohara, Y Ueda, K Yamakawa Tetrahedron Lett. 29 313 (1988) 165. T Sato, T Ytoh, T Fujisawa Tetrahedron Lett. 28 5677 (1987) 166. G Stork, I Paterson, F K C Lee J. Am. Chem. Soc. 104 4686 (1982) 167. S Masamune, P Ma, H Okumoto, J W Ellinghoe, Y Ito J. Org. Chem. 49 2834 (1984) 168. G Solladie, G Moine J. Am. Chem. Soc. 106 6097 (1984) 169. G Solladie, F Matloubi-Moghadam J. Org. Chem. 47 91 (1982) 170. E J Corey, L O Weigel, A R Chamberlin, H Cho, D H Hua J. Am. Chem. Soc. 102 6613 (1980) 171. J Nakami, T Taniguchi, S Gomyo, T Kakihara Chem. Lett. 1103 (1994) 172. S Yamagiwa, H Sato, N Hoshi, H Kosugi, H Uda J.Chem. Soc., Perkin Trans. 1 570 (1979) 173. R Tanikaga, Y Nozaki, T Tamura, A Kaji Synthesis 134 (1983) 174. K Burgess, I Henderson Tetrahedron Lett. 30 4325 (1989) 175. H Tabuchi, T Hamamoto, S Miki, T Tejima, A Ichihara J. Org. Chem. 59 4749 (1994) 176. K J Hale, J Cai Tetrahedron Lett. 37 4233 (1996) 177. T Yoshida, S Saito Bull. Chem. Soc. Jpn. 55 3047 (1982) 178. T E Alvarez, T Cuvigny, C Herve du Penhoat,M Julia Tetrahedron 44 119 (1988) 179. S Hanessian, T A Grillo J. Org. Chem. 63 1049 (1998) 180. B Lygo Synlett 793 (1992) 181. A Bartlett, F R Green III J. Am. Chem. Soc. 100 4858 (1978) 182. H-J Gais, T Leed Angew. Chem., Int. Ed. Engl. 23 145 (1984) 183. B M Trost, J Lynch, P Renaut, D H Steinman J. Am. Chem. Soc. 108 284 (1986) 184. D F Taber, L J Silverberg, E D Robinson J.Am. Chem. Soc. 113 6630 (1991) 185. S H Kang, W J Kim, Y B Chae Tetrahedron Lett. 29 5169 (1988) 186. A M Moiseenkov, B T Zhuzbaev, V V Veselovsky, K M Turdybekov, A V Buevich, S M Adekenov, Yu T Struchkov Izv. Akad. Nauk, Ser. Khim. 126 (1993) c 187. V V Veselovsky, B T Zhuzbaev, A M Moiseenkov Mendeleev Commun. 167 (1992) 188. E L Grimm, M L Coutu, S Levac, in The 16th International Symposium on the Organic Chemistry of Sulfur (ISOCS) (Abstracts of Reports), Merseburg, 1994 p. 119 189. G Solladie, C Frechou, G Demailly, C Greck J. Org. Chem. 51 1912 (1986) 190. G Solladie, A Rubio,M C Carreno, J L Garcia Ruano Tetrahedron Asymmetry 1 187 (1990) 191. G Solladie, C Gerber Synlett 449 (1992) 192. G Solladie, C Ziani-Cherif, F Jesser Tetrahedron Lett.33 931 (1992) 193. G Solladie, O Lohse J. Org. Chem. 58 4555 (1993) 194. E J Corey, P Carpino Tetrahedron Lett. 31 7555 (1990) E N Prilezhaeva 195. J Nokami, M Ohkura, Y Dan-oh, Y Sakamoto Tetrahedron Lett. 32 2409 (1991) 196. G Solladie, J Hutt, C Frechou Tetrahedron Lett. 28 61 (1987) 197. G Solladie, C Dominguez J. Org. Chem. 59 3898 (1994) 198. J L Garcia Ruano, A M Martin Castro, H Rodriguez J. Org. Chem. 59 533 (1994) 199. K Mori, Y Takahashi Liebigs Ann. Chem. 1057 (1991) 200. P-u Park, C A Broca, B F Johnson, Y Kishi J. Am. Chem. Soc. 109 6205 (1987) 201. H Naito, E Kawahara, K Maruta, M Maeda, S Sasaki J. Org. Chem. 60 4419 (1995) 202. J E Baldwin, R M Adlington, D Bebbington, A T Russell Tetrahedron 50 12015 (1994) 203.D Tanner, H M He Tetrahedron 45 4309 (1989) 204. M T Mujica,M M Afonso,A Galindo, J A Palanzuela Synlett 983 (1996) 205. M R Binns, R K Haynes, A G Katsifis, P A Schober, S C Vonwiller J. Am. Chem. Soc. 110 5411 (1988) 206. R K Haynes, A G Katsifis, S C Vonwiller, T W Hambley J. Am. Chem. Soc. 110 5423 (1988) 207. D H Hua,G Sinai-Zingde, S Venkataraman J. Am. Chem. Soc. 107 4088 (1985) 208. D H Hua, S Venkataraman, R A Ostrander, G-Z Sinai, P J McCann,M J Coulter, M R Xu J. Org. Chem. 53 507 (1988) 209. D H Hua, S Venkataraman, R Chan-Yu-King, J V Paukstelis J. Am. Chem. Soc. 110 4741 (1988) 210. D H Hua J. Am. Chem. Soc. 108 3835 (1986) 211. D H Hua, M J Coulter, I Badejo Tetrahedron Lett. 28 5465 (1987) 212.L L Vasil'eva, V I Mel'nikova, E T Gaidullina, K K Pivnitskii Zh. Org. Khim. 19 941 (1983) d 213. D H Hua, J-G Park, T Katsuhira, S N Bharathi J. Org. Chem. 58 2144 (1993) 214. D H Hua, S N Bharathi, J A K Panangadan, A Tsujimoto J. Org. Chem. 56 6998 (1991) 215. K Ogura, G Tsuchihashi J. Am. Chem. Soc. 96 1960 (1974) 216. J Martel, C Huynh, E Toromanoff, G Nomine Bull. Soc. Chim. Fr. 982 (1967) 217. J Martel, C Huynh Bull. Soc. Chim. Fr. 985 (1967) 218. L Velluz, J Martel, G Nomine C.R. Hebd. Seances Acad. Sci., Ser. C 268 2199 (1969) 219. M Julia, A Guy-Rouaoult Bull. Soc. Chim. Fr. 1411 (1967) 220. R V M Campbell, L Crombie, D A R Findley, R W King, G Pattenden, D A Whiting J.Chem. Soc., Perkin Trans. 1 897 (1975) 221. F M Hauser, R P Rhee J. Org. Chem. 43 178 (1978) 222. F M Hauser, R P Rhee J. Org. Chem. 45 3061 (1980) 223. F M Hauser, D Mal J. Am. Chem. Soc. 106 1862 (1984) 224. F M Hauser, P Hewawasam, D Mal J. Am. Chem. Soc. 110 2919 (1988) 225. F M Hauser, S Prasanna, D W Combs J. Org. Chem. 48 1328 (1983) 226. F M Hauser, D W Combs J. Org. Chem. 45 4071 (1980) 227. F M Hauser, S Prasanna J. Am. Chem. Soc. 103 6378 (1981) 228. F M Hauser, D Mal J. Am. Chem. Soc. 106 1098 (1984) 229. F M Hauser, D Mal J. Am. Chem. Soc. 105 5688 (1983) 230. F M Hauser, V M Baghdanov Tetrahedron 40 4719 (1984) 231. F M Hauser, S Prasanna Tetrahedron 40 4711 (1984) 232. F M Hauser, P Hewawasam, Y S Rho J. Org. Chem.54 5110 (1989) 233. F M Hauser, R A Tommasi J. Org. Chem. 56 5758 (1991) 234. F M Hauser, Y Caringal J. Org. Chem. 55 555 (1990) 235. D Mal, N K Hazra Tetrahedron Lett. 37 2641 (1996) 236. R A Russell, N W Warrener J. Chem. Soc., Chem. Commun. 108 (1981) 237. M G Dolson, B L Chenard, J S Swenton J. Am. Chem. Soc. 103 5263 (1981) 238. A I Meyers,W B Avila J. Org. Chem. 46 3881 (1981) 239. Y Tamura,M Sasho, S Akai, A Wada, Y Kita Tetrahedron 40 4539 (1984) 240. M D Mashkovskii Lekarstvennye Sredstva (Medicinals) (Moscow: Novaya Volna, 1996) Vol. 2, p. 2615 241. B M Trost Tetrahedron 33 2615 (1977) 242. J Tsuji Tetrahedron 42 4361 (1986) 243. J Tsuji Palladium Reagents in Catalysis (New York: Wiley, 1995)Sulfones and sulfoxides in the total synthesis of biologically active natural compounds 244.B M Trost, L Weber J. Org. Chem. 40 3617 (1975) 245. P S Manchand, H S Wong, J F Blount J. Org. Chem. 43 4769 (1978) 246. J Tsuji, I Shimizu, I Minami, Y Ohashi, T Sugiura, K Takahashi J. Org. Chem. 50 1523 (1985) 247. D Eren, E Keinan J. Am. Chem. Soc. 110 4356 (1988) 248. R Bouzbouz, B Kirschleger Synthesis 714 (1994) 249. R Bouzbouz, B Kirschleger Synlett 763 (1994) 250. B M Trost Angew. Chem., Int. Ed. Engl. 28 1173 (1989) 251. A Heumann, M Reglier Tetrahedron 51 975 (1995) 252. J P Genet, G M Gaudin Tetrahedron 43 5315 (1987) 253. F Colobert, J P Genet Tetrahedron Lett. 26 2779 (1985) 254. A S Kende, I Kaldor, R Aslanian J. Am. Chem. Soc. 110 6265 (1988) 255. J A Marshall, R C Andrews, L Lebioda J.Org. Chem. 52 2378 (1987) 256. B M Trost, T R Verhoeven J. Am. Chem. Soc. 101 1595 (1979) 257. B M Trost, T R Verhoeven Tetrahedron Lett. 2275 (1978) 258. B M Trost, T R Verhoeven J. Am. Chem. Soc. 99 3867 (1977) 259. A Brandes, H M R Hoffmann Tetrahedron 51 145 (1995) 260. H M R Hoffmann, A Brandes Tetrahedron 51 155 (1995) 261. J Pohlmann, C Sabater, H M R Hoffmann Angew. Chem., Int. Ed. Engl. 37 633 (1998) 262. B M Trost, S J Brickner J. Am. Chem. Soc. 105 568 (1983) 263. B M Trost,M Ohmori, S A Boyd, H Okawara, S J Brickner J. Am. Chem. Soc. 111 8281 (1989) 264. B M Trost, J T Hane, P Metz Tetrahedron Lett. 27 5695 (1986) 265. S A Godleski, E V Villhauer J. Org. Chem. 51 486 (1986) 266. A Furstner, H Weintritt J.Am. Chem. Soc. 120 2817 (1998) 267. C A Kingsbury, D J Cram J. Am. Chem. Soc. 82 1810 (1960) 268. T Yoshimura, E Tsukurimishi, Y Iizuka, H Mizuno, H Isaji, C Shimasaki Bull. Chem. Soc. Jpn. 62 1891 (1989) 269. B M Trost, K K Leung Tetrahedron Lett. 4197 (1975) 270. B M Trost, T N Salzmann J. Org. Chem. 40 148 (1975) 271. J H Babler, R A Haack J. Org. Chem. 47 4801 (1982) 272. K C Nicolaou, R E Zipkin, N A Petasis J. Am. Chem. Soc. 104 5558 (1982) 273. K Ishigami, T Kitahara Tetrahedron 51 6431 (1995) 274. H Konno, H Makabe, A Tanaka, T Oritani Tetrahedron 52 9399 (1996) 275. K Tanaka, H Ushio, Y Kawabata, H Suzuki J. Chem. Soc., Perkin Trans. 1 1445 (1991) 276. D F Taber, B P Gunn J. Org. Chem. 44 450 (1979) 277. J R Williams, J D Leber Synthesis 427 (1977) 278.D N Jones, A C F Edmonds, S D Knox J. Chem. Soc., Perkin Trans. 1 459 (1976) 279. S I Goldberg,M S Sahli J. Org. Chem. 32 2059 (1967) 280. D H Hua, S N Bharathi, P D Robertson, B A Tsujimoto J. Org. Chem. 55 2128 (1990) 281. T Ohnuma, T Oishi, Y Ban J. Chem. Soc., Chem. Commun. 301 (1973) 282. K Seki, T Ohnuma, T Oishi, Y Ban Tetrahedron Lett. 723 (1975) 283. Y Ban, T Ohnuma, K Seki, T Oishi Tetrahedron Lett. 727 (1975) 284. R E Donaldson, P L Fuchs J. Am. Chem. Soc. 103 2108 (1981) 285. D K Hutchinson, P L Fuchs J. Am. Chem. Soc. 109 4755 (1987) 286. J E Toth, P R Hamann, P L Fuchs J. Org. Chem. 53 4694 (1988) 287. T P Burkholder, P L Fuchs J. Am. Chem. Soc. 110 2341 (1988) 288. T P Burkholder, P L Fuchs J.Am. Chem. Soc. 112 9601 (1990) 289. M Isobe, in Perspectives of Organic Chemistry of Sulfur Vol. 28 (Eds B Zwanenberg, A J H Klunder) (Amsterdam: Elsevier, 1987) p. 209 290. M Isobe, M Kitamura, T Goto Tetrahedron Lett. 3465 (1979) 291. M Isobe, Y Ichikawa, Y Funabashi, S Mio, T Goto Tetrahedron 42 2863 (1986) 292. M Kitamura,M Isobe, Y Ichikawa, T Goto J. Org. Chem. 49 3517 (1984) 293. M Isobe, M Kitamura, T Goto J. Am. Chem. Soc. 104 4997 (1982) 294. M Kitamura,M Isobe, Y Ichikawa, T Goto J. Am. Chem. Soc. 106 3252 (1984) 295. Y Jiang,M Isobe Tetrahedron 52 2877 (1996) 296. Y Jiang, Y Ichikawa, M Isobe Tetrahedron 53 5103 (1997) 297. K Tsuboi, Y Ichikawa, Y Jiang, A Naganawa, M Isobe Tetrahedron 53 5123 (1997) 298.G H Posner Acc. Chem. Res. 20 72 (1987) 407 299. G H Posner, J P Mallamo, K Miura J. Am. Chem. Soc. 103 2886 (1981) 300. G H Posner,M J Chapdelaine, C M Lentz J. Org. Chem. 44 3661 (1979) 301. G H Posner, C Switzer J. Am. Chem. Soc. 108 1239 (1986) 302. G H Posner,M Hulce, J P Mallamo, S A Drexler, J Clardy J. Org. Chem. 46 5244 (1981) 303. G H Posner, T P Kogan,M Hulce Tetrahedron Lett. 25 383 (1984) 304. G H Posner, E Asirvatham J. Org. Chem. 50 2589 (1985) 305. G H Posner, T P Kogan, S R Haines, L L Frye Tetrahedron Lett. 25 2627 (1984) 306. G H Posner,M Weitzberg, T G Hamill, E Asirvatham, H Cun-Heng, J Clardy Tetrahedron 42 2919 (1986) 307. R A Holton, R M Kennedy, H B Kim,M E Krafft J. Am. Chem. Soc. 109 1597 (1987) 308.K Mori, S Aki, M Kido Liebigs Ann. Chem. 83 (1993) 309. J C Carretero, R G Arrayas, I S de Gracia Tetrahedron Lett. 37 3379 (1996) 310. N Toyooka, Y Yotsui, Y Yoshida, T Momose J. Org. Chem. 61 4882 (1996) 311. M B Berry, G J Rowlands, D Craig, P S Jones Chem. Commun. 2141 (1997) 312. C Iwata, K Hattori, S Uchida, T Imanishi Tetrahedron Lett. 25 2995 (1984) 313. C Iwata, Y Moritani, K Sugiyama,M Fujita, T Imanishi Tetrahedron Lett. 28 2255 (1987) 314. C Iwata,M Fujita, K Hattori, S Uchida, T Imanishi Tetrahedron Lett. 26 2221 (1985) 315. C Iwata,M Fujita, Y Moritani, K Hattori, T Imanishi Tetrahedron Lett. 28 3135 (1987) 316. S G Pyne, P Bloem, S L Chapman, C E Dixon, R Griffith J. Org. Chem. 55 1086 (1990) 317. S G Pyne, S L Chapman J.Chem. Soc., Chem. Commun. 1688 (1986) 318. A W M Lee,W H Chan, Y Tao, Y K Lee J. Chem. Soc., Perkin Trans. 1 477 (1994) 319. N Itoh, H Matsuyama, M Yoshida, N Kamagata,M Iyoda Bull. Chem. Soc. Jpn. 68 3121 (1995) 320. E N Prilezhaeva, L V Tsymbal,M F Shostakovskii Dokl. Akad. Nauk SSSR 138 122 (1961) e 321. O De Lucci, G Modena Tetrahedron 40 2585 (1984) 322. O De Lucci, L Pasquato Tetrahedron 44 6755 (1988) 323. L A Paquette, H-S Lin, M J Coghlan Tetrahedron Lett. 28 5017 (1987) 324. L A Paquette, H-S Lin, B P Gunn,M J Coghlan J. Am. Chem. Soc. 110 5818 (1988) 325. S F Martin, B G Anderson, D Daniel, A Gaucher Tetrahedron 53 8997 (1997) 326. C Herdeis, C Hartke Heterocycles 29 287 (1989) 327. C Herdeis, C Hartke-Karger Liebigs Ann.Chem. 99 (1991) 328. D Gomez-Pardo, J d'Angelo Tetrahedron Lett. 33 6637 (1992) 329. T Kametani,M Aizawa, H Nemoto Tetrahedron 37 2547 (1981) 330. D Craig, D A Fischer, O Kemal, A Marsh, T Plessner, A M Z Slawin, D J Williams Tetrahedron 47 3095 (1991) 331. M C Clasby, D Craig, A Marsh Angew. Chem., Int. Ed. Engl. 32 1444 (1993) 332. G-D Zhu, W H Okamura Chem. Rev. 95 1877 (1995) 333. M C Clasby, D Craig, A A Jaxa-Chamiec, J Y Q Lai, A Marsh, A M Z Slawin, A J P White, D J Williams Tetrahedron 52 4769 (1996) 334. E J Corey, P Da Silva Jardine, T Mohri Tetrahedron Lett. 29 6409 (1988) 335. E J Corey, P Da Silva Jardine, J C Rohloff J. Am. Chem. Soc. 110 3672 (1988) 336. E J Corey, P Da Silva Jardine Tetrahedron Lett. 30 7297 (1989) 337. S Danishefsky, F J Walker J. Am. Chem. Soc. 101 7018 (1979) 338. S Danishefsky,M Hirama, N Fritsch, J Clardy J. Am. Chem. Soc. 101 7013 (1979) 339. S Danishefsky Tetrahedron 53 8689 (1997) 340. C Maignan, R A Raphael Tetrahedron 39 3245 (1983) 341. Y Arai, S Kuwayama, Y Takeuchi, T Koizumi Synth. Commun. 16 233 (1986) 342. C Maignan, F Belkasmioui Tetrahedron Lett. 29 2823 (1988)408 343. J Martynow,M Dimitroff, A G Fallis Tetrahedron Lett. 34 8201 (1993) 344. Y Arai, M Yamamoto, T Koizumi Chem. Lett. 1225 (1986) 345. Y Arai, M Yamamoto, T Koizumi Bull. Chem. Soc. Jpn. 61 467 (1988) 346. Y Arai, K Hayashi,M Matsui, T Koizumi,M Shiro, K Kuriyama J. Chem. Soc., Perkin Trans. 1 1709 (1991) 347. Y Arai, Y Hayashi, M Yamamoto, H Takayema, T Koizumi J. Chem. Soc., Perkin Trans. 1 3133 (1988) 348. T Takayama, A Isobe, T Koizumi Chem. Pharm. Bull. 35 433 (1987) 349. M Lee, I Ikeda, T Kawabe, S Mori, K Kanematsu J. Org. Chem. 61 3406 (1996) 350. T Takahashi, A Isobe, Y Arai, T Koizumi Synthesis 189 (1989) 351. H Takayama, K Hayashi, T Koizumi Tetrahedron Lett. 27 5509 (1986) 352. Y Arai, M Matsui, T Koizumi, M Shiro J. Org. Chem. 56 1983 (1991) 353. Y Arai, T Kontani, T Koizumi Chem. Lett. 2135 (1991) 354. I Alonso, J C Carretero, J L Garcia Ruano J. Org. Chem. 59 1499 (1994) 355. I Alonso, J C Carretero, J L Garcia Ruano, L M Martin Cabrejas, I Lopez Solera, P Raithby Tetrahedron Lett. 35 9461 (1994) 356. D A Evans, C A Bryan, C L Sims J. Am. Chem. Soc. 94 2891 (1972) 357. G H Posner Pure Appl. Chem. 62 1949 (1990) 358. G H Posner, A Haces, W Harrison, C M Kinter J. Org. Chem. 52 4836 (1987) 359. G H Posner, T D Nelson Tetrahedron 46 4573 (1990) 360. G H Posner, C M Kinter J. Org. Chem. 55 3967 (1990) 361. G H Posner, D G Wettlaufer J. Am. Chem. Soc. 108 7373 (1986) 362. G H Posner, D G Wettlaufer Tetrahedron Lett. 27 667 (1986) 363. V V Veselovsky, Z G Makarova, A I Lutsenko, N A Shpiro, V M Zhulin, A M Moiseenkov Izv. Akad. Nauk SSSR, Ser. Khim. 810 (1988) c 364. M J Kurth, D H Burns,M J O'Brien J. Org. Chem. 49 731 (1984) 365. R A Gibbs, K Bartels, R W K Lee,W H Okamura J. Am. Chem. Soc. 111 3717 (1989) 366. M C Aversa, A Barattucci, P Bonaccorsi, P Giannetto,D N Jones J. Org. Chem. 62 4376 (1997) 367. P Gosselin, E Bonfand, C Maignan Synthesis 1079 (1996) 368. P Gosselin, E Bonfand, C Maignan J. Org. Chem. 61 9049 (1996) 369. S S P Chou,W H Lee Synthesis 219 (1990) 370. A V Lozanova, V P Gul'tyai, A N Karaseva, A M Moiseenkov Izv. Akad. Nauk SSSR, Ser. Khim. 1370 (1983) c 371. J D Winkler, H S Kim, S Kim Tetrahedron Lett. 36 687 (1995) 372. S R Desai, V K Gore, S V Bhat Synth. Commun. 20 523 (1990) 373. T S Chou, S G Lee, N K Yao Tetrahedron 45 4113 (1989) 374. H F Schmitthenner, S M Weinreb J. Org. Chem. 45 3372 (1980) 375. S F Martin, C-y Tu, M Kimura, S H Simonsen J. Org. Chem. 47 3634 (1982) 376. T Nomoto, H Takayama Heterocycles 23 2913 (1985) 377. J Leonard, S P Fearnley, D M B Hickey Synlett 272 (1992) 378. S Yamada, T Suzuki, H Takayama Tetrahedron Lett. 22 3085 (1981) 379. Y Iwasaki, M Shimizu, T Hirosawa, S Yamada Tetrahedron Lett. 37 6753 (1996) 380. K C Nicolaou, W E Barnette, P Ma J. Org. Chem. 45 1463 (1980) 381. D J Hart,W L Wu Tetrahedron Lett. 37 5283 (1996) 382. B M Trost,M G Organ, G A O'Doherty J. Am. Chem. Soc. 117 9662 (1995) 383. B M Trost, A S Tasker, G RuÈ ther, A Brandes J. Am. Chem. Soc. 113 670 (1991) 384. T L Ho Tandem Organic Reactions (New York: Wiley, 1992) 385. L F Tietze, U Beifuss Angew. Chem., Int. Ed. Engl. 32 131 (1993) 386. R A Bunce Tetrahedron 51 13103 (1995) 387. D P Curran, H Liu, H Iosien, S-B Ko Tetrahedron 52 11385 (1996) 388. J R Hwu, S-C Tsay Chem. Commun. 161 (1998) 389. G H Posner Chem. Rev. 86 831 (1986) 390. J Nokami, T Ono, S Wakabayashi, A Hazato, S Kurozumi Tetrahedron Lett. 26 1985 (1985) 391. J P Adams, I Bowler,M A Collins, D N Jones, S Swallow Tetrahedron Lett. 31 4355 (1990) E N Prilezhaeva 392. J Leonard, A B Hague,M F Jones Tetrahedron Lett. 38 3071 (1997) 393. C E Masse,M Yang, J Solomon, J S Panek J. Am. Chem. Soc. 120 4123 (1998) 394. H Miyoka, Y Isaji, Y Kajiwara, I Kunimune, Y Yamada Tetrahedron Lett. 39 6503 (1998) 395. C H Heathcock, R C D Brown, T C Norman J. Org. Chem. 63 5013 (1998) 396. K Domon, H Takikawa, K Mori Eur. J. Org. Chem. 981 (1999) 397. Y Shirai, M Seki, K Mori Eur. J. Org. Chem. 3139 (1999) 398. Y Mori, K Yaegashi, H Furukawa J. Org. Chem. 63 6200 (1998) 399. A FuÈ rstner, T Gastner, J Rust Synlett 29 (1999) 400. H Kosugi, J Ku, M Kato J. Org. Chem. 63 6939 (1998) 401. A Sinha, Sa C Sinha, Su C Sinha, E Keinan J. Org. Chem. 64 2381 (1998) 402. D A Evans, P H Carter, E M Carreira, A B Charette, J A Prunet, M Lautens J. Am. Chem. Soc. 121 7540 (1999) 403. H M Eng, D C Myles Tetrahedron Lett. 40 2275 (1999) 404. N Toyooka,M Okamura, H Takahata J. Org. Chem. 64 2182 (1999) 405. J B Baudin, G Harean, S A Julia, O Ruel Tetrahedron Lett. 32 1175 (1991) 406. P R Blakemore, P J Kocienski, S Marzcak, J Wicha Synthesis 1209 (1999) 407. J A Lafontaine, D P Provencal, C Gardelli, J W Leahy Tetrahedron Lett. 40 4145 (1999) 408. T Kakiuchi, H Kinoshita, K Inomato Synlett (Spec. Issue) 901 (1999) 409. L A Paquette, L Barriault, D Pissarnitski J. Am. Chem. Soc. 121 4542 (1999) 410. A Arnone, P Bravo, W Panzeri, F Viani, M Zanda Eur. J. Org. Chem. 117 (1999) 411. G Solladig, N Wilb, C Bauder Eur. J. Org. Chem. 3021 (1999) 412. J C Carretero, R G Arrayes Synlett 49 (1999) 413. J C Carretero, R G Arrayes, I S de Gracia Tetrahedron Lett. 38 8537 (1997) 414. J de Vicente, R G Arrayes, J Canada, J C Carretero Synlett 53 (2000) 415. J G Urones, I S Marcos, N M Garrido, P Basabe, S G San Feliciano, R Coca, D Diez Synlett 1364 (1998) 416. O Arjona, F Iradier, J Plumet, M P Martinez-Alcazar, H Hernvndez-Cano, I Fonseca Tetrahedron Lett. 39 6741 (1999) 417. C D Jones, N S Simpkins, G M P Giblin Tetrahedron Lett. 39 1021; 1023 (1998) 418. L E Brieaddy, F Liang, P Abraham, J R Lee, F I Garroll Tetrahedron Lett. 39 5321 (1998) 419. I N Houpis, A Molina, I Dorziotis, R A Reamer, R P Volante, P J Reider Tetrahedron Lett. 38 7131 (1997) 420. P Devin, L Fensterbank,M Malacria J. Org. Chem. 63 6764 (1998) a�Chem. Nat. Compd. (Engl. Transl.) b�Chem. Pharm. J. (Engl. Transl.) c�Russ. Chem. Bull. (Engl. Transl.) d�Russ. J. Org. Chem. (Engl. Transl.) e�Dokl. Chem. Technol., Dokl. Chem. (Engl

ISSN:0036-021X    

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Russian Chemical Reviews 69 (5) 409 ± 434 (2000) `Living'-chain radical polymerisation G V Korolev, A P Marchenko Contents I. Introduction II. `Living'-chain anionic polymerisation III. `Living'-chain radical polymerisation IV. The progress in investigations on `living'-chain polymerisation V. Alkoxyamines as agents for `living'-chain radical polymerisation VI. Transition-metal halide complexes with organic ligands as agents for `living'-chain radical polymerisation VII. Three-dimensional `living'-chain radical polymerisation VIII. Other agents for `living' radical polymerisation Abstract. compounds of types various to devoted is review The The review is devoted to various types of compounds used as agents for `living' radical polymerisation, such as alkoxy- used as agents for `living' radical polymerisation, such as alkoxy- amines o radicals, carrier chain the of addition upon formed amines formed upon addition of the chain carrier radicals, R., t , to scientific co-ordination and financial backing. stable nitroxyl radicals, as well as products of the addition of the stable nitroxyl radicals, as well as products of the addition of the radicals to transition metal complexes with different ligands, radicals to transition metal complexes with different ligands, etc.In all cases, the mechanism of the action of these agents consists in In all cases, the mechanism of the action of these agents consists in their free stable a dissociation reversible their reversible dissociation A X where >R.+X., where X. is is a stable free radical or a metal-containing complex which can accept radicals radical or a metal-containing complex which can accept radicals R chain quadratic the with compete thus and .(R.+X.?A) A) and thus compete with the quadratic chain termination. studies the to paid is attention Particular termination. Particular attention is paid to the studies which which allowed of mechanism the of formulation quantitative a allowed a quantitative formulation of the mechanism of `living' `living' radical mathematical a of form the in polymerisation radical polymerisation in the form of a mathematical model model suitable the of parameters the both predicting for suitable for predicting both the parameters of the polymerisation polymerisation and mass (molecular polymer resulting the of properties the and the properties of the resulting polymer (molecular mass and and polydispersity). The bibliography includes 359 references polydispersity).The bibliography includes 359 references. I. Introduction `Living' radical polymerisation, or, more precisely, `living'-chain radical polymerisation is a new line of investigation in the area of radical polymerisation, known from the early 1990s. The origi- nation and development of this area of scientific exploration has become possible owing to the discovery in the last two decades of a new elementary act of polymerisation processes involving the chain carrier radicals R., namely, the reversible addition of R. to several metal complexes or to stable free radicals (in particular, to nitroxyl radicals). Numerous studies on `living' radical chains (LRC) reported over the last three years (100 articles and more per annum) confirm that this new field is of great scientific and technological impor- tance and appears to have considerable promise.Most prominent in this research area are Matyjaszewski's group in the USA and Fukuda's group in Japan. In these research groups, studies on G V Korolev, A P Marchenko Institute for Problems of Chemical Physics, Russian Academy of Sciences, 142432 Chernogolovka, Moscow Region, Russian Federation. Fax (7-096) 576 40 09. Tel. (7-096) 517 10 89. E-mail: korolev@icp.ac.ru (G V Korolev), amarch@icp.ac.ru (A P Marchenko) Received 15 December 1999 Uspekhi Khimii 69 (5) 447 ± 475 (2000); translated by AMRaevsky #2000 Russian Academy of Sciences and Turpion Ltd DOI 10.1070/RC2000v069n05ABEH000567 409 409 410 411 412 423 428 429 LRC are carried out by polymer chemists in co-operation with mathematicians and physicists, which indicates the high level of This review is concerned with systematisation and critical review of a great body of data on LRC accumulated to date.The authors of the review have worked in the area of LRC since its inception. They appeared to be among the pioneers of the elementary processes which provide the basis for `living'-chain radical polymerisation. II. `Living'-chain anionic polymerisation The concept of a `living' polymer chain or simply a `living' chain (LC) appeared in studies of anionic polymerisation and goes back to Szwarc.1 He recognised that if a growing polymer anion (a chain carrier, RA) cannot be quadratically terminated (RA+ RA?`dead' polymer), then, in the absence of reactive impurities (X) capable of breaking the polymer chain following a linear mechanism (RA+X?`dead' polymer), anionic polymerisation proceeds without chain breaking, as a `living' process.In this case, the lifetime (t) of growing polymer chains exceeds the time necessary for complete conversion (t). In other words, the polymer anions RA remain `living' not only during the polymerisation, but also following completion of the process, i.e., after complete consumption of the initial monomer. `Livingness' of polymer chains is confirmed by the fact that the polymerisation process restarts upon addition of a fresh portion of the same monomer or any other monomer which can undergo anionic polymerisation at the same centres RA.Aconventional anionic polymerisation proceeds in such a way that the initiation of RA is a relatively fast reaction which takes a time interval ti much shorter than the time necessary for complete conversion (t). The condition ti 55 t implies that the initiation of all chains occurs nearly simultaneously and that they grow synchronously throughout the polymerisation, so that the num- ber-average molecular mass (Mn) of the resulting polymer is proportional to time. The molecular mass distribution of the polymer chains narrows monotonically as Mn increases and reaches very low values (the polydispersity index, Mw/Mn , approaches a value of 1.0) already at not too high Mn values (several tens of monomer units).This remarkable property is inherent in the `living' chains only (t>t and ti 55 t). In the case t 55 t (short-lived chains), which corresponds to radical poly- merisation, the lowest polydispersity of the polymer is either 1.5 or410 2.0 depending on the type of chain termination reaction (dispro- portionation or recombination). The use of these valuable properties of the products of `living' polymerisation has led to design of a novel class of polymeric materials, viz., block copolymers of the AnBmAn type, where A is a polystyrene block, B is a polyisoprene or polybutadiene block, and m and n are the numbers of monomer units in the blocks. At particular m and n values and at the temperatures which are above the glass transition temperature of the elastic block B, but below the glass transition temperature of the block A, these types of copolymers behave as vulcanised rubbers possessing very good physicochemical properties.This is due to a specific structure of the block copolymers, viz., the presence of glassy domains comprising several blocks A arranged regularly in a continuous elastic B-block matrix. The domains playing the role of cross-link points of the polymer network are essentially the same size, which is provided by very low polydispersity of the blocks A. The sizes and regular spatial arrangements of the blocks, which govern the physicochem- ical properties of the material, depend on n and the m/n ratio. At temperatures above the glass transition temperature of the block A, the copolymer behaves as a nonvulcanised rubber.Depending on temperature, these polymers possess the properties of vulcanisate or devulcanisate. They have played an outstanding role both in the polymer technology and in ecology since in this case the recovery of wastes and exhausted products has become much easier. At the same time, `living' anionic polymerisation requires an extremely labour-consuming procedure for the removal of impur- ities X from an initial reaction system to prevent chain breaking. Additionally, the number of pairs of the monomers of the types A and B is rather limited. Thus, the idea of performing a `living'- chain radical polymerisation appeared to be quite attractive. III. `Living'-chain radical polymerisation The fundamental distinction between `living'-chain radical and `living'-chain ionic polymerisation is that quadratic chain termi- nation is of great importance in the former case and plays a negligible role in the latter.In other words, `living'-chain radical polymerisation includes deactivation of growing active centres by termination between them (R+R?`dead' polymer).{ Thus, implementation of `living'-chain polymerisation requires basically different approaches, since in this case it is the main participant of the polymerisation process rather than a removable (e.g., by purification) impurity that plays the role of chain terminator, which results in a situation where t 55 t. Therefore, meeting the main condition for `living' radical polymerisation, t>t, requires the development of a procedure for extending the lifetime of active centres (chain carriers) R.This also requires the retention of their high reactivities towards the monomer molecules (M) in order to provide the possibility for the polymer chain to grow following the `R+M?chain' mechanism. This means that radicals R should be deactivated in order to preclude quadratic chain termination and, at the same time, should retain their activities in order to provide the polymer chain propagation (R+M). At first glance, this problem seems to be intractable. The main advantage of `living'-chain polymerisation consists in the possibility of obtaining a desired product with narrow polydispersity. At the same time, the second condition necessary for exploitation of this advantage, ti 55 t, is also not met in the case of radical polymerisation.Here, initiation of new chains occurs throughout the polymerisation process rather than during a short initial period ti, thus disturbing the simultaneous chain propagation and unavoidably increasing the polydispersity of the resulting polymer even in those cases where the lifetime of radical R can be extended to time intervals t>t. Eventually, `living'-chain radical polymerisation seems to have no chance of success. However, a new elementary act of { Hereafter, in some instances the radical sign will be omitted for simplicity. G V Korolev, A P Marchenko radical polymerisation has been discovered, namely, temporary entrapment of the chain carrier radical R by an acceptor A (R+A>RA) followed by release of R (the so-called reversible inhibition).This made it possible to solve both problems, i.e., to extend the time interval t (t>t) and to achieve simultaneous propagation of all chains, thus meeting the condition ti 55 t. Later, yet another solution to the problem was found, consisting of carrying out the reactions R1+A?R1A and R1A+R2?R2A+R1, where R1 and R2 are the growing poly- mer chains of the same nature but different lengths, and/or the growing chains of different nature. Mention may be made that these two solutions differ only in the type of regeneration of the entrapped (accepted) chain carrier radicals. In the former case, the RA adduct dissociates into the initial components, whereas in the latter case the entrapped chain carrier radical R1 is released from the R1A adduct following the radical substitution reaction R1A+R2?R2A+R1.Among the substances suggested for the use as acceptorsAare stable free radicalsRs (nitroxyl radicals, triphenylmethyl, etc.) and metal complexes (porphyrin, phthalocyanine and cobaloxime cobalt complexes, copper and iron complexes with halide and organic ligands, etc.). Active chain carrier radicals R react with stable radicals Rs to give adducts in which the R7Rs covalent bond is relatively weak and thus can dissociate at 373 ± 423 K. For instance, if R is a growing polystyrene chain and Rs is a stable nitroxyl radical, the bond strength in the R7Rs adduct is estimated at E=125.4 kJ mol71, which provides a rather high rate constant for bond dissociation, k1=1074± 1075 s71, already at 373 K. First, let us consider the above-mentioned elementary reac- tions as applied to the problem of `living' chains taking the R+A>RA reaction as an example.Let us denote the rate constants for dissociation and reverse recombination as k1 and k2, respectively, the acceptor A as X (in order to specify it as a stable free radical) and the adduct as RX. If RX is used instead of conventional initiators (peroxides, azodinitriles, etc.) of radical polymerisation, the mechanism of the process can be described by the following scheme: Scheme 1 k1 R+X initiation RX kp chain propagation R+M R0 k2 temporary RX R+X chain termination kt permanent P R+R At particular values of rate constants k1, k2, kp and kt, this four-stage mechanism provides a negligible contribution of chain termination reactions.Provided that kt[R] 55 k2[X], the prevail- ing chain `termination' by the R+X reaction simply makes the chain temporarily inactive (a `dormant' chain, RX) until the next dissociation act of RX. In such a manner the condition t>t is met. In the final stage of polymerisation (after complete con- sumption of the initial monomer), almost all chains, except for a small fraction of `dead' (quadratically terminated) chains that form a conventional random (statistical) polymer P, appear to be `dormant' in the form of RX. Obviously, the addition of a fresh portion of the initial or another monomer (if a block copolymer is synthesised) will re-activate the chain carriers R, which means that the situation will be quite adequate to a `living' polymerisation.To meet the second essential condition, viz., simultaneous chain initiation (ti 55 t), it is sufficient that the half-life of the adduct RX, equal to 0.69/k1, be much (10 to 100 times) shorter than the time necessary for complete conversion, t. Provided that 0.69/k1 55 t, each growing chain manages to be both in active and `dormant' state tens or hundreds times. This synchronising mechanism of chain propagation provides a very low polydisper- sity of the polymer. It should be noted that corresponding fitting procedure for numerical values of rate constants uses the k1 and kp`Living'-chain radical polymerisation constants as well as the temperature (taking into account the temperature dependence of k1 and kp) as independent variables.{ Thus, the use of acceptors X that temporarily entrap the chain carrier radicalRand then release the initial speciesXandRmakes it possible to solve the problem of implementation of a `living'- chain radical polymerisation.Unlike anionic polymerisation in which the chain carrier cannot undergo quadratic chain termina- tion at all, it is appropriate to call the process discussed above a pseudo-`living' polymerisation (and, correspondingly, to consider pseudo-`living' chains), since the radical chains propagate only in the form of active chain carriers R following their `recovery' from the `dormant' state and thus can undergo quadratic termination. It should be noted that the four-stage process discussed above is a non-steady-state process. Therefore, correct quantitative estimates of the parameters of the process can be obtained only after solving corresponding systems of differential equations rather than algebraic equations, as is the case of a steady-state process.Finally, mention may be made that a `living'-chain radical polymerisation process following this mechanism is stable towards such disturbing factors as additional initiation 1 I R k0 , where I is an initiator supplied from an external source or the monomer itself (self-initiation involving the monomer molecules occurs, e.g., in the styrene polymerisation at temperatures above 373 K). Provided that the k01[I] value is at least 5 to 10 times smaller than the k1[RX] value, this disturbing factor can be ignored. This condition can be met, as will be shown in the next Sections of the review dedicated to consideration of particular experimental data. The other type of `living'-chain polymerisation using the following elementary stages, R2A+R1 R1A and R1A+R2 R1+A differs from that discussed above (using the R+A>RA reac- tion) only in that it requires the use of an initiator I (or the process should be performed under conditions of spontaneous initiation involving the monomer), since the R1A adduct does not initiate polymerisation.} IV.The progress in investigations on `living'-chain polymerisation The progress in studies on `living'-chain radical polymerisation can be divided into three stages. 1. The discovery of temporary entrapment of chain carrier radicals R by compound A with the formation of labile adducts R7A from which R can be released by dissociation (or following a radical substitution reaction, as was shown later).This phenom- enon was called reversible inhibition. 2. The use of reversible inhibition for designing a `living'-chain radical polymerisation process (theoretical analysis, experimental studies). 3. Implementation of `living' chain radical polymerisation following a procedure which includes an exhaustive system of proofs of successful polymerisation (registration of changes in the average molecular mass, molecular mass distribution and other characteristics during monomer conversion). It is hard to mention a pioneering work for stages 1 and 2. More correct is to consider a number of pioneering studies carried out independently by investigators from different research groups. { The rate constants k2 and kt depend only slightly on both the nature of the reagents (R and X) and the temperature (their numerical values lie within the limits 1074k24108, 1074kt436107 litre mol71 s71).} The only exception are metal halide ± alkyl halide systems in which free radicals can be generated (see Section VI). 411 However, the third stage undoubtedly began with a pioneering study carried out by investigators from Canada.2 Taking the radical polymerisation of styrene in the presence of a stable iminoxyl radical (X) as an example, they were the first to show that the chain carrier (the growing polystyrene chain) R is alternately present in the reaction system in the deactivated (in the form of adduct RX) and active (in the form of free radicals R+X) states. This was proved by corresponding kinetic studies and by measurements of molecular mass distribution and average molecular mass of the resulting polymer during the conversion.Unlike unsuccessful attempts of their predecessors, the success of investigators from this research group is due to an extremely fortunate (chance or predicted?) choice of styrene as the mono- mer, since the presence of a phenyl substituent in the a-position with respect to the R7X bond, which undergoes dissociation, makes this bond more labile, which allows its dissociation at a sufficiently high rate at temperatures below 423 K. This fact appeared to be essential since at T>423 K the contribution of hydride transfer accompanying the dissociation increases and the dissociation mechanism changes from reversible R+X RX to irreversible RX R0(=)+XH, where R0(=) denotes the `dead' (terminated by intramolecular disproportionation) polystyrene chain with the end group con- taining a double bond and XH is the corresponding hydroxyl- amine.This pioneering work 2 initiated the appearance of numerous publications and their number seems to have no limit as yet. At the same time, it should be remembered that the communication cited was preceded by a number of experimental and theoretical studies carried out at the first two stages. A scheme of the development of investigations in the area of `living' polymerisation is presented below (Scheme 2). This scheme of pioneering studies may seem to be too cumbersome and overburden with details; however, it reflects the state-of-the-art in this area.First, at first glance different-type and non-related phenomena have been observed in studies of com- pounds of different chemical nature, such as alkoxyamines, macrocyclic cobalt compounds (later, copper and iron com- plexes), dithiocarbamates, etc. These studies were carried out concurrently and independently. Then, it was appreciated that, despite different chemical nature of compounds studied, all of them obey identical kinetic regularities as regards their ability to entrap temporarily (reversibly) active free radicals (including growing polymer chains) and release them after certain time intervals. Simultaneously, the investigators perceived the possi- bility of using this type of acceptors (`trappers') as agents for `living' radical polymerisation. (This was best shown by Smir- nov.5) Then, several types of `living'-chain polymerisations were reported (each of these studies formed the basis for an independ- ent investigation line).Further development of these investigation lines is based on these initial pioneering works. In conclusion, it should be noted that we cannot say unambig- uously who was the pioneer of `living'-chain anionic polymer- isation.Undoubtedly, Szwarc 1, 46, 47 has not only systematised and thoroughly analysed the key phenomena related to `living' carban- ions, thus having created a well-founded scientific discipline, but was also the first who discovered many of these phenomena. Nevertheless, his studies were preceded by investigations of other researchers.As early as 1936, Abkin and Medvedev 48 developed an original procedure for the determination of the lifetime (t) of growing carbanion polymer chains and found that for anionic polymerisation of butadiene catalysed by sodium metal the t value is so long that it exceeds the time necessary for complete conversion of the monomer. In other words, they discovered a `living' chain carrier carbanion and established that the polymerisation pro- ceeded without chain breaking (in a `living' manner). However,412 First step Second step Third step this study received little attention and in 1956 Szwarc et al.46, 47 re- discovered `living' polymerisation of vinyl monomers as though it were a new phenomenon. V. Alkoxyamines as agents for `living'-chain radical polymerisation 1.A brief history of investigations As long ago as the 1970s, it was found 36, 37 that entrapment of active free (e.g., polymethacrylate) radicals R by stable free (e.g., iminoxyl) radicals X at moderate temperatures (below 323 K) results in the formation of stable adducts RX (alkoxyamines) which can release the initial radicals X and R upon raising the temperature to 373 ± 423 K. More recently, this property of the adducts RX was used to perform one of the first `living' radical polymerisations.5 Other stable (e.g., phenylmethyl) radicals were also tried as X;49, 50 however, these attempts failed. In majority of studies, nitroxyl radicals were used, which react with hydrocarbon chain carrier radicals to give the corresponding alkoxyamines. First of all, mention should be made of the pioneering works 5, 37, 38 (see Scheme 2), as well as of the studies in which alkoxyamines were used as initiators.34, 51 ± 55 It is these studies that best showed the salient features of `living'-chain polymer- isation, namely, a reduction of polydispersity and an increase in molecular mass during monomer conversion and the correspond- ence between the number of growing polymer chains (nc) and that of alkoxyamine molecules introduced into the system (na).This correspondence means that at any degree of conversion (G ), the following relationship is valid G[M]0MM=nc=na , Mn where [M]0 is the concentration of A monomer in the initial system, MM is the molecular mass of the monomer and Mn is the number-average molecular mass of the polymer at a given degree of conversion.These publications 34, 51 ± 54 were followed by a number of studies 2, 56 ± 61 in which alkoxyamines were synthesised in situ from nitroxyl radicals introduced into the polymerisation system and radical initiators (peroxides, azodinitriles). The initiators were chosen so that their half-lifes would be a factor of several tens or even several hundreds shorter than the time necessary for Kinetic studies of iniferters of radical polymerisation 39 ± 45 (1982) Discovery of reversible dissociation>recombi- nation of alkoxyamines 36 (1979) and kinetic features of this process 37, 38 (1987) Theoretical analysis of the scheme of radi- cal polymerisation in the presence of alkoxy- amines and metal complexes, conclusion about the possibility of performing `living' polymerisation.First experimental study 5 (1990) Implementation of several types of `living' radical polymerisation 2 ±4 (1993 ± 1995). Three types of reaction systems, (i) styrene ± adduct RX (alkoxyamine), (ii) butyl acrylate ± organometallic complex based on a porphyrin Co complex and (iii) vinyl monomers ± halide different-ligand copper and iron complexes with organic ligands G V Korolev, A P Marchenko Scheme 2 Synthesis of low-molecu- lar mass polymers and oligomers by radical polymerisation of various vinyl monomers in the presence of nitro- xyl adducts 34, 35 (1986) Discovery and investigation of reversible trapping of chain carrier radicals by metal comp- lexes (cobaloximes and cobalt complexes of porphyrins and phthalocyanines) 6 ± 8, 10 ± 33 (1982 ± 1987) Kinetic studies of reversible inhibition of the radical poly- merisation of butyl acrylate in the presence of porphyrin cobalt complexes 6 ±9 (1983) complete conversion.Polymerisation of monomers in the presence of nitroxides (without added initiators) also belongs to processes in which alkoxyamines are synthesised in situ. The reaction is self- initiated by the monomer, as is the case of autopolymerisation of styrene.61 ± 65 Studies dealing with the development of procedures for modification of alkoxyamines by catalytic amounts of strong organic acids or other compounds aimed at improving their efficiency occupy a special place.61, 66 ± 68 However, such a mod- ification has little effect and its mechanism is still to be clarified. The most serious drawback of alkoxyamines as agents for `living' polymerisation is that they are effective only in the polymerisation of styrene and its derivatives.69 ± 72 For other monomers, alkoxyamines appear to be rather ineffective. They find a limited application to homopolymerisation of polar mono- mers (acrylates, methacrylates) 61, 73 ± 78 and their copolymerisa- tion with some other monomers.79 ± 83 The most plausible reason for reduction of the efficiency of alkoxyamines in the polymer- isation of polar monomers is that the C7ON bond in their molecules is too strong.The temperature necessary fior dissocia- tion of this bond at sufficient rate is too high, so that irreversible intramolecular disproportionation occurs instead of reversible dissociation into the initial radicals R and X.This irreversible reaction results in the formation of inert products, viz., a hydrox- ylamine and an unsaturated compound R(=) with the terminal double bond. In styrene and its derivatives, as well as in the copolymers of styrene with polar monomers, the C7ON bond is weakened because of the effect of phenyl substituent.84, 85 In the copolymerisation of styrene with polar monomers, the weakening effect of the styrene unit is achieved through the polar monomer unit 85 (the effect of the penultimate unit). 2. Synthesis of alkoxyamines Several methods for the synthesis of adducts RiMnX, where Ri is the initiator radical (e.g., Ph7CO7O. formed upon decomposi- tion of dibenzoyl peroxide, or BPO), M is the monomer (e.g., styrene) and X is the nitroxyl radical (e.g., 2,2,6,6-tetramethyl-1- piperidinyloxy, or TEMPO) have been reported.34, 51 ± 55 Depend- ing on the composition, i.e., the [Ri] : [X] : [M] ratio in the reaction mixture, adducts with different content of M (from n=1 to n ^ 10) can be obtained.Obviously, these methods are effective only under the reported reaction conditions.34, 51 ± 55 Later, the`Living'-chain radical polymerisation possibility of designing the syntheses of any adducts of the RiMnX type has been demonstrated.86 A mathematical method was developed for calculation in the steady-state approximation of the yields of the adducts synthesised in the polymerisation processes described by the simplified Scheme 3 which includes the initiation, chain propagation and chain termination stages. This scheme assumes that only a linear chain termination occurs in the system (quadratic chain termination can be ignored because of a very high concentration of an agent X responsible for the linear chain termination).Scheme 3 Initiation (zeroth stage) I 2 ki Ri . Chain propagation (first stage) kpi RiM., Ri+M kp RiM.+M RiMM., _____________ RiMn71M.+M kp RiMnM.. Chain termination (second stage) kx R RiX (A0), i +X. kx RiMX (A1), RiM.+X. RiMM.+X. kx RiM2X (A2), _____________ RiMnX (An). RiMn71M.+X. kx Here I is the initiator; X. is the stable free radical; M is the monomer;Ri, RiM., ... ,RiMn71M. are active free radicals andAn are products of the corresponding reactions. Analysis of Scheme 3 makes it possible to derive the following expressions for instantaneous rates of formation of any adduct, from A0 to An , during the synthesis.daA0a dt xaXaaRia a k a k WikxaXa piaMa a kxaXa a Wi piaMa=kxaXa a 1 , (1) 1 k (2) dt daA1a a kxaXaaR1a a WikxaXakpiaMa piaMa a kxaXaUOkpaMa a kxaXaU a Ok a daA0a dt kp=kpi a kxaXa=kpiaMa , 1 W (3) ikxaXakpiaMakpaMa dt daA2a a kxaXaaR2a a piaMa a kxaXaUOkpaMa a kxaXaU2 a Ok a daA1a dt kxaXa=kpaMa a 1 , 1 _________________________ (4) daAna a kxaXaaRna a dt Ok W piaMa a kxaXaUOkpaMa a kxaXaUn a ikxaXakpiaMaOkpaMaUn¢§1 1 , k a daA1a dt !n¢§1 xaXa=kpaMa a 1 where Wi is the rate of initiation and R1=RiM, R2=RiM2 , ... , Rn=RiMn . For any stage of the synthesis, the yield (Y) of each adduct An at instant t is calculated by the formula 413 dt, (5) daAna dt Y a Ot 0 where the form of the function describing the dependence of d[An]/dt on t is given by formulae (1) ¡¾ (4) which take into account the dependences of the concentrations of all reagents on time.(6) The dependence of [I] on t is described by the familiar integral of the rate of a unimolecular reaction [I]t=[I]0 exp(7kit), while the dependence of [X] on t is given by the equation [X]t=[X]072f ([I]07[I]t)=[X]072f [I]0[17exp(7kit)], (7) where f is the fraction of free radicals that did not undergo intracage recombination (this quantity is also called the efficiency of initiation, f&0.5). From Eqn (7) it follows that the concen- tration of stable radical X at instant t is equal to the difference between the initial concentration of this radical, [X]0, and the concentration of free radicals generated by the time t as a result of the decomposition of the initiator I.If the synthesis is carried out under standard conditions (the monomer is taken in a large excess, [M]0 44 [I]0 ^ [X]0), the concentration [M] is constant at any instant. If the synthesis is performed either under specific conditions (without a large excess of M) or in such a way that the adducts RiMnX with large n values are obtained, the form of the function [M]t is determined by the integral of the stationary rate d[M]/dt. For long chains (n>10), the following approximation is valid (8) ^ kpaMa k ¢§daMa dt (9) kx [M]=[M]0 exp xaXa Wi , whence, taking into account expressions (6) and (7), it follows that ¢§kpki c , where (10) c a a t Ot Ot aIat aXa 0 ¢§ 2 f aIa0a1 ¢§ expO¢§kitUa .aIa0 expO¢§kitU aXa 0 0 This calculation procedure makes it possible to predict the results of synthesis and to choose optimum conditions, since the values of all constants (ki, kpi, kp and kx) appearing in Eqns (1) ¡¾ (10) can be rather accurately estimated from the reported data (see, e.g., Ref. 87). The results of calculations for the styrene ¡¾TEMPO¡¾BPO system, obtained for three temperatures, are listed in Table 1. The reliability of the calculations has been confirmed exper- imentally. Both the type of the main adduct (A1=RiMX) and its content ([A1]100/ n n X[An]>90%) in the overall product XAn nearly coincide with the corresponding calculated data. As can be seen from Table 1, the target productA1 is the main product in the temperature range 348 ¡¾ 368 K.According to calculations, non-peroxide compounds (e.g., azonitriles) are unsuitable for use as initiators since only peroxide radicalsRi with the free valence at the oxygen atom ensure a rather high value of the kpi/kp ratio (several orders of magnitude). If the values of kpi and kp are comparable, the adduct RiX (n=0) is formed as the main product instead of the target RiMnX adduct. However, RiX cannot be used as the agent for `living' polymer- isation because its C7ON bond energy is too high. The results of calculations for the styrene ¡¾TEMPO¡¾ dicyclo- hexyl peroxydicarbonate (DCPDC) system 86 (Table 2) imply that the main adduct is Me Me CHPh N . O O C O CH2 O Me Me414 Table 1. Results of calculations of the yields of the adducts RiMnX in the course of `living' polymerisation of styrene (M) in the presence of stable free radicals X (TEMPO) and initiator (BPO).1075kpi T/K 105ki /s71 (see a) Yields of adducts A06106, A16104, and A26105 (mol litre71) after every hour from the beginning of the process 1077kx (see a) kp (see a) 1 2 3 4 5 6 6.2, 6.9, 2.0 8.6,9.9, 3.3 3.5, 3.8, 1.0 5.2, 5.7, 1.8 11.2, 13.4, 4.2 10.8, 13.1, 4.5 12.4, 15.4, 5.4 13.5, 17.1, 6.0 10.8, 13.1, 4.9 14.1, 18.3, 7.4 15.3, 20.4, 8.5 15.8, 21.3, 9.0 16.0, 21.7, 9.3 10.2 12.5 15.2 1.8 2.1 2.6 262 352 464 2.6 8.3 25.2 348 358 368 Note. Initial concentrations: [TEMPO]=4.861073 mol litre71, [BPO]=2.361073 mol litre71. a Dimensionality is litre mol71 s71. Table 2. Results of calculations of the yields of adducts in the course of `living' polymerisation of styrene using DCPDC as the initiator.1075kpi T/K 105ki /s71 (see a) Yields of adducts A06106, A16104, and A26105 (mol litre71) after every hour from the beginning of the process 1077kx (see a) kp (see a) 1 2 3 4 5 6 6.9, 7.8, 1.8 4.0, 4.3, 0.9 10.8, 12.9, 3.1 12.0, 14.7, 3.7 10.8, 12.8, 3.5 14.3, 18.2, 5.3 15.6, 20.5, 6.2 16.1, 21.5, 6.6 16.3, 21.9, 6.8 16.0, 21.2, 7.1 16.4, 22.0, 7.5 16.5, 22.1, 7.6 16.5, 22.1, 7.6 16.5, 22.1, 7.6 5.8 7.3 9.1 1.0 1.3 1.6 117 164 226 3.0 12.0 44.5 323 333 343 Note. Initial concentrations: [TEMPO]=4.861073 mol litre71, [BPO]=2.361073 mol litre71. a Dimensionality is litre mol71 s71. Dicyclohexyl peroxydicarbonate decomposes into radicals much faster than BPO (for DCPDC, the ki value is 100 times greater than for BPO).This allows implementation of syntheses at lower temperatures, which is an additional `insurance' against the risk of possible side reactions due to dissociation of RiMnX and ignored in Scheme 3. According to calculations, there is little point in synthesising the adductswith long polystyrene chain (n ^ 10) using a one-step process. In this case, a considerable amount of hard-to-remove contaminating adducts of nearly identical compositions can be formed, even if a very carefully `adjusted' procedure with optimum `recipe' is employed. Because of this, long-chain adducts RiMnX (n=10) should be synthesised using a two-step procedure which includes (i) the synthesis ofRiMX(n=1) and (ii) a controlled/`living' bulk polymerisation ofM (inorder to extend theMnblockuntil desiredmolecularmass value) at a higher temperature atwhich the rate of reversible dissociation ofRiMX is high enough.In such a manner, it is possible to extend the polymer chains by about 10 units over a period of 3 ¡¾ 4 h at 393 Kand to obtain theRiM10Xadducts withapolydispersity index of 1.15 andmore (GPC data). It thus follows that currently the synthesis of alkoxyamines is developed to the extent that it can be performed as a kinetically controlled process with accurate prediction of results. 3. Determination of the rate constant of reversible dissociation of alkoxyamines at the C7ON bond Reversible dissociation of RiMnX (BX), which is the `heart' of the mechanism of `living'-chain radical polymerisation, is described by Scheme 4. Scheme 4 k1 B.+X., BX BX, B.+X.k2 kt P, B.+B. where P is the recombination (or disproportionation) product of radicals B. and k2 ^ kt ^ 107¡¾ 108 litre mol71 s71. Since dissociation of BX is a non-steady-state process, run- ning concentrations of all compounds involved in the process can only be found after solving the system of differential equations (11) ¡¾ (13). G V Korolev, A P Marchenko 9.9, 11.6, 3.5 8.3, 9.5, 2.8 12.2, 15.0, 4.7 14.3, 18.4, 6.8 16.1, 21.8, 9.4 9.1, 10.6, 2.5 13.0, 16.2, 4.1 16.4, 22.1, 6.9 16.5, 22.1, 7.6 (11) daBa dt a k1aBXa ¢§ ktaBaOaBa a aXaU, (12) daXa dt a k1aBXa ¢§ ktaBaaXa, (13) (14) daBXa a ¢§k1aBXa a ktaBaaXa, dt [BX]=[BX]07[X], [P]=[X]7[B]. (15) The following analytical solutions of the system of equations interval time a (11) ¡¾ (15) were obtained for (k1kt[BX]0/3)71/2 55 t 55 (kt[BX]0/24k21 ) which covers almost 1=3 1t (16) , [X]=[BX]0 entirely the range of practically significant t values (from fractions of a second to tens of days) 88: 3k2 ktaBXa0 1=3 k1 (17) .[B]=[BX]0 3k2t aBXa20t From Eqn (16) it follows that if the kt value is estimated to sufficient accuracy, the value of k (18) 1 a aXa3=2k1t =2 aBXa0O3tU1=2 can be determined in the experiments on the decomposition of BX in inert media from the ESR measurements of the kinetics of accumulation of radicals X.. The most reliable kt estimate is kt ^ 107 ¡¾108 litre mol71 s71. From Eqn (15) it follows that the data on the kinetics of accumulation of P can be used instead of the corresponding data for X. if time t is rather long and [X] 44[B]. This can be done if for any reason it is more convenient to perform experimental measurements of [P].In most cases, ESR measurements of the kinetics of accumu- lation of radicals X. in order to determine the k1 value are carried out under conditions of reversible decomposition of alkoxy- amines.85, 89 ¡¾ 91 Recently,92 yet another procedure for the measurement of the k1 values has been developed. It includes measurements of the`Living'-chain radical polymerisation consumption of radical B. in the reaction with benzoquinone (BQ), which is a highly efficient acceptor of radicals B., instead of measuring the consumption of B. in the reaction B.+X.. Each BQ molecule entraps two radicals B. with the rate constant kx&105 litre mol71 s71 (for styryl radical at T=333 ± 353 K).If benzoquinone (*1072 mol litre71) is introduced into the system, then, according to Scheme 4, the deactivation rate of radicals B. by BQ will be Wx=kx[BQ][B]=103[B] while the rate of the reverse transformation of B. into BX will be W2=k2[X][B]=102[B] (according to ESR data, [X] ^ 1076 mol litre71 at k2 ^ 108 litre mol71 s71). Thus, the addition of BQ decreases the rate of the reverse reaction in Scheme 4 by at least an order of magnitude, which is tantamount to nearly complete suppression of this reaction. Under these conditions, the rate of accumulation of X. as obtained from ESR measurements will be virtually equal to the rate of dissociation of BX. This method for the determination of k1 eliminates difficulties associated with side reactions ignored by Scheme 4, such as, e.g., disproportionation of BX with the formation of XH and a polymer P(=) with a double bond in the end group.The side reactions transform a paramagnetic speciesX. into an `ESR stealth', thus disturbing the results of measurements. The new method 92 is also more advantageous than that reported by Fischer 88 because the k1 constant is determined here without using the kt value, which can only be determined with an accuracy of an order of magnitude. Therefore, the accuracy of the new method is higher by an order of magnitude. An original method for measurement of the constant k1 was suggested.93 Here, the k1 value is determined separately rather than in combination with the kt value. This is achieved by performing the measurements in the bulk of the monomer.In this case, owing to the reaction with the monomer, the active dissociation product of the initial alkoxyamine (RMnX), viz., a hydrocarbon radical RM:n, manages to extend its chain by several monomer units before the next act of conversion into alkoxyamine as a result of the reaction with iminoxyl.M M RM ... RMnX RMná1 nák , k1 7X. RMn RMnák +X. k2 RMnákX. This procedure makes it possible to distinguish between the initial alkoxyamine RMnX and `heavy' alkoxyamines RMn+kX, RMn+2kX, ..., RMn+mkX and allows determination of k1 from the data on the decrease in the concentration of the initial RMnX. The reversible character of the dissociation presents no problems to determination of the constant k1, since only the first acts of dissociative decomposition of each initial molecule RMnX are measured experimentally.The next decomposition acts that follow the reversible reduction involve compound RMn+mkX (m=1, 2,...) for which no measurements have been performed. A procedure for separate determination of the concentration of the initial alkoxyamine RMnX (M is styrene, n=1) in the mixture with `heavy' alkoxyamines RMn+mkX using gel-perme- ation chromatography has been developed.93 For n=1, the peak of the initial alkoxyamine on the chromatogram of the mixture can be resolved to an accuracy of 10%± 20%, which is corre- spondingly the accuracy of the determination of k1. The k1 values thus obtained [k1=2.061013exp(7124200/RT) s71] should be considered the most reliable. The limitation inherent in this method is due to the fact that it can only be applied to alkoxy- amines containing one monomer unit per molecule.For n>1, the resolution of the peak of the initial compound in a mixture of substances containing n+mk monomer units decreases substan- tially. From this viewpoint, the use of the new method 92 discussed above (competitive entrapment of active hydrocarbon radicals by benzoquinone) seems to be more convenient for n>1, since it has no limitations as regards the n values for the initial alkoxyamine. The method for assessing the constant k1 in combination with kp and kt, based on measurement of the k1kp/kt ratio appears to be 415 the most popular.58, 89, 94 ± 101 This requires plotting the kinetic curve WM(t)=7d[M]/dt=kp[M][R] and the curve of accumu- lation of the iminoxyl radical [X]t.If the equilibrium in a system k1 R.+X. RX k2 is established much faster than any perturbation (e.g., the reaction R.+R.) is developed, the function [X]t can be calculated using the formula [X]t=k1[RX]/k2[R], where the concentrations ofRXand R. depend on t. The [RX] value is determined from the relation- ship [RX]=[RX]07[X]t, where [RX]0 ^ 1072 mol litre71 and [X]t ^ 1076 ± 1075 mol litre71. Hence to sufficient accuracy we get [RX] ^ [RX]0. For a fixed t=tf, the [R] value is determined from the kinetic curve [R]=WM(tf)/kp[M], where [M] is the running concentration at the same instant t=tf . Then, by comparing theWM(t) and [X]t curves for the same t we can calculate the ratio k1kp k2 0âMä . ^ âXätWMÖtÜ âRXä Reliability of calculations can be checked for independence of the parameter k1kp/kt on the conversion time t.The accuracy of the estimate of the constant k1 by this method is also obviously dependent on the reliability of the values chosen for kp and kt. Usually, the values kp=26103 (for T=393 K) 102 and kt=107 ± 108 litre mol71 s71 are used. As a rule, calculations of `living' polymerisation processes are carried out using the con- stant k1 in the form of the ratio K=k1/k2 (the equilibrium constant), thus it is the equilibrium constant value that is the main goal of quantitative estimates reported in many studies. Nevertheless, it should be noted that the scatter of k1 values reported by different authors is extremely wide and, which is most important, the reasons for this phenomenon are unclear.For instance, the rate constant of dissociation of 1-phenyl-1-(2,2,6,6- tetramethylpiperidinyl-1-oxy)ethane (1) in deuterated styrene was reported to be*1073 s71 at 396 K.103 On the other hand, the k1 value obtained for the dissociation of the same compound at a higher temperature (413 K) was reported 104 to be equal to &861075 s71 (dissociation in tetrachlorobenzene). Such a wide scatter in the k1 values can hardly be explained by the solvent effect alone. In conclusion, let us dwell on the side reaction of irreversible dissociation of alkoxyamines which occurs at high temperatures (above 408 ± 433 K). Apparently, it is this reaction that makes alkoxyamines with increased (as compared to styrene-containing derivatives) strength of the C7ON bond `inoperative'.This side reaction was first studied taking a model alkoxy- amine 1 as an example.104 Me Me MePhCH N O 1 Me Me It was concluded that dissociation of this alkoxyamine with the cleavage of the C7ON bond follows two pathways resulting in (i) an active hydrocarbon radical and theTEMPOstable radical and (ii) hydride transfer to give an unsaturated hydrocarbon and hydroxylamine. The competition between the two types of cleavage of the C7ON bond was studied in detail by high-resolution NMR spectroscopy 105 taking alkoxyamines obtained upon radical decomposition of dibenzoyl peroxide in styrene as examples. Me Me O O CHPh N O PhC CH2 2 (BS-TEMPO) Me Me416 Me Me O N PhCO(CH2CHPh)nCH2CHPhO Me Me 3 (PS-TEMPO with Mn=1100,Mw/Mn=1.03) Thermal decomposition of alkoxyamines 2 and 3 was perform- ed in perdeuterated toluene in the temperature range 393 ± 433 K.The products obtained during the conversion were analysed by 1H NMR spectroscopy. This required preliminary assignment of the 1H NMR spectra of mixtures using the 1H NMR spectra of model compounds and specially developed auxiliary calibrations. The obtained rate constants (kdec) of irreversible decomposition of alkoxyamines 2 and 3 were 4.761014exp(7157 000/RT) and 5.761014exp(7153 000/RT) s71, respectively. Most probably, the irreversible decomposition reaction competes with reversible dissociation, i.e., the former occurs concurrently rather than sequentially (as the second stage after the dissociation of alkoxyamines into an active hydrocarbon radical and TEMPO).One can calculate the ratio kdec/k1= Pdec=29exp(729 000/RT), which characterises the contribution of the side reaction of irreversible decomposition of alkoxyamines as a function of temperature, using the value k1=2.061013exp(7124 200/RT) s71 (Ref. 93). At 433 K, we have Pdec ^ 1072, which means that no more than 1% of the dissociating alkoxyamine molecules undergo irreversible decom- position. At first glance, this is a negligible value. However, taking into account the half-life of alkoxyamine (at this temperature t1/2=0.69/k1 ^ 0.5 min), we obtain that the alkoxyamine man- ages to enter into a reversible dissociation>recombination cycle hundreds of times over the time necessary for complete conversion (several hours). Therefore, at first glance small losses of the alkoxyamine due to the irreversible decomposition in each cycle are accumulated and become comparable with its initial concen- tration (complete deactivation).As temperature decreases (e.g., down to 393 K), the Pdec value becomes nearly halved; however, the t1/2 value increases dramatically (by about a factor of 40) with concomitant sharp decrease in the number of reversible cycles and losses due to deactivation of the alkoxyamine. 4. Kinetics of alkoxyamine-mediated polymerisation of styrene The kinetics of styrene polymerisation in the presence of alkoxy- amines was reported in most detail by Greszta and Matyjaszew- ski.106 The main goal of this study was to reveal key features of the process, which make it possible to infer the details of the mechanism of `living'-chain polymerisation. A short list of the most important characteristics of `living'-chain styrene polymer- isation is presented below.� The rate of polymerisation is proportional to the concen- tration of e monomer (i.e., the process is first-order with respect to the monomer) and independent of the concentration of alkoxy- amine (a zero order process with respect to alkoxyamine) or of the concentration of a stable nitroxyl radical (as a rule, TEMPO), if the alkoxyamine is synthesised in situ. � The molecular masses of polymers increase linearly with the degree of polymerisation (conversion). This is valid until at leastMn&20 000 ± 30 000. � The polydispersity of the resulting polymer, which is characterised by the Mw/Mn ratio, decreases usually with con- version and then increases at later stages of the process.The Mw/Mn value varies depending on the reaction conditions, but, as a rule, remains less than 1.3. � Throughout the polymerisation, the concentration of the stable nitroxyl radical, as determined by ESR spectroscopy, is 0.1% ± 1.0% from the initial concentration of alkoxyamine (or its precursor, TEMPO) introduced into the reaction system.107 This makes it possible to draw some conclusions. The fact that the polymerisation rate,W, of the monomer is independent of the G V Korolev, A P Marchenko concentrations of alkoxyamine and the stable nitroxyl radical (TEMPO) and coincides with the rate of self-initiated polymer- isation of the monomer shows that self-initiation is primarily responsible for maintaining the concentration of active centres [R], which, in turn, controls the polymerisation rate (W*[R]).Thus, the rate of self-initiation (Wi) (or, generally, any radical initiation) controls the polymerisation rate. Despite the controlling effect ofWi with respect toW, alkoxy- amine used as the agent for `living' polymerisation controls almost completely the length of growing polymer chains so that they grow throughout the polymerisation process (at least, most of them do not undergo termination). This can only occur ifWi 55 WA (WA is the dissociation rate of alkoxyamine, WA=k1[A]), i.e., if each chain initiation act corresponds to many dissociation>recombi- nation acts of alkoxyamine, so that each newly initiated chain manages to be involved repeatedly in this reversible cycle.The narrowing of molecular mass distribution of the resulting `living' polymer down to a Mw/Mn value of 1.3 (cf. Mw/Mn= 1.5 ± 2.0 for conventional radical polymerisation) also suggests the `living' character of polymer chains. On the other hand, the increase in the Mw/Mn ratio at later stages of polymerisation indicates some side reactions. The fact that the relative concentration of a stable nitroxyl radicalX. is low ([X]/[A]=1072 ±1073) and changes only slightly during the time necessary for nearly complete conversion of the monomer indicates that the equilibrium constant K=k1/k2 of the following process is very low. k1 A R.+X. k2 This equilibrium is shifted rather slowly under the action of disturbing factors (first of all, quadratic chain termination, R.+R.) which are developed during the polymerisation; hence, it may be always thought that k1[A] ^ k2[R][X], where [A] ^ [A]0.If K can be measured independently, then, using this value, one can assess the concentration of active centres [R] over a period necessary for nearly complete conversion. For instance, the equilibrium constant of alkoxyamine-mediated `living' polymerisation performed under standard conditions (T=393 K) is 10711 mol litre71,106 hence [R]=k1[A]/k2[X]= 1079 ± 1078 mol litre71. Usually, the concentration of alkoxy- amine is 1072 mol litre71 and that of the nitroxyl radical is 1075 ± 1074 mol litre71. Therefore, the polymerisation process proceeds almost entirely at [X] 44 [R], which provides a complete control of the reversible dissociation>recombination cycle over the chain propagation, since quadratic chain termination makes a negligible contribution in this case.Actually, in the presence of dissociating alkoxyamine each growing chain undergoes either a linear termination following the mechanism k2 A R.+X. (a fictitious, temporarily termination, since the adduct A can dissociate, thus retaining the `livingness' of the chain) or a quadratic termination following the pathway kt `dead' polymer. R.+R. The contribution of the latter process determines the extent to which the alkoxyamine-mediated chain propagation can be not in control. Quantitatively, the contributions of linear and quadratic termination are characterised by the probabilities a1 and a2 . a1=k2âRäâXä á ktâRä2 , k2âRäâXä a2=k ktâRä2 2âRäâXä á ktâRä2 .Thus, taking into account that [X] 44 [R] and k2 ^ kt , we get a1&1 and a2 55 1.`Living'-chain radical polymerisation 5. Kinetics of alkoxyamine-mediated `living' radical polymerisation Initially, the kinetic analysis of a polymerisation process proceed- ing in the presence of alkoxyamines (as well as other reversible inhibitors, iniferters and other agents) was performed in the framework of rather rough approximations which oversimplified the situation under consideration. Most concisely, the mechanism of this polymerisation process is described by Scheme 1. This scheme should only be augmented with a new stage to describe the generation of active radicals upon decomposition of initiators I (organic peroxides, hydroperoxides, azonitriles, etc.) with the initiation rateWi=ki [I] (Scheme 5). Scheme 5 I R ki .initiation k1 R.+X. RX reversible inhibition k2 RX R.+X. kp RM. chain propagation R.+M kt P chain termination R.+R. For a self-initiated polymerisation of the monomer, Wi=kim[M]n, where n can take any value depending on the specific generation mechanism of R.. For styrene, this mechanism involves the reactions 108, 109 kd , 2CH2 CHPh M D k0iCHPh +CH2 +CH2 CPh, M. D. which proceed at 393 Kwith the rate constants kd=361078 (see Refs 110 and 111) and k 0i =561078 litre mol71 s71 (see Refs 106 and 112). The n value lies between 2 and 3. Reversible inhibition steps are the key stages of the reactions. Competitive entrapment of radical R. by a stable free radical X. prevents the growing chains R.from being terminated quadrati- cally. During the time interval between acts of chain initiation (or regeneration) the radicals R. manage to react with the monomer, thus extending the polymer chain. It is an easy matter to perform the kinetic analysis of such a polymerisation scheme (Scheme 5). In the steady-state approxi- mation, the polymerisation rateWis calculated as follows 1=2. (19) W à kpâMä kt Wi This expression for W is the same as that used to describe a conventional radical polymerisation without reversible inhibition. This result is obvious. Indeed in the steady state the reversible inhibition reactions responsible for `living' polymerisation make no contribution to the stationary concentration of growing polymer chains [R]s (and, correspondingly, to theW value), since all radicals R.and X. generated in the stage RX?R.+X. leave the reaction system by the stage R.+X.?RX. Therefore, if the time necessary for establishment of a steady state in the polymer- isation system (ts) is much shorter than that necessary for complete conversion (t), the alkoxyamine present in the system has no effect on the polymerisation kinetics from the moment 417 ts 55 t onwards, i.e., nearly from the beginning of the polymer- isation process. However, the chain propagation regime in the presence of alkoxyamine differs fundamentally from that in conventional radical polymerisation. Actually, in the latter case the average integrated chain length (n) at instant t is given by the following expressionWdt , (20) Widt 0Ñt n à Ñ0t where ÑtWdt is the total number of monomer units in the chains 0 and ÑtW0 idt is the total number of the initiated chains.In a Wdt 0 , (21) particular case, for W^const and Wi^const, we get n^W/Wi^const. On the other hand, for `living' polymerisation the average integrated chain length (nx) at instant t will be determined by the total number of `dead' and `living' chains accumulated by the instant t &;t Wi dt á âRXät 0 nx à Ñt 0 where [RX]t is the stationary (quasi-stationary) concentration of alkoxyamine at instant t, which in turn is equal to the concen- tration of `living' chains. `Living'-chain polymerisation proceeds if ÑtWidt 55 [RX]t . In this case, the nx value is calculated by the formula Wdt 0 (22) . ^ nx^ Ñt âRXät G âRXät Here, [RX]t ^ const; if an iminoxyl is used as alkoxyamine, then k1/k2 55 1 and [RX]t ^ [RX]0.Unlike conventional radical polymerisation in which the chain length remains virtually unchanged throughout the process [Eqn (20)], `living' polymer- isation in the presence of alkoxyamine is characterised by linear increase in nx with the degree of conversion G [Eqn (22)] provided that the overall concentration of chains generated by the initiator throughout the polymerisation process is much lower than the equilibrium (initial) concentration of the additive RX. These are the results of the simplest and obvious analysis of the steady-state `living'-chain polymerisation process described by Scheme 5. It should be noted that in the absence of additional initiation the system cannot reach the steady state and the analysis is complicated.Theoretical studies on the mechanism of `living' radical polymerisation can be divided into two groups. 1. Early studies 5, 113 aimed at revealing salient features of the mechanism responsible for the transformation of usual radical polymerisation into `living' polymerisation. 2. More recent studies 88, 106, 114 ± 118 on the kinetic analysis of the polymerisation mechanism and molecular mass distributions of polymeric products formed in the system carried out with the use of supercomputers and sophisticated mathematical proce- dures. Obviously, the mechanism presented in Scheme 5 is unsuit- able for analysing the molecular mass distributions (MMD). To this end, Scheme 5 should be augmented with equations for chains of different length containing n (n=1, 2, ...) monomer units instead of the equations for a growing chain of an infinite length, while the chain propagation reaction should be written as a sequence of n stages.Reversible inhibition and quadratic termi- nation reactions should also be divided into a variety of identical418 stages in which reagents R of different chain length are involved. The chain length effect of the reagent R on the rate constants can be ignored by assuming that they are the same for identical reactions. However, the number of differential equations to be integrated numerically increases by two orders of magnitude and more (instead of 5 equations shown in Scheme 5) even if the analysis is restricted to not very long chains. Calculations ofMMD for the chains up to 500 monomer units long (n=500) have been reported,115 as well as some artificial simplifying procedures (introduction of special subsystems and `closure reactions').113 Let us consider the results obtained in three theoretical studies 88, 106, 114 in which the results of calculations were com- pared in detail with the latest experimental results.Computer simulation 106 of a process described by Scheme 5 for M=styrene and X=TEMPO was performed using the PREDICI programme package.119 ¡¾ 121 The numerical values of the rate constants and concentrations of reagents (for 393 K) are listed below. Ref. Numerical value Parameter Rate constants of reactions/litre mol71 s71 kp kd k0i kt 102, 122 110, 111 112 123, 124 2000 361078 561078 107 10 Concentration/mol litre71 [M] [RX] 106 106 1072 Unlike the values of rate constants kp , kd , k 0i and kt , the values of k1 , k2 and some other rate constants were attenuated in the course of computer simulation because of a wide scatter of the data reported in different publications.According to calculations,106 Scheme 5 adequately describes all experimentally observed characteristic features of the process (see previous Section) assuming that K=k1/k2410710 mol litre71. Based on detailed quantitative comparison of calculated and experimental dependences of the polydispersity index, Mw/Mn , on the degree of polymerisation, the values of the constants k1 and k2 were refined to be K ^ 10711 mol litre71; k1=861074 s71 and k2=86107 litre mol71 s71. This also made it possible to augment Scheme 5 with new stages necessary for improving the agreement between calculated and experimental data.kt2D D.+P, D+Rkdec P(=)+XH. RX Here, P(=) is the polymer with a double bond in the end group, XH is hydroxylamine, kt2D=50 litre mol71 s71 is the rate con- stant of chain transfer to dimer D formed in the self-polymer- isation of the monomer (see above), kdec is the rate constant of dissociation reaction accompanied by hydride transfer and kdec ^ 1075 s71 (see Ref. 104). These calculations have also confirmed that the reactions shown in Scheme 5 satisfy the principle of stationary concentra- tions. Using the above-mentioned values of rate constants, con- centrations and temperature, the steady state is reached at a degree of polymerisation of less than 1%, i.e., nearly from the beginning of the polymerisation process.The calculated stationary concen- trations of growing chains [R] and stable iminoxyl radical [X] were found to be 1078 and 1075 mol litre71, respectively. Similar results have also been obtained 114 for the same styrene ¡¾TEMPO reaction system using another type of computa- tional procedure (the Monte Carlo stochastic algorithm 125 ¡¾ 128). This makes it possible to perform calculations without recourse to supercomputers. The results of calculations for T=393 K were supplemented with those obtained for T=363 K114 which were then compared with the experimental results obtained at the same G V Korolev, A P Marchenko temperature.78 The parameters listed below provided the best fit between the calculated and experimental data.Numerical value Parameter Concentration/mol litre71 [M] [RX] 8.75 3.761073 ¡¾ 4.461072 Rate constants of reactions k1/s71 k2/litre mol71 s71 kp/litre mol71 s71 kt/litre mol71 s71 kd/litre mol71 s71 k0i /litre mol71 s71 kdec/s71 2.561073 2.56108 950 107 1.561079 4.561079 861076 The polydispersity indices, Mw/Mn , obtained analytical- ly 90, 129 and found from simulation have also been compared.114 TheMw/Mn ratio was calculated using the formula (23) Mw Mn a 1 gx a 1x 2 a Ob ¢§ 1UO2 ¢§ xU ¢§ a ¢§ b , 1 ¢§ O1 ¢§ xU1aa b ¢§ 2aO1 ¢§ aU Ob2 ¢§ a2Ux2 where x is the degree of monomer conversion, g=[M]0/[RX], a=[R]/[RX] and b=k2[X]/kp[RX]. It was found that the results of computer simulation fit well the theoretical curve. Fischer 88 reported the most detailed computer simulation.He analysed two types of `living'-chain polymerisation, without addi- tional initiation (Scheme 1) and with varied intensity of initiation in order to establish the range of the effect of the initiation on polydispersityMw/Mn (Scheme 5). Different versions of syntheses of the adducts RX were also considered, including the synthesis in situ and those with different dynamics of reversibility (this was achieved by varying the constants k1 and k2 over a wide range). The first case (see Scheme 1) corresponds to a non-steady-state process. For very short times, t 55 [k21 (kt [RX]0/k171)]71/2^ (k1kt [RX]0)71/2, the following relation is valid (24) [R]=[X]=k1[RX]0t . 1, 1=3 k1 , 0 [R]=aRXa For the time interval (k1kt[RX]0/3)71/255t55kt[RX]0/24k2 which covers almost entirely the range of practically significant t values, one obtains 1=3 1t , 0 [X]=aRXa taRXa0U2t 3Ok (25) 3k2 ktaRXa0 [RX]=[RX]07[X]^[RX]0 , [P]=[X]7[R]^[X], 1t2 .[M]=[M]0exp 1=3

ISSN:0036-021X    

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Russian Chemical Reviews 69 (5) 435 ± 450 (2000) Mechanochemistry of catalysts V V Molchanov, R A Buyanov Contents I. Introduction II. Synthesis of catalytic systems III. Effect of mechanochemical activation on catalytic properties of compounds IV. The role of defects as active centres for chemical processes V. Catalytic reactions under conditions of mechanochemical activation VI. The nature of the effect of mechanochemical activation on the reactivity of solids Abstract. the for activation mechanochemical of use the on Data Data on the use of mechanochemical activation for the preparation The generalised. are supports and catalysts of preparation of catalysts and supports are generalised. The effect effect of properties catalytic the on activation mechanochemical of mechanochemical activation on the catalytic properties of of various occurring reactions Catalytic noted.is systems various systems is noted. Catalytic reactions occurring under under conditions discussed. are activation mechanochemical of conditions of mechanochemical activation are discussed. The The hypotheses concerning the nature of the effect of mechanochem- hypotheses concerning the nature of the effect of mechanochem- ical activation on the reactivity (including catalytic properties) are ical activation on the reactivity (including catalytic properties) are considered. The bibliography includes 197 references considered. The bibliography includes 197 references. I. Introduction An interesting, though, in our view, insufficiently studied problem is the application of mechanochemistry to heterogeneous catal- ysis.In both these fields, investigators are still on the way to creating general theories which would allow prediction of the behaviour of solids in various chemical and catalytic processes. In mechanochemistry as well as in catalysis, much is dependent on the solution of the problem of revealing catalytically active and reactive centres. For this reason, studies carried out at the border- line of the two sciences can favour to a considerable extent their mutual enrichment. The development of mechanochemistry has begun with stud- ies of grinding processes. It was found that grinding changes not only the sizes of particles of a material, but also their physico- chemical properties.This provided the ground for introducing the term `mechanochemical activation' (MCA). Grinding of substan- ces is widely used in the chemical industry, including preparation of catalysts. The processes occurring under mechanical treatment of solids are described in sufficient detail in a number of monographs and reviews,1±5 and we will not dwell upon them. Let us only note the consequences of mechanochemical treatment on catalytic properties of solids or on the synthesis of catalytic systems. Physicochemical changes resulting from MCA are the conse- quence of relaxation of the field of stresses in a solid after V V Molchanov, R A Buyanov G K Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, ul. Akad.Lavrent'eva 5, 630090 Novosibirsk, Russian Federation. Fax (7-383) 234 30 56. Tel. (7-383) 234 45 53 (V V Molchanov), Tel. (7-383) 234 27 57. E-mail: buyanov@catalysis.nsk.su (RA Buyanov) Received 5 October 1999 Uspekhi Khimii 69 (5) 476 ± 493 (2000); translated by V D Gorokhov #2000 Russian Academy of Sciences and Turpion Ltd DOI 10.1070/RC2000v069n05ABEH000555 435 436 441 445 445 446 mechanical impact on it. In all cases, irrespective of the relaxation mode, changes in the thermodynamic potentials of compounds under activation occur. The physicochemical properties of sub- stances are related to the free energy G, for example, DG=7RTln k2 , k1 DG=RT ln c , c? DG=RTln p , p? DG=¡lDT , Tp where k1 and k2 are the rate constants of forward and reverse reactions, c and c? are the current and equilibrium solubilities, p and p?are the current and equilibrium vapour pressures, l and Tp are the heat and temperature of a phase transition, respectively.The free energy in turn depends on the sizes of particles of a compound and the presence of defects in it. , DG=2sV ¡ 1 r2 1 1 r where s is the surface tension, V is the molar volume, r1 and r2 are the radii of the particles of fine and coarse fractions, respectively; DG=7kT lnW, where k is the Boltzmann constant, W is the thermodynamic probability equal to the possible modes of the distribution of defects in the lattice. It should be noted that the symbols r1 and r2 refer not only to the real physical size of particles but also to the sizes of ordered areas between the extended defects.5 The relaxation channel of the stress field related to the formation of fresh surface was studied most thoroughly.Many studies were devoted to the investigation of the kinetics of this process. Both the simplest regularities of coarse grinding (see Khodakov's monograph 6) and more advanced models of fine grinding were considered which take into account the pulsed character of the mechanical impact and the effect of mechanical activation on the formation of fresh surface.7±11 These models have a formal character and are far from being capable of describing all experimental results, particularly those derived from studies of compounds with anisotropic properties.Detailed investigation of the chemical properties of the fresh surface436 showed 2, 5, 12 that MCA of silicon, germanium, tin and magne- sium oxides leads to the formation of different centres on their surfaces which have predominantly a radical nature. Interactions of these centres with various gases were described. The data obtained may be used for the prediction of processes occurring in the synthesis of catalytic systems and modification of their surfaces. Yet another general channel of relaxation of the stress field is the formation of defects of the crystal structure and the exit of these defects onto the surface of crystallites. Numerous studies systematised in monographs 1, 3, 4 showed that it was the forma- tion of defects rather than fresh surface, that was the cause of higher, MCA-induced reactivities and catalytic activities of com- pounds.There is a suggestion (based on indirect data) that it is the defects of the crystal structure that are the catalytically active centres. In our opinion, in order to elucidate the effect ofMCAon the catalytic activity, it is necessary to relate physicochemical features of defects to the nature of the catalysis considered as a sequence of chemical transformations of the catalyst and reagents. The process of formation of defects has a thermodynamic nature: the system tends to minimise its free energy, while the localisation of the excess energy on defects is thermodynamically more advantageous than the regular distribution of elastic stresses over all the bonds of the crystal lattice.The appearance of defects is, as a rule, accompanied by changes in the electronic properties of activated compounds. For example, electronic levels are formed in the forbidden bands, the forbidden bands become narrower, the conductivity electrons appear in semiconductors, and the electron-donor properties are enhanced in semiconduc- tors and dielectrics. The electronic theory of catalysis considers the influence of all these changes on the catalytic properties. These are the basic channels of relaxation of the field of stresses arising upon mechanical impact on solids. Other emissive phenomena also take place; however, their influence on the catalytic properties and peculiarities of the synthesis of catalysts is not very obvious, and we will consider them henceforth only where necessary.Studies devoted to the investigation of the effect of mechanical treatment on catalysts may be divided into three groups. In the first group the MCA effect is used for the synthesis of catalytic systems: in the second group the effect of MCA on the catalytic properties of compounds is dealt with and in the third group catalytic reactions under MCA conditions are considered. II. Synthesis of catalytic systems The methods of mechanochemistry can be used for both synthesis of catalysts, supports and sorbents and control of their perform- ance. One of the first examples of the systematic and purposeful use of MCA for the preparation of catalysts is the preparation of a polymerisation catalyst based on titanium and aluminium chlor- ides.It was found that grinding of titanium(III) chloride in a ball mill increases its catalytic activity in the propylene polymerisa- tion.13 It turned out that in this case the a- and g-TiCl3 phases pass to the d-modification, which is more active in this reaction.14 Aluminium ± titanium chloride catalysts are prepared by joint grinding of either metallic aluminium and TiCl4 15 phases or titanium and aluminium chlorides,16, 17 or the chlorides with the addition of trialkylaluminium.18 In all probability, this techno- logical technique was discovered purely empirically, and its scientific substantiation was started only after the publication of the corresponding patents.15 ± 18 The processes occurring during mechanical treatment of catalysts were described in Refs 19 ± 21.Somewhat later, an analogous study of titanium ± magnesium chloride catalysts was carried out.22 ± 24 Summing up the results obtained, one can state that upon MCA of mixtures of TiCl3 with AlCl3 and TiCl4 with MgCl2 an interaction between the compo- nents takes place. In the former case, this leads to the formation of solid solutions with the structure of d-TiCl3, while in the latter case V V Molchanov, R A Buyanov titanium chloride is fixed on the surface of magnesium chloride. Discrepancy between some results should be noted: the catalyst prepared by joint activation of titanium and magnesium chlorides possesses high activity according to Kashiwa,22 while Zakharov et al.24 found that it is not very active, although the conditions and duration of activation were similar in both studies.Systematic studies on the application of MCA for the prepa- ration of catalysts were carried out at the Ivanovo Institute of Chemical Technology. These studies were aimed at solving the problem of intensification of the interaction between solids and solutions containing other components of the catalysts. Mechan- ical treatment accelerated the interaction of iron, zinc and aluminium oxides with a solution of chromic acid.25 ± 27 Upon treatment of aluminium oxide in an ammonium-carbonate sol- ution of zinc,28 of a- and g-aluminium oxides 29 and of magnesium oxide 30 in an ammonium-carbonate solution of copper, sorption of ions from the solution onto the surface of the solid component was observed.This technological approach both favoured the interaction of components and allowed regulation of some opera- tional properties of the catalysts: their catalytic activities, strength and mouldabilities. The activities of chromium catalyst in the methanol synthesis,27 of complex oxide and magnesium ± copper catalysts in the vapour conversion of CO,29, 30 of aluminium ± nickel catalyst in the vapour conversion of hydrocarbons 31 increased. The enhancement of the strength of iron ± chromium,26 aluminium ± copper ± zinc ± chromium 29 and aluminium ± nickel 31 catalysts, zinc ± aluminium spinel and aluminium oxide used as supports 28, 29 was also observed.In addition, a-aluminium oxide acquired mouldability by the extrusion method, which allowed the preparation of granules of complex shape.32 Studies aimed at the development of a sulfur sorbent were carried out at the same Institute. Dispersion of zinc oxide in solutions of carboxymethylcellulose and poly(vinyl alcohol) enhanced its mouldability by the extrusion method, increased its specific surface and sorption capacity with respect to sulfur- containing compounds.33 An analogous effect was achieved upon dispersion of zinc oxide with aluminium oxide in an ammonium-carbonate solution.34 According to Shirokov and Il'in,28 the enhancement of the sorbent strength results from the hydration of the surface of aluminium oxide and formation of zinc aluminate, which plays the role of a binding agent.Treatment of zinc oxide in a planetary or vibratory mill led to an increase in its static and dynamic sulfur sorption capacity and enhancement of its cleavage strength and abrasion resistance.35, 36 Based on these studies, a technology of production of a sulfur absorbent was developed.37 The method of MCA was applied for the preparation of catalysts of deep oxidation used for the after-burning of flue gases. Studies by Bulgarian investigators were aimed at the enrichment of the surface of cobalt oxide with copper oxide owing to local overheating arising during MCA.38, 39 Upon treat- ment of a mixture of cobalt and copper oxides, the copper oxide phase disappeared as a result of formation of a mixed oxide compound on the surface.38 Comparison of different techniques of grinding of a mixture of oxides (in a planetary or vibratory mill, in a mechanical mortar) showed that the use of the vibratory mill is the most efficient.39 Presumably, the copper ions are incorporated into the voids in the layer of the cobalt cations.An attempt was made to perform the mechanochemical synthesis of analogous systems using magnesium, zinc and manganese oxides 40 instead of copper oxide; however, these oxides did not interact in a vibratory mill. The cobalt ± copper oxide catalysts prepared using MCA possessed higher activities in the CO oxidation and were more resistant to poisoning with sulfur dioxide 38, 39 than the catalysts obtained by conventional methods.Massive copper and cobalt oxides are efficient catalysts of deep oxidation. However, practical application of these oxides is problematic because it is difficult to mould them. This problem may be solved by subjecting the oxides to a short-time MCA in a planetary mill before moulding.41 ± 43 The authors relate theMechanochemistry of catalysts positive effect to hydration of the surface of copper oxide upon interaction of a mechanically activated oxide with water 41, 43 and to changes in the morphology of cobalt oxide particles.41 The use ofMCAfor the synthesis of lanthanum cobaltites and manganites proved to be successful.44, 45 Activation of mixtures of oxides and carbonates made it possible to reduce the temperature of formation of the corresponding perovskites by 250 ± 300 K; the interaction at lower temperatures was more complete when the initial components were in the form of carbonates.As regards the specific surface and catalytic activity, the catalysts prepared using MCA were superior to the analogous systems obtained by tradi- tional ceramic technology and were close to the catalysts prepared by the co-precipitation method; the advantage of the MCA consists in the absence of deleterious wastes. The preparation of skeletal catalysts is very energy-consuming since the initial alloys of the corresponding metals with aluminium are obtained by the pyrometallurgical method.Besides, definite difficulties are associated with the completeness and rate of aluminium leaching. The use of MCAsolves both these problems. The beneficial influence of MCA on the properties of skeletal nickel was reported for the first time over four decades ago.46 Treatment of an aluminium ± nickel alloy in a vibratory mill increased the activity of the catalyst obtained after leaching in the reactions of cyclohexene hydrogenation and propan-2-ol dehydrogenation. Comparatively recently, methods were devel- oped for the preparation of nickel ± aluminium alloys by the so- called `mechanical alloying', i.e. by mechanochemical activation of a mixture of powders of nickel and aluminium metals.47, 48 The use of `mechanical alloys' makes it possible to increase the degree of aluminium leaching and to prepare Raney catalysts which are more active in the reactions of hydrogenation of phenylacetylene, potassium maleate and nitrobenzene.47, 49, 50 The skeletal catalysts prepared from the alloys obtained by the `mechanical alloying' method may have a more complex composition and contain modifying additives.51 It should be noted that not any composi- tion of the `mechanical alloys' makes them advantageous.Thus the pyrometallurgical alloys containing >80% of aluminium are better leached and ensure higher catalytic activity. The advantages of MCA are most clearly manifested in the regeneration of worked-out skeletal catalysts: its use for the preparation of `mechanical alloys' makes it possible not only to restore the properties of skeletal nickel but also to achieve the activity several times higher than that before regeneration.52 The higher activity of the catalysts prepared from `mechanical alloys' is possibly explained by the fact that after leaching nickel passes to a metastable state with the structure NiAl, whereas leaching of pyrometallurgical alloys leads to the formation of the face-centred cubic lattice.53 The `mechanical alloying' method was also used for the preparation of hydrides of intermetallic magnesium com- pounds.54 The `mechanical alloys' are hydrogenated more easily than the pyrometallurgical ones, and hydrogen present in the hydrides obtained is more mobile.Hydrides of magnesium inter- metallides proved to be efficient hydrogenation catalysts.55 Com- pared to conventional catalysts, their advantage is particularly noticeably manifested in the reactions of selective hydrogenation of alkynes and dienes to alkenes.Thus the hydride with compo- sition Mg2FeH6 provides a nearly 100% selectivity of hydro- genation of butadiene to butenes,56 while Mg2CoH5 ensures the 100% selectivity of hydrogenation of acetylene to ethylene.57 It should be noted that such a high selectivity in these reactions is reached on none of the known traditional catalysts. Preparation of hydrides through the `mechanical alloying' stage is a waste-free energy-saving method which was used for the synthesis of new catalytic systems, e.g., Mg2FeH6, Mg2CoH5 and Mg3CoH5.The application of MCA for the preparation of iron ± potas- sium dehydrogenation catalysts is described in sufficient detail in the literature. These catalysts are traditionally obtained by mixing iron oxide with potassium carbonate and potassium silicate. Thermal treatment of the paste obtained in water vapour leads 437 to the formation of the active component, viz., potassium ferrite. Pretreatment of iron oxide in a disintegrator makes it possible to reduce the temperature of its reaction with alkali metal carbo- nates, to increase the yields of the corresponding ferrites and the rates of their formation. Higher degrees of conversion of ethyl- benzene to styrene and a higher selectivity of styrene formation are reached 58 on the catalysts obtained from iron oxide treated in a disintegrator.Both these parameters are improved as the specific energy of treatment is increased.59, 60 In addition, such catalysts are better mouldable and possess higher strength.59 Upon treat- ment of a mixture of iron oxide and potassium carbonate in a planetary mill, potassium ferrite is formed directly in the drum.61 If dehydrogenation is performed with the catalyst obtained after thermal treatment of a mixture activated in water vapour, the process begins at 670 K, whereas on the initial catalysts it starts only at 800 K. The mechanically activated catalyst exhibits an increased activity until 880 Kat which it drops to the activity level of the initial specimen, which is associated with the annealing of defects in the crystal structure.61 Numerous studies were devoted to the use of MCA for the preparation of alumina-based catalysts and supports.Shirasaki et al.62 showed that grinding of corundum in water facilitates its formation; analogous data were obtained later by Il'in et al.32 The mouldability of alumina increases after MCA of the initial aluminium hydroxide.63 In this case the resulting alumina is not inferior in its strength and sorption properties to the oxide formed from precipitated aluminium hydroxide the production of which provides large volumes of wastes. The possibility of regulation of some operational properties of catalysts with the aid of MCA was noted.32, 62, 63 The possibilities of the use of MCA for the preparation of alumina-based catalysts and supports based on aluminium oxide are described in more detail in a series of papers from the Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences.Transformations of aluminium hydroxide in the course of MCA and during subsequent treatments were studied in detail. Upon activation of hydrargillite, grinding of crystals, shift of hydroxylic packs, cleavage of crystals into plates and dehydration with formation of molecular water which remains in the bulk among activation products occur.64 ± 66 Analogous processes also take place upon MCA of bayerite.67 The maximum quantity of excess energy accumulated in hydrargillite is 33 kJ mol71.This value is reached at the thickness of plates commensurable with the size of the unit cell of hydrargillite;68 in this state hydrargillite manifests its maximum chemical activity. In studies of thermal transformations of activated hydrargillite, a new state of alumina was revealed and denoted as p-Al2O3.69, 70 This is characterised by the presence of aluminium cations in the pentacoordinated state. The structure of this oxide was established, and it was found that p-Al2O3 is capable of dissociative chemisorption of ammonia.71 Thermal transformations of all aluminium hydroxides subjected to MCA proceed in the same manner:72 1023 ± 1123K 423 ± 873K p-Al2O3 GG, BE, BA 1173 ± 1273K a-Al2O3, MZ where GG, BE and BA are hydrargillite, bochmite and bayerite, respectively;MZ is the spinel-like phase of alumina.On the other hand, non-activated aluminium hydroxides are transformed into corundum each in its own mode which is more complex than that considered above. It should be noted that the temperature of phase transition of activated hydroxides into corundum is 200 K lower than that of non-activated ones.72 Detailed investigation of the processes which occur during MCA of aluminium hydroxides has allowed the development of techniques for the preparation a wide range of alumina-based catalysts, supports and sorbents. Thus depending on conditions, hydration of activated hydrargillite and p-Al2O3 leads to the formation of bayerite or pseudobochmite from which different438 aluminas are formed after thermal treatment.73 The mechanism of hydration of the hydrargillite and p-Al2O3 MCA products has been established.74, 75 Methods for the preparation of hydroxyaluminates of a number of divalent metals on the basis of the products of MCA of aluminium hydroxides were developed.Interaction of activated hydroxides with solutions of magnesium and zinc salts or with zinc oxide leads to the formation of the corresponding hydroxyalumi- nates.76 ± 78 Under the same conditions, p-Al2O3 also enters into analogous interactions.77 Presumably, hydroxyaluminates are formed through the stage of intercalation of salts.77, 78 Yet another field of application of activated aluminium hydroxides is the synthesis of various aluminosilicates.In the MCA of kaolinite, processes analogous to those revealed in the activation of hydrargillite occur, viz., shift and turn of layers as well as dehydration with the formation of molecular water remaining within the compound's structure.79 In contrast to MCA of hydrargillite, mechanical activation of kaolinite does not alter the pathways of its thermal transformations.80 The initial stage of thermal treatment includes formation of metakaolinite containing pentacoordinated aluminium cations.70, 80 Upon MCA of a mixture of hydrargillite and silica gel, hydrated aluminosilicate is formed 81, 82 from which an alumino- silicate spinel is formed first upon heating and then mullite.Anon- activated mixture undergoes transformations which differ in many aspects.By varying conditions of hydration and thermal treatment of activated mixtures of hydrargillite and silica gel, it is possible to obtain amorphous aluminosilicates, kaolinite, mont- morillonite, aluminosilicate spinel of high purity and mullite with large specific surface and without admixtures of corundum and cristobalite.73 Furthermore, zeolites of types A, X, Y were obtained,73, 83 and the possibility of synthesis of over 100 other zeolites is predicted,84 i.e., good prospects are open for the development of little-waste methods for the preparation of zeolites. Some aluminosilicates were synthesised using the so-called `soft mechanochemical synthesis',85 which involves MCA of hydrated or moist mixtures.It is suggested that in this case conditions are close to hydrothermal ones. The use of this method allows preparation of mullite without admixtures of other phases, a number of other aluminosilicates, as well as aluminates, tita- nates, zirconates, tungstates and vanadates of alkaline-earth metals. According to Avvakumov,85 the method of `soft mecha- nochemical synthesis' may be used for performing acid ± base reactions proceeding with liberation of water. New methods, including MCA, were developed for the syn- thesis of heteropolyacids (HPA) and catalysts based on them. A broad spectrum ofHPAwas obtained using mechanical activation of molybdenum and tungsten oxides and their mixtures with vanadium, silicon, aluminium and iron oxides.The most success- ful proved to be the use of MCA for the preparation of phospho- molybdic and phosphomolybdenovanadic HPA,86 ± 89 in particular high-purity H6P2Mo18O62 and H3+nPMo127nVnO40 with n=0 ± 4. The process is characterised by the total absence of deleterious wastes and flue gases, the time of synthesis is substantially reduced, energy consumption is decreased, losses of expensive raw materials are precluded, fire-hazard stages are absent, while the yield of HPA reaches the quantitative level. When developing methods for the preparation of HPA, we revealed new oxide compounds of molybdenum and vanadium in the system V2O57nMoO3.90 It is their formation that is the reason for such a smooth synthesis of HPA. Reactions of compounds of the system V2O57nMoO3 with phosphoric acid and its salts under conditions of MCA lead to the formation of HPA with composi- tion H3+nPMo127nVnO40, where n53, or their salts.87 Appa- rently, an important role in these reactions is played by water of crystallisation since activation under the same conditions of a mixture containing anhydrous phosphates does not lead to the formation of HPA salts.V V Molchanov, R A Buyanov A waste-free method for the preparation of a catalyst for L-sorbose acetonation (one of the stages in the synthesis of vitamin C) was developed.89 The catalyst is a mixture of phos- phomolybdic heteropolyacids and provides higher yields of iso- propylidene-L-sorbose than does oleum, which is normally used for this purpose, and precludes harmful acidic wastes.Mechano- chemical activation is also used for the regeneration of the catalyst after isolation of the target product.89 The application ofMCAfor the synthesis of nickel catalysts of decomposition of hydrocarbons proved to be rather effective. The reaction proceeds with the elimination of hydrogen and formation of filamentous carbon which is a material possessing specific, and in a number of cases, unique, physicochemical properties. Cata- lysts for these reactions are traditionally obtained by co-precip- itation from solutions of nickel, copper and aluminium salts. MCA of nickel oxide or its mixtures with other oxides together with compounds of lamellar structure (magnesium and alumi- nium hydroxides, graphite) produces more efficient catalysts of decomposition of hydrocarbons than those obtained by co- precipitation.91 ± 93 They operate for a long time without loosing their activities, which provides higher degrees of transformation, e.g., of methane.This makes cost-effective the production of hydrogen from hydrocarbons. The carbonaceous material formed can be used as a sorbent, a support for catalysts and as a catalyst. Besides synthetic purposes, MCA is also used for improving certain operational characteristics of catalysts and supports. Thus treatment of a suspension of zeolite in a bead mill in the presence of surfactants made it possible to increase its strength.94 Treat- ment of aluminium hydroxide in a vibratory mill facilitates its moulding and enhances the strength of granules of the final product.63 As noted above, analogous results were obtained upon treatment of iron ± chromium 26 and aluminium ± zinc 28 catalysts, catalyst of vapour conversion of CO,29 aluminium, zinc, copper and cobalt oxides.34, 35, 41 ± 45 The reasons for the increase in the strength of a phosphate catalyst of dehydrogen- ation resulting from the application of MCA were considered by Molchanov and Goidin.In the non-activated catalyst processes of baking, phase transition and recrystallisation of calcium phos- phate occur 95 at virtually the same temperature. The last two processes induce mechanical stresses in the catalyst pellets which decrease their strength. Prior MCA reduces the phase transition temperature by 300 ± 350 K and favours the completion of recrys- tallisation before the beginning of baking, which enhances sub- stantially the strength of pellets.Modification can also occur as a result of changes in sorption properties of a specimen due to grafting of various groups, formation of fresh surface and outcrops of defects to the surface. Mechanochemical grafting is used for the preparation of fillers for rubbers and plastics (see, e.g., Ref. 96). We failed to find in the literature any examples of this kind of modification of surfaces of catalysts, supports or sorbents, though, in our opinion, this method is promising. However, the effect of formation of fresh surface upon MCA is used for the preparation of catalysts.25 ± 30 The influence of defects in the crystal structure on properties of the surface was also revealed.97, 98 Mechanochemical activation of a number of oxide supports leads not only to the increase in their sorption capacity but also to a substantial decrease in the temper- ature of reduction of supported salts to metals and also to a higher catalytic activity of supported nickel in the ethylene hydrogena- tion.Data on the use of MCA for the preparation of catalysts are presented in Table 1. We made an attempt to generalise the regularities of mecha- nochemical synthesis, i.e., the interaction of compounds directly in the mill without any additional treatment. The mechanochem- ical synthesis occurs in the cases where the reagents have similar crystal structures; in the acid ± base interaction, where one of the reagents is a strong acid or base (such a process is considered in sufficient detail by Avvakumov 85); in the formation of pseudo- melts where an intense mechanical stirring can increase theMechanochemistry of catalysts Table 1.Application of MCA for the preparation of catalysts. Initial products a-TiCl3, g-TiCl3 TiCl3+AlCl3+R3Al TiCl3+AlCl3 TiCl4+MgCl2 a-Fe2O3 or a-Al2O3+H2CrO4, Fe2O3+H2CrO4 ZnO+H2CrO4 Al2O3+Zn2+ in ACS H2CrO4+Al(OH)3+ZnO+ +CuCO3 . Cu(OH)2 MgO+Cu2+ in ACS CuAl2O4+ethanol or acetone solution a-Al2O3 ZnO+CMC (or PVA or PEG) ZnO+Al2O3 in ACS ZnO CoO+CuO CuO, Co3O4 La2O3+Co3O4, La2(CO3)3+CoCO3 . Co(OH)2 of flue gases) La2O3+Mn2O3 (or MnO2 or Mn3O4) Al ±Ni (alloy) Ni+Al Ni+Al+M(M=V, Cr, Mn, Fe, Co, Mo, W) Ra/Ni (used)+Al Mg+Ni (or Fe or Co) M2CO3+Fe2O3 (M=K, Rb, Cs) Aluminium hydroxides Aluminium hydroxides+SiO2 MoO3 or its mixture with V2O5 NiO+Al(OH)3 or CuO+Mg(OH)2 Ca ±Cr ± Ni-phosphate catalyst IM-2204 ZnO, TiO2, Al2O3, ZnAl2O4 Note.Abbreviations: ACS, ammonium-carbonate solution; CMC, carboxymethylcellulose; PVA, poly(vinyl alcohol); PEG, poly(ethylene glycol); Ra/Ni, Raney nickel; BM, ball mill; BdM, bead mill; UD, ultrasonic disintegrator; VM, vibratory mill; PM, planetary mill; DS, disintegrator. mobilities of molecules of at least one of the reagents to the level of their mobilities in a melt. But even if no reactions occur in the mill, MCA all the same facilitates substantially other stages of the catalyst's preparation.This is determined by changes in the thermodynamic potentials due to the formation of defects, changes in electronic properties, appearance of fresh surface, etc. The most substantial effect is Final product obtained or the result Apparatus Additional effects for MCA BM d-TiCl3 "" d-TiCl3 solid solution with d-TiCl3 structure "BdM fixation of TiCl4 on the MgCl2 surface catalysts of vapour conversion of CO 7 catalyst of methanol synthesis sorption of Zn2+, formation of ZnAl2O4 catalyst of vapour conversion of CO BdM 77 the same improved quality of binding agent 7BM, VM possibility of moulding by extrusion sulfur adsorbent the same USD 7VM, PM "catalyst of after-burning improved capacity for moulding by extrusion LaCoO3 (catalyst of after-burning LaMnO3 (catalyst of after-burning of flue gases) Ra/Ni the same PM ""VM PM alloys, precursors of Ra/Ni modified Raney nickel " Ra/Ni " alloys, precursors of intermetallic hydrides "DS catalyst of ethylbenzene dehydrogenation PM """ various crystalline modifications of Al2O3 formation of hydroxyaluminates through intercalation of Mg and Zn salts aluminosilicates, zeolites heteropolyacids catalysts of decomposition of hydrocarbons to C and H2 regulation of the processes of crystallisation and baking changes in sorption properties """ observed for high degrees of homogenisation of mixtures of reagents, which facilitates appreciably mutual diffusion.The interaction of components in the MCA is determined by different properties of solids, such as chemical compositions and reactivities, hardness and fragility, crystal structure and bond strength, melting temperatures and others. For this reason, there is no integral theory or any versatile reference points so far which 439 Ref. 13, 14 18 19 ± 21 increased activity in the propylene polymerisation 7increased activity in the ethylene polymerisation the same increased activity, enhanced strength 22 ± 24 25, 26 27 28 increased activity increased strength of the catalyst for desulfurisation increased activity 29 30 31 the same Enhanced strength 32 33, 37 34, 35 36 38, 39 7improved capability for moulding, increased sulfur capacity enhanced strength, increased sulfur capacity the same increased activity in CO oxidation, resistance to poisoning with SO2 increased CuO activity in butane oxidation 41 ± 43 44 7 45 7 46 increased activity in cyclohexene hydrogenation PriOH dehydrogenation increased activity in hydrogenation reaction 47 ± 50 51 the same 52 55 ± 57 "high selectivity of hydrogenation of dienes and acetylenes to alkenes Increased activity, enhanced strength 58 ± 60 64 ± 75 76 ± 78 77 73, 81 ± 85 86 ± 89 91 ± 93 total absence of waste high activity and stability 95 enhanced strengthd 97, 98 decrease of the temperature of reduction of deposited salts, increased activity of supported metals440 would make it possible to predict the result of joint MCA of at least binary systems.So far one can be satisfied solely with some specific speculations. In our opinion, a kind of activated state arises in the MCA of mixtures of compounds. Relaxation after discontinuing of load results either in the formation of new compounds or in the return to the initial compounds which are however characterised by higher dispersion and excess energy. Naturally, the former is only possible in the absence of thermodynamic restrictions for the reaction of components. But even if the formation of new compounds is possible in principle, one cannot be sure that this possibility is realised under the MCA conditions.A substantial importance has the transition of at least one of the compounds subjected to activation to the viscous-fluid state. Here, it is possible to draw an analogy with the processes of adhesion of liquids or melts or mixing of liquids where several interacting components pass to the viscous-fluid state. In this state, the number and area of contacts between reagents increase substan- tially, and in the case of chemical affinity, interaction between them becomes possible. If we continue to draw an analogy with the processes of adhesion, then the phase passing to the viscous-fluid state should be called adhesive, while the other phases should be termed substrates.Correct methods for the calculation or deter- mination of thermodynamic potentials in the adhesion or mixing of melts could also be used for predicting the possibility of the occurrence of mechanochemical synthesis. In particular, one can use the known expressions for the adhesion and cohesion works (Wad andWc , respectively), i.e., the energies that should be spent for the separation of the adhesive and substrate over the interface or for the separation of components of the adhesive to an infinite distance. Wad=g(1+cos y), Wk=2g , where g is the surface energy of adhesive (in our case, for the phase which passed to the viscous-fluid state), y is the angle of wetting. In the mechanochemical synthesis, the following processes presumably take place successively. First, one or several compo- nents pass to the viscous-fluid state.As this process is not momentary, grinding and activation of other components occur simultaneously. After formation of the viscous-fluid phase its adhesion on the surface of other components occurs. If Wad>Wc , total wetting takes place. This condition is always fulfilled in the case of formation of chemical bonds between the adhesive and substrate. As a rule, the adhesion forces are stronger than the cohesion forces, i.e., than the forces of intermolecular attachment in the viscous-fluid phase. Because of this, relaxation of stresses in repeated loading of substrate ± adhesive particles is manifested in the cleavage of bonds inside the viscous-fluid phase rather than in the separation over the interface.The separated part of the adhesive wets the free surface of the substrate which is formed as a result of grinding. Mechanical loading of the substrate phase with the fixed adhesive should lead to phenomena analo- gous to the effect of adsorption-induced dispersion since the surface energy of the interface (an analogue of the surface tension for solids) tends to a minimum upon complete wetting. Intensifi- cation of the dispersion processes leads to an increase in the surface of wetting. Atoms and molecules belonging to the inter- face possess high mobilities due to both the viscous-fluid state and the external mechanical impact. This favours an increase in the rates of mutual diffusion.All the above-mentioned factors result in the formation in MCA of lamellar structures either at the molecular level, as in the system V2O5 ±MoO3, or at the micro- level, as in the mechanical alloying of metals 99 or upon applica- tion of metals onto solid supports by means of MCA of their mixtures 100, 101 (see below). If complete wetting does not occur, i.e., none of the interacting phases passes to the viscous-fluid state, the phases undergone activation are dispersed and their particles several nanometres in V V Molchanov, R A Buyanov size prove to be homogeneously mixed, which facilitates substan- tially the diffusive transfer which is necessary for the interaction of components during subsequent treatments of activated mixtures.Owing to the changes in thermodynamic potentials, the reactiv- ities of components increase in both cases. Thus,MCAcan successfully be used for the direct synthesis of catalytic systems, for facilitating the interaction of components during further treatments (calcination, hydration, sorption, etc.) and for the improvement of performances of the products obtained (their mouldability, strength, sorption and catalytic properties). The most important advantage of the mechanochem- ical methods is the possibility to develop wasteless technologies of the production of catalysts based on them. The importance of the development of wasteless methods is determined by the fact that at present the world production of catalysts is estimated at hundreds of thousands of tons.A considerable part of catalysts is obtained using precipitation methods, which are accompanied by large volumes of wastes. Over half the elements of the Periodic system, including highly toxic ones, are used in the production of catalysts and supports. It may be said without exaggeration that the preparation of catalysts, supports for them and adsorbents are environmentally most deleterious industries. The application of wasteless methods can not only improve the environmental situation in areas of production of catalysts but also decrease their cost owing to lower expenses for neutralisation of wastes. Examples of successful replacement of precipitation methods by wasteless methods based on the use ofMCAare the preparation of supports and catalysts based of alumina 64 ± 84 and the synthesis of catalysts of decomposition of hydrocarbons.91 ± 93 The use of wasteless methods of HPA synthesis is environmentally friendly.86 ± 89 Yet another advantage of mechanochemical methods is the decrease in energy consumption.This is achieved owing to the reduction of temperature and time of interaction of components. Thus the preparation of aluminides of several metals, which are precursors of skeletal catalysts, by pyrometallurgical methods requires heating to melting temperatures and in some cases multi- ple alternations of fusion and grinding are needed. Alloying under theMCAconditions is completed within a few minutes, and in this case the possibilities of variation of the composition of alloys are substantially extended.47 ± 53 The same advantages are realised in the preparation of hydrides of intermetallic compounds from `mechanical alloys'.54 ± 57 Heteropolyacids are formed by reactions of metal oxides with phosphoric acid at its boiling temperature (*373 K) for several hours, whereas the application of MCA makes it possible to decrease the temperature to 323 ± 343 K and the reaction time to a few minutes (some HPA can be prepared at room temperature within a few seconds).86 ± 89 There are numer- ous other examples of a substantial decrease in the temperatures of interaction of components and phase transitions. The reduction of energy consumption improves indirectly the environmental sit- uation since energy production is one of the most deleterious for the environment.With the use of MCA novel catalysts have been synthesised, including those never isolated earlier in the form of individual chemical compounds. Often such systems possessing unique catalytic and chemical properties cannot be synthesised by other methods. This is exemplified in the preparation of alumina p-Al2O3 69, 70 and Raney nickel with the structure of the type NiAl,53 as well as in the synthesis of hitherto unknown hydrides of magnesium intermetallides 99 and new compounds in the system V2O5 ±MoO3.90 The application of new catalytic systems pre- pared using MCA makes it possible to increase the efficiency of catalytic processes, which is often difficult or impossible to achieve by conventional methods.Broad possibilities are opened by the use of MCA for the regulation of processes which occur in the course of formation of catalytic systems (crystallisation, baking, phase transitions, etc.). The temperatures of all these processes and their rates can be varied with the aid of MCA. This makes it possible to govern theMechanochemistry of catalysts strength, parameters of a porous structure and the specific surface area of catalysts. Mechanochemical modification of catalysts and supports is not described in sufficient detail in the literature. It is, however, clear that MCA increases the strength of specimens, improves their mouldability and regulates sorption properties. It should be noted that structures formed upon mechanochemical synthesis are non-equilibrium and possess increased reactivities, including those in the target reactions. This phenomenon will be considered in more detail below.However, a broad range of issues has not been duly described as yet. Thus the possibilities of the use of short-living active sites for the modification of catalytic and sorption systems were not virtually studied. Few studies were devoted to the methods of mechanochemical grafting of various functional groups onto the surface of solids to be used in processes of sorption and catalysis. Potential possibilities of the methods of mechanochemistry are tremendous, as regards the search for novel catalytic systems hitherto unknown as chemical compounds. The list of similar topics could be continued but even those cited above are sufficient for becoming aware of the advisability of intensification of studies in this field.III. Effect of mechanochemical activation on catalytic properties of compounds 1. Metal catalysts Apparently, the effect of mechanical impact on catalytic proper- ties of compounds was first revealed by Eckell 102 who has compared the activity of nickel foil in the ethylene hydrogenation before and after rolling. The rolling led to a substantial increase in the nickel activity which decreased after annealing the foil at 473 ± 573 K. Analogous results were obtained in studies of formic acid decomposition.103, 104 Correlation of the catalytic activities of the specimens studied 102, 103 with the physical properties of mechanically treated metals made it possible to suggest that the catalytically active centres are dislocations.105 This suggestion was confirmed later in numerous examples by Japanese investigators.It was shown 106 ± 112 that cold treatment of metals (twisting, rolling, moulding) increased the catalytic activity of copper, nickel, silver, gold and platinum in decomposition reactions of diazonium chloride, formic acid and hydrogen peroxide, dehy- drogenation of ethanol, hydrogenation of cinnamic acid, oxida- tion of ethanol and ortho ± para conversion of hydrogen. It was concluded that both dislocations and point defects are responsible for the increase in catalytic activity.Thermal annealing led in all cases to a decrease in activity to the level of activity of untreated metals; and properties of catalysts such as hardness, electro- conductivity and thermo-EMF changed simultaneously. Many investigators 106 ± 112 relate this to the disappearance of defects. The reasons for the increase in the catalytic activity of metals resulting from mechanical impact were elucidated in more detail in studies of the effect of treatment of nickel and cobalt powders in ball and vibratory mills on their activities in the hydrogenation of benzene and fats. An extreme dependence of cobalt activity on the time of treatment was revealed and the transition of the cubic form of metal to the hexagonal one was established.113, 114 Examination of a cobalt powder subjected to treatment in mills with subsequent heating, using a set of physicochemical methods, showed that the increase in the catalytic activity of the metal in benzene hydro- genation is determined by the presence of defects and a distorted crystal lattice, as well as by the density of defects.115 ± 118 Deacti- vation of catalysts upon heating was associated with dislocation and annihilation of vacancies.118 A nickel powder treated in a ball mill increased its activity in the hydrogenation of benzene,113, 119 phenol and higher alco- hols 120 and fats.121 Correlation of the nickel activity in the above-mentioned reactions with changes in its physicochemical properties suggests that the increase in activity is to a larger extent associated with disordering of the crystal lattice than to the 441 surface area increase.120, 121 In their completing study, the authors attempted to relate changes in the catalytic properties of mechan- ically activated nickel to changes in its crystal structure.122 Specific rate constants of hydrogenation of fats and ortho ± para conver- sion of hydrogen were found to be linearly dependent on the number of distortions of the crystal lattice and the density and energy of dislocations.The activation energy of reactions was inversely proportional to the energy of dislocations.122 The data obtained would seem to provide an unambiguous proof that dislocations in metals are catalytically active centres. However, the method of determination of specific activities of catalysts used by the authors cannot unfortunately be regarded as correct. The rates of reactions were estimated from the degree of conversion referred to a unit surface.But the degree of conversion is an integral (as regards time and concentrations) magnitude and cannot serve as a measure of the catalytic activity. The models used for the determination of the number and density of disloca- tions were far from being perfect. Analogous drawbacks are also inherent in the above-cited studies by Japanese researchers.116 ± 122 Nonetheless, all these publications made a substantial contribu- tion to the understanding of the nature of the effect of mechanical impact on the catalytic activities of metals.2. Oxide catalysts The effect of mechanical treatment on the catalytic properties of oxide systems was revealed for the first time in studies of the catalytic activity of lead oxide in the decomposition of hydrogen peroxide as a function of time of treatment in a ball mill.123 The effect of mechanical treatment on the activity of V2O5, Fe3O4 and Fe2O3 in the oxidation of sulfur dioxide was studied more than two decades later.124, 125 The dependence of the catalytic activity of vanadium oxide on the time of treatment has two maxima,124 while the activities of both iron oxides pass through one max- imum.125 The increase in catalytic activity is presumed to be related to distortions of the crystal lattice rather than to a larger surface area.Mechanical activation of iron oxides was also used in the oxidation and vapour conversion of CO.126, 127 The depend- ences of the Fe2O3 activity on the treatment time has an extremal character in both reactions, whereas the same dependence for Fe3O4 is described by a curve with saturation. Fe3O4 subjected to mechanical treatment is more active than the industrial catalyst of vapour conversion of CO;127 however, no satisfactory explanation of this effect has been given so far. Mechanical treatment of vanadium and iron oxides leads to an increase in their adsorption capacity with respect to sulfur dioxide and hydrogen sulfide;124, 128, 129 the positions of the maxima of the catalytic activities and adsorption capacities virtually coincide on the time dependence curves.An attempt was made to elucidate the reasons for the effect of mechanical activation on the catalytic properties of calcium and copper oxides in the decomposition of N2O and ortho ± para conversion of hydrogen.130 ± 132 There is a quantitative depend- ence between the catalytic activity of calcium oxide in the decom- position of N2O and the concentration of defects in the crystal lattice. This is evidenced by the same degree of decrease, resulting from thermal treatment, of both the catalytic activity and some parameters (determined by the X-ray diffraction method) which characterise the defectiveness of activated samples. The increase in the copper oxide activity is rationalised within the framework of the electronic theory of catalysis.It is presumed that as a result of mechanical treatment the conductivity of n-type passes to the conductivity of p-type, while the activity of the catalyst in the decomposition of N2O is determined by the ease of electron transfer in elementary stages.132 Changes in the catalytic proper- ties of copper oxide in the ortho ± para conversion of hydrogen are related to magnetic properties,131 while no mention is made about electronic properties. Mechanical treatment can not only increase, but also decrease catalytic activity. Examples of this type, though not numerous, are the decrease in the zinc oxide activity in the decomposition of442 hydrogen peroxide and photooxidation of propan-2-ol after treat- ment in a ball mill.133 ± 135 The activity of zinc oxide drops linearly as the degree of disorderliness of the crystal lattice increases.The activation energy of hydrogen peroxide decomposition on mechanically treated zinc oxide decreases with the increase in the number of paramagnetic centres which are edge dislocations.136 The increase in the activity of zinc oxide, treated under analogous conditions, in the decomposition of hydrogen peroxide is related to a distortion of the crystal lattice.137 ± 139 A compara- tive study of the effect of nickel and zinc grinding in a ball mill on the activation energy of hydrogen peroxide decomposition 139 made it possible to conclude that the differences observed are determined by the type of conductivity of these semiconductors possessing the p-type and n-type conductivities, respectively. Changes in catalytic properties occur not only upon treatment in a mill, but also under other types of mechanical impact.Thus the effect of compacting pressure on the properties of a number of catalysts was reported.140 ± 150 The accompanying changes in acidic properties of potassium hydrogensulfate and tungstic acid induce an increase in their activities in the acetylene polymer- isation and propylene hydration, respectively.140 ± 141 The activ- ities of chromium-containing oxide catalysts in the dehydrogenation of alcohols 142 ± 148 and of an aluminium ± cobalt ± molybdenum catalyst in hydrogenolysis of thio- phene 149, 150 show extremal dependences on the compacting pressure.The changes in catalytic activities are rationalised with the use of data on porous structures and variation of the interplanar distances. However, it should be noted that the methods used for the determination of the activity of catalysts in the studies cited are incorrect.140 ± 150 Yet another type of mechanical impact is the treatment of materials with shock waves. The activity of numerous simple and complex oxides as well as their mixtures in the CO oxidation increases after the application of shock waves.151 This is related to the appearance of anionic vacancies and other perturbations of the crystal structure. The increase in the titanium dioxide activity is not associated with the presence of paramagnetic centres Ti3+ and paramagnetic defects.152 It should be noted that upon application of shock waves appreciable admixtures of the reactor construction material are introduced into catalysts, and these admixtures can affect their catalytic properties.151 Therefore, it is not excluded that high activity of titanium dioxide observed by Golden et al.152 is explained by the presence of copper oxide compounds of which the reactor was made.By varying conditions of shock load one can regulate catalytic properties of fluorite;153 not only an increase in the degree of transformation on this catalyst was observed, but also wide-range changes in the ratio of propan-2-ol dehydrogenation and dehydration rates. Activation of supported catalysts is of definite interest.Thus treatment of a mixture of metallic nickel and quartz in a vibratory mill results in coating of quartz with nickel, and this makes it possible to reach a high rate of benzene hydrogenation.100 The increase in catalytic activity is explained by distortions of the crystal lattice of nickel. Schulz et al.101 treated a mixture of nickel ± ruthenium alloy and aluminium oxide in a similar manner. The system obtained was studied in detail by physicochemical methods; however, no data on its catalytic properties were reported. Of some interest is the preparation of alloys with non- equilibrium composition which preserve their thermal stabilities up to 673 ± 773 K. Chromium, vanadium and molybdenum oxides supported on silica gel were also subject to mechanical treatment.154 ± 156 Their catalytic activities in ethylene polymer- isation,154 propylene metathesis 155 and methane oxidation to formaldehyde 156 increased after activation in a vibratory mill in different media.Possible mechanisms of formation of active centres of these catalysts involving radical centres of silica were considered. Though, the authors do not provide any conclusive evidence of these mechanisms. A possible mechanism of the catalytic oxidation of methane is also discussed.156 Of interest is the fact of an increase in the selectivity of formaldehyde formation V V Molchanov, R A Buyanov resulting from a virtually complete suppression of the reactions of deep oxidation of methane on activated catalysts; however, this effect is observed only at low degrees of methane conversion (1% ± 2%).156 Unfortunately, in all studies the activity of depos- ited catalysts was determined without due account for the specific surface of the active component.In a number of cases, indeed, there are no corresponding methods, but they do exist for supported metals. Without knowledge of the specific surface of active component, it is impossible to establish the reason for the effect of mechanical activation on catalytic properties; further- more, there is a risk of reaching conclusions which are opposite to the real situation. Analysis of a large body of available experimental data allows one to avoid mistakes made in some works and to continue studies of the effect of mechanical treatment on catalytic properties of compounds at a more perfect level using modern methods. This concerns primarily the methods for the determination of catalytic activity. In the studies discussed below, the catalytic activity was determined, in our opinion, in the most correct manner, viz., in the gradient-free (with regard to temperature and concentrations) conditions, while the reaction rates were referred to a catalysts unit surface.In addition, a set of modern research methods were used in these studies in order to determine the nature and concentration of defects formed in the MCA. Oxides which are effective catalysts of deep oxidation were the subjects of studies. Activation of copper oxide in a planetary mill even for a few seconds increased 2 ± 5-fold the specific rate of butane oxidation.43, 157 Presumably, the reasons for this are structural perturbations in the subsurface layer and the increase in the surface concentration of Cu+ ions, which are the centres of chemisorption.157 On the contrary, cobalt oxide decreases its activity in the oxidation of butane,158 and this is explained by the removal of excess oxygen in the course of mechanical treatment.A decrease in activity was also observed upon mechanical treatment of iron(III) oxide 159 having a defective structure. It is presumed that the treatment results in the disappearance of surface and subsurface defects with a local spinel symmetry.It was reported159 that specific catalytic activity of a-Fe2O3 depended almost linearly on the concentration of extended defects determined by the method of small-angle X-ray scattering.The graph which we plotted on the basis of these data (Fig. 1) confirms the conclusion made by the authors. Activation of manganese oxides induced a 2 ± 5-fold increase in the specific rate of CO oxidation depending on the chemical composition of the oxide.160 An increase in the activity of Mn2O3 is explained, as for Mn3O4 , by the appearance of extended defects. In this case, an increase in the oxygen content is also observed. The authors relate the appearance of active centres of Mn2O3 to the formation of steps on the faces h120i, whereas the activity of MnO is believed to be associated with the formation of g-Mn2O3 on the surface.Sadykov et al.161 have generalised and analysed the data on the effect of MCA on the defectiveness and reactivity of oxide catalysts of deep oxidation. 10716w/molecule m72 s71 2.0 1.0 0.0 I (rel. units) 200 100 Figure 1. Dependence of the specific rate of CO oxidation on a-Fe2O3 (w) on the integral intensity of small-angle scattering (I ) (according to the data of Ref. 159).Mechanochemistry of catalysts In the MCA of zinc oxide the following three processes occur successively, viz., accumulation of shear defects, relaxation of the structure resulting from grinding and agglomeration of particles formed upon grinding.162 Accumulation of defects is accompa- nied by the increase in the specific activity of the catalyst for the oxidation of CO; upon fissuring or breaking of crystallites over shear defects the activity returns to the preactivation level.163, 164 A catalytic act is supposed to involve oxygen chemisorbed at sites of the exit of shear defects onto the surface.164 Accumulation of defects occurs in a very narrow range of activation times; apparently, it is due to the fact that the effect of activation was not revealed in the above-cited studies.133 ± 136 An unambiguous evidence of the role of defects as the centres responsible for the increase in catalytic activity was obtained in studies of titanium dioxide.Figure 2 shows the linear dependence of the specific rate of CO oxidation on TiO2 on the concentration of planes of crystallographic shear.165 To our knowledge, there are only three studies which revealed experimentally the quantitative dependence of the specific catalytic activity on the concentration of defects.122, 159, 165 Only this dependence may be regarded as a strict proof that defects are the active centres of catalysis.How- Table 2. The effect of MCA on catalytic properties of various compounds. Catalyst Ni Cu Ni Ag Au Pt Co Ni PbO V2O5 Fe2O3, Fe3O4 CuO CaO NiO KHSO4 H2WO4 Cr2O3+CuO or/and ZnO TiO2, ZnO, BaTiO3, NiO, TiO2+WO3, TiO2+Fe2O3 TiO2 CaF2 Ni+SiO2 CrO3+SiO2 MoO3+SiO2 V2O5+SiO2 CuO Co3O4 Fe2O3 MnO2, MnO, Mn3O4, Mn2O3 ZnO TiO2 Reaction hydrogenation of ethylene decomposition of formic acid decomposition of diazonium chloride dehydrogenation of ethanol hydrogenation of cinnamic acid, dehydrogenation of ethanol, decomposition of H2O2, ortho ± para conversion of hydrogen decomposition of formic acid, decomposition of H2O2, dislocations oxidation of ethanol decomposition of H2O2 decomposition of formic acid, hydrogenation of cinnamic acid decomposition of H2O2, hydrogenation of benzene hydrogenation of benzene hydrogenation of phenol and mixtures of higher unsaturated alcohols hydrogenation of fats, ortho ± para conversion of hydrogen dislocations decomposition of H2O2 oxidation of SO2 to SO3 the same oxidation of CO vapour conversion of CO decomposition of N2O, ortho ± para conversion of hydrogen decomposition of N2O decomposition of H2O2 polymerisation of acetaldehyde hydration of propylene dehydrogenation of PriOH oxidation of CO the same dehydrogenation and dehydration of PriOH hydrogenation of benzene polymerisation of ethylene metathesis of propylene oxidation of methane to formaldehyde oxidation of butane the same oxidation of CO the same "" 107 w/mol m72 s71 30 20 10 5 10 10 Figure 2.Dependence of the specific rate ofCOoxidation on TiO2 on the concentration of planes of crystallographic shear (CPCS). ever, Schrader et al.122 used an incorrect method for the determi- nation of specific catalytic activity, and in this case such a conclusion cannot be regarded as correct. The data on the effect of mechanical impact on the activity of catalysts of different nature are presented in Table 2.Active centre 7dislocations the same "vacancies, dislocations the same point defects, dislocations defects and distortions of the structure distortions of the lattice the same 7distortions of the lattice the same 7distortions of the lattice defects of the lattice the same distortions of the lattice new acidic centres new proton centres distortions of the lattice anionic vacancies distortions of the lattice 7distortions of the lattice :SiO.+Crn+ (n<6) :SiO.+Mo4+ 7surface Cu+ ions excess oxygen defects with a local symmetry of spinel extended defects, steps shear defects planes of crystallographic shift 720CPCS/spin g71 443 Ref.102 103 ± 105 106, 107 107 108, 109 110 111 112 113 ± 118 113, 119 120 121, 122 123 124 125 126 127 130, 131 132 137 ± 139 140 141 142 ± 148 151 152 153 100 154 155 156 43, 157, 161 158, 161 159, 161 160, 161 162 ± 164 165444 3. Annihilation of defects as a factor of deactivation of catalysts In the process of operation, catalysts are known to loose gradually their activity and selectivity, to degrade, etc. The reason for deterioration of properties of catalysts, which can also be differ- ently manifested in the use of systems subjected to MCA, were examined in detail.166 The problem of the lifetime of systems with increased reactivities resulting from MCA has an independent significance and is fairly topical.In a number of instances, the mechanism of the disappearance of defects resembles in many respects mutual annihilation of particles and antiparticles. For example, this seems to be the case of the interaction of dislocations with the counter-directed BuÈ r- gers vectors of the same magnitude or the interaction of vacancies with the internodal ion. In virtually all of the studies cited in this section, a decrease in catalytic activity resulting from the disap- pearance of defects was noted. Most often, the annihilation of defects is induced by thermal annealing. This concerns both metal 106 ± 122 and some oxide 123, 130, 138 catalysts. The activity of mechanically activated copper oxide in the butane oxidation decreases when a specimen is stored for a long time and as a result of catalytic reaction.157 In our opinion, this occurs due to processes which are analogous to those taking place in the course of annealing, although the rate of the disappearance of defects is substantially lower due to a decreased temperature.Sometimes, other factors are also found to play a role. Thus the degradation of crystallites of zinc oxide over shear defects leads to relaxation of the crystal structure.162 For iron oxide, a mechanism was proposed for the disappearance of defects due to the shear of layers.159 The recovery of the initial stoichiometry of compounds can be yet another reason for deactivation.For instance, the removal of excess oxygen from cobalt oxide in the process ofMCA leads to a decrease in its activity in the butane oxidation,158 while the disappearance of the planes of crystallographic shear in titanium dioxide in oxidative media makes it less active in the oxidation of CO.165 All these facts altogether gave us ground for supplementing the existing list of reasons for deactivation of catalysts 166 with one more factor, i.e., annihilation of defects of the crystal structure.163, 167 In some cases, mechanical treatment can lead to a complete and irreversible inactivation of catalysts. Thus mechanical treat- ment of zeolite FeZSM-5 destroys its crystal structure and leads to the total loss of activity in the phenol oxidation by dinitrogen oxide.168 For the same reason, aluminium oxide looses its ability for coke formation after mechanical treatment,169 which is a positive factor under the condition of preservation of useful properties by this material, e.g., high sorptional capacity.97 It is commonly assumed that the defects disappear at suffi- ciently low temperatures, so the effect of increase in activity upon MCA cannot be used for practical purposes. However, there are many well known chemical processes which occur at temperatures substantially lower than the temperatures of annealing of defects. For example, skeletal catalysts prepared with the use of mechan- ical melting are effective in the hydrogenation reactions at temper- atures of 373 K and below.The catalysts of deep oxidation preserve their elevated activities acquired upon MCA for at least tens of hours.157 In a number of cases, annealing of defects requires unusually high temperatures.For example, the activity of iron ± potassium catalyst in the dehydrogenation of n-butenes is decreased only upon heating to temperatures above 903 K,61 which is the operation conditions of an industrial reactor. Thus, the increase in the catalytic activity by MCA may be used for practical purposes, too. 4. Effect of mechanochemical activation on the selectivities of catalysts Very few studies have been devoted to the investigation of the effect of MCA on the selectivities of catalysts. Treatment of molybdenum disulfide in a vibratory mill changes its selectivity in the thiophene hydrodesulfuration, the direction of this change V V Molchanov, R A Buyanov being dependent on the composition of the medium in which this treatment is carried out.170 This is attributed to changes in the ratio of crystallographic facets possessing different catalytic properties.Upon grinding in heptane, the ratio of the surfaces of basal and lateral facets of molybdenum disulfide is 72 : 28, whereas upon grinding in air it is 5 : 95. At close degrees of thiophene conversion the ratios of concentrations of butane and butenes formed on these samples reach 0.7 and 3.0, respectively. In addition, the sample with a larger proportion of lateral facets is capable of sorbing a larger amount of hydrogen, chemisorption beginning at substantially lower temperatures.The use of fluorite subjected to MCA increases the selectivity of acetone formation from propan-2-ol.151 Treatment of a suspension of VOHPO4 in ethanol in a planetary mill leads to the increase of the portion of the surface formed by the facets h001i of vanadium hydrogen- phosphate, which are transformed into the facets h100i of vanadyl pyrophosphate upon thermal treatment.171 The elevated content of the latter favours an increase in the selectivity of maleic anhydride formation upon oxidation of n-butane. We observed a decrease in the selectivity of butadiene formation upon dehydro- genation of n-butenes on a mechanically activated iron ± potas- sium catalyst.61 Iron carbide Fe3Csubjected toMCAincreases the selectivity of formation of hydrocarbons Cn , where n52, and decreases the alkene : alkane ratio in the reaction of CO2 hydro- genation. Analogous effects are observed with a carbide catalyst synthesised by mechanochemical interaction of metallic iron with carbon.172 The authors do not discuss the nature of this phenom- enon.In virtually all the cases, changes in selectivity are related to the changes in the nature of the crystallographic facets upon grinding, while the influence of defects is not considered in any of the cited studies. In our opinion, it is necessary to take into account that the selectivity of multiroute reactions is determined by the ratio of several reactions, one of which yields the target product.Each reaction occurs on its own active centres, and by varying their ratio one can regulate selectivity. MCA can be a possible way of regulating the selectivity of catalysts. The increase in the selectivity of formation of target products is favoured by higher activity and a larger number of active centres responsible for the occurrence of major reactions and by a lower activity or a lower concentration of centres on which side reactions take place. By studying the dependence of the yield of various products on structural changes, one can establish the relationship between the occurrence of specific reactions and the presence of the corre- sponding structures, and this will contribute to the development of the theory of prediction of catalytic action.Thus, the relevant, sufficiently numerous literature data point to a substantial influence of mechanical impact on the activities and selectivities of catalysts. Despite the long-standing opinion that it is impossible to use this effect for practical purposes because of the metastability of defects, some studies revealed high thermal stability of active states resulting from MCA and a substantial increase in the activities of catalysts of a number of industrially important low-temperature reactions. This is promising for the development of industrial technologies for increasing the activities of catalysts by MCA. The reasons for the effect of MCA on the catalytic properties of compounds cannot nowadays be regarded as elucidated.The overwhelming majority of studies only state the facts of changes in catalytic properties resulting from mechanical impacts. The cata- lytically active centres are usually denoted with general terms, viz., defects, distortions of the crystal lattice, etc., without definition of their structures. Sometimes, changes in the activity (as a rule, its increase) are attributed to the appearance of specifie defects: dislocations in the structure of various metals,105 ± 112, 122 planes of crystallographic shear in the lattice of titanium dioxide,165 steps on the facets h120i of Mn2O3,160 dislocations with the known BuÈ rgers vectors in some oxides.161 We know only three stud- ies 122, 159, 165 which provided direct experimental evidence of the participation of defects of definite type in the increase in theMechanochemistry of catalysts catalytic activity.The results of these studies allow description of the structure of active centres at the atomic level. In our view, the best successes in the investigation of the influence of defects on the activity of catalysts were achieved in the study of N2O decom- position on copper oxide (the electronic theory of catalysis 132 was used for its description) and in the investigation of the nature of the chemisorbed or surface oxygen involved in elementary cata- lytic acts.157 ± 161, 164 IV. The role of defects as active centres for chemical processes Analysis of the literature data shows that compounds subjected to MCA exhibit increased reactivities in various chemical processes, viz., simple chemical transformations, sorption processes and catalytic reactions.This indicates that defects are the active centres of all above-mentioned transformations. Let us consider a few examples of the versatile character of MCA action. Thus MCA of iron oxides increases both their catalytic activities in the CO oxidation and vapour conversion of CO125 ± 127 and the sorption capacity with respect to hydrogen sulfide.128, 129 Mecha- nochemical activation of vanadium(V) oxide induces symbatic modification of its sorption capacities with respect to sulfur dioxide and its activity in the SO2 oxidation to SO3.124 In addition, vanadium oxide manifests an increased activity in the reactions with hydrogen peroxide and alkalis after MCA.173 Zinc and titanium oxides the structure of which contains shear defects, exhibit an increased activity in the CO oxidation 162 ± 165 and at the same time increased sorption capacities with respect to nickel and copper salts.97, 98 In addition, MCA increases the sorption capacity of zinc oxide with respect to hydrogen sulfide,36 while titanium dioxide becomes more reactive in reactions involving oxygen 165 and sulfuric acid.3 The increase in reactivity is manifested also in a lower temperature of reduction, by hydrogen, of nickel chloride deposited on oxide supports subjected to MCA.97, 98 After activation of zinc ferrite with the structure of spinel, the rate of its dissolution in hydrochloric acid is substan- tially increased 174 together with the sorption capacity of zinc ferrite with respect to hydrogen sulfide.175 In this state, zinc ferrite exhibits higher catalytic activity in the oxidation of CO.Thus, if the sites of the exit of defects on the surface are catalytically active centres, they play simultaneously the role of sorption centres for salts from solutions and chemisorption of various gases, as well as of the reaction centres where simple chemical reactions take place. This refers not only to those defects which result from MCA but also to other defects. Thus the appearance of planes of twinning in the particles of metallic nickel in the formation of filamentous carbon leads to the increase in the specific rate of butadiene hydrogenation.176 The reactivity of such nickel in the reaction with molecular bromine is also increased.As a result of interaction of silver supported on corundum with the reaction medium, one observes formation of interblock bounda- ries. These defects are the active centres of ethylene oxidation to ethylene oxide.177 In the above-mentioned systems the character of oxygen chemisorption on silver and of hydrogen on nickel is changed.178 Among uranium nitrides used as catalysts in the synthesis of ammonia, the maximum activity is characteristic of the sample with compositionUN1.7 with an ordered structure, i.e., it has defects in the crystal structure of a definite type.179 This nitride is also distinguished by a special character of chemisorp- tion of nitrogen and a higher reactivity in the reaction with hydrogen.These data show that the mechanically induced defects of the crystal structure exhibit higher activity in the three chemical processes differing in their nature and mechanisms: simple chem- ical transformations, sorption and catalysis (Table 3). The increase in the sorption capacity of different oxides with respect to gases and the concomitant increase in their catalytic activities in the CO oxidation with formation of the same active centres is well explicable since chemisorption is an elementary 445 Table 3. Chemical processes depending on defects in the catalyst's structure. Chemical transformation Sorption Catalyst Catalytic reaction oxidation of CO oxidation ± reduction ZnO O2, H2Se, Ni2+ the same Ni2+ TiO2 Ni2+, H2S " oxidation, dissolution in acids ZnAl2O4, leaching ZnFe2O4 Fe2O3 dissolution in acids H2S " stage of a catalytic reaction.But the fact that the increase in the activities of oxides in chemical reactions and stronger sorption of ions from solutions on them correlates with these two effects is surprising. Taking into account the versatility of active centres, one may suggest that the increase in chemical activity is explained not by changes in the mechanism of processes, but has a more common origin. It is changes in the thermodynamic potentials of compounds as a result of MCA that can be such a reason. V. Catalytic reactions under conditions of mechanochemical activation Scarce data on catalytic reactions occurring under MCA con- ditions may be divided into two groups: some of them are regarded as pseudocatalytic (the term proposed by P Yu Butyagin) and all other as really catalytic reactions.The so-called pseudocatalytic reactions represent a recurrent sequence of simple chemical trans- formations of reagents involving a solid. Each of these trans- formations may be regarded as an analogue of an elementary act in the stepwise mechanism of a catalytic reaction. Their motive forces are continuous induction of active centres as a result of mechanical impacts. For the reaction to continue after the interaction of reagents with the centre, the latter should be regenerated due to the supply of mechanical energy.In contrast to this, in the catalytic reactions the active centres are regenerated in subsequent elementary acts as a result of chemical trans- formations. Oxidation of carbon, hydrogen and CO under the conditions of mechanical activation of quartz 180 ± 182 represents examples of pseudocatalytic reactions. The mechanism of CO oxidation was described by Butyagin.5 Apparently reactions of polymerisation occurring upon mechanical activation of various materials in the medium of the corresponding monomers belong to the same type.183 ± 185 Radical or charged centres of freshly formed surface act as initiators of the growth of polymeric chains. The truly catalytic reactions include, e.g., the synthesis of ammonia which takes place upon treatment of the catalyst with carborundum particles 186 in a jet mill 186 and in a ball mill,187 hydrogenation of benzene on nickel in a vibratory mill,188 ± 190 and of ethylene on iron,190 and oxidation of SO2 on vanadium(V) oxide.124 All the above-listed reactions, except for the last men- tioned one, proceed with high conversion degrees at room temper- ature.To accelerate the reactions of hydrogenation, solids possessing high hardness, e.g. corundum, were introduced into the reaction volume; these reactions can proceed even in the presence of catalytic poisons (thiophene).188 The activation energy of sulfur dioxide oxidation in the temperature range 623 ± 773 K under conditions of MCA was 5 kcal mol71, this energy being much lower than that in the conventional catalysis (32 ± 34 kcal mol71).Methanation of CO2 on metal catalysts under mechanical activation is also carried out at elevated temper- atures.191 Catalytic hydrogenation of CO to methane on the inert alloy Zr0.5Ni0.5 saturated with hydrogen is believed to follow two pathways.192 One of them includes the stage of dissociative chemisorption of CO with the liberation of elementary carbon and its subsequent hydrogenation; this is confirmed by studies of individual stages of the process under the MCA conditions. The446 occurrence of the reaction through the second pathway is presum- ably associated with the generation of short-living active states on the catalyst surface. We undertook systematic studies of catalytic reactions under theMCAconditions.This refers to many reactions: CO oxidation on oxides and metals, synthesis of ammonia on the industrial catalyst CA-1B, pyrolysis of butane on magnesium oxide, hydro- genolysis of butadiene on hydrides of magnesium inermetallides, synthesis of boric acid esters with the use of spherical granules of zeolites as catalysts, grinding bodies and absorbents of water formed in the reaction, as well as numerous reactions of hydro- genation and reduction of functional groups.163, 193 These reac- tions do not occur in the absence of catalysts, while the composition of the catalysts themselves is not changed in the course of the process. This indicates that they are indeed the accelerators of the process rather than mere reagents. The reactions of hydrogenation and reduction of solid organic compounds have been studied in sufficient detail.The most efficient catalysts of such processes proved to be hydrides of intermetallic compounds. The mechanochemical reactions of catalytic hydrogenation or reduction involve only the terminal unsaturated bonds and functional groups; no reactions take place when these bonds and groups occupy internal positions. By varying conditions of mechanical activation, one can regulate the selectivity of reactions which has been clearly exemplified in transformations of caryophyllene a-oxide.163 Apparently, in many cases, the mechanisms of reactions differ under the MCA conditions from those in traditional catalysis.Thus in the hydro- genation of butadiene under usual conditions on the hydride Mg2FeH6 the selectivity of formation of butenes is close to 100%,56 whereas under the MCA conditions complete hydro- genolysis occurs on this catalyst.193 How can MCAaffect the course of catalytic reactions? One of the most important advantages of catalysis is the possibility of an easier overcoming the reaction activation barrier or, more pre- cisely, its elementary act. This is as a rule achieved by supplying the catalyst and reagents with external energy, most often in the form of heat. The energy can also be supplied by sonication (sonoca- talysis) or as electromagnetic radiation (radiation-induced catal- ysis or photocatalysis depending on the radiation wavelength).We took the liberty of introducing a new term `mechanochem- ical catalysis', i.e., the catalysis in which the energy is supplied by mechanical impact on catalysts and reagents. As a result of such impact, not only the activities of catalysts are increased, but also the chemical reactivities of solid reagents and, besides, the regularities of activation of catalysts are changed. Since any measurements inside the working chambers of mills are not technically feasible, it may only be suggested what kind of processes occur during mechanical activation. The simplest way is to suppose that the energy is supplied by means of transformation of the mechanical energy to thermal energy, after which a catalytic reaction occurs in a usual manner.Indeed, some investigators believe that the temperatures up to 1500 ± 2000 K are developed at the sites of contact of grinding bodies with the compound under activation (the theory of magmaplasma). However, this view is not corroborated by valid experimental evidence. A conclusion based on calorimetric meas- urements which states that during grinding the temperature reaches 650 ± 900 Kseems to be better substantiated. Nonetheless, in this case, too, it is difficult to explain why at these temperatures either ammonium nitrate (published data) or some organic com- pounds (own results) virtually do not decompose. Apparently, introduction of compounds which can be readily activated changes the friction coefficients, while the temperatures in the working chambers are substantially lower under conditions of mechanochemical catalysis than those mentioned above.Hence, the transformation of the mechanical energy to thermal energy can explain only some of experimental data. V V Molchanov, R A Buyanov We believe that the most probable way of activation of reagents is the transfer of excess energy concentrated in the short-living centres formed in the course of cleavage of the catalyst's crystallites. Such centres have, as a rule, a radical nature, and the thermodynamic requirement for the reduction of their energy is fulfilled at the expense of bonding. The reactants situated in the immediate proximity of such a centre react with the unsaturated bond and pass to the activated state.In this case, the vibratory and electronic levels are excited, electronic levels appear in the forbidden bands (especially when defects of the crystal lattice are available), and the forbidden band becomes narrower. It is these processes that are the result of energy redistribution according to the scheme: mechanical energy? excess energy of the catalyst?excess energy of a reactant. In contrast to other types of catalysis, the mechanochemical catalysis induces continuous formation of defects, their migration, interaction and annihilation. It is known that compounds are sorbed predominantly on sites of the exit of defects onto the surface and migrate together with these defects. Even dislocations of molecules into the bulk of solids were detected.Migration of point defects and dislocations is described in sufficient detail in the literature, but there is little information about the migration of planar defects. The planar defects are formed upon shear and turn the layers of cations and anions relative to each other. Apparently, recovery of the normal packing in some places and formation of shear defects in others occur in the MCA. In this situation, the places of exit of such defects migrate over the surface of crystal- lites. Interaction and annihilation of defects result in release of energy, and since the reactants are localised basically on defects, a part of the released energy is most probably spent in the activation of reactants. We believe that the three modes of energy transfer mentioned above are the most probable since they are indirectly confirmed experimentally.One should not however rule out other ways of energy transfer to reactants. For example, the acceptor com- pounds may be activated by capturing the so-called mechanoelec- trons. Several reports discuss the problem of participation of high- frequency phonons in the activation processes. Upon mechanical activation of solids, different types of electromagnetic radiation arise which can also induce activation of reactants in the mode similar to that of the radiation-induced catalysis or photocatal- ysis. Concomitant realisation of several described channels of energy redistribution is not precluded either. VI. The nature of the effect of mechanochemical activation on the reactivity of solids Using theoretical concepts, it is possible to predict to some extent, and in a number of cases to make approximate quantitative estimates of the effect of MCA on the properties of catalysts and catalytic reactions.Changes in the thermodynamic potentials of catalysts should induce changes in the equilibrium constants of formation of intermediate products, e.g., chemisorbed com- pounds, towards their higher concentrations. With correct data on the values of thermodynamic potentials, it is possible to establish how changes in the catalyst's state influence its activity. To this end, use is made of the known expressions which relate the rate of a catalytic reaction to thermodynamic parameters. Such an approach is described, for example, by Boreskov.194 At the qualitative level, one may say that the shift of equilibrium towards higher concentration of intermediates should lead to an increased reaction rate.It is obvious that both the magnitude of activity and its increment due to MCA have definite limits which are deter- mined by the chemical nature of the compound subject to activation. The maximum of stored excess energy is determined by the type of crystal structure of a compound and by the nature of defects arising during MCA. In addition, if the appearance of defects results in changes in the heat of chemisorption of theMechanochemistry of catalysts reactants, the activation energy of reaction (E) is also changed in conformity with the equation of Brùnsted and Polanyi: E=E0aq , where the activation energy E0 and the coefficient a depend on the type of reaction and q is the heat of chemisorption.This will also affect the rate of catalytic reactions. Upon formation of fresh surfaces by crystal splitting, localised free valences appear, the number of which may be close to the number of surface atoms. The presence of free valences favours the increase in the adsorp- tion and chemical activities of the catalyst with respect to the gas and liquid phases and also solutes. Within the lifetime of such states, which ranges from 1074 to 1077 s (see Ref. 3), all processes of `chemical relaxation' have enough time to occur, including chemical reactions with contacting compounds.4 The appearance of defects leads to changes in the electronic properties of a solid, which will be discussed below, and to changes in the geometry of the surface due to the appearance on it of sites for the exit of extended defects. Changes in the regular structure affect not only the sites of the exit of defects onto the surface themselves but also considerable areas around them.Relevant calculations indicate that at fairly moderate concentrations of dislocations (1011 ± 1012 cm72) the part of distorted structure amounts to 70%± 80% of all the surface.3 For this reason, the defects of the crystal structure will substantially influence the processes of adsorption and hence the catalytic properties of a substance.This influence is realised through the geometric factor, i.e., the geometric correspondence of the structure of reactants to the surface of catalysts. Apparently, the selectivity of multiroute reactions should vary most substantially. The sorption properties of the surface in the places of the exit of the defects of crystal structure should differ from those of the remaining surface, first, because of changes in the surface geometry and, second, due to the fact that such places serve as traps of electrons and possess special electronic properties.195 The effect of defects on the catalytic properties of compounds is apparently also manifested in the variation of the energy of bonding between atoms in the lattice of catalysts which is determined by changes in the interatomic distances in the course of formation of extended defects.For example, the strength of the oxygen bond in oxides is well known to correlate with the catalytic activity of oxides in the reactions of oxidation. It is not excluded that the appearance of defects can result in changes in the nature of the chemisorbed reagents. Thus upon MCA of quartz the activated catalyst generates singlet oxygen; an analogous phenomenon is observed with the reduced and hence defective vanadium oxide.196 This induces changes in the catalytic properties of this oxide in the oxidation reaction of naphthalene to phthalic anhydride. Changes in the electronic properties of catalysts resulting from MCA can have a substantial effect on the redox and other reactions requiring transfer of electrons.We have already noted above that chemisorption is possibly influenced by changes in the surface properties in the places of the exit of defects where electrons are localised. It may also be expected that during the occurrence of both catalytic and ordinary reactions the conduc- tivity electrons and the electrons belonging to anions with enhanced electron-donor properties will be involved in the ele- mentary acts with electron transfer. According to the literature data, the catalytic properties of compounds can be influenced by the peculiarities of transition of electrons from one electronic level to another, work of electron release, position of the Fermi level, width of the forbidden band, availability of electronic levels in it, etc.All these parameters may be influenced by means of MCA. All the changes listed above favour the increase in the reactivities of components in the synthesis of catalysts, modifica- tion of their sorption properties due to the formation of new surface and the appearance of places for the exit of defects onto the surface, as well as changes in the specific catalytic activity. By now, a considerable body of experimental data has been accumulated on the dependence of the catalytic activity on the mechanical impact. 447 However, the authors of the overwhelming majority of works confine themselves either to a trivial statement of such influence or to attempts to explain specific situations that they have observed.Comparison of different viewpoints would possibly allow interpretation of experimental observations, formulation of gen- eral theoretical concepts and creation of the scientific ground for the purposeful control of the processes occurring. Of special interest is the elucidation of the reasons of the effect of MCA on the catalytic activity of compounds and selectivity of reactions of different nature (redox, acidic and other reactions). To this end, physical theory of mechanical impact should be combined with concepts of the chemical nature of the catalytic activity. It is possible that this will not however allow creation of an integral theory, as it is still the case in the heterogeneous catalysis on the whole, but there is a possibility to formulate local theoretical conceptions relevant to individual types of catalysis.The problem of estimation of the specific activity of a catalyst is of crucial importance. The well known Boreskov's rule on the approximately constant specific activities of catalysts of the same chemical compositions 194 may be regarded only as a statement of the chemical nature of a catalytic act which was formulated by Berthelot as far back as 1877: `Owing to a chemical impact of contacting substances, intermediate compounds are formed which in turn are degraded as they emerge and eventually vanish in the final metamorphosis.197 If the catalytic properties of compounds were determined solely by the chemical composition of active centres, then it would be absurd to expect that the same centres could display different activities, and no additional experiments would have been required.The constancy of specific catalytic activity is approximate in the extent to which the total set of properties of the surface of catalysts is reproduced. The actual level of the development of the scientific bases underlying the preparation of catalysts does not allow high reproducibility. However, from the viewpoint of applied science this is not required in most cases. The term `approximate constancy' means that the activity of catalysts is also influenced by other factors which were not denied by Boreskov either (see his monograph,194 p. 47). In his opinion, these factors can induce differences in properties of individual facets of crystals and the non-equilibrium states of the catalyst's surface.But even the catalysts with completely the same chemical, structural and other characteristics would possess an approximate rather than absolute constancy of specific activity. It is the role of additional factors which influences the specific catalytic activity that was the topic of our review. The activity of a catalyst with defects is somewhat higher than its activity in the equilibrium state. The degree of increase in activity depends on the amount of excess energy which is stored in defects and influences the catalytic properties through the variation of thermodynamic potentials. This amount of energy is determined by the physico- chemical nature of the catalytically active sites.The non-equilibrium structural and phase states of catalysts arising in the process of their preparation should be subject to annealing in the course of reaction, and the catalysts should pass to the steady state. However, there are numerous examples of rather high stability of such states of solid catalysts at elevated temperatures in real reaction media. This is explained by the fact that thermal annealing of defects is an activation process, and if the conditions do not permit overcoming of the activation barrier, some metastable structures of higher reactivity may exist for a rather long time. Further studies of the nature of the structural factors and of their role in a chemical act will allow a deeper insight into the detailed mechanism of catalysis.The progress in this field can be achieved using novel MCA techniques and modern physical methods of research. The review was supported by the Russian Foundation for Basic Research (Project No. 00-15-97440).448 References 1. V V Boldyrev Eksperimental'nye Metody v Mekhanokhimii Tverdykh Neorganicheskikh Veshchestv (Experimental Methods in Mechanochemistry of Solid Inorganic Compounds) (Novosibirsk: Nauka, 1983) 2. P Yu Butyagin Usp. Khim. 53 1769 (1984) [Russ. Chem. Rev. 53 1025 (1984)] 3. E G Avvakumov Mekhanokhimicheskie Metody Aktivatsii Khimicheskikh Protsessov (Mechanochemical Methods of Activation of Chemical Processes) (Novosibirsk: Nauka, 1986) 4.G Heinicke Tribochemistry (Berlin: Akademie-Verlag, 1984) 5. P Yu Butyagin Kinet. Katal. 28 5 (1987) a 6. G S Khodakov Fizika Izmel'cheniya (The Physics of Grinding) (Moscow: Nauka, 1972) 7. Yu T Pavlyukhin, Ya Ya Medikov, V V Boldyrev Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (2) 3 (1983) 8. S V Vossel', N T Vasenin, E E Pomoshchnikov, V F Anufrienko, V A Mikhailov Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (17) 102 (1986) 9. E L Gol'dberg, S V Pavlov Sib. Khim. Zh. (4) 147 (1992) 10. S V Pavlov, E L Gol'dberg Sib. Khim. Zh. (1) 126 (1993) 11. E L Gol'dberg, S V Pavlov Sib. Khim. Zh. (1) 131 (1993) 12. V A Radzig, A A Bobyshev, in Catalyse et Environment. Techniques d'Analyses Physico-Chimiques Appliquees a la Catalyse.7 Colloque Franco-Sovietiquee de Catalyse, Strasbourg, 1987 p. 172 13. G Natta, I Pasquon Adv. Catal. 11 2 (1959) 14. G Natta, P Corradini, G Allegra J. Polym. Sci. 51 399 (1961) 15. US P. 3 010 787; Ref. Zh. Khim. 4 L 139 (1963) 16. US P. 3 032 509; Ref. Zh. Khim. 15 T 39 (1963) 17. US P. 3 032 510; Ref. Zh. Khim. 15 T 40 (1963) 18. US P. 3 034 992; Ref. Zh. Khim. 20 L 123 (1963) 19. E G M Tornqvist, J T Richardson, Z W Wilchinsky, R W Looney J. Catal. 8 189 (1967) 20. W R Carradine, H F Rase J. Appl. Polym. Sci. 15 889 (1971) 21. Z W Wilchinsky, R W Looney, E G M Tornqvist J. Catal. 28 351 (1973) 22. N Kashiwa Polym. J. 12 603 (1980) 23. V A Zakharov, D V Perkovets, G D Bukatov, S A Sergeev, E M Moroz, S I Makhtarulin Kinet.Katal. 29 903 (1988) a 24. V A Zakharov, D V Perkovets, G D Bukatov Kinet. Katal. 29 1202 (1988) a 25. Yu G Shirokov, A P Il'in, I P Kirillov Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (7) 45 (1979) 26. USSR P. 1 235 523; Byull. Izobret. (21) 16 (1986) 27. A P Il'in, N N Smirnov, Yu G Shirokov, D V Afanas'v, in Nauchnye Osnovy Prigotovleniya i Tekhnologii Katalizatorov (Tez. Dokl. II Vsesoyuz. Soveshch.), Minsk, 1989 [Scientific Foundations of the Preparation and Technology of Catalysts (Abstracts of Reports of the Second All-Union Meeting), Minsk, 1989] p. 91 28. Yu G Shirokov, A P Il'in, in Nauchnye Osnovy Prigotovleniya Katalizatorov (Tez. Dokl. Vsesoyuz. Soveshch.), Novosibirsk, 1983 [Scientific Foundations of the Preparation of Catalysts (Abstracts of Reports of the All-Union Meeting), Novosibirsk, 1983] p.56 29. Yu G Shirokov Vopr. Kinet. Katal. 3 (1984) 30. N N Smirnov, A P Il'in, E N Novikov, Yu G Shirokov Izv. Vyssh. Ucheb. Zaved., Khim. Khim. Tekhnol. 32 (4) 83 (1989) 31. USSR P. 1 253 661; Byull. Izobret. (32) 46 (1986) 32. A P Il'in, A N Trofimov, Yu G Shirokov, in Nauchnye Osnovy Pri- gotovleniya i Tekhnologii Katalizatorov (Tez. Dokl. II Vsesoyuz. Soveshch.), Minsk, 1989 [Scientific Foundations of the Preparation and Technology of Catalysts (Abstracts of Reports of the Second All-Union Meeting), Minsk, 1989] p. 93 33. Yu G Shirokov, A P Il'in, I P Kirillov, L I Titel'man, O P Khrutskii, O P Akaev Zh. Prikl. Khim. 52 1228 (1979) b 34. A P Il'in, I P Kirillov, Yu G Shirokov Izv.Vyssh. Ucheb. Zaved., Khim. Khim. Tekhnol. 22 246 (1979) 35. V L Gartman, V G Ikonnikov Vopr. Kinet. Katal. 99 (1986) 36. V G Ikonnikov, L I Titel'man, O V Rastegaev, Yu G Shirokov Vopr. Kinet. Katal. 93 (1986) 37. URRS P. 1 301 483; Byull. Izobret. (13) 31 (1987) 38. S A Angelov, R P Bonchev Appl. Catal. 24 219 (1986) 39. S A Angelov, R P Bonchev Dokl. Bolg. Akad. Nauk 40 63 (1987) V V Molchanov, R A Buyanov 40. S A Angelov, R P Bonchev, in Heterogeneous Catalysis (Abstracts of Reports of the 6th International Symposium on Heterogeneous Catalysis), Sofia, 1987 Part 1, p. 394 41. L A Isupova, V Yu Aleksandrov, V V Popovskii, G N Kryukova, in Proceedings of the 2nd Czechoslovakian Conference on Preparation and Properties of Heterogeneous Catalysts (Abstracts of Reports), Bechyne-near-Tabor, 1985 p.74 42. L A Isupova, V V Popovskii, V Yu Aleksandrov, G N Kryukova, E M Moroz, V A Balashov in Kataliticheskaya Ochistka Gazov (Tez. Dokl. 4-i Vsesoyuz. Konf.), Alma-Ata, 1985 [Catalytic Purification of Gases (Abstracts of Reports of the Fourth All-Union Conference), Alma-Ata, 1985] Part 1, p. 91 43. L A Isupova, V Yu Aleksandrov, V V Popovskii, E M Moroz Zh. Prikl. Khim. 61 1976 (1988) b 44. I A Pauli, E G Avvakumov, L A Isupova, V A Poluboyarov, V A Sadykov Sib. Khim. Zh. (3) 133 (1992) 45. L A Isupova, V A Sadykov, L P Solovyova, M P Andrianova, V P Ivanov, G N Kryukova, V N Kolomiichuk, E G Avvakumov, I A Pauli, O V Andryushkova, V A Poluboyarov, A Ya Rozovskii, V F Tretyakov, in Scientific Bases for the Preparation of Heterogeneous Catalysts (Abstracts of Reports of the 6th International Symposium), Louvian-La-Neuve, 1994 Vol.2, p. 231 46. S L Kiperman, A A Balandin, I R Davydova Izv. Akad. Nauk SSSR, Otd. Khim. Nauk 1482 (1957) c 47. V V Boldyrev, G V Golubkova, T F Grigor'eva, E Yu Ivanov, O T Kalinina, S D Mikhailenko, A B Fasman Dokl. Akad. Nauk SSSR 297 1181 (1987) d 48. E Yu Ivanov, T F Grigor'eva, G V Golubkova, V V Boldyrev, A B Fasman, S D Mikhailenko, O T Kalinina Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (19) 80 (1988) 49. A B Fasman, S D Mikhailenko, O T Kalinina, E Yu Ivanov, T F Grigor'eva, V V Boldyrev, G V Golubkova Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (19) 83 (1988) 50.L G Nishchenkova, V P Gostikin, S V Litvinova, in Vysokodispersnye Materialy na Osnove Platinovykh Metallov i Ikh Soedinenii v Katalize i Sovremennoi Tekhnike (Highly Dispersed Materials Based on Platinum Metals and Their Compounds in Catalysis and Modern Technics) (Ivanovo: Ivanovo Chemical Technological Institute, 1991) p. 81 51. L G Nishchenkova, E Yu Ivanov, G V Golubkova, in Vysokodispersnye Materialy na Osnove Platinovykh Metallov i Ikh Soedinenii v Katalize i Sovremennoi Tekhnike (Highly Dispersed Materials Based on Platinum Metals and Their Compounds in Catalysis and Modern Technics) (Ivanovo: Ivanovo Chemical Technological Institute, 1991) p. 76 52. L G Nishchenkova, G V Golubkova, in Vysokodispersnye Materialy na Osnove Platinovykh Metallov i Ikh Soedinenii v Katalize i Sovremennoi Tekhnike (Highly Dispersed Materials Based on Platinum Metals and Their Compounds in Catalysis and Modern Technics) (Ivanovo: Ivanovo Chemical Technological Institute, 1991) p.79 53. G V Golubkova, E Yu Ivanov, T F Grigor'eva Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (3) 60 (1990) 54. E Yu Ivanov, I G Konstanchuk, A A Stepanov, V V Boldyrev Dokl. Akad. Nauk SSSR 286 385 (1986) d 55. V V Molchanov, A A Stepanov, I G Konstanchuk, R A Buyanov, V V Boldyrev, V V Goidin Dokl. Akad. Nauk SSSR 305 1406 (1989) d 56. USSR P. 1 638 865; Byull. Izobret. (31) 226 (1996) 57. USSR P. 1 638 866; Byul. Izobret. (31) 226 (1996) 58. M I Volkov, E G Stepanov, L V Strunnikova, G R Kotel'nikov Vopr.Kinet. Katal. 100 (1986) 59. G R Kotel'nikov, L V Strunnikova, A S Okuneva, E G Stepanov, in Ispol'zovanie Fiziko-Khimicheskikh i Matematicheskikh Metodov v Issledovanii Protsessov Polucheniya Monomerov i Sinteticheskogo Kauchuka (The use of Physicochemical and Mathematical Methods in Investigation of Processes of the Preparation of Monomers and Synthetic Rubber) (Moscow: TsNIITENeftekhim, 1984) p. 26 60. M I Volkov, E G Stepanov, T N Sudzilovskaya, G R Kotel'nikov Vopr. Kinet. Katal. 36 (1984) 61. V V Molchanov Khim. Promst (7) 386 (1992) 62. T Shirasaki, Y Ochiai, K Muranaka Kogyo Kagaku Zasshi 71 1363 (1968); Chem. Abstr. 70 41 115 (1969)Mechanochemistry of catalysts 63. N V Mal'tseva, G M Belotserkovskii Zh.Prikl. Khim. 56 1009 (1983) b 64. S M Paramzin, Yu D Pankrat'ev, E A Paukshtis, O P Krivoruchko, B P Zolotovskii, R A Buyanov Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (11) 33 (1984) 65. S M Paramzin, O P Krivoruchko, B P Zolotovskii, R A Buyanov, V V Malakhov,G N Kryukova,N N Boldyreva Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (17) 39 (1984) 66. B P Zolotovskii, S M Paramzin, O P Krivoruchko, R A Buyanov Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (17) 80 (1987) 67. S M Paramzin, L M Plyasova, O P Krivoruchko, B P Zolotovskii, S V Bogdanov, G N Kryukova, E A Paukshtis, R A Buyanov Izv. Akad. Nauk SSSR, Ser. Khim. 1209 (1988) c 68. S M Paramzin, Yu D Pankrat'ev, V M Turkov, B P Zolotovskii, O P Krivoruchko, R A Buyanov Izv. Sib. Otd.Akad. Nauk, Ser. Khim. Nauk (5) 47 (1988) 69. O P Krivoruchko, V M Mastikhin, B P Zolotovskii, S M Paramzin, D P Klevtsov, R A Buyanov Kinet. Katal. 26 763 (1985) a 70. D P Klevtsov, O P Krivoruchko, V M Mastikhin, R A Buyanov, B P Zolotovskii, S M Paramzin Dokl. Akad. Nauk SSSR 295 381 (1987) d 71. B P Zolotovskii, S M Paramzin, A G Pel'menshchikov, E A Paukshtis, D P Klevtsov, N V Ermolaeva, R A Buyanov, G M Zhidomirov Kinet. Katal. 30 1439 (1989) a 72. S M Paramzin, B P Zolotovskii, O P Krivoruchko, V M Mastikhin, G S Litvak, R A Buyanov, L M Plyasova, D P Klevtsov Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (1) 33 (1989) 73. B P Zolotovskii, R A Buyanov, V A Balashov, O P Krivoruchko, A Ya Bakaev, V E Loiko, A A Samakhov, V I Bashin, in Nauchnye Osnovy Prigotovleniya i Tekhnologii Katalizatorov (Tez.Dokl.), Novosibirsk, 1990 [Scientific Foundations of the Preparation and Technology of Catalysts (Abstracts of Reports), Novosibirsk, 1990] p. 108 74. B P Zolotovskii, S M Paramzin, V I Zaikovskii, R A Buyanov, L M Plyasova, V E Loiko, G S Litvak Kinet. Katal. 31 751 (1990) a 75. S M Paramzin, B P Zolotovskii, V I Zaikovskii, R A Buyanov, V E Loiko, L M Plyasova, G S Litvak, V M Mastikhin Kinet. Katal. 32 234 (1991) a 76. O P Krivoruchko, R A Buyanov, S M Paramzin, B P Zolotovskii Kinet. Katal. 29 252 (1988) a 77. S M Paramzin, B P Zolotovskii, R A Buyanov, L M Plyasova, O N Novgorodova Kinet. Katal. 32 507 (1991) a 78. B P Zolotovskii, R A Buyanov, S M Paramzin, L M Plyasova Kinet.Katal. 32 1248 (1991) a 79. D P Klevtsov, V M Mastikhin, O P Krivoruchko, B P Zolotovskii, R A Buyanov, G N Kryukova, E A Paukshtis Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (9) 62 (1988) 80. D P Klevtsov, O P Krivoruchko, V M Mastikhin, B P Zolotovskii, R A Buyanov Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (2) 75 (1985) 81. D P Klevtsov, O P Krivoruchko, V M Mastikhin, E A Paukshtis, B P Zolotovskii, R A Buyanov Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (9) 70 (1988) 82. D P Klevtsov, B P Zolotovskii, O P Krivoruchko, R A Buyanov Zh. Prikl. Khim. 61 914 (1988) b 83. D P Klevtsov, O P Krivoruchko, V M Mastikhin, B P Zolotovskii, R A Buyanov React. Kinet. Catal. Lett. 36 319 (1988) 84. B P Zolotovskii, D P Klevtsov, S M Paramzin, R A Buyanov, in Mekhanokhimicheskii Sintez v Neorganicheskoi Khimi (Mechanochemical Synthesis in Inorganic Chemistry) (Novosibirsk: Nauka, 1991) p.125 85. E G Avvakumov Khim. Inter. Ustoich. Razvitiya 2 541 (1994) e 86. Russ. P. 2 019 513; Byull. Izobret. (17) 81 (1994) 87. Russ. P. 2 076 070; Byull. Izobret. (9) 151 (1997) 88. Russ. P. 2 076 071; Byull. Izobret. (9) 151 (1997) 89. Russ. P. 2 080 923; Byull. Izobret. (16) 78 (1997) 90. V V Molchanov, L M Plyasova, V V Goidin, O B Lapina, V I Zaikovskii Neorg. Mater. 31 1225 (1995) f 91. V V Chesnokov, V I Zaikovskii, R A Buyanov, V V Molchanov, L M Plyasova Kinet. Katal. 35 146 (1994) a 92. Russ. P. 2 042 425; Byull. Izobret. (24) 118 (1995) 449 93. Russ. P.2 071 932; Byull. Izobret. (2) 162 (1997) 94. B M Pavlikhin, T V Kurchatkina, I A Zelepukhina, O P Greben'kova Neftepererab. Neftekhim. (3) 7 (1986) 95. V V Molchanov, V V Goidin Khim. Promst (12/13) 613 (1993) 96. E V Terlikovskii, V Yu Tretinnik, in Fiziko-Khimicheskaya Mekhanika i Liofil'nost' Dispersnykh Sistem (Physicochemical Mechanics and Lyophilicity of Dispersed Systems) (Kiev: Naukova Dumka, 1988) p. 79 97. R A Buyanov, V V Molchanov Khim. Promst (3) 151 (1996) 98. V V Molchanov, R A Buyanov, V V Goidin Kinet. Katal. 39 465 (1998) a 99. E Yu Ivanov, Doctoral Thesis in Chemical Sciences, Institute of Problems of Materials Technology, Academy of Sciences, Ukr. SSR, Kiev, 1991 100. R Schrader, P Nobst, G Tetzner, D Petzold Z. Anorg.Allg. Chem. 365 255 (1969) 101. R Schulz, A van Neste, P A Zielinski, S Boily, F Czerwinski, J Szpunar, S Kaliaguine Catal. Lett. 35 89 (1995) 102. J Eckell Z. Elecktrochem. Angew. Phys. Chem. 39 433 (1933) 103. G RienaÈ cker Z. Elecktrochem. Angew. Phys. Chem. 46 369 (1940) 104. G RienaÈ cker, J VoÈ lter Z. Anorg. Allg. Chem. 296 210 (1958) 105. L E Cratty, A V Granato J. Chem. Phys. 26 96 (1957) 106. I Uhara, S Yanagimoto, K Tani, G Adachi Nature (London) 192 867 (1961) 107. I Uhara, S Yanagimoto, K Tani, G-Y Adachi, S Teratani J. Phys. Chem. 66 2691 (1962) 108. I Uhara, T Hikino, Y Numata, H Hamada, Y Kageyama J. Phys. Chem. 66 1374 (1962) 109. I Uhara, S Kishimoto, T Hikino, Y Kageyama, H Hamada, Y Numata J. Phys. Chem. 67 996 (1963) 110.I Uhara, S Kishimoto, Y Yoshida, T Hikino J. Phys. Chem. 69 880 (1965) 111. S Kishimoto,M Nishioka J. Phys. Chem. 76 1907 (1972) 112. S Kishimoto J. Phys. Chem. 67 1161 (1963) 113. R Schrader, H Grund, G Tetzner Z. Chem. 3 356 (1963) 114. R Schrader, G Tetzner, H Grund Z. Anorg. Allg. Chem. 342 204 (1966) 115. R Schrader, G Tetzner, H Grund Z. Anorg. Allg. Chem. 342 212 (1966) 116. R Schrader, G Tetzner, H Grund Z. Anorg. Allg. Chem. 343 308 (1966) 117. G Tetzner, R Schrader Z. Anorg. Allg. Chem. 407 227 (1974) 118. G Tetzner, R Schrader Z. Anorg. Allg. Chem. 409 77 (1974) 119. R Schrader, H Grund, G Tetzner Chem. Ing. Techn. 39 806 (1967) 120. R Schrader,W Staedter Acta Chim. Acad. Sci. Hung. 55 39 (1968) 121. R Schrader,W Staedter, H Oettel Chem.Techn. 23 363 (1971) 122. R Schrader,W Staedter, H Oettel Z. Phys. Chem. 249 87 (1972) 123. G L Clark, R Rowan J. Am. Chem. Soc. 63 1302 (1941) 124. R Paudert Chem. Techn. 17 449 (1965) 125. R Paudert Monatsber. Deutschen Akad. Wissenschaft. 9 719 (1967) 126. R Schrader, G Jacob Chem. Techn. 18 414 (1966) 127. R Schrader,W Vogelsberger Z. Anorg. Allg. Chem. 368 187 (1969) 128. R Schrader, G Tetzner Z. Anorg. Allg. Chem. 309 55 (1961) 129. R Schrader, Z Kroll, S Seifert Z. Anorg. Allg. Chem. 336 11 (1965) 130. R Schrader, E Thiem Z. Phys. Chem. 238 41 (1968) 131. R Schrader, B Fritsche Z. Anorg. Allg. Chem. 379 17 (1970) 132. R Schrader, J Deren, B Fritsche, J Ziolkowski Z. Anorg. Allg. Chem. 379 25 (1970) 133.H Takahashi, K Tsutsumi Dechema-Monographien 57 475 (1967); Chem. Abstr. 67 76 995 (1967) 134. H Takahashi, K Tsutsumi J. Chem. Soc. Jpn. 71 1345 (1968) 135. H Takahashi, K Tsutsumi Rep. Inst. Ind. Sci. Univ. Tokyo 20 37 (1970); Ref. Zh. Khim. 9 B 1072 (1971) 136. Y Sadahiro J. Soc. Mater. Sci. Jpn., 29 125 (1980); Ref. Zh. Khim. 15 B 1297 (1980) 137. Y Sadahiro, K Shimidzu Hokkaido Kyoku Daigaku Kiyo, Sect. 2A 18 26 (1967); Chem. Abstr. 70 41 119 (1969) 138. Y Sadahiro, K Shimidzu Zairyo 17 475 (1968); Chem. Abstr. 69 68 540 (1968) 139. Y Sadahiro, K Shimidzu J. Chem. Soc. Jpn. 71 1374 (1968) 140. Y Ogino, T Kawakami, K Tsurumi Bull. Chem. Soc. Jpn. 39 639 (1966) 141. Y Ogino, T Kawakami, T Matsuoka Bull. Chem. Soc. Jpn. 39 859 (1966)450 142. S Nakajima, Y Ogino Shokubai 8 287 (1966).Chem. Abstr. 69 39 052 (1968) 143. Y Ogino, S Nakajima J. Catal. 9 251 (1967) 144. T Ono, Y Ogino Shokubai 8 284 (1966); Chem. Abstr. 69 39 059 (1968) 145. Y Ogino, T Ono Bull. Chem. Soc. Jpn. 40 2223 (1967) 146. A Uda, T Ono, Y Ogino J. Chem. Soc. Jpn. 71 1352 (1968) 147. A Uda, T Ono, Y Ogino J. Chem. Soc. Jpn. 71 1358 (1968) 148. Y Takamidzawa, T Ono, Y Ogino J. Chem. Soc. Jpn. 70 1611 (1967) 149. Y Saito,M Ichimura, Y Ogino J. Chem. Soc. Jpn. 73 266 (1970) 150. H Katsuzawa, H Saito, Y Saito, Y Ogino Bull. Jpn. Petrol. Inst. 13 26 (1971); Ref. Zh. Khim. 23 B 1116 (1971) 151. S S Batsanov, G K Boreskov, G V Gridasova, N P Keier, L M Kefeli, V M Kudinov, V I Mali, I S Sazonova Kinet.Katal. 8 1348 (1967) a 152. J Golden, F Williams, B Morosin, E L Venturini, R A Graham, in Shock Waves Condensed Matter (Abstracts of Reports of AIP Conference), Menlo Park, 1981 p. 72; Ref. Zh. Khim. 18 B 1104 (1982) 153. S S Batsanov, V P Bokarev, I A Kostenchuk, Yu S Mardashev, I N Temnitskii React. Kinet. Catal. Lett. 20 43 (1982) 154. A A Bobyshev, V B Kazanskii, I R Kibardina, V A Radtsig, B N Shelimov Kinet. Katal. 30 1427 (1989) a 155. A A Bobyshev, V B Kazanskii, I R Kibardina, B N Shelimov Kinet. Katal. 33 363 (1992) a 156. O V Krylov, A A Firsova, A A Bobyshev, V A Radtsig, D P Shashkin, L Ya Margolis Catal. Today 13 381 (1992) 157. L A Isupova, V Yu Aleksandrov, V V Popovskii, V A Balashov, A A Davydov, A A Budneva, G N Kryukova React.Kinet. Catal. Lett. 31 195 (1986) 158. L A Isupova, V Yu Aleksandrov, V V Popovskii, E M Moroz, G S Litvak, G N Kryukova Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (1) 39 (1989) 159. V A Sadykov, L A Isupova, S V Tsybulya, S V Cherepanova, G S Litvak, E B Burgina, G N Kustova, V N Kolomiichuk, V P Ivanov, E A Paukshtis, A V Golovin, E G Avvakumov J. Solid State Chem. 123 191 (1996) 160. L A Isupova, V A Sadykov, I A Pauli, O V Andryushkova, V A Poluboyarov, G S Litvak, G N Kryukova, E V Burgina, L P Solov'eva, V N Kolomiichuk, in Mekhanokhimiya i Mekhanokhimicheskaya Aktivatsiya (Tez. Dokl. Mezhdunar. Seminar), S.-Peterburg, 1995[ Mechanochemistry and Mechanochemical Activation (Abstracts of Reports of International Seminar), St. Petersburg, 1995] p. 24 161. V A Sadykov, L A Isupova, N N Bulgakov Khim. Inter. Ustoich. Razvitiya 6 215 (1998) e 162. E M Moroz, S V Bogdanov, V I Zaikovskii, V V Molchanov, R A Buyanov Kinet. Katal. 30 993 (1989) a 163. R A Buyanov, B P Zolotovskii, V V Molchanov Sib. Khim. Zh. (2) 5 (1992) 164. V V Molchanov, E G Avvakumov, in Tez. Dokl. VI Vsesoyuz. Seminara po Dezyntegratornoi Tekhnologii, Tallin, 1989 (Abstracts of Reports of the Sixth All-Union Seminar on Disintegration Technology), Tallin, 1989] p. 61 165. E G Avvakumov, V V Molchanov, R A Buyanov, V V Boldyrev Dokl. Akad. Nauk SSSR 306 367 (1989) d 166. R A Buyanov Kinet. Katal. 28 157 (1987) a 167. V V Molchanov, R A Buyanov, E G Avvakumov, V V Boldyrev, in Tez. Dokl. II Vsesoyuz. Soveshch. po Dezaktivatsii Katalizatorov, Ufa, 1989 (Abstracts of Reports of the Second All-Union Meeting on Deactivation of Catalysts, Ufa, 1989) Part 1, p. 3 168. A S Kharitonov, V B Fenelonov, T P Voskresenskaya, N A Rudina, V V Molchanov, L M Plyasova, G I Panov Zeolites 15 253 (1995) 169. V V Chesnokov, V V Molchanov, E A Paukshtis, T A Konovalova Kinet. Katal. 36 759 (1995) a 170. G C Stevens, T Edmonds J. Less-Common Met. 54 321 (1977) 171. V A Zazhigalov, J Haber, J Stoch, L V Bogutskaya, 172. A Trovarelli, P Matteazzi, G Dolcetti, A Lutman, F Miani 173. V V Molchanov, G M Maksimov, L M Plyasova, V V Goidin, I V Bacherikova Appl. Catal. A, Gen. 135 155 (1996) Appl. Catal. 95 L9 (1993) I V Kozhevnikov Neorg. Mater. 29 555 (1993) f V V Molchanov, R A Buyanov 174. Yu T Pavlyukhin Izv. Sib. Otd. Akad. Nauk, Ser. Khim. Nauk (12) 45 (1987) 175. V SÏ epela k, K Tka cova, U Steinike, in Proceedings of the International Conference on Environment and Mineral Processing, Ostrava, 1994 Part 1, p. 125 176. V V Molchanov, V V Chesnokov, R A Buyanov, N A Zaitseva, V I Zaikovskii, L M Plyasova, V I Bukhtiyarov, I P Prosvirin, B N Novgorodov Kinet. Katal. 39 416 (1998) a 177. S V Tsybulya, G N Kryukova, S N Goncharova, A N Shmakov, B S Balzhinimaev J. Catal. 154 194 (1995) 178. V I Bukhtiyarov, in Interfacial Science (Ed.MWRoberts) (Oxford: Blackwell, 1997) p. 109 179. G I Panov, G K Boreskov, A S Kharitonov, E M Moroz, V I Sobolev Kinet. Katal. 25 123 (1984) a 180. R Schrader, G Glock, K KoÈ hnke Z. Chem. 9 156 (1969) 181. A V Bystrikov, A I Streletskii, P Yu Butyagin Kinet. Katal. 21 1148 (1980) a 182. I V Kolbanev, I V Berestetskaya, P Yu Butyagin Kinet. Katal. 21 1154 (1980) a 183. S SchoÈ nner, R Schrader, K-H Steinert Z. Anorg. Allg. Chem. 432 215 (1977) 184. Y Tamai, S Mori Z. Anorg. Allg. Chem. 476 221 (1981) 185. V A Kuznetsov, A G Lipson, D M Sakov, P V Fedenyuk, A M Shapiro, I K Martynov, I A Gagina, Yu P Toporov Izv. Akad. Nauk SSSR, Ser. Khim. 2730 (1990) c 186. G Heinicke, K Meyer, U Senzky Z. Anorg. Allg. Chem. 312 180 (1961) 187. P A Thieûen, G Heinicke, N Bock Z. Chem. 14 76 (1974) 188. G Heinicke Ropa Uhlie 4 150 (1962); Chem. Abstr. 57 11 904 (1962) 189. G Heinicke, I Lischke Z. Chem. 3 355 (1963) 190. G Heinicke, I Lischke Z. Chem. 11 332 (1971) 191. S Mori, W-C Xu, T Ishidzuki, N Ogasavara, J Imai, K Kobayashi Appl. Catal. 137 255 (1996) 192. P Yu Butyagin, A N Streletskii, O S Morozova, I V Berestet- skaya, A B Borunova Dokl. Akad. Nauk 336 771 (1994) d 193. V V Molchanov, R A Buyanov, V V Gojidin, in The 2nd International Conference on Mechanochemistry and Mechanical Activation (INCOME-2) (Abstracts of Reports), Novosibirsk, 1997 p. 125 194. G K Boreskov Geterogennyi Kataliz (Heterogeneous Catalysis) (Moscow: Nauka, 1986) 195. M I Molotskii Kristallografiya 17 1015 (1972) g 196. S A Zav'yalov, I A Myasnikov, L M Zav'yalova Dokl. Akad. Nauk SSSR 284 378 (1985) d 197. A Mittasch, E Theis From Davy and DoÈbereiner to Deacon. 50 Years of Heterogeneous Catalysis (Berlin: Verlag Chemie, 1932) a�Kinet. Catal. (Engl. Transl.) b�Russ. J. Appl. Chem. (Engl. Transl.) c�Russ. Chem. Bull. (Engl. Transl.) d�Dokl. Chem. Technol., Dokl. Chem. (Engl. Transl.) e�Chem. Sustainable Devel. (Engl. Transl.) f�Inorg. Mater. (Engl. Transl.) g�Crystallogr. Rep. (

ISSN:0036-021X    

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Russian Chemical Reviews 69 (5) 451 ± 459 (2000) Biodegradable starch-based polymeric materials A I Suvorova, I S Tyukova, E I Trufanova Contents I. Introduction II. The structure of starch III. Effects of water and plasticisers on the properties of starch IV. Mixtures of starch with synthetic polymers V. Conclusion Abstract. temper- additives, low-molecular-weight of effects The The effects of low-molecular-weight additives, temper- ature properties and structure the on action mechanical and ature and mechanical action on the structure and properties of of starch are discussed. Special attention is given to mixtures of starch are discussed. Special attention is given to mixtures of starch with ethylene of co-polymers synthetic with starch with synthetic polymers, polymers, e.g., ., co-polymers of ethylene with vinyl derivatives cellulose acid, acrylic alcohol, vinyl acetate, vinyl acetate, vinyl alcohol, acrylic acid, cellulose derivatives and and other in used be can mixtures These polymers.natural other natural polymers. These mixtures can be used in the the development (films, materials safe environmentally novel of development of novel environmentally safe materials (films, coat- coat- ings, packaging materials) and various articles for short-term use. ings, packaging materials) and various articles for short-term use. The references 105 includes bibliography The bibliography includes 105 references. I. Introduction Modern-day technology calls for the development of polymeric materials the properties of which do not change even after long- term use.The effects of environmental factors (e.g., water, atmospheric oxygen, sunlight and biological agents, such as microbes, fungi, insects, etc.) reduce the service life of many articles prepared from polymeric materials. All this raises the problem of creation and application of special-purpose stabilisers and bioprotectors.1 However, the immense bulk of polymeric materials and articles made thereof puts forward a problem of their further destruction or disposal after the termination of their service life. Many polymers are decomposed in the environment over a relatively long period of time; therefore, the production of biodegradable materials is as important as their stabilisation.Polymers, particularly household plastics and films, must be rapidly decomposed after use under the influence of chemical (atmospheric oxygen, water), physical (sunlight, heat) and bio- logical (bacteria, fungi, yeasts, insects, etc.) environmental fac- tors.2, 3 These factors produce a synergistic effect, eventually resulting in the fragmentation of the polymer owing to the destruction of its macromolecules and their conversion into low- molecular-weight compounds that can be further involved in the natural circulation of substances. In the strict sense, the term `biodegradation of a polymer' implies deterioration of its physical and chemical properties and a decrease of its molecular mass A I Suvorova, I S Tyukova, E I Trufanova Urals State University, prosp.Lenina 51, 620083 Ekaterinburg, Russian Federation. Fax (7-343) 261 59 78. Tel. (7-343) 261 60 46. E-mail: Anna.Suvorova@usu.ru (A I Suvorova), Irina.Tyucova@usu.ru (I S Tyukova) Received 20 December 1999 Uspekhi Khimii 69 (5) 494 ± 504 (2000); translated by R L Birnova #2000 Russian Academy of Sciences and Turpion Ltd DOI 10.1070/RC2000v069n05ABEH000505 451 451 453 455 458 down to the formation of CO2, H2O, CH4 and other low- molecular-weight products under the influence of microorganisms in both aerobic and anaerobic conditions.4, 5 Microorganisms or enzymes produced by them cause the decomposition of natural polymers (e.g., cellulose, starch, chitin, polypeptides, etc.) into low-molecular-weight compounds which are further involved in the metabolism of the elemental forms of life.6 Enzymes play the role of catalysts favouring the degradation of the main polymeric chain. Specific enzymes evolved in the course of evolution can selectively destroy natural high-mole- cular-weight compounds, such as cellulose, proteins and other natural polymers.For example, amylase induces the degradation of the starch molecule. Enzymes causing the destruction of synthetic polymers, e.g., polyalkenes or polyvinyl polymers, are absent in Nature. However, these classes of polymers are espe- cially extensively used in the production of packaging materials and articles for short-term use. These wastes constitute the greater part of municipal garbage in all industrially developed coun- tries.2, 7 ± 9 The interest in materials based on natural polymers (e.g., starch, chitin) has increased considerably in the recent years, because owing to their structural features these compounds can be involved in natural circulation and thus be environmentally safe.The problem of development of biodegradable polymeric materials has been considered in detail in reviews.10 ± 13 It was shown that the use of natural renewable polymers is the most promising and economically advantageous approach. The syn- thesis of novel biodegradable polymers and chemical modification of natural polymers were described by Vasnev.14 The methods for estimating the biodegradability of polymeric materials based mainly on the analysis of products of the activity of bacteria which decompose polymers have been developed and standar- dised in many countries.4, 15 ± 17 Here we survey the most recent data concerning the properties of materials prepared from starch or its mixtures with synthetic polymers.II. The structure of starch Starch is a natural polysaccharide which is accumulated in plant tubers, seeds, stalks and leaves in the course of their vital activity. The main sources for the commercial production of starch are potatoes, wheat, corn and rice. Starch comprises two polymeric components, viz., amylose and amylopectin, they are built of a-D- glucopyranose residues but differ in both structure and function. The amylose content in native starch usually varies from 20 mass% to 30 mass %, while amylopectin constitutes the greater part (70%) of the starch molecule.At the same time, the452 amylose content in high-amylose starch can reach 50 mass% to 70 mass %.18 Amylose (1) is a linear polymer, which consists of a-(1,4)-D- glucopyranoside residues with the average molecular mass of *102 to 103 kg mol71. In cellular starch, the helical chains of amylose form complexes with lipids. Amylopectin (2) contains a-(1,4)- and a-(1,6)-linked glucose residues. Extended linear chains involve a-(1,4)-bonds and a great number of shorter branchings are linked through a-(1.6)-bonds. CH2OH CH2OH O O OH OH O O OH OH 1 CH2OH O OH O CH2 O OH CH2OH O O OH OH O O OH OH 2 The molecular mass of amylopectin is approximately 105 kg mol71. The branchings in the starch molecule may con- tain, on the average, up to twenty glucose residues.Amylopectin molecules also form helices; it is noteworthy that shorter side chains form double helices.19, 20 The spatial structure of amylopectin has not been clearly understood yet. A number of models have been proposed 21 in order to establish a correlation between the character of branch- ings in the chains of amylopectin and its ability to form regular crystalline regions. The Robin ± Mercier scheme 22 (Fig. 1) pro- Figure 1. A structural model of amylopectin; A are crystalline regions, B are amorphous regions.22 CH2OH O OH O OH A BAAB A I Suvorova, I S Tyukova, E I Trufanova 15 nm 6 nm 4 nm 5 3 4 1 2 Figure 2.The structure of native starch;20 (1) helices of amylopectin, (2) hybrid helices of amylose and amylopectin, (3) free lipids, (4) free amylose, (5) V-structures of amylose. vides an example of such models. This model takes account of the presence of amorphous regions in the amylopectin molecule formed by chain branchings and of crystalline regions consisting of linear, parallelly stacked fragments. The degree of crystallinity of natural starch depends on its origin and varies from 15% to 45%. The structure of starch formed by regular stacking of the double chains of amylose and amylopectin and incorporating lipid molecules which form com- plexes with them is schematically represented in Fig.2. Using wide-angle X-ray scattering,19, 23 it was shown that the crystalline structures of starch isolated from different parts of plants differ considerably. This polysaccharide was found to exist in three polymorphous modifications. Starch from gramineous seeds has the so-called A-structure, tuber starch has the B-structure, while starch extracted from roots and stalks of plants has the C-struc- ture. The crystalline structures of the A- and B-types are associ- ated with the amylose fragment and consist of parallel coiled right double helices with anti-parallel packing. Each turn of the helix comprises six a-D-glucose residues. The conformations of the double helices of amylose in A- and B-structures are identical, but the A-structure is represented by a unit cell of the orthorhombic type (a=1.190 nm, b=1.770 nm, c=1.052 nm), whereas the B-structure is represented by a hexagonal unit cell (a=b=1.85 nm, c=1.04 nm).Besides, in natural starch amylose complexes with lipids form structures of the V-type. The content of crystal- line structures of the A- and B-type in starch samples of different origin was found to be 56% and 44%, respectively.24 The presence of these structures was confirmed by IR spectroscopy.25 Starch contains a large proportion of amorphous regions. However, the glass-transition temperature (Tg) of dry starch cannot be measured because it lies above the temperature at which the decomposition of the polymer occurs; its calculation is based on the estimation of the plasticising effect of water which penetrates into the amorphous regions of the starch molecule and decreases Tg.The concentration dependence of Tg of the starch ± water system can be described by the equation 26 Tc= 244.971565o+2640o2 , where o is the content of water (w/w) in swollen starch. Extra- polation of these data for Tg of the starch samples plasticised with water to various degrees gave Tg values ranging from 230 to 250 8C.20, 26 Starch is present in plants in the form of granules having the diameter from 2 to 100 mm.27 The structure of these supramolec- ular granules is complex and has not yet been finally elucidated. It is known that starch granules comprise both crystalline and amorphous regions. The amorphous regions form a continuous phase and incorporate crystals of a lamellar type.27 Microscopic analysis of the supramolecular structure of starch granules 28Biodegradable starch-based polymeric materials revealed that the lamellae predominantly consist of amylopectin.Their sizes depend on the origin of starch and their localisation in the granules and vary from 20 to 500 nm. Starches isolated from different natural sources differ in their sensitivities to destructive factors, such as temperature and enzymic hydrolysis. Thermolysis of starch granules isolated from potatoes, wheat, barley, rice, corn and tapioca was studied at fixed temperatures (170 ± 325 8C).29 It was found that corn starch exhibits the highest resistance to heating, whereas barley starch is the least thermostable.This may be due to the differences in the molecular masses and ratios of linear and branched components of starches having different biological origin. III. Effects of water and plasticisers on the properties of starch Starch is a typical hydrophilic polymer; it may contain up to 30 mass%± 40 mass%of bound water. It is known 23 that differ- ent structures of starches of the A- and B-types bind differently to water. In structures of the B-type, water is mobile and can easily enter and leave the complex (Fig. 3). In crystallites of the A-type, water of hydration forms a layered structure and is firmly bound to the surrounding double helices of amylose. Therefore, A-struc- tures are less sensitive to the atmospheric moisture than B-struc- tures.a b Figure 3. The schematic representations of the crystalline structures of amylose with water. (a) A-amylose complex, (b) B-amylose complex. The hatched areas designate absorbed water. Studies of the effect of water on starch provide additional information about the structure of this polymer. Dissolution of starch in water is a complex process, which strongly depends on temperature. Swelling of starch in saturated water vapour at room temperature results in the formation of a gel which retains the predominant polymer-to-polymer contacts.30 This process does not result in complete dissolution of starch as is evidenced by the shape of the isotherm of water vapour sorption 31 characteristic of systems with limited swelling of a polymer.However, the mobility of starch molecules increases with an increase in the amount of absorbed water as a result of which the linear component of the polymer, viz., amylose, forms a true solution with water. This is accompanied by the formation of a two-phase swollen gel ± solution system. A high-energy interaction with water of several samples of amylose starch having a crystalline structure of the B-type and the chain length of 12 ± 55 residues was established by scanning calorimetry and sorption.32 However, at room temperature the energy of the interaction of the components is too low to compensate for the oppositely directed entropic contribution. Therefore, complete destruction of the polymer-to-polymer con- tacts and solubilisation of starch do not occur.Water is a poor solvent for amylose starch at room temperature. The solubility of starch increases with temperature. The swelling of dispersions (2.6 mass %) of corn and pea starches in water was studied by laser diffractometry.33 It was found that heating above gelatinisation temperatures significantly changes both the sizes of starch granules and their distribution according 453 to size. The maximum increase in the diameter of starch granules is *3.5-fold.33 The behaviour of the starch ± water system at a wide range of temperatures was studied by differential scanning calo- rimetry (DSC), dilatometry, rheology and polarisation micro- scopy using rice,34 potato 26, 35 and wheat 35 starches as examples. The sizes of starch granules first increase slightly in excess of water at 35 to 55 8C and then increase sharply (by 55%) at 65 8C, reaching the maximum at 75 8C.At temperatures above 75 8C, starch granules are destroyed and crystallinity disappears. The viscosity of the system kept at the temperatures indicated above increases until the gelatinisation step is reached. At higher temper- atures, amylose is separated from amylopectin due to partial destruction of the physical lattice nodes after which starch dissolution begins. Cooling of aqueous solutions of starch again results in the formation of gels which contain swollen granules consisting predominantly of amylopectin; the amylose component of starch is predominantly localised in the intergranular space.The dissolution of rice starch was studied by DSC and was interpreted 34 as a phase transition, since the thermograms dis- played a peak of heat absorption at 75 8C corresponding to the gel transition. Using DSC, it was shown that the increase in the water content in wheat starch from 2.8 mass% to 90 mass% and subsequent heating induced several structural transitions due to melting of amylopectin crystallites and its complexes with lipids as well as due to melting of amylose in the swollen samples.36 The content of amylose and amylopectin, their molecular masses and the content of lipids depend on the origin of starch. These factors affect the interaction of starch with water.The gel- forming abilities of starches isolated from the grains of hard and soft corn,37 hard wheat and potatoes grown in different geo- graphical zones, from rice 34 and green herbs 38 have been studied. It was shown that starches isolated from gramineous plant seeds contain less amylose than potato starch and have lower values of the temperature and enthalpy of gelatinisation. In contrast, starches isolated from green herbs, which contain more amylose (up to 30 mass %) of high molecular mass (up to 4.56103 kg mol71) and highly branched amylopectin, have higher values of these parameters. Studies on the structure and gelatinisation of amylopectin samples (Mw=0.26103716103 kg mol71) specially prepared from yellow corn revealed 21 that the gels kept at constant temper- ature (4 8C) are typical representatives of thermoreversible gels formed by physical lattice nodes.The crystallinity of such gels increases upon storage as can be evidenced from wide-angle X-ray scattering data 21 and the increase in the area of the endothermal peak on the DSC curves 21, 39 resulting from the increase in the enthalpies of melting of starch crystallites. Apparently, water which plays the role of a plasticiser by increasing the mobility of starch granules increases the crystallinity as in the case of the synthetic polymers.40 It was also shown 21 that the structural perfection of amylopectin crystallites depends on the conditions of gel crystallisation. The interaction of starch samples differing in the amylose content with water was studied by Shogren and Jasberg.18 The behaviour of corn starch containing 28 mass% of amylose in the swelling and subsequent gelatinisation differs considerably from the behaviour of starch with the amylose content of 50 mass%to 70 mass% at equal molecular masses of the polymers.These differences affect starch concentrations at which gelatinisation begins, enthalpies of gelatinisation and the syneresis rates of the gels.The effect of the molecular mass of the amylose starch on its solubility was studied by Moates et al.32 With a change in the molecular masses from 2 to 10 kg mol71 in systems with the same degree of swelling (0.8), the dissolution temperature of starch increases from 57 to 119 8C.Extrapolation to infinitely high molecular mass gives a dissolution temperature of 147 8C. It was found 41, 42 that homogenisation of wheat or potato starch in water is facilitated by mechanical action on the system, e.g., by extrusional stirring of the components. It was shown 42454 that the threshold of a twin-screw extruder of the mixer driver is 120 ± 150 kW h71 below which the system cannot pass into the fluid state. This limiting value depends on the viscosity of the mixture, which is proportional to the molecular masses of amylose and amylopectin. Plasticisation of starch with water and its simultaneous exposure at elevated temperature and under mechanical stress makes it possible to change considerably the physical and mechanical properties of the starch ± water system.The reason for these changes is in irreversible destruction of starch granules, mechanical stress being the crucial factor in this process. Reproc- essing of plasticised starch on standard technological equipment for moulding of plastic materials (e.g., extruders, casting machines, etc.) permits one to obtain materials possessing differ- ent physical properties. Glycerol and oligomeric polyglycols can also exert a plasticis- ing effect on starch. These plasticisers are generally used in combination with water. The thermoplastic properties of mate- rials obtained by extrusion of mixtures of potato starch with glycerol and water were studied by van Soest et al.43 Two speci- mens were studied based on the native starch, viz., that with Mw=37 000 kg mol71 and that withMw=1900 kg mol71 pre- pared by partial acid hydrolysis.The specimens containing less than 9 mass% of water were glass-like and had elasticity moduli from 400 to 1000 MPa. If the water content in these materials was from 9 mass%to 15 mass %, they acquired elastic properties but became soft and fragile with an increase in the water content above 15 mass %. The differences in the thermoplastic properties of these materials are due to the presence of water rather than to the differences in the molecular weights of the starches. Thermo- mechanical analysis revealed that Tg of the extruded samples decreased appreciably with an increase in the water content (Table 1). It was assumed 43, 44 that the properties of starch- based thermoplastic materials are determined by the formation of a complex network consisting of linear chains of amylose and branched molecules of amylopectin in which hydrogen bonds play a crucial role.A lower value of the fracture energy of an elastic material prepared from low-molecular-weight starch can be attributed both to the shorter length of the amylose chain and to smaller molecular mass and branching of the amylopectin mole- cules. Table 1. The changes in Tg of extruded samples of potato starch plasticised with water.43 Tg /8C Water content (mass %) material prepared from native starch material prepared from hydrolysed starch 14 11 77 5 25 8 42 7 5 59 58 The effects of glycerol (14 mass%± 39 mass%) and water (1 mass%± 28 mass %) on the phase behaviour of barley starch were studied using DSC and dynamic thermomechanical analy- sis.45 Samples with low content of water and glycerol formed homogenous monophasic systems.Strong interaction of starch with glycerol in samples containing less than 20% of water presumably impedes crystallisation of amylopectin as a result of which the system remains amorphous and monophasic. With an increase in the concentration of the plasticising agents, the mixture separates into a starch-enriched and a starch-depleted phases as evidenced from the appearance of mechanical loss peaks corres- ponding to Tg of the individual phases. Simultaneous use of water and glycerol as plasticisers makes it possible to obtain flexible starch-based thermoplastic materials by A I Suvorova, I S Tyukova, E I Trufanova compression moulding 46 and extrusion.47 The materials prepared from corn, potato and wheat starches were characterised by constant (with respect to starch) content of glycerol (1 : 0.3), contained from 8 mass%to 25 mass% of water and were elastic (Tg<20 8C).Studies of mechanical properties of such materials established a dependence of the elasticity modulus and breaking stress (sp) both on the content of the plasticising agents and on the origin of starch.46, 47 The difference in mechanical properties is presumably due to the higher content of amylopectin in corn starch, which is plasticised with water more readily than potato starch enriched with high-molecular-weight amylose.47 The mechanical properties of plasticised starch depend on the storage time prior to testing.48, 49 Storage of thermoplastic materi- als prepared from corn 48 and potato 49 starch at high relative humidity (up to 90%) results in an increase in their breaking stress, while their elongation at disruption decreases.The reason for this phenomenon is the time-dependent post-crystallisation of starch in the presence of water and glycerol; the degree of crystallinity of B-type structures in the tested samples increases from 5% to 30%. The amylose and amylopectin components of starch plasti- cised with water and glycerol manifest different abilities for structural rearrangements.50 Analysis of extrusion samples of specially prepared high-amylose and high-amylopectin starches (the amylose content varied from 0% to 70%) revealed 50 that in amylose-enriched materials further crystallisation occurs much faster than in amylopectin-enriched ones.The higher ability of plasticised amylose for post-crystallisa- tion was also established in samples of the amylose starch obtained by compression moulding.51 The elasticity moduli of plasticised, partially crystallised samples comprising structures of the V- and B-types were practically the same immediately after moulding. After storage, the elasticity moduli of the samples prepared from normal corn starch was *100 MPa, whereas those of the high-amylose starch were of about 700 MPa.These differences seem to be due to the fact that high-amylose starches contain more amorphous structures capable of additional crystal- lisation.51 Storage of samples also causes certain changes in Tg due to the condensation of amorphous regions of starch as a result of formation of additional nodes on the physical lattice and con- formational rearrangement of the macromolecules, leading to the formation of molecular and intramolecular double helices of amylose and amylopectin.39 In addition to glycerol and polyglycols, other substances can exert a plasticising effects on starch. Calorimetric determination of Tg of starch films containing water and additives (10% ± 20%) of glycerol, sorbitol, sodium lactate, urea, ethyleneglycol, dieth- yleneglycol, polyethyleneglycol (PEG-200) and glycerol diacetate was carried out by Lourdin et al.52 All these compounds, with the exception of glycerol diacetate, formed homogeneous systems with starch; their Tg decreased monotonically with an increase in the concentration of the plasticisers.The glycerol acetate ± starch system was characterised by phase separation; the value of Tg did not change in the presence of the plasticiser. The water in the starch not only transfers the system into a thermoplastic state upon extrusion, but also partly protects the polymer from destruction. For example, sage starch which con- tained from 34% to 47% of water was incapable of dextrinisation (i.e., degradation leading to low-molecular-weight and oligomeric carbohydrates) but was easily gelatinised, if the extrusion was carried out under drastic conditions (150 8C, high screw speeds).53 According to other investigators, the processing of this polysac- charide into a thermoplastic material is always accompanied by destruction.Thus, mixing of yellow corn starch 54 with water (18 mass% or 23 mass%) in a two-screw extruder decreases its molecular mass from 3.366105 to 46104 kg mol71. After repeated extrusion in a single-screw extruder at 110 or 130 8C, the decrease in the molecular mass is less pronounced. It was proposed 54 to use the value of specific mechanical energy applied to the polymer on moulding for the calculation of the expectedBiodegradable starch-based polymeric materials decrease in the molecular mass when choosing the type of the extruder and the regime of moulding of thermoplastic materials. Water and other agents containing hydroxy groups are used as additives in the preparation of thermoplastic materials for single or short-term use.A significant drawback of these materials is their low resistance to water. Therefore, in recent years starch mixtures with synthetic polymers have acquired increasing impor- tance together with thermoplastic materials prepared from starch without additives. These materials combine characteristic proper- ties of their synthetic component with biodegradability owing to the presence of a natural biodegradable component, viz., starch. IV. Mixtures of starch with synthetic polymers Composite starch mixtures with various synthetic polymers were first proposed in the 1970 ± 1980's.55 ± 59 Most often, starch is used for the modification of polyethylene (PE), a film material designed for short-term use (e.g., packaging of food stuffs, agriculture and medicine, etc.).In these mixtures, starch usually plays the role of a filling agent, which ensures the biodegradation of the polymeric item after its service life is over.60 Thermoplastic mixtures of synthetic polymers with starch are typically prepared from starch plasticised with glycerol and water. The components are mixed in an extruder at *150 8C, which temperature ensures good gelati- nisation of the polysaccharide 61 and leads to the formation of two-phase mixtures the biodegradation of which begins from the surface of a starch-enriched film.Small amounts of pro-oxidants favour biodegradation by inducing oxidative decomposition of the material under natural conditions.62 A PE± starch ± vegetable oil mixture is an example of such a composition.63 Vegetable oil plays the role of a pro-oxidant and simultaneously facilitates the mixing of the natural and synthetic polymers in the course of moulding. Starch is poorly compatible with non-polar PE; therefore, investigations into improvement of the affinity of the natural and synthetic polymers should be aimed at preparing starch mixtures with co-polymers of ethylene with other more polar monomers as well as at producingmodified starcheswith enhanced affinity for PE.1. Mixtures of starch with ethylene co-polymers Co-polymers of ethylene with vinyl acetate (EVAc) or the prod- ucts of saponification of acetate groups in these co-polymers are most commonly used as components of starch mixtures. These mixtures are prepared from yellow or native corn as well as from high-amylose starch Hylon VII by extrusion with the ethylene ± vinyl alcohol co-polymer [EVAl, 56% of CH2CH(OH) units]. Their structural characteristics were studied by wide-angle X-ray scattering, scanning and transmission electron microscopy and DSC.64 Heterogeneous mixtures of EVAl with yellow corn starch displayed a clearly defined boundary between the phases; the sizes of the domains were proportional to the extrusion time. In heterogeneous mixtures of EVAl with native corn and Hylon starches, the inhomogeneities decreased faster than in the case of yellow corn starch; the boundaries between the phases as seen in the electron micrographs were diffuse. There was a decrease in the melting temperature of the synthetic polymer, which testified to partial miscibility of the components at the interphaces. Simmons and Thomas 65 prepared phase-separated mixtures of various compositions, which contained domains (0.1 ± 3 mm) enriched either with starch or with EVAl depending on the composition.At the starch content of 55 mass%± 60 mass %, the phase reversal was accompanied by drastic changes in the domain sizes. An analysis of the phase compositions of starch mixtures revealed that the compatibility of the components increased with an increase in the amylose content in the starch.Fibres cast from these mixtures manifested reduced sensitivity to moisture and low initial rates of enzymic biodegradation even in starch-enriched systems. The surface of these fibres was coated with a layer of a synthetic co-polymer, since the matrix phase of 455 the system was EVAl with the starch content of up to 70 mass %.64, 65 The water resistance and mechanical properties of starch mixtures are determined by the ratio of their constituents. Absorption of moisture by films 66 prepared by blowing of mixtures of native corn starch pre-plasticised with glycerol and water and EVAl [1 : 1 (mixture A); 2 : 1 (mixture B)] varied from 2% to 11% and was greater in the films prepared from mixture B.The breaking strength of the films prepared from mixture A was one-third of that for films prepared from pure EVAl and even less for films prepared from mixture B. The use of electron irradiation (flux energy 2.5 MeV, 2500 Gray s71) in the formation of thermoplastic EVAl ± starch mixtures makes it possible to modify the structure and rheological properties of these compositions.67, 68 EVAl was shown to be resistant to irradiation, which causes predominantly destruction of starch macromolecules by changing their supramolecular organisation and thus facilitating the mixing of starch with EVAl. The mechanical and rheological properties of irradiated mixtures differ substantially from those of the original samples.The mixtures containing high-amylose starch appeared to be the most resistant to irradiation, which can be attributed 68 to chemical reactions of the linear molecules of the amylose starch with the synthetic polymer under the influence of irradiation. The conditions for moulding of starch mixtures with EVAl strongly influence their degradability. The favourable effect of the structural anisotropy of starch ± EVAl mixtures which appears in the injection moulding on the resistance of the mixtures to the action of physiological solutions (estimated from the mass loss and changes in the mechanical properties upon ageing for 80 days) and ethylene oxide used for the sterilisation of materials in clinical practice was demonstrated by Reis et al.69 In-depth studies into the properties of starch mixtures with EVAc and with EVAc modified with maleic anhydride (EVAMA) were carried out by Ramkumar et al.70 ± 74 Mixtures of commercial corn starch (25 mass% of amylose, 75 mass% of amylopectin) with co-polymers containing 18 mass% (EVAMA-18) and 28 mass% (EVAMA-28) of CH2CHOAc units and about 0.8 mass% of anhydride fragments were prepared by extrusion carried out at different temperatures, screw speeds and mixing times.A dynamic mechanical analysis 72 performed at different shear rates (0.005 ± 0.5 s71) and frequencies (0.1 ± 100 s71) in a broad range of temperatures revealed that all the mixtures under study displayed two regions of relaxation transition temperatures, i.e.,730 8C for the synthetic polymer and 40 8C for starch, which testifies that these systems are heterogeneous.The introduction of anhydride fragments into the co-polymer macromolecule causes a shift in the transition temperatures, which suggests improved compatibility of the components. The changes in the crystallinity of starch granules in the course of mixing were demonstrated by DSC.72 The starch ±EVAMA mixtures are characterised by lower values of heats of melting (Table 2), i.e., the structure of starch granules in these mixtures changes to a greater degree. Repeated compression moulding of the mixtures also decreases the heat of melting. With an increase in the starch content in the mixtures, the viscosity of the systems changes, reaching a maximum level at 70 mass% of starch.The absolute viscosities of the mixtures containing EVAMA-18 are higher than those of starch ± EVAMA-28 mixtures. It is noteworthy that the viscosities of starch mixtures of any composition exceed the additive values.72, 73 The ability of starch mixtures to absorb water strongly depends on the moulding conditions, e.g., temperature, screw speed and injection pressure. Starch ±EVAMA mixtures absorb water more readily than starch ± EVAc mixtures (22 mass%± 37 mass% or 20 mass%± 27 mass% of water, respectively). Contrariwise, in the presence of water the values of diffusion coefficients and structural relaxation times calculated from the anomalous sorption model were higher for starch ±EVA mix- tures.These differences were attributed to the different degree of456 Table 2. The heats of melting of starch mixtures with ethylene co- polymers.70 Heats of melting a of samples /J g71 Sample following additional compression moulding following extrusion 75.8 95.5 7 101.0 19.7 98.0 46.9 7 26.0 68.7 56.6 7 Starch ±EVAb 20 : 80 40 : 60 Starch ±EVAMA-18 b 40 : 60 70 : 30 Starch ±EVAMA-28 b 40 : 60 70 : 30 a The heat of melting of dry starch is 35.9 J g71; b The figures in parentheses designate the starch : co-polymer ratios. starch destruction during the formation of mixtures with EVAc and EVAMA rather than to the presence of anhydride groups in the co-polymer.70 Using wide-angle X-ray scattering, it was shown 73 that 20-week storage of starch mixtures with a synthetic polymer leads to structural rearrangements resulting in the restoration of the crystalline structure of starch, which was completely lost in the course of moulding.The changes in crystallinity are especially well-pronounced during the first five weeks following moulding; as a result, the resistance of starch samples to rupture increases. After storage of the samples at 10 8C, the structural changes become less apparent, but are manifested on storage at 50 8C, since relaxation transitions in starch occur around this temper- ature.72 From the data taken altogether, Ramkumar et al.70 ± 74 con- cluded that the presence of anhydride fragments in the co-polymer chain is favourable for the improvement of compatibility of the starch mixture constituents.Mixtures of co-polymers of EVAc and EVAMA with the starch content of 70 mass%manifest good mechanical and moulding properties and are fairly resistant to water. Mixtures of starch with an ethylene ± propylene co-polymer (EP), polystyrene (PS), an ethylene ± propylene ± maleic anhyd- ride co-polymer (0.8 mass %, EPMA) as well as with a styrene ± maleic anhydride co-polymer (8 mass %, SMA) obtained by extrusion at 120 ± 180 8C were studied at different effective mechanical moulding energies.75 ± 79 In these studies, the effects of the composition (40 mass%± 70 mass%of starch) and mould- ing conditions on the structure and properties of starch mixtures were analysed.As in the case of starch ±EVAMA mixtures,70, 72 the miscibility of components improved in the presence of anhydride fragments in the synthetic polymer chain. This phe- nomenon was interpreted 75 ± 79 as the chemical reaction between starch and the synthetic polymer under the influence of high temperatures and shear stress in the extruder on moulding. This reaction results in the formation of ester bonds between the carboxy groups in the co-polymer chain and the primary hydroxy groups of starch. [(CHCH(CO2H)] n (CH2CH2) m [CH2CH(OAc)]k CH2OC O O OH O OH A I Suvorova, I S Tyukova, E I Trufanova Comparison of mechanical characteristics of the mixtures suggests that the co-polymers containing anhydride fragments react more strongly with starch (Table 3).76 The breaking strength of starch ±SMA mixtures is lower than that of pure SMA or PS but higher than that of starch ± PS mixtures.In EPMA-containing compositions, the increase in the starch content up to 70 mass% increases the breaking strength of the systems. The increased resistance of starch mixtures with polymers containing anhydride groups is a result of enhanced interphasic adhesion at the boundary between the structural inhomogeneities caused by the reaction of the anhydride groups of the synthetic polymer with the hydroxy groups of starch. Table 3. The breaking strengths of polymers and polymer ± starch mixtures.76 Sample sp /MPa Starch : co-polymer ratio 60 : 40 SMA Starch ±SMA 70 : 30 60 : 40 60 : 40 PS Starch ± PS EPMA Starch ±EPMA 70 : 30 33.2 18.4 17.7 31.0 9.6 6.2 6.4 8.3 >8.9 2.8 70 : 30 EP Starch ±EP Starch mixtures with EPMA and SMA are easy to mould, display satisfactory mechanical characteristics and are biodegrad- able by spores of the fungus Penicillium funiculogum, which is facilitated with an increase in the starch content.At low starch content, starch granules remain encapsulated within the synthetic polymer and are thus hardly accessible to microorganisms.76 Starch ±EPMA and starch ±SMA films are highly hydro- philic. Adsorption of water by these specimens depends on the method for the preparation of the mixtures and the moulding regime, since mechanical action induces decomposition of starch granules.Both compositions are rather resistant to water at room temperature despite high starch content (50 mass%± 80 mass %); after keeping in water for two months, they absorb as little as 10 mass%± 30 mass% of H2O. The resistance of starch mixtures with EPMA to water under conditions mimicking sterilisation (121 8C, 10 min) is higher than that of starch mixtures with SMA.76 Using scanning electron microscopy, it was shown 78 that a material possessing good mechanical properties can be prepared by varying the compositions of three-component mixtures (starch ±SMA±EPMA) and moulding conditions. Starch gran- ules in this material have a size of 1 to 5 mm.A thermoplastic material was obtained 80 by extrusion of a mixture of wheat, potato, corn or rice starch (36 mass%) with an ethylene ± acrylic acid co-polymer (used as ammonium salt, EAA, 41 mass %), water (12.5 mass %), urea (8.4 mass %) and poly- ethylene glycol (PEG, 2,1 mass %). Mechanical characteristics of films depended on the origin of starch as well as on the contents of water and PEG. The films based on wheat starch possessed the highest values of the elasticity modulus (*180 MPa). The mechanical characteristics deteriorate with an increase in the concentration of the plasticiser. Thermooxidation resistance of mixtures of low-pressure poly- ethylene (LPPE) with a methyl methacrylate ± butadiene ± styrene co-polymer (MBS), with EAA and plasticised starch at 190 8C was studied 81 ± 83 using thermogravimetry, DSC and IR spectro- scopy both upon continuous heating and in the isothermal regime.It was shown that MBS and EAC accelerate, whereas starchBiodegradable starch-based polymeric materials decelerates thermooxidation of LPPE. A ternary LPPE ±EAA± starch system appeared to be the most resistant to temperature, apparently due to the stabilising effect of the co-polymer at the PE ± starch interface. 2. Mixtures of starch with cellulose derivatives and other natural polymers A great number of investigations of the past decade 84 ± 92 were devoted to studies of starch mixtures with other natural polymers, such as pectins, cellulose, etc., or products of their chemical modification.The feasibility of production of biodegradable packaging films for food stuffs as well as for biomedical purposes from starch ± gutta-percha mixtures was studied by Arvanitoyan- nis et al.84 Biodegradable starch mixtures with natural water-soluble polysaccharides, viz., pectins, were studied 85 ± 87 using dynamic mechanical analysis, dilatometry, scanning electron microscopy and IR spectroscopy. Plant cell wall pectins contain esterified polygalacturonic acid residues, the degree of esterification depending on the origin of pectin. The pectins studied were isolated from citrus plants, sugar beet, almonds and water-melon rinds.85 ± 87 The rupture strength and elasticity modulus of films cast from aqueous solutions practically do not depend on the origin of pectin.The rupture strengths of glycerol-plasticised films of pectin ± starch mixtures change only slightly with an increase in the plasticiser content up to 45 mass %. Further increase in the glycerol content up to 75% sharply decreases the rupture strength and increases 10-fold the chain elongation at break. The increase in the starch content in the mixtures attenuates the plasticising effect of glycerol and thus makes the films more rigid. The level of mechanical properties of pectin ± starch ± glycerol films corre- spond to the mean values of the mechanical characteristics of films prepared from ordinary synthetic polymers (sp=27 MPa, elasticity modulus 26103 ± 36103 MPa). A change in the dynamic strain at a constant frequency of 1.6 Hz over a broad range of temperatures (from7100 to 7200 8C) causes the appearance of three regions of mechanical relaxation, viz., at 750, 25 and *100 8C.The position of mechanical losses peaks depends on the amount of the plasticiser (glycerol) added, viz., the transition temperature decreases with an increase in the glycerol concentration. Using IR spectroscopy, it was shown 83 that the position of the band corresponding to the carboxy group of pectin changes noticeably after addition of glycerol, whereas the posi- tions of the absorption bands characteristic of starch change to a lesser degree. The results of spectral studies 83 suggest that plasticised films prepared from starch mixtures are highly com- patible with pectin.However, phase homogeneities of the systems under study were not proved. Extrusion of corn starch mixtures with microcrystalline cellu- lose and methyl cellulose (MC) in the presence of additives, e.g., plasticisers (polyols), or without them was used to produce edible films.88 The increase in the concentration of the cellulose compo- nent increases the rupture strength and decreases the elongation at break and the permeability of films for water vapour. Thermoplastic films plasticised with triacetylglycerol were obtained by hot moulding of mixtures of potato or corn starch with cellulose diacetate (CDA).89 The ratio of the polymeric components in the mixtures was varied at a constant concentra- tion of triacetylglycerol (35 mass%) relative to the total polymer mass.It was shown that the effective viscosity of the mixture decreases with an increase in the starch content from 10 mass%to 80 mass %, while the fluidity index of the melt increases from 2 to 70 g within 10 min, which was interpreted as an increase in the plasticiser content relative toCDAwith a rise in the starch content in the system. Potato starch forms more viscous compositions with CDA than corn starch. Commercial plasticised films were prepared from starch ±CDA mixtures by injection moulding.90 In their mechan- ical properties, these films are similar to polystyrene films but are additionally biodegradable. In these mixtures, biodegradation 457 first affects starch and the plasticiser and only afterwards involves CDA.The compositions containing starch and cellulose acetate are unstable in sea water but can be used as biodegradable non- toxic plastics for short-term use in air. Using static sorption of water vapour, it was shown 91, 92 that water-soluble starch forms mixtures with MC and carboxy- methylcellulose (CMC), which are thermodynamically compat- ible if the starch content is below 25 mass %; with an increase in the starch content, the systems become microheterogenous. The rate of biodegradation of such films by microorganisms in water ± soil suspensions as determined by the evolution of carbon dioxide depends on the degree of swelling and solubility of the components of the polymeric mixture in water, which facilitates their biodegradation.The rate of biodegradation of MC and CMC mixtures with starch in aqueous media does not depend on the phase state of the system and increases with an increase in the starch content. Starch mixtures with ternary co-polymers based on capro- lactam, dodecalactam and salts of adipic or sebacic acids with hexamethylene diamine were obtained by compression mould- ing.93 The mixtures of components containing up to 30 mass%of starch are compatible as evidenced from the negative iodine test and the presence of a single relaxation dielectric loss peak around 50 8C. The resistance of these mixtures to water depends on the number of non-polar methylene groups between the amide bonds of the co-polymer. In systems with the same content of starch, the stability of the mixture containing a dodecalactam-based co- polymer is higher.The biodegradation of these films in water, as in the majority of starch-containing mixtures, is facilitated with an increase in its concentration in the system. Extrusion of a mixture of starch, EVAl and inorganic com- pounds, e.g., hydroxyapatite, was used to obtain biodegradable materials.94 These compositions contain more than 30 mass%of natural or synthetic hydroxyapatite and resemble bone both in exterior and in mechanical properties. Scanning electron micro- scopy and X-ray diffractometry data testify to the homogeneity of their microstructure. All the polymeric mixtures mentioned above could find practical application in the future.The thermoplastic materials (e.g., Mater Bi, Novon, Bioflex) manufactured in Italy, USA, Canada and Germany (predominantly for `fast food' enterprises) provide examples of commercial compositions based on starch.7, 95 ± 97 Novon, a thermoplastic material prepared from plasticised starch, usually contains modified derivatives of polysaccharides. Mater Bi represents a mixture of starch with polycaprolactone or EVAl and usually contains glycerol as the plasticiser. The materials prepared from these compositions are highly stable and compete favourably with PE films in mechanical properties.96, 97 The films prepared by extrusion and blowing can be used in the production of plastic bags for carrying small loads (*3 to 5 kg).The biodegradability of Mater Bi materials under aerobic and anaerobic conditions in water and in compost has been studied in detail.95 It was shown that the plasticiser is washed out rapidly in aqueous media. The starch : polycaprolactone ratio remains con- stant (54 : 46) under aerobic conditions during biodegradation with bacteria; under anaerobic conditions, the biodegradation predominantly affects starch. 3. Chemical modification of starch Yet another method for the preparation of starch-based materials is chemical modification of starch, which consists in polymer- analogous transformations (most commonly, by esterification of the hydroxy groups) or introduction of fragments of different chemical origin into the polysaccharide macromolecule (e.g., the synthesis of the so-called graft co-polymers).In this review, we shall consider the properties of the compositions containing the products of polymer-analogous conversions of starch and their mixtures with other polymers.458 Starch acetates differing in the degree of substitution (from 1.5 to 2.5) were obtained from high-amylose corn starch.98 According to DSC data, their Tg values changed from 165 to 185 8C; after plasticisation with water, Tg decreased to 35 ± 95 8C. Extrusion of highly substituted starch acetate containing 15 mass% of water was used to obtain foamed materials, which surpassed foamed polystyrenes in plasticity and stability on compression. It is assumed 98 that such materials can be used in the production of packaging materials for agricultural and food industries.Mechanical properties of films prepared from acetylated starch are determined by the origin of starch,99 being dependent on the content of amylose and amylopectin in the original polymer.100 The films with a high content of branched amylopec- tin acetate display high rupture strengths but are fragile.100 Starch acetates are much less hygroscopic than non-modified starch.100 Using four samples of acetylated corn starch with a fixed (from 3.3 mass% to 66 mass %) content of amylose as examples, it was shown that esterification increases the solubility and swelling capacity of starch in organic media.99 Acetylated starch gels are less rigid and more elastic and transparent than the gels formed by the original starch.The low-amylose starch acetate is an exception. However, in contrast to native starch, the acetylated products are less biodegradable, since esterification prevents the action of enzymes on starch.99 Mixtures of acyl derivatives of starch with yet another biodegradable polymer, viz., poly-3-hydroxybutyrate (PHB), are highly recommended as candidates for starch compositions.101 The components of the polymeric composition are incompatible as evidenced from the independence of the positions of their characteristic absorption bands in the IR spectra on their ratio. However, the temperature and enthalpy of melting of partially crystallised PHB decrease after the addition of starch acetate, which affects the morphological properties of PHB crystallites and increases its ability for crystallisation.Carboxymethyl starch was obtained by treatment of yellow corn starch and pigweed starch (the degree of substitu- tion=0.1 ± 0.2) with chloroacetic acid.102 Small additions of carboxymethyl starch were used for the extrusion of various food stuffs derived from semolina. It was found that modified starch improves processing of these products. Elastic edible films were prepared from hydroxypropyl starch mixed with gelatine and plasticised with polyols and water (up to 25 mass%) by Arvanitoyannis et al.103 The permeability of these films for oxygen and CO2 increases with an increase in the content of the plasticiser in the system, which deteriorates the quality of packaging materials for food stuffs.Higher fatty acid esters of starch are promising reagents for mixing with non-polar polymers, such as PE and polypropy- lene.104 The reaction of starch with the corresponding acid chlorides in DMSO gave starch octanoates and dodecanoates with the degree of substitution of 1.8 and 2.7. The ester groups containing higher alkyl radicals improve the affinity of starch for the non-polar synthetic polymer and act as internal plasticisers. The compatibility of starch dodecanoate with PE is higher than that of starch octanoate. The starch dodecanoate ± PE mixtures manifest higher thermal stabilities, greater elongation at break upon rupture and lower moisture absorption than starch octa- noate ± PE mixtures.However, being introduced into PE at any ratios, these substances decrease the rate of biodegradation of the mixture in comparison with starch ± PE mixtures. Starches modified by the introduction of cholesterol resi- dues 105 and mixed with high-pressure PE were used for the production of blown films. In comparison with non-modified starch, these materials are more homogenous and more stable. Biodegradation in a compost of films prepared from these mixtures occurs even faster than that of non-modified starch ± PE mixtures, apparently due to the loosening of the starch structure caused by bulky cholesterol fragments. The preparation and investigation of properties of the systems based on chemically modified starch has found lesser application A I Suvorova, I S Tyukova, E I Trufanova than the preparation of systems from mixtures of native starch with other polymers.V. Conclusion Studies carried out in the past decades have demonstrated that biodegradable materials should combine high mechanical and other essential operational and technological properties (e.g., stability, low gas permeability, environmental safety, easy mould- ing, etc.) with biodegradability. Biodegradable materials based on starch or starch mixtures with synthetic polymers are the most readily available and have found wide practical application. The properties of starch-based polymeric materials including their biodegradability depend on the compatibility of the mixture components and the structure of the systems thus prepared.However, the thermodynamic and energetic characteristics of the interaction of starch with synthetic polymers within the mixtures and the structure of such systems are still poorly known. It is these properties of starch mixtures with synthetic polymers that must be subject of comprehensive analysis in order to establish the general regularities with the ultimate goal to select the components and technologies for the preparation of polymeric materials, which are stable in various media and biodegradable. The widening of the range of biodegradable polymeric systems is very important for future studies; therefore it is hoped that the results described in this review will be useful for further studies based on the use of this environmentally important scientific approach.References 4. A Calmon-Decriaud, V Bellon-Maurel, F Silvestre Adv. Polym. Sci. 1. K Z Gumargalieva, G E Zaikov Int. J. Polym. Mater. 35 179 (1997) 2. M Day, K Shaw, D Cooney J. Environ. Polym. Degrad. 2 121 (1994) 3. A-C Albertsson, S Karlsson Chem. Tecnol. Biodegrad. Polym. 7 (1994) 135 207 (1998) 5. G Swift, in Biodegradable Plastics and Polymers (Eds Y Doi, K Fukuda) (Amsterdam: Elsevier, 1994) p. 228 6. M R Timmins, R W Lenz Trends Polym. Sci. 2 15 (1994) 7. J Lorcks Polym. Degrad. Stab. 59 245 (1998) 8. E D Beach, R Boyd, N D Uri Sci. Total Environ. 175 219 (1995) 9. M Day, K Shaw, D Cooney, J Wafts, B Harrigan J Environ Polym. Degrad. 5 137 (1997) 10.G M Chapman ACS Symp. Ser. 575 29 (1994) 11. G J L Griffin Chem. Technol. Biodegrad. Polym. 18 (1994) 12. A-C Albertsson, S Karlsson Acta Polym. 46 114 (1995) 13. C Bastioli, in Degradable Polymers. Principles and Application (Eds G Scott, D Gilead) (London: Chapman and Hall, 1995) p. 112 14. V A Vasnev Vysokomol. Soedin., Ser. B 39 2073 (1997) a 15. M Vikman,M Itivaara, K Poutanen J. Environ. Polym. Degrad. 3 23 (1995) 16. S Urstadt, J Augusta R-J MuÈ ller, W-D Deckwer J. Environ. Polym. Degrad. 3 121 (1995) 17. I Kleeberg, C Hetz, R M Kroppenstedt, R-J MuÈ ller, W-D Deckwer Appl. Environ. Microbiol. 64 1731 (1998) 18. R L Shogren, B K Jasberg J. Environ. Polym. Degrad. 2 99 (1994) 19. J M W Blanshard, in Starch, Properties and Potential (Ed.T Galliard) (New York: Wiley, 1987) p. 16 20. K Poutanen, P Forssel Trends Polym. Sci. 4 128 (1996) 21. C M Durrani, A M Donald Polym. Gels Networks 3 1 (1995) 22. J P Robin, C Mercier, R Charbonniere, A Guilbot Cereal Chem. 51 389 (1974) 23. S P Rowland (Ed.) Water in Polymers (Symp. Ser.) (Washington, DC: American Chemical Society, 1980) 24. P Cairns, T Ya Bogracheva, S G Ring, C L HaÈ dley, V J Morris Carbohydr. Polym. 32 275 (1997) 25. J J G van Soest, H Tournois, D Dewit, J F G Vliegenthart Carbohydr. Res. 279 201 (1995) 26. D Benczedi, I Tomka, F Escher Macromolecules 31 3055 (1998)Biodegradable starch-based polymeric materials 27. T Galliard, P Bowler, in Starch, Properties and Potential (Ed. T Galliard) (New York: Wiley, 1987) p.55 28. D J Gallant, B Bouchet, P M Baldwin Carbohydr. Polym. 32 177 (1997) 29. W Ciesielski, P Tomasik Carbohydr. Polym. 31 205 (1996) 30. S Li, J Tang, P Chinachotti J. Polym. Sci., Part B, Polym. Phys. 34 2579 (1996) 31. A I Suvorova, I S Tyukova, E I Trufanova, in IUPAC Symposium on Molecular Architecture for Degradable Polymer (Abstracts of Reports), Stockholm, 1997 p. 128 32. G K Moates, T R Noel, R Parker, S G Ring Carbohydr. Res. 298 327 (1997) 33. M A Rao, P E Okechukwu, P M S Dacilva, J C Oliveira Carbohydr. Polym. 33 273 (1997) 34. A-I Yeh, J-Y Li J. Cereal Sci. 23 277 (1996) 35. C J A M Keetels, T van Vliet, P Walstara Food Hydrocolloids 10 343; 355; 363 (1996) 36. J K Jang, Y R Ryun Starch/StaÈrke 48 48 (1996) 37.G R Kereliuk, F W Sosulski Food Sci. Technol. 29 349 (1996) 38. B Madhusudhan, R N Tharanthan Carbohydr. Polym. 29 41 (1996) 39. J J G van Soest, R C Bezemer, D de Wit, J F G Vliegenthart Ind. Crops Prod. 5 1 (1996) 40. J P Mercier,G Groeninckx,M Lesne J. Polym. Sci., Part C (16) 2059 (1967) 41. H Potente, J Liu, A RuÈ cker Starch/StaÈrke 48 171 (1996) 42. G Della Valle, Y Boche, P Colonna, B Vergnes Carbohydr. Polym. 28 255 (1995) 43. J J G van Soest, K Benes, D de Wit, J F G Vliegenthart Polymer 37 3543 (1996) 44. J J G van Soest, K Benes, D de Wit, Starch/StaÈrke 47 429 (1995) 45. P M Forssell, J M Mikkila, G K Moates, R Parker Carbohydr. Polym. 34 275 (1997) 46. S H D Hulleman, F H P Janssen, H Feil Polymer 39 2043 (1998) 47.G Della Valle, A Buleon, P J Carreau, P-A Lavoie, B Vergnes J. Rheol. 42 507 (1998) 48. J J G van Soest,D de Wit, J F G Vliegenthart J. Appl. Polym. Sci. 61 1927 (1996) 49. J J G van Soest, S H D Hulleman, D de Wit, J F G Vliegenthart Carbohydr. Polym. 29 225 (1996) 50. J J G van Soest, P Essers J. Macromol. Sci., Pure Appl. Chem. A34 1665 (1997) 51. J G van Soest, D E Borger J. Appl. Polym. Sci. 64 631 (1997) 52. D Lourdin, L Coignard,H Bizot, P Colonna Polymer 38 5401 (1997) 53. S Govindasamy, O H Campanella, C G Oates Carbohydr. Polym. 30 275 (1996) 54. J L Willett, M M Millard, B K Jasberg Polymer 38 5983 (1997) 55. G J L Griffin Adv. Chem. Ser. 134 159 (1974) 56. BRD Appl. 2 322 440; Chem. Abstr. 80 134 242 (1974) 57.BRD Appl. 2 455 732; Chem. Abstr. 83 148 390 (1975) 58. F H Otey, R P Westhoff, Ch R Russel Ind. Eng. Chem., Prod. Res. Dev. 16 305 (1977) 59. US P. 4 133 784; Chem. Abstr. 90 122 500 (1979) 60. H RoÈ per, H Koch Starch/StaÈrke 42 123 (1990) 61. N St-Pierre, B D Favis, B A Ramsay, J A Ramsay, H Verhoogt Polymer 38 647 (1997) 62. G Scott Trends Polym. Sci. 5 360 (1998) 63. P Krishna Sastry, D Satyanarayana, D V Mochan Rao J. Appl. Polym. Sci. 70 2251 (1998) 64. S Simmons, E L Thomas J. Appl. Polym. Sci. 58 2259 (1995) 65. S Simmons, E L Thomas Polymer 39 5587 (1998) 66. P J Stenhouse, J A Ratto, N S Schneider J. Appl. Polym. Sci. 64 2613 (1997) 67. A D Sagar,M A Villar, E L Thomas, R C Armstrong, E W Merrill J. Appl. Polym.Sci. 61 139 (1996) 68. A D Sagar,M A Villar, E L Thomas, R C Armstrong, E W Merrill J. Appl. Polym. Sci. 61 157 (1996) 69. R L Reis, S C Mendes, A M Cunha,M J Bevis Polym. Int. 43 347 (1997) 70. U R Vaidya,M Bhattacharya,D H S Ramkumar,M Hakkarainen, A C Albertsson, S Karlsson Eur. Polym. J. 32 999 (1996) 71. D H S Ramkumar,M Bhattacharya, U R Vaidya Eur. Polym. J. 33 729 (1997) 72. D H S Ramkumar, Z Yang, M Bhattacharya Polym. Networks Blends 7 31 (1997) 459 73. D H S Ramkumar,M Bhattacharya, D Zhang Polym. Networks Blends 7 51 (1997) 74. D H S Ramkumar,M Bhattacharya J. Mater. Sci. 32 2565 (1997) 75. K Seethamraju, M Bhattacharya, U R Vaidya, R G Fulcher Rheol. Acta. 33 553 (1994) 76. U R Vaidya,M Bhattacharya J. Appl. Polym. Sci. 52 617 (1994) 77. M Bhattacharya, U R Vaidya, D Zhang, R Narayan J. Appl. Polym. Sci. 57 539 (1995) 78. U R Vaidya,M Bhattacharya, D Zhang Polymer 36 1179 (1995) 79. Z H Yang,M Bhattacharya, U R Vaidya Polymer 37 2137 (1996) 80. B Shi, P A Seib J. Macromol. Sci., Pure Appl. Chem. A33 655 (1996) 81. D Bikiaris, J Prinos, C Panayiotou Polym. Degrad. Stab. 56 1 (1997) 82. D Bikiaris, J Prinos, C Perrier, C Panayiotou Polym. Degrad. Stab. 57 313 (1997) 83. D Bikiaris, J Prinos, C Panayiotou Polym. Degrad. Stab. 58 215 (1997) 84. I Arvanitoyannis, I Kolokuris, A Nakayama, S Aiba Carbohydr. Polym. 34 291 (1997) 85. D R Coffin, M L Fishman J. Agric. Food Chem. 41 1192 (1993) 86. D R Coffin, M L Fishman J. Appl. Polym. Sci. 54 1311 (1994) 87. M L Fishman, D R Coffin, J J Unruh, T Ly J. Macromol. Sci., Pure Appl. Chem. A33 639 (1996) 88. E Psomiadou, I Arvanitoyannis, N Yamamoto Carbohydr. Polym. 31 193 (1996) 89. S V Kraus, A L Peshekhonova, O A Sdobnikova, L G Samoilova Khranenie Pererab. Sel'khozsyr'ya 6 11 (1996) 90. J M Mayer, G R Elion, Ch M Buchanan, B K Sullivan, Sh D Pratt, D L Kaplan J. Macromol. Sci., Pure Appl. Chem. A32 775 (1995) 91. A I Suvorova, E I Trufanova, in The MRS-96 Spring Meeting (Abstracts of Reports), San Francisco, 1996 p. 423 92. A I Suvorova, I S Tyukova, E I Trufanova J. Environ. Polym. Degrad. 7 35 (1999) 93. A I Suvorova, I S Tyukova, E I Trufanova, in The 5th Inter- national Science Conference `Biodegradable Plastics and Polymers' (Abstracts of Reports), Stockholm, 1998 p. 105 94. R L Reis, A M Cunha, P S Allan,M J Bevis Adv. Polym. Technol. 16 263 (1997) 95. M Scandola, L Finelli, B Sarti, J Mergaert, J Swings, K Ruffieux, E Wintermantel, J Boelens, B de Wilde, W-R MuÈ ller, A SchaÈ fer, A B Fink,H G Bader J. Macromol. Sci., Pure Appl. Chem. A35 589 (1998) 96. C Bastioli, A Cerutti, I Guanella, G C Romano, M Tosin J. Environ. Polym. Degrad. 3 81 (1995) 97. C Bastioli Polym. Degrad. Stab. 59 263 (1998) 98. R L Shogren Carbohydr. Polym. 29 57 (1996) 99. H J Liu, L Ramsden, H Corke Carbohydr. Polym. 34 283 (1997) 100. C Fringant, J Desbrieres, M Rinaudo Polymer 37 2663 (1996) 101. L L Zhang, X M Deng, S J Zhao, Z I Huang Polym. Int. 44 104 (1997) 102. M Bhattacharya,R S Singhal, P R Kulkarni Carbohydr. Polym. 31 79 (1996) 103. I Arvanitoyannis, A Nakayama, S Aiba Carbohydr. Polym. 36 105 (1998) 104. S Thiebaud, J Aburto, I Alric, E Borredon, D Bikiaris, J Prinos, C Panayiotou J. Appl. Polym. Sci. 65 705 (1997) 105. B G Kang, S H Yoon, S H Lee, J E Yie, B S Yoon, M H Suh J. Appl. Polym. Sci. 60 1977 (1996) a�Polym. Sci. (Engl. Transl

ISSN:0036-021X    

出版商:RSC    

年代:2000

数据来源: RSC