摘要:

Asymmetric Processes ANDREW C. REGAN Department of Chemiktry, University of Manchestel; Oxford Road, Manchester MI 3 9PL, UK Reviewing the literature published between January 1994 and March 1995 1 2 2.1 2.1.1 2.1.2 2.1.3 2.2 2.2.1 2.2.2 2.3 2.4 2.5 3 3.1 3.2 3.3 4 4.1 4.1.1 4. I .2 4.1.3 4.2 4.2.1 4.2.2 4.3 4.3.1 4.3.2 4.3.3 4.3.4 4.3.5 4.4 5 6 Introduction Chiral auxiliaries Reactions of enolates Alkylation Aldol reactions Other react ions Reactions of carbanions SAMP and RAMP hydrazones Other carbanions Michael additions of chiral nucleophiles 0 t her addit ion react ions Miscellaneous uses of chiral auxiliaries Chiral reagents Chiral bases Asymmetric protonation Other chiral reagents Chiral catalysts Oxidations Epoxidat ion Dihydroxylation Other oxidations Reductions Hydrogenation Other reductions Carbon-carbon bond forming reactions Catalytic asymmetric aldol reactions Other additions of carbon nucleophiles to carbonyl groups Palladium-catalysed reactions Cycloadditions Other carbon-carbon bond forming reactions Enzymes and antibodies Miscellaneous asymmetric processes References 1 Introduction This review covers the literature from January 1994 to March 1995.Since asymmetric synthesis is such an active area, it would be impossible to be exhaustive, and a highly selective choice of examples has had to be made. 2 Chiral auxiliaries 2.1 Reactions of enolates 2.1.1 Alkylation New chiral auxiliaries for the alkylation of enolates continue to appear, with various advantages being claimed for their use. The camphor-derived acylated auxiliary 1 gives uniformly high diastereoselectivities ( > 99.1 : 0.1) for alkylations of the sodium or potassium enolates, with only one example of slightly worse selectivity, of 99 : 1 for reaction with methyl iodide (Scheme l).' It is noteworthy that such high selectivities are obtained even for reactions with small electrophiles (such as methylation) since this is not the case for some widely used auxiliaries.Conjugate addition of the enolates to crotonate derivatives is also described, and the auxiliary is removed conventionally by reduction with LiAlH4. R2 dr 299.9:O.l Scheme 1 The use of pseudoephedrine as a chiral auxiliary for alkylations has been advocated by Myers.' It was found to be superior to ephedrine, giving different selectivities, and also conferring crystallinity on the derivatives.As with ephedrine, both enantiomers are available at a similar price to each other, although pseudoephedrine is currently substantially more expensive than ephedrine. Alkylations of the lithium enolates of N-acylpseudoephedrines 2 proceed in selectivities of 94 to >99% de, with lithium chloride being used to accelerate the reactions (Scheme 2). The auxiliary can be removed from the products 3 by several different methods, such as acidic hydrolysis, or reduction with either borane-lithium pyrrolidide or LiAl(OEt),H. It is also possible to convert the products directly into aldehydes (with LiAlH4 + EtOAc) or ketones (with RLi) . Regan: Asymmetric processesi. 2 LDA, LiCl ii. R ~ x OH Me R2 3 9699% de Scheme 2 Davies has introduced the cyclic urea derivative of trans-cyclohexane-l,2-diamine as an auxiliary with C2 symmetry.3 Both nitrogen atoms can be reacted to give the diacyl derivative 4, and both acyl groups can be alkylated via a chelated bis-syn-enolate (Scheme 3).The C2 symmetry means that there are only three possible diastereoisomers of the alkylation products 5, and the diastereoselectivity of each alkylation is greater than the ratio of isomers of products obtained (for example a ratio of products of 85 : 14 : 1 represents a 92 : 8 selectivity at each alkylation). The auxiliary is removed reductively using Et,B-AcOH followed by LiAlH4. The thione analogues were also investigated, but proved not to be useful because the enolates decompose. 0 + 2other isomers 4 5 R2 R' = Me, R2 = Pr, dr = >96:<3:(0) Scheme 3 The alkylation of 2-cyano esters of an isoborneol sulfonamide auxiliary 6 gives moderate (80 : 20) to good ( > 98: 2) diastereoselectivities (Scheme 4).4 The isomers 7 can be separated and then, unusually, v i.LDA ii.R2X, HMPA c R' 14 examples, dr = 80:20 to >98:2 i. separate isomers ii. H2. Rh-AI2O3 1 \/ 0 ' t . 2 ~ MeMgBr Et20 p& R' El R' 0 the auxiliary is removed by hydrogenation of the nitrile, followed by cyclisation to form enantio- merically pure disubstituted P-lactams 8. A new benzopyranoisoxazolidinone auxiliary for amide enolate alkylations has been reported;' rather than being derived from a starting material from the chiral pool, it is prepared in racemic form by a [3 + 21 nitrone cycloaddition, and then resolved with camp horsulfonic acid.2.1.2 Ado1 reactions The acylated chiral lactam 9 gives good selectivities for the syn-aldol products 10 ( ~ 9 7 % de) in the boron enolate aldol reaction,6 with the methyl group being a sufficiently bulky substituent on the lactam ring to give good stereocontrol (Scheme 5). The auxiliary is readily removed by LiOH, since the gem- dimethyl group hinders attack on the lactam carbonyl (attack of hydroxide on the oxazolidinone carbonyl of Evans' auxiliaries can be a problem during removal). Alkylation reactions give similar stereoselectivities to those obtained using Evans' oxazolidinone auxiliaries. Me$~kMe 0 0 i. BupBOTf MedNv,,,., Me ii. PhCHO Me \ \ Me Me 84% 9 10 de >97% Scheme 5 Other new auxiliaries reported for asymmetric aldol reactions include a camphor-derived oxazolidinone which, unusually, gives good selectivities (86 : 14 to > 99 : 1) for boron aldol reactions of the unsubstituted acetyl derivative 11 (Scheme 6).7 The stereoselectivities are explained by invoking a boat-like non-chelated transition state.The acylated camphor-derived bicyclic lactam 12 gives reasonably good selectivity for one of the syn- aldol products; however the isomer 13 gives a syn :anti ratio of only 2.2 : 1 with isobutyraldehyde (Scheme 7).' The oxazinanone auxiliary 14 is derived from gulonic acid via a nitrene insertion reaction, and its N-propionyl derivative gives good syn-selectivity in a lithium enolate aldol reaction 11 i. 9-BBN-OTf CHpCI, 2. RCHO R 0 9 examples, dr 86:14 to >99:1 Scheme 4 2 Contemporary Organic Synthesis Scheme 6R' R = alkyl, cycloalkyl, aryl 9 examples, 73-97% de Scheme 7 Scheme 9 with benzaldehyde.' Diels-Alder reactions using the corresponding a,/?-unsaturated amides as dienophiles with cyclopentadiene are also successful.The auxiliary can be removed from the products by reduction with LiBH4 without epimerisation, in contrast to a similar galactose-derived auxiliary. Asymmetric aldol additions of chiral enolates on to ketones are not generally as reliable as those on to aldehydes. To circumvent this problem the aldol reaction of an achiral silyl enol ether or silyl ketene acetal on a chiral a-keto ester 15 has been described (Scheme 8).1° The auxiliary is derived from L-quebrachitol, a natural cyclitol from the rubber tree.The tin-mediated aldol reaction proceeds in 94-98% de and allows access to tertiary alcohol products. n TBDMS R z;S (or TBDMS) SnC12, CH2C12 X = Bu', OR' R * O > X " 0 6 examples, de 94 to >98% 15 Scheme 8 2.1.3 Other reactions A new synthesis of a-amino acids is based on the copper-catalysed addition of Grignard reagents to the a,/?-unsaturated oxazolidinone 16 (Scheme 9)." The stereoselectivity arises during protonation of the intermediate chiral enolate formed during the Michael addition step. The use of aryl and vinyl Grignard reagents results in complete selectivity, however alkyl Grignard reagents are less selective. The stereoselectivity is improved at higher tempera- ture and the auxiliary can be removed by hydrogenation, although it is destroyed during this process.Another asymmetric synthesis involving Michael addition uses a chiral imidazolidinone enolate as the nucleophile reacting with an achiral acceptor; the addition is followed by intramolecular alkylation to generate chiral cyclopropanes of potential biological interest . I 2 Finally, lithium enolates of acylated Evans' oxazolidinones have been coupled using titanium tetrachloride to give dialkyl succinic acid derivatives, with good selectivity for one of the chiral isomers over the me~o-forrn.'~ 2.2 Reactions of carbanions 2.2.1 SAMP and RAMP hydrazones New applications of Enders' SAMP, RAMP [(S)-( -)- and (R)-( +)-l-amino-2-(methoxy- methy1)pyrrolidinel and related hydrazones continue to be reported. The SAEP [(S)-l-amino-2-( l-ethyl- l-methoxypropyl) pyrrolidine] hydrazones of allyloxy aldehydes 17 are deprotonated by lithium diisopropylamide (LDA) and then undergo [2,3] Wittig rearrangement with good diastereoselectivity (Scheme lo), which is higher than with the corresponding SAMP hydrazones.I4 Previously used chiral auxiliaries for the [2,3] Wittig rearrangement have generally been carboqlic acid derivatives.As well as hydrolysis to the protected a-hydroxy aldehydes, the hydrazone products 18 can also be converted to nitriles, using a method which has also been reported for alkylated hydrazones.15 SAMP hydrazones of silyl protected a-hydroxy aldehydes undergo alkylation with good selectivity ( > 87% ee after removal of hydrazone), but in low yield because of difficult deprotonation.Changing the protecting group to benzyl or BOM (benzyloxymethyl) gives higher yields but lower selectivities. Ally1 Grignard reagents add to SAMP hydrazones of aldehydes in the presence of CeCl,; cleavage of the hydrazine product with methyl chloroformate results in protected homoallylic amines in 90-98% ee, which have been ozonolysed to give optically active protected /?-amino acids." Radical addition of Bu,SnH to an allene results in an alkenyl radical which undergoes intramolecular attack onto a SAMP hydrazone to give a cyclopentene; however the selectivity is only 50% de." Me0 Me0 k/ ~.LDA. A/ N' THF-HMPA f 3 ' ~ 0 , J - ( ~ ii. TBDMSCI -78% a,, A2 17 OTBDMS 18 81-92% de Scheme 10 Regan: Asymmetric processes 32.2.2 Other carbanions An asymmetric synthesis of epoxides depends upon methylene transfer to ketones from a sulfoximine 19 which also bears a chiral ligand derived from menthol (Scheme 1 l).I9 Previous examples involving methylene transfer from sulfoximines with stereo- genic sulfur atoms rather than chiral ligands have given low ees (<40%).Me - , i.NaH-DMSO I\ 4 examples R' = Ar, R2 = H, alkyl 5646% 88 Scheme 11 Asymmetric Wadsworth-Emmons reactions can be used to desymmetrise ketones during the alkene synthesis. Menthol-derived phosphonates have previously given only moderate selectivities; however the camphor-derived phosphonate 20 gives the alkene 21 in 86% ee (Scheme 12).20 The isomer of 20 which is epimeric at the phosphorus atom is much less selective. O 20 B u ' a C02Me Bu'eo THF. -35 "C, 48 h' 79% 21 86% ee Scheme 12 The anions of chiral phosphonamides derived from cyclohexane-l,2-diamine can be reacted with sulfonyl azides, which following hydrolysis and reduction results in an asymmetric synthesis of a-aminophosphonic acids (in 63-99% ee), which are of interest as analogues of a-amino acids and peptides.2' A chiral auxiliary has been applied for the first time to the [2,3] sigmatropic rearrangement of sulfonium ylides;" the auxiliary is attached directly to the sulfur by a rhenium atom, and gives products in 86-98% de.2.3 Michael additions of chiral nucleophiles The enamine derived from the cyclic P-keto ester 22 and cx-methylbenzylamine adds to acryloyl chloride in the presence cf a Lewis acid to give 23, which has a stereogenic quaternary centre (Scheme 13).23 The ester group in 22 deactivates the enamine, which then requires a reactive electrophile for satisfactory c ow BFpOEt,, reflux PhH 22 ii.~ ' C O C I THF. reflux Ph 85% 23 Scheme 13 reaction. A closely related enamine has been deprotonated with LDA, and undergoes Michael addition to an alkene with two ester activating groups in 95% ee after hydr~lysis.~~ Opposite selectivities are obtained in THF and in toluene with addition of hexamethylphosphoramide (UMPA). The enamine formed between ct-methyl- benzylamine and acetylbutyrolactone adds to acrolein or methyl vinyl ketone; cyclisation via an aldol-dehydration sequence gives spiro bicylic ketones with a stereogenic spiro centre.25 The same chiral amine has been used to form enamines with 4,4-disubstituted cyclohexanones; intramolecular Michael addition followed by hydrolysis then gives bridged bicyclic ketones (for certain bridge sizes) in up to 90% ee.26 A number of examples of Michael addition of chiral nitrogen-centred nucleophiles to a$-unsaturated esters have been reported, as a route to P-amino acid derivatives.Trapping of the intermediate enolates with electrophiles has also been studied. For example, Davies has found that the alkylation of the intermediate enolate formed by addition of the lithium amide 24 to the ester 25 is not very elective.^' However if the enolate is generated in a separate second step, a high selectivity for the anti-isomer 26 is obtained, because of different enolate geometries being involved (Scheme 14).On the other hand, using the magnesium analogue of 24 does allow methylation of the intermediate enolate to give the opposite syn- isomer in 90% de." If the unsaturated ester is already substituted with a-methyl group, then , PhhN' Li Ph INJh0 2. Me1 1 25 ii. H30+ Scheme 14 Me 26 30: 1 4 Contemporary Organic Synthesisprotonation of the intermediate lithium enolate gives the same syn-isomer in 98% de.29 Electrophilic hydroxylation of the intermediate lithium enolate using Davis' oxaziridine gives the anti-a-hydroxy- p-amino ester, usually in >90% de," and this has been applied to the synthesis of the Tax01 side chain.3' esters are possible using the lithium amides of TMS- SAMP 27 (Scheme 15).32 If methyl esters or unsilylated SAMP are employed instead, then 1,2- rather than 1,4-addition is observed.The inter- mediate lithium enolates have also been alkylated, using HMPA as an additive, to give the anti-isomers in > 96% de.33 The enantiomeric anti-a-methyl- p-amino ester has also been formed by methylation of the enolate resulting from Michael addition of the lithium amide of a resolved dinaphtha~epine.~~ Similar types of Michael addition to tert-butyl L O M e H' 'SiMe3 F: N 27 i. BuLi, THF, -78 "C 0 3247% Scheme 15 93-9870 de 5046% NH2 0 R i 4 0 H -98% ee Related to the above methods, achiral lithium amides have been added in conjugate fashion to a chiral oxazole derivative of naphthalenecarboxylic acid, with methylation of the intermediate anion, in 99% de.3s 2.4 Other addition reactions Nucleophilic addition of silyl enol ethers or ally1 silanes to iminium ions 28 substituted with a chiral pyrrolidine auxiliary results in alkylpyrrolidinones 29 in up to 98% de (Scheme 16).36 The auxiliary can be cleaved by borane and recycled.In a similar process, a silyl ketene acetal adds to a chiral imine of benzaldehyde to give, after cleavage of the auxiliary, p-amino esters in 88% ee.37 Chiral primary amines can be prepared using a similar strategy, by addition of Grignard reagents to benzaldehyde imines which are N-substituted by camphor-derived sulfenimines or ~ulfinimines.~' Imines prepared from a-methyl- benzylamine and highly substituted ketones can be reduced by borohydride, followed by destructive removal of the auxiliary by hydrogenation, to give neopentyl primary amines in 84-97% ee.39 to pyridine-3-carbaldehyde derivatised as a chiral Lithium organocuprate reagents have been added 13 examples, I up to >99:1 dr 29 Scheme 16 FOR2 @%:, i.R12CuLi ii.R~COCI a&" Me R1 Ph Me Ph 30 up to ~ 9 5 % de Scheme 17 5% HCI aq I ?OR2 0 CHO R 1 31 N,N-acetal30 (Scheme 17), with high selectivity for attack at C-4, and in up to 95% de in a route which gives access to protected chiral 174-dihydropyridines The well-known Diels-Alder addition of chiral fumarate esters as dienophiles has been extended to the use of chiral maleate esters of 2-phenylcyclo- hexan01.~* Lewis acid-catalysed addition to cyclopentadiene gives the endo-adduct in 99 : 1 dr. The N-acryloyl derivative of proline benzyl ester has been used in a 1,3-~ycloaddition to an azomethine ylide to give substituted pyrrolidines in 82-98% de.43 3 1.40.41 2.5 Miscellaneous uses of chiral auxiliaries A chiral binaphthyl has been prepared by asymmetric Ullmann coupling of two molecules of a bromonaphthalene bearing an oxazoline chiral auxiliary, in a dr of 32 : 1 .44.45 Ullmann coupling of bromoaryl oxazolines results in chiral biaryls in a de which increases with time from 26% to 86%, as a result of thermodynamic eq~ilibration."~ Intra- molecular Ullmann coupling of two bromonaphthol Regun: Asymmetric processes 5Rr 'r' 'OBn i YO 37 80% ee 32 100% de Scheme 20 Scheme 18 units linked by a tartrate-derived tether as in 32 proceeds in 100% de (Scheme 18), and the tether can be removed with N-bromosuccinimide (NBS) to give binaphth01.~~ Several new syntheses of chiral sulfoxides employ- ing auxiliaries have appeared.The mixture of isomeric chlorosulfite esters 33 reacts with dimethyl zinc to give mainly one sulfinate ester 34 (Scheme 19); the phenylcyclohexanol auxiliary is then displaced with a Grignard reagent with inversion to give the sulfoxide 35.48 The same type of Grignard reaction on tert-butylsulfinate esters of diacetone glucose has the attraction that either diastereo- isomer of the sulfinate can be prepared depending upon the conditions of esterification, allowing access to either enantiomer of the s~lfoxide.~~ Stoichiometric chiral ruthenium complexes of alkyl methyl sulfides can be oxidised quantitatively with dimethyldioxirane, and treatment with sodium iodide then releases the sulfoxide in up to 98% ee.5" B B 33 97%- 34 96:4 dr Scheme 19 The optically pure sulfoxide 36 (R = Bn) undergoes an intramolecular Pummerer reaction with chirality transfer to give the P-lactam 37 in 80% ee (Scheme 20).5' Replacement of the benzyl group with R = (S)-or-methylbenzyl results in a modest enhancement of the selectivity to 85% de.One approach to the synthesis of epoxides which also results in carbon-carbon bond formation is the reaction of a sulfonium ylide with an aldehyde or ketone. Sulfonium ylides bearing a chiral auxiliary have been prepared as diastereoisomeric mixtures at the sulfur atom, and reacted with aldehydes to give trans-disubstituted epoxides in variable ees of 0-43%.52 The Pauson-Khand reaction has recently been extended to include the use of chiral auxiliaries, and an intramolecular example uses a chiral acetal a~xiliary.'~ 2-Phenylcyclohexanol has also been used as an auxiliary for this reaction, in both inter-54 and intra-m~lecular~~ examples.A polymer supported C2-symmetric pyrrolidine auxiliary has been used for asymmetric iodolactonisaton reaction^.^^ anti- P-Amino alcohols have been prepared in 90-93% ee by reaction between aldehydes and a chiral ally1 borane containing a terminal nitrogen atom, in a process which unusually creates a 1,2-difunctionaI molecule by construction of the 1,2-C-C bond as well as the two chiral centres.57 The proline-derived enamine of cyclohexanone 38 undergoes palladium- cataiysed allylation to give 39 in >98% ee (Scheme 2 1 y n ~ O A C 0 Pd(PPh&, 0.1 equiv. PPh3, 4 equiv.CHC13, reflux 0 39 38 >98% ee Scheme 21 Lastly, Ley has introduced the bis(dihydropyran) 40 as a chiral protecting group for polyols (Scheme 22).59360 Asymmetric protection of a symmetrical polyol such as 41 takes place with complete Me %Me + HO' "OH 40 OBz 41 CSA, CHC13 reflux Me 70% BnO OBn HO BnO-oH -- BnO 43 42 100%de Me Scheme 22 6 Contemporaiy Oiganic Synthesisselectivity to give the 'matched adduct' 42, where both methyl groups are equatorial, and all the spiro oxygen atoms are mutually axial. The other hydroxy groups can then be manipulated conventionally, followed by removal of the dispiroketal, to give the chiral protected cyclitol 43. Acrylate esters of dispiroketal diols have also been employed in asymmetric Michael and Diels-Alder reactions.61'62 3 Chiral reagents 3.1 Chiral bases Several applications of chiral lithium amide bases have appeared.Arene chromium tricarbonyl complexes, e.g. 44 have been deprotonated with 45 and trapped with TMSCl to give the chiral complex 46 (Scheme 23)."' The base 47 has been used in aldol reactions to give Jyn-products from ketones and anti-products from hindered esters (Scheme 24).64 In order to obtain good selectivity, both coordinating methoxy groups in 47 are required, and the amine also has to be deprotonated a second time with BuLi in the reaction, before addition of the aldehyde. Me Me PhLNh Li Ph 45 - TMSCI, THF, -78 "C 'cr(C0)3 83% 44 Scheme 23 Pri, pJSiMe3 . . 'cr(co), 46 84% ee i. MeOn8-OMe HO 1 0 TMEDA Ph' 47 - ii. BuLi iii. PhCHO Scheme 24 tie 78% ee Koga has reported full experimental details for the preparation of his phenylglycine-derived bases,65 and Majewski has used this type of base with LiCl as an additive to deprotonate tropinone in up to 92% ee.66 The symmetrical cyclopentene epoxide 48 has been deprotonated and ring opened in 95% ee using the readily available dilithiated norephedrine 49 to give 50 (Scheme 25),67 which is an inter- mediate for the sythesis of carbovir.Similar work on the silyl-protected trans-epoxide using a proline- derived base has also been reported, including the conversion of the product into (-)-ca~bovir.~~ The same group has also used catalytic amounts of the same base, with a stoichiometric amount of LDA, to open cyclohexene epoxide in 75% ee with 0.2 equiv.of base, and 59% ee with only 0.05 equiv. of base.69 6" 0 48 Scheme 25 LiHN MeWPh OLi 49 66% * HO p" 50 95% ee Chiral metal alkoxide bases have been much less studied, however 51 has been used for the Michael addition shown in Scheme 26, giving 52 in 84% ee, with other examples showing less sele~tivity.~~ Exactly the same reaction has also been carried out using sodium hydride or tert-butoxide in the presence of 0.1 equiv. of a camphor-derived crown ether, in 83% ee, although other examples showed moderate ~electivity.~' A norephedrine-derived potassium alkoxide has been used for an elimination reaction on a symmetrical 1,2-dibromide, to give a chiral exocyclic bromoalkene in good yield and > 99% ee after recry~tallisation.~~ Chiral lithium amide bases were not effective in this reaction. i.H2N OLi 51 C02Me THF, -78 OC Ph' 'C02Me * Ph LC02Me 52 84% ee ii. CHpCHC02Me 68% Scheme 26 Butyllithium in the presence of the natural chiral diamine (-)-sparteine has been used by Beak in a number of asymmetric reactions. N-tert-Butoxy- carbonylpyrrolidine is deprotonated by this system, and the anion can be reacted with a range of electrophiles in 59-96% ee.73 The anion generated by ortho-lithiation of the benzamide 53 reacts with alkyl chlorides in up to 95% ee (Scheme 27),74 and interestingly gives the opposite enantiomer of the products using alkyl toluene-p-sulfonates instead of bromides. pi2NYo P+2NYo 9 i. Bu'Li, (-)-spamine ii. RX (X = CI, OTs) 52-95?-!0 ee 53 Scheme 27 3.2 Asymmetric protonation Several examples of protonation of achiral enolates or enol equivalents by chiral proton donors have appeared, and some of these are shown in Table 1.Regan: Asymmetric processes 7Table 1 Asymmetric protonation reactions Entry Proton Donor Substrate ee Ref. HO Me ~ B u 94% OSiR3 binaphthol + SnCI4 6" 79-96% Ph o$eph & I'I-C,,H~~ 96% 75 76 77 78 79 80 There are now several examples of protonation in high ee using simple chiral reagents, some of which are commercially available (eg. entry 1). Protona- tion using a catalytic quantity (0.2 equiv.) of N-isopropylephedrine is possible (entry 3), with a ketone present as the stoichiometric proton source. Silyl enol ethers are represented by entry 4, where the commercially available binaphthol is the protic acid, assisted by SnCl, as a Lewis acid.In entry 5, a silyl enol ether is first converted into the lithium enolate, and in entry 6 it is protonated by a polymer-bound ester of a chiral a-hydroxy acid in high ee, whereas use of the methyl ester instead surprisingly gives no asymmetric induction at all. 3.3 Other chiral reagents Several applications of enolates generated by chiral reagents have appeared. Mukaiyama has extended his tin-mediated aldol reaction to protected or-hydroxy thioesters 54 (Scheme 28),81 where the choice of protecting group determines whether the reaction proceeds by a chelated or open transition state, allowing access to either the syn- or anti-aldol products. Chiral boron reagents designed with the aid of molecular modelling have also been used for aldol reactions of a-alkoxy and a-halo thioesten8* A boron enolate is also involved in the first example of a [2,3] Wittig rearrangement involving a chiral reagent (Corey's bis-~ulfonamide),~~ rather than a chiral auxiliary. A titanium enolate is presumed to be an intermediate in the reaction of diketene with benzaldehyde, promoted by titanium tetraisoprop- oxide and a chiral Schiff base,84 and the product is * R m S E t St1(0Tf)~, BUS~(OAC)~ (2-0 OSiMe3 / SEt +RCHO Et OBn CH2C12, -78 "C OBn i- 54 antksyn 298:2 9598% ee Scheme 28 ( )(OYo)Ti C02Bn C02Bn O Ph xo Ph 2 & C02Bn d C 0 2 B n 12, CUO, CH2C12 I 96% i - 85% ee Scheme 29 equivalent to an aldol reaction between benzalde- hyde and the y-carbon of isopropyl acetoacetate, in 84% ee.Scheme 29 shows an intramolecular iodine- promoted alkylation of a malonate, which is also presumed to proceed via a chiral titanium en01ate.~~ Other titanium-based chiral reagents include the use of a titanium dichloride coordinated by a tartrate-derived diol for the conjugate addition of dialkyl zinc reagents to nitroalkenes in 68-90% ee.86 A chiral titanium reagent has also been used for the addition of trimethylsilyl cyanide to aldehydes shown in Scheme 30.*' The chiral sulfoximine reagent 55 is prepared by a Kagan asymmetric oxidation, and the reaction is useful in that it forms the silyl-protected cyanohydrins directly, and as the (S)-enantiomers, which are less readily available by enzymatic methods.i. B O H H OH * RxCN 55 RCHO + Me3SiCN Ti(OPr'), 74-91~~ ee ii. 5% HF aq. Scheme 30 Thiols have been used for the asymmetric ring- opening of symmetrical aziridines in up to 88% ee, using a reagent prepared from diethylzinc and diiso- propyl tartrate.88 A rather different reaction which also uses zinc and tartrate-derived reagents is the asymmetric Simmons-Smith cyclopropanation shown in Scheme 31," which has also been more recently improved for larger scale reactions." A chiral aluminium tris(binaphtho1ate) has been used to promote an asymmetric Claisen rearrange- ment at -78 "C in 61-92% ee,91 and the selectivity has been rationalised by modelling studies, with the aluminium reagent creating a chiral pocket which 8 Contemporaiy Oeanic SynthesisR' I R' I 91-94% ee Scheme 31 folds the ether in the correct conformation for rearrangement.4 Chiral catalysts 4.1 Oxidations 4.1.1 Epoxidation Several developments in the asymmetric epoxidation of unfunctionalised alkenes using Mn-salen catalysts, e.g. 56, have been reported by Jacobsen (Scheme 32).An improved synthesis of the catalyst allows the preparation of 56 on both laboratory and 100 kg scales.92 A detailed study of epoxidation of cis-cinnamate esters found that steric effects were important, with isopropyl esters giving higher ees than methyl or ethyl The Jacobsen method works well for conjugated cis-disubstituted alkenes, but gives slower rates and poorer ees (<65%) for trans-disubstituted alkenes. However, cis-disub- stituted alkenes can be converted into the trans- epoxides in a non-concerted oxidation, allowing rotation about the C-C bond in an intermediate, using catalyst 57 with the addition of a quinine derivative (Scheme 33).94 Epoxidation of cyclic conjugated dienes usually gives only moderate ees, with catalyst 57 being more selective than 56, although 2-acetoxycyclohexa-1,3-diene reacts in 90% ee.9s Dihydronaphthalene 59 is epoxidised in 86% ee, however this can be improved to >98% ee by selectively removing the minor enantiomer of the product in a kinetic resolution by an unusual (7 56 R = Bu' ~ ~ R = o s P ~ ~ 58 R = OMe Scheme 32 NaOCI.57 (4 mol%) * 4Me+PhAMe PhCl quininederived sait ' (25 mol%) p~ Ph-Me 955 81% ee Scheme 33 Regan: Asymmetric processes 59 Scheme 34 --0 86% ee '0 298% ee + asymmetric C-H hydroxylation (Scheme 34), with this second step requiring a change of catalyst.96 The same substrate 59 has also been epoxidised in 70% ee using a manganese complex of a chiral porphyrin, which can itself be prepared in one step from pyrrole and an optically active aldehyde.97 Trisubstituted alkenes have been found to be good sustrates for the Jacobsen epoxidation, but give the opposite sense of induction to that expected by extrapolation of results from the cis- and trans- disubstituted cases.98 A different Mn-salen complex has also been used for epoxidation of trisubstituted alkenes by K a t ~ u k i .~ ~ A synthesis of optically active cyclobutanones relies on Sharpless epoxidation of the cyclopropane 60 (Scheme 35); the spiro epoxide intermediate is not isolated, but underogoes spontaneous ring expansion to give 61 in very high yield and enantioselectivity.60 Scheme 35 TBHP (+)-diethyl tartrate Ti(OPr'), 3 A mol. sieves Me OTBDMS 61 - - 98% 95% ee 4.1.2 Dihydroxylation A considerable amount of work has appeared on the Sharpless asymmetric dihydroxylation (AD) reaction, which is successful for many types of unfunctionalised alkene (Scheme 36 shows typical conditions). A comprehensive review by Sharpless has appeared,""' and must be considered essential reading for any chemist planning to use this reaction. Sharpless has also made a comparison of K2CO3 3 equiv. H20-Bu'OH 1:l MeS02NH2 1 equiv. R'+R2 OH Scheme 36 9the various ligands which have been proposed for the AD reaction, and concludes that his (DHQD),PHAL ligand (hydroquinidine 1,4-phthal- azinediyl diether) is superior to those suggested by others.'" The asymmetric AD reaction has been extended to several different classes of alkene.trans- 1,2-Disubstituted allylic halides react successfully if the reaction is buffered with NaHC03 to suppress hydrolysis of the halide and epoxide formation,lo2 although unsubstituted ally1 iodide reacts in only 70% ee. The halo diol products were also converted to hydroxy epoxides with NaOH. Alkenes containing allylic sulfide, disulfide and dithiane functionalities react preferentially at the alkene double bond without oxidation of the sulfur atom, for reasons which are unclear.1o3 cis- 1,2-Disubstituted alkenes are normally poor substrates for the asymmetric AD reaction, however with cis-allylic alcohols the free OH group enhances the selectivity, presumably via hydrogen bonding.lo4 On the other hand, in a trans- allylic alcohol, the hydroxy group has a varying and deleterious effect,"' and in some geraniol deriva- tives the AD reaction is selective for the double bond remote to the hydroxy group.Cyclic cis-disub- stituted conjugated alkenes have also been studied, and give variable ees, with a few being greater than 9O%.lo6 A protected benzene-1,Zdiol 62 gives much better selectivity than cyclohexa-1,3-diene (Scheme 37) and has been used as the basis of an asymmetric synthesis of conduritol E 63.'07,'0s Ally1 and vinyl silanes undergo the AD reaction with moderate ees, except when the alkene is trans- 1,2-disub~tituted.'~~ A study of the AD reaction of polyenes concludes that, for non-conjugated cases the subsititution pattern and steric effects determine the regio- selectivity, and for conjugated polyenes the more electron rich double bond reacts if it is sterically accessible.However there are several exceptions, and the level of predictability is not high."' Anoma- lous stereoselectivity has been reported in the case of 1,l-disubstituted alkenes, which give the opposite for the conversion of stilbene into hydrobenzoin on a 1 kg scale in a flask of only 5 1 v01ume."~ Other applications include the preparation of the Tax01 side chain,'14 preparation of carbohydrates by combining the AD reaction with an enzymatic aldol reaction,"' and the preparation of a precursor for Mosher's acid.'16 C ~ r e y " ~ and Sharpless"' have each proposed models to rationalise the stereoselectivity.The models are similar, but differ in the conformation of the aromatic spacer in the transition state, and in the location of the alkene. Sharpless also proposes an L-shaped cleft, as opposed to Corey's U-shaped pocket. Sharpless has made a detailed kinetic study of the reaction, showing that the rate is influenced mainly by the 0-9 substituent of the alkaloid ligand.'" It is proposed that this substituent gives to rise to a stabilising stacking interaction with the alkene in the transition state, and molecular model- ling studies on the osmaoxetane intermediate in the [2 + 21 pathway support this.120 A revised mnemonic to predict the outcome of asymmetric AD reactions is also given."' 4.1.3 Other oxidations The Kagan asymmetric oxidation of aryl sulfides to sulfoxides has been scaled up to the multi-kilogram level in the synthesis of a pharmaceutical inter- mediate 64 (Scheme 38).12' This asymmetric oxida- tion has also been applied to some organometallic sulfides, including ferrocenyl"' and tricarbonyl( $- arene)chr~mium'~~ examples.Sulfides have also been oxidised in moderate ees using a stoichio- metric amount of a camphorsulfonylimine and hydrogen peroxide;124 however catalytic turnover of the imine is possible using smaller amounts, and interestingly, dialkyl sulfides are the substrates which give some of the best results. Ph Ph enantiomer to that predicted by the general empirical rule."' OH 64 98-99% 00 Scheme 38 63 H 62 85% 88 Scheme 37 A polymer-supported AD catalyst has been prepared by polymerising alkenes derived from DHQ and DHQD with ethylene glycol dimethacryl- ate."' This gives a heterogeneous AD reaction which is almost as enantioselective as the normal reaction.Several useful applications of the AD reaction have been reported, including experimental details Kinetic resolution in the asymmetric Baeyer- Villiger oxidation of cyclic ketones to lactones has been achieved using a chiral copper catalyst 65 and molecular oxygen, with an aldehyde present as an oxygen atom acceptor (Scheme 39). The asymmetric Baeyer-Villiger oxidation has previously only been effectively achieved using enzymes. Cyclohexene undergoes allylic oxidation using a copper catalyst and a bis-oxazoline ligand in 77% ee, which is the best enantioselectivity yet achieved for catalytic allylic oxidation."' 10 Contemporaly 07ganic SynthesisU &Ph 69% ee Scheme 42 Scheme 39 4.2 Reductions 4.2.1 Hydrogenation Asymmetric hydrogenation of alkenes using Rh or Ru catalysts and chelating diphosphine ligands has been intensively studied for many years now. Full details have appeared of the preparation of isoqui- nolines by hydrogenation of (2)-enamides (Scheme 40);'26 the N-acyl function is essential as a tether for the catalytic metal centre, and this is a common feature of this type of asymmetric hydgrogenation. A new ferrocenyl diphosphine ligand'27 has been used for enantioselective hydrogenation of a$-unsaturated ketones and P-keto esters, and also for allylic alkylation and hydroboration. A new cationic 2,2'-bis (dipheny1phosphino)-1,1 '-binaphthyl (B1NAP)-RU catalyst is useful for hydrogenation of mubstituted P-keto esters, a-keto and a-hydroxy esters, and also allylic alcohols and a$-unsaturated acids 'Ar \Ar up to 99.5% ee Scheme 40 The asymmetric hydrogenation of ketones which lack an extra heteroatom to anchor the Ru or Rh catalyst is much more difficult to achieve; however Noyori has developed a practical method for aromatic ketones (Scheme 41),'29 which uses a chiral 1,2-diamine 66 to enhance the activity of the catalyst, which would normally not be active for this reduction. Buchwald has used a catalyst prepared from the chiral titanium-binaphthol complex 67 for the H2 RuC12(BIN~)(drnf), KOH.Pr'OH, II P h h H I 66 OH Ar 'R H2N Ar/l;\R 88 to >99% ee H2, 80 psi 9!5-99% ee hydrogenation of imines'" (Scheme 42) and enamines.'31 Cyclic imines work well, usually giving 95-99% ee at 80 psi of hydrogen; acyclic imines require up to 2000 psi and give lower enantio- selectivities.Enamines also work well, giving products in 89-98% ee at 15 or 80 psi of hydrogen. The same complex 67 has also been used with poly- methyl hydrosiloxane to give asymmetric hydrosilyla- tion of alkyl aryl ketones;13* desilylation gives the secondary alcohols, usually in >95% ee, however the enantioselectivities are much lower for dialkyl ketones. Hydrogenation of acyl hydrazones 68 using a DuPHOS-Rh catalyst (Scheme 43) has been used to achieve overall asymmetric reductive amination of ketones.'33 The acyl hydrazine products are reductively cleaved with SmI, to give the chiral primary amines, or alternatively can be hydrolysed to the hydrazines.68 DuPHOS = 1,2-bis[(2S,5S)-2,5-dialkylphospholan-l -yl]bentene Scheme 43 4.2.2 Other reductions Palladium-catalysed asymmetric reduction of allylic carbonate esters has been used to form a-chiral terminal alkenes with transposition of the double bond (Scheme 44).134 Formic acid is used as the reducing agent, and unusually, a monodentate phosphine ligand, e.g. (R)-MOP, is required, since with BINAP the reaction is both slow and not very selective. The same reaction has been used on vinyl silanes to give chiral ally1 ~i1anes.l~~ Chiral oxaborolidines are now widely used catalysts for asymmetric reductions using borane. New oxaborolidines have appeared, such as 69, which is formed in situ from the corresponding ~ R1p OC02Me Pd2($afigFC'3 proton sponge HCOzH R2 8 examples, 75-87% ee MOP = 2-(diphenylphosphino)-2'-methoxy-l,1 '-binaphthyl Scheme 41 Regan: Asymmetric processes Scheme 44 1169 70 Scheme 45 amino alcohol (Scheme 45).136 The oxaborolidine 70 is formed from the amino indanol, which is prepared in both enantiomeric forms via asymmetric epoxidation on an industrial scale, and is now commercially available.37 Polymer-supported oxaborolidines have been used for reductions of aryl alkyl ketones, with enantioselectivities almost as good as with the non-polymer-supported catalyst.138 4.3 Carbon-carbon bond forming reactions 4.3.1 Catalytic asymmetric aldol reactions The Mukaiyama aldol-type reaction of silyl ketene acetals of acetate thioesters (Scheme 46) is catalysed by l,l'-bi(2-naphthol) (BINOL)-TiC12, and it has been established by crossover experiments that a 15 examples, 60-95% ee Scheme 46 direct intramolecular transfer of the silyl group to the aldehyde occurs.139 With the ketene acetals of propionate thioesters, the syn :anti selectivity is dependent upon the geometry of the ketene acetal, and this suggests that a cyclic transition state is involved rather than an open one.These pieces of experimental evidence support a 'silatropic ene' pathway for this aldol-type reaction. Similar aldol- type reactions have been carried out using a catalyst prepared from BINOL and Ti(OPri)4, with a wide range of aldehydes in good enantioselectivities (89-98%) which are highly solvent dependent.I4' Similar reactions with 0-silylketene acetals, rather than S-silylketene acetals, had not previously given high enantioselectivities, however this has now been achieved using a catalyst 71 prepared from a tri- dentate ligand, Ti(OPr'),, and 3,5-di-tert-butyl- salicylic acid, in 94-97% ee for a wide range of aldehydes (Scheme 47).14' A similar catalyst prepared without the salicylic acid is also effective for the aldol-type reaction of a simple enol ether, 2-methoxypropene, but gives good enantio- selectivities only with straight chain aldehydes, and poorer ones with a-branched examples. 142 The Mukaiyama aldol reaction can also be promoted by a polymer-bound N-sulfonylvaline and borane, in similar ee to the non-polymeric reagent.'43 Although But 'But Scheme 47 0 RCHO + CNJN,OMe I Me [Au(c-C6H1 NC)2]BF4 1 mol% &,NxNnO Fe PPhpe -PPhP 1 mol% I 1.COnC. HCI, M?H 2. -0, Et3N 0. A N v 72 93-99% ee Scheme 48 IMeOh F~HBOC 73 e the polymer-bound reagent is used in stoichiometric quantities, because the reaction is slow, it can easily be recovered and recycled several times. A gold( 1)-catalysed aldol reaction of an isocyano Weinreb amide initially gives the heterocyclic products 72, which can then be readily converted into the protected a-amino-P-hydroxyamides 73 (Scheme 48).'44 4.3.2 Other additions of carbon nucleophiles to carbonyl groups The asymmetric addition of dialkylzinc reagents to aldehydes is currently receiving considerable atten- tion, and the catalysts employed usually have two heteroatoms with a /3-relationship, such as p-amino alcohols.A recent example shown in Scheme 49 unusually employs the a-branched diisopropylzinc, hexane Scheme 49 OH 92% ee 12 Contemporary Organic Synthesispropylzinc, rather than the commonly used diethyl- zinc, and N,N-dipropylnorephedrine is found to be slightly more effective than the N,N-dibutyl analogue, which is the best catalyst for diethyl~inc.’~~ The polymer-supported N-butylnorephedrine 75, with a six-methylene spacer, is a reasonably efficient although not as good as the non-polymer- supported analogue 76 (Scheme 50); however without the spacer, polymer-supported catalysts are much less active and less stereoselective, presumably because of steric hindrance from the polymer matrix. Me, Ph *,‘ / \ polymer Bu 75 82% ee for reaction Et2Zn + PhCHO Me, Ph OH j+ Ph-O-N\ Bu 76 99% ee for reaction Etgn + PhCHO Scheme 50 New catalysts for the addition of diethylzinc to aldehydes include the air-stable zinc bis(arene- thiolate) complex 7714’ (Scheme Sl), and the cyclic aminothiol 78,’48 which is derived from nor- ephedrine with retention of configuration, and gives good enantioselectivities for a-branched or aromatic aldehydes, but much lower ones for straight-chain aldehydes.Alkynylzinc reagents can be prepared from alkynes and diethylzinc, and add to aldehydes in 38-95% ee using a chiral P-alkoxy alcohol 79 as a cat a1 ys t . 149 Scheme 51 Ph, Me )+ HS 0 78 79 ) q A r Ho Ar Knochel has prepared a variety of organozinc reagents and studied their addition to aldehydes using the bis-trifluoromethanesulfonamide 80.Hydroboration of terminal alkenes, followed by conversion of the organoboranes to organozinc reagents and addition to aldehydes, allows a one-pot synthesis of chiral alcohols resulting from the overall addition of alkenes to aldehydes (Scheme 52).”’ Asymmetric addition of functionalised dialkylzincs to a-silyloxy aldehydes results in a synthesis of mono-protected chiral 1,2-diols, and is an alterna- OH RkHO flNHTf 50-96% 88 v’NHTf 80 8 molX Scheme 52 tive to asymmetric epoxidation or dihydroxylation. 15’ Addition of small dialkylzincs, e.g. Me2Zn, to P-monosubstituted-a$-unsaturated aldehydes usually gives poor enantioselectivities, however, compensating for the small alkyl group on zinc by increasing the steric bulk in the titanium alkoxide has a dramatic effect (Scheme 53).1’2 Additions to P-silyl- and p-stannyl-a$-unsaturated aldehydes have also been re~0rted.I’~ ?H * R’&R2 Ti(OR)4 ~ 1 w ~ ~ ~ + R22Zn (YNHTf v‘NHTf Ti(OPi)4: 0% ee 8 mot% Ti(OB&: 93% ee Scheme 53 4.3.3 Palladium-catalysed reactions Palladium-catalysed allylic substitution reactions proceed in moderate to very good (40-96%) enantioselectivities using chiral dihydrooxazole ligands of the types 81 and 82 with a tethered phosphorus or sulfur atom (Scheme 54); the preparation of these ligands has been detailed,’54 and the origin of the enantioselectivity discussed in terms of a combination of steric and electronic effects.I5’ Modifying the ligand to 83, where a chiral - YR2 R 1 p R 2 M+-CH(C02Me)2 OAc PdL’, Me02C C02Me Ligands: \ R 81 R 82 Ph 83 Scheme 54 Kegan: Asymmetric processes 13acetal replaces the dihydrooxazole, also results in an effective catalyst.156 Generally, acyclic allylic acetates have been used, but cyclic systems have also been used successfully, with five- to eight-membered cycloalkenyl products being obtained in up to 85% ee.157 A different type of catalyst for this reaction uses a C,-symmetric binaphthyl-containing amino- phosphine ligand 84. ''* Isosparteine, a chiral diamine prepared in two steps from naturally occur- ring sparteine, has been found to be an effective ligand,ls9 and is better than sparteine itself. The polymer 85, prepared from a chiral C,-symmetric 1,2-diamine gives good enantioselectivities for this reaction,16' and has also been used for asymmetric reduction of acetophenone, for which it is rather less effective.The related palladium-catalysed annulation of allenes shown in Scheme 55 employs a bis-oxazoline ligand, and involves formation of an intermediate n-ally1 palladium complex, followed by intra- molecular substitution.'61 1 Pd(OAc);! (5 mot%)), Ag3P04, DMF 82% ee Scheme 55 The palladium-catalysed Heck reaction can result in the formation of a new stereogenic centre if the alkene double bond is reformed away from its original position, and making this process asymmetric is of current interest. An intramolecular example is shown in Scheme 56, where use of both the trifluoromethanesulfonate leaving group and the silver salt is essential for high enantioselectivity.'" An intermolecular example employs a cyclic acetal of ~is-butene-1,4-diol;'~' after the asymmetric Heck coupling with phenyl trifluoromethanesulfonate, hydrolysis and oxidation result in a chiral butyro- lactone.Forming a new stereogenic tertiary sp' centre during an asymmetric Heck reaction with acyclic alkenes can be problematic, because of diffi- culty controlling the double bond position in the ,OTBDMS moTBDMs Ct2Pd[(R)-BlNAP] 10 mot% NMP, 60 "C, Ag3PO4 product. One solution to this is to employ a silyl group to terminate the reaction and control the double bond position, as shown in Scheme 57.'64 The use of reductive Heck-coupling reactions, which employ formate salts to reductively cleave the organopalladium intermediates, is another way to preserve chirality formed during the coupling reaction, and asymmetric versions have appeared with reasonably good enantioselectivities on both norbornene and heterobicyclic alkenes (Scheme 58).'65-167 Again, aryl trifluoromethanesulfonate give much better enantioselectivities than aryl iodides.DMF, 80 "C, 24 h 90% ee Scheme 57 YHSGMe &PPh2 & +PhOTf R3N, HCOzH, DMSO 65 OC, 20 h 71.4% ee Scheme 58 4.3.4 Cycloadditions Asymmetric catalysis of Diels-Alder reactions using chiral Lewis acids has been widely studied, with boron- and aluminium-based catalysts being commonly used. A new BINOL-derived borate catalyst which is very effectively combined with a Bronsted acid is shown in Scheme 59. This gives very high ees with both cyclopentadiene and an acyclic diene.168 Another boron-based catalyst is prepared from polymer-bound N-sulfonylvaline and b ~ r a n e , ' ~ ~ similar to that discussed above for asymmetric aldol reactions, but gives only a moderate 65% ee.A hetero-Diels-Alder reaction of a glyoxylate ester is catalysed by an N-triflurometha- nesulfonyloxaborolidine in 94% ee.I7O Me catalyst 10 mot70 ACHO -t 0 CH&I2,-78"CL CHO H Scheme 56 Scheme 59 14 Contemporary Organic SynthesisTransition metals used as chiral Lewis acids for Diels-Alder reactions include a titanium-BINOL complex, which, using juglone as the dienophile, gives products in enantioselectivities of 79-96% which are highly dependent on the absence of molecular sieve^.'^' Iron has also been used in a diphosphine-cyclopentadienyl complex,'72 which is very effective (up to 99% ee) using a-bromoacrolein as the dienophile. Kobayashi has reported asymmetric Diels-Alder reactions between cyclo- pentadiene and (achiral) a,P-unsaturated-N-acyl- oxazolidinones using a catalyst prepared by simply mixing together BINOL, Sc(OTf),, and cis- 1,2,6-trimethylpiperidine (Scheme 60).'73 Interest- ingly, by using Yb(OTf)3 together with different achiral additives, the enantioselectivity of this reaction can be + 0 BINOL-Sc(OTf)3 cis- 1.2.6-trimethyl piperidine Q O 7697% ee Scheme 60 Ene reactions of glyoxylates are also catalysed by a titanium-BINOL complex (Scheme 61)17' similar to that used for Diels-Alder reactions above, and 1,4-asymmetric control has also been achieved in this process.'76 0 C02Me 89 % ee Scheme 61 Whilst not a concerted cycloaddition, the formal [2+2+2] cocyclisation of three alkyne units has been achieved with 73% enantioselectivity, between two prochiral alkyne groups using a nickel catalyst with a chiral diphosphinylferrocene ligand (Scheme 62).17' \ R2 20 mol% 73% ee acetylene 4 equiv.THF, 23 "C Scheme 62 Regan: Asymmetric processes 4.3.5 Other carbon-carbon bond forming reactions The Michael addition of dibenzyl malonate to cyclo- hexenone is catalysed by a complex prepared from La(OPri)3, a 1,3-diketone and BINOL, in 92% ee (Scheme 63).17* The identical reaction is also catalysed in a lower 71% ee by a simple proline- derived ammonium salt, which is presumed initially to form an iminium ion with the cyclohexenone. Proline itself can also be used as its rubidium salt to catalyse the asymmetric Michael addition of nitroalkanes to cycloalkenone~.'~~ 0 R3 Scheme 63 0 h CO@n C02Bn 92% ee Carbenoids can be formed from a-diazo esters by catalysis by chiral metal complexes, and undergo a number of asymmetric reactions.Asymmetric cyclo- propanation of styrene employs a catalyst formed in situ from a ruthenium complex and a chiral bis- oxazoline,'80 and a catalyst formed from Cu(OTf), and a C,-symmetric diamine is also effective for this reaction.lX1 A different chiral bis-oxazoline has also been used with a Cu' complex for addition of the carbenoid to the C=N double bond of an imine, resulting in aziridine formation with modest enantioselectivity.lX2 Asymmetric intramolecular C-H insertion of a carbenoid can be achieved using a dirhodium salt of a protected @-amino acid (Scheme 64);'*3 this has been previously used for carbocycle construction and here is used to form a P-lact am.Scheme 64 An entirely different use of a chiral bis-oxazoline is to promote the asymmetric addition of MeLi to N-arylimines (Scheme 65).'*4 The enantioselectivity is increased from 82% to 91% if a stoichiometric, rather than a catalytic, amount of the bis-oxazoline is used. enolate has been achieved using a catalytic amount of a chiral tetraamine, and a stoichiometric amount of an achiral diamine, in excellent enantioselectivity (Scheme 66).IX5 Alk-1 -ynylboranes, prepared in situ from alk- 1-ynylstannanes, undergo addition to aldehydes in Asymmetric alkylation of an achiral lithium 15N,C6H4-flMe MeLi, PhMe, -63 "C z Ph Me Me 0.2 equiv. Scheme 65 " Ar Ph d H Me 82% ee, 91% ee using ' equiv' ligand The asymmetric oxidation of monosubstituted benzenes to 'benzenediols' by Pseudomonas putida is well-known.The oxidation of 1,4-disubstituted benzenes gives only moderate enantioselectivities using the l? putida mutant UV4; however after removal of the 4-iOdO group by hydrogenation, a wild type I? putida can be used to remove the (3s) enantiomer selectively, leaving the ( 3 R ) product in good ee.I9' Kinetic resolution of racemic a-amino esters by alcalase has been combined with in situ racemisation of the unreacted material by pyridoxal-5-phosphate, to give almost complete conversion to the amino acid product, which precipitates out of the reaction mixture in 87-95% yields and 90-98% ee.192 Resolution of chiral alcohols by enzyme-catalysed esterification is well-established; more unusual is that an alcohol containing a stereogenic silicon atom ph nn N N NMe2 H Me 96% ee 0.05 equiv.MeN2(CH&NMe2 2 equiv. Scheme 66 undergoes kinetic resolution using papain to give the ester in 67% ee, and unreacted alcohol in 92% ee.193 The asymmetric synthesis of (R)-cyanohydrins using oxynitrilase from almonds is likewise widely known. The enzyme from the plant Sorghum bicolor, which gives the (S)-cyanohydrins, has previously been laborious to obtain. However it has been reported that the shoots of the plant can be simply lyophilised, powdered and washed, and used without any purification or immobilisation of the enzyme being necessary (Scheme 68).'94 the presence of catalytic to stoichiometric quantities of a chiral oxaborolidine to give alkynyl alcohols in 85-96% ee."' The catalyst is available as either enantiomer, and is readily recovered.Aldehydes are also involved in the intramolecular hydroacylation of pent-4-enals, using a Rh-BINAP catalyst, to give 4-alkylcyclopentanones in 17-99% ee.Is7 HO CN Sorghum bicolor shoots OH PhCHO + c 4.4 Enzymes and antibodies MeXMe Pi20 PhACN Because of the wide and almost routine use of 90% ee enzymes as asymmetric catalysts, and the availability of many reviews on this topic, only a few recent developments have been selected. Horseradish peroxidase catalyses not only its natural reaction, but also the two-electron oxidation of sulfides to sufoxides, and a single site-specific mutation of the enzyme (Phe-41 -+Leu-41) accelerates the reaction in Scheme 67 by a factor of ten, and dramatically improves the enantioselectivity from 7 to 94%.Is8 ! horseradish peroxidase P h O ' b mutant enzyme: Phe41 +Leu41 P h O ' b Scheme 68 The development of artificial enzymes is a continuing but elusive goal for chemists.One example of current endeavours is a polymer prepared by copolymerisation, using a small amount of a chiral a-aminophosphinate ester as a template. After removal of the phosphinate template the imprinted polymer shows modest enantioselectivity in the hydrolysis of esters of the corresponding %-amino acids. 195 5 Miscellaneous asymmetric processes Scheme 67 The enantioselective monoesterification of meso- diols by ( - )-camphanoyl iodide gives mono-esters in 74-88% de, which can be readily improved to 97-98% after recrystallisation.Ig6 The enantiomeric 94% ee (mutant enzyme) 7% ee (wild-type enzyme) A multi-gram scale enantioselective antibody- catalysed hydrolysis of an enol ether gives an %-substituted cyclopentanone in 86% ee, and this involves recovering the antibody and reusing it five times in conventional laboratory apparatus.ls9 The first antibody-catalysed oxidation at a carbon atom has been reported,I9" and is the epoxidation of an unfunctionalised trisubstituted alkene, using hydrogen peroxide as the stoichiometric oxidant.purity of partially resolved alcohols can be improved by reaction with a difunctional reagent such as oxalyl chloride, after removal of the meso- diastereoisomer and hydrolysis (Scheme 69). 197 A simple method for enriching the enantiomeric purity of methyl tolyl sulfoxide of 86% ee is by flash chromatography on ordinary silica gel, which gave 14 fractions, varying from 99% ee for the first fraction to 63% ee for the 1 a ~ t .l ~ ~ There are only a few examples known of fractionation of enantiomers 16 Contemporary Organic Synthesis2 R*OH + (COC1)2 * O w 0 er=x R*O OR* dr= 3 : (1-4 : 2(1-4 (I?,/?) : (SS) : meso V separate, hydrolyse I R*OH er = 3/(1-4 for example: er = 0.92 - er= 0.9964 YHO I.+ Et ,.OH Et .OH &job Scheme 69 dkmeso = 6436 12% ee by chromatography on an achiral phase, and this phenomenon presumably depends upon auto- association of the sulfoxide in the mobile phase to give diastereoisomeric aggregates of differing mobilities.Enolate formation from enantiomerically pure a-amino acid derivatives usually gives racemised products; however the alkylation shown in Scheme 70 proceeds in 82% ee with no external chiral ligand, and so the enolate is presumed to retain its stereochemistry, as in 86.'99 Scheme 71 0 0 F 88 - LiTMP P h-Go2Et THF. LI \ -78 'C - AN..- mc- Me L 86 1 Me1 BOL 82% ee Scheme 70 An asymmetric autocatalytic reaction can occur when the product of the reaction is itself the chiral catalyst, and an example of this is shown in Scheme 71,200 and although the enantioselectivity is currently modest, this is an unusual type of effect. The total spontaneous resolution of a racemate has been observed in the crystallisation of (+_)-namedine 88, an intermediate required for the synthesis of the alkaloid (-)-galanthamine, which is being investigated for the treatment of Alzheimer's disease2" Racemic 88 in supersaturated solution can be seeded with either enantiomer, and crystal- lisation gives 84-85% recovery of enantiomerically pure material (Scheme 72).Deuterium labelling experiments suggest that racemisation occurs in solution in the presence of triethylamine, by a retro- Michael ring-reclosure sequence. Scheme 72 04% recovery 100% ee Finally, a remarkable and fantastic report claimed that enantioselective addition of Grignard reagents to aldehydes in high ee (e.g. 98% ee for methyl magnesium iodide and naphthaldehyde), was effected only by an external static magnetic field, with no chiral reagents being present.'02 The report that either enantiomer of the products could be formed randomly, but with consistently high ee, and the lack of any known theoretical basis for these results (since a static magnetic field is not chiral) gave rise to considerable interest among chemists, and in the secondary literature.However, the claims turned out to be spurious, for there later appeared, in a single issue of the same journal, two indepen- dent attempts to reproduce the ~ o r k , ~ ~ " ~ " ~ which failed even in the original authors' laboratory and using their magnet, and also a retraction and an editorial ~tatement.~'~ References 1 C. Palomo, F. Berree, A. Linden and J. M. Villal- gordo, J. Chem. SOC., Chem. Commun., 1994, 1861. 2 A. G. Myers, B. H. Yang, H. Chen and J. L. Gleason, J. Am.Chem. SOC., 1994, 116,9361. 3 S. G. Davies, G. B. Evans and A. A. Mortlock, Etra- hedron: Asymmetry, 1994, 5, 585. 4 C. Cativiela, M. D. Diazdevillegas and J. A. Galvez, J. 0%. Chem., 1994,59, 2497. 5 A. Abiko, 0. Moriya, S. A. Filla and S. Masamune, Angew. Chem., Int. Ed. Engl., 1995, 34, 793. Regan: Asymmetric processes 176 S. G. Davies, G. J. M. Doisneau, J. C. Prodger and H. J. Sanganee, Tetrahedron Lett., 1994, 35, 23 73. J. 0%. Chem., 1994, 59, 8187. Musselman, Tetrahedron Lett., 1994, 35, 8521. and P. K. G. Hodgson, Tetrahedron: Asymmetry, 1994, 5, 2447. 10 T. Akiyama, K. Ishikawa and S. Ozaki, Synlett, 1994, 275. 11 P. A. Lander and L. S. Hegedus, J. Am. Chem. Soc., 1994, 116,8126. 12 T. Taguchi, A. Shibuya, H. Sasaki, J. Endo, T. Mori- kawa and M.Shiro, Tetrahedron: Asymmetry, 1994, 5, 1423. 13 N. Kise, K. Tokioka, Y. Aoyama and Y. Matsumura, J. 0%. Chem., 1995, 60, 1100. 14 D. Enders, D. Backhaus and J. Runsink, Angew. Chem., Int. Ed. Engl., 1994, 33, 2098. 15 D. Enders and A. Plant, Synlett, 1994, 1054. 16 D. Enders and U. Reinhold, Synlett, 1994, 792. 17 D. Enders, J. Schankat and M. Matt, Synlett, 1994, 795. 18 C. D. Bernardhenriet, J. R. Grimaldi and J. M. Hatem, Tetrahedron Lett., 1994, 35, 3699. 19 S. S. Taj and R. Soman, Tetrahedron: Asymmetry, 1994, 5, 1513. 20 S. E. Denmark and I. Rivera, J. Org. Chem., 1994,59, 6887. 21 S. Hanessian and Y. L. Bennani, Synthesis, 1994, 1272. 22 P. C. Cagle, A. M. Arif and J. A. Gladysz, J. Am. Chem. SOC., 1994, 116, 3655. 23 N. S. Barta, A. Brode and J. R. Stille,J.Am. Chem. SOC., 1994, 116, 6201. 24 K. Ando, K. Yasuda, K. Tomioka and K. Koga, J. Chem. SOC., Perkin Trans. I , 1994, 277. 25 A. Felk, G. Revial, B. Viossat, P. Lemoine and M. Pfau, Tetrahedron: Asymmetry, 1994, 5, 1459. 26 F. Dumas, V. Maine, C. Cave and J. Dangelo, Tetra- hedron: Asymmetry, 1994, 5, 339. 27 S. G. Davies and I. A. S. Walters, J. Chem. SOC., Perkin Trans. 1, 1994, 1129. 28 M. E. Bunnage, S. G. Davies, C. J. Goodwin and 1. A. S. Walters, Tetrahedron: Asymmetry, 1994, 5, 35. 29 S. G. Davies, 0. Ichihara and I. A. S. Walters, J. Chem. Soc., Perkin Trans. I , 1994, 1141. 30 M. E. Bunnage, A. N. Chernega, S. G. Davies and C. J. Goodwin, J. Chem. SOC., Perkin Trans. I , 1994, 2373. J. Chem. SOC., Perkin Trans. 1, 1994, 2385. Int. Ed. Engl., 1995,34, 455.Synthesis, 1994, 1322. 59, 649. 1994, 116, 6437. Lett., 1994, 35, 61 19. 35, 3737. 7 T. H. Yan, A. W. Hung, H. C. Lee and C. S. Chang, 8 R. K. Boeckman, A. T. Johnson and R. A. 9 M. R. Banks, J. 1. G. Cadogan, 1. Gosney, S. Gaur 31 M. E. Bunnage, S. G. Davies and C. J. Goodwin, 32 D. Enders, H. Wahl and W. Bettray, Angew. Chem., 33 D. Enders, W. Bettray, G. Raabe and J. Runsink, 34 J. M. Hawkins and T. A. Lewis, J. 0%. Chem., 1994, 35 N. Shimano and A. I. Meyers, J. Am. Chem. SOC., 36 H. Suzuki, S. Aoyagi and C. Kibayashi, Tetrahedron 37 Y. Matsumura and T. Tomita, Tetrahedron Lett., 1994, 38 T. K. Yang, R. Y. Chen, D. S. Lee, W. S. Peng, Y. Z. Jiang, A. Q. Mi and T. T. Jong, J. 0%. Chem., 1994, 59, 914. 39 N. Moss, J. Gauthier and J. M. Ferland, Synlett, 1995, 142.40 S. Raussou, R. Gosmini, P. Mangeney, A. Alexakis and M. Commercon, Tetrahedron Lett., 1994,35, 5433. M. Commercon and A. Alexakis, J. Org. Chem., 1994, 59, 1877. 42 K. Maruoka, M. Akakura, S. Saito, T. Ooi and H. Yamamoto, J. Am. Chem. SOC., 1994, 116, 6153. Letschert,Angew. Chem., Int. Ed. Engl., 1994, 33, 683. 44 T. D. Nelson and A. I. Meyers, J. Org. Chem., 1994, 59, 2655. 45 T. D. Nelson and A. I. Meyers, J. Org. Chem., 1994, 59, 7184 46 T. D. Nelson and A. I. Meyers, Tetrahedron Lett., 1994,35, 3259. 47 B. H. Lipshutz, F. Kayser and Z . P. Liu, Angew. Chem., Int. Ed. Engl., 1994, 33, 1842. 48 J. K. Whitesell and M. S. Wong, J. Org. Chem., 1994, 59, 597. 49 N. Khiar, I. Fernandez and F. Alcudia, Tetrahedron Lett., 1994, 35, 5719. 50 W. A. Schenk, J.Frisch, W. Adam and F. Prechtl, Angew. Chem., Int. Ed. Engl., 1994, 33, 1609. 51 K. Hiroi, J. Abe, K. Suya, S. Sat0 and T. Koyama, J. Org. Chem., 1994, 59, 203. 52 V. K. Agganval, M. Kalomiri and A. P. Thomas, Tetrahedron: Asymmetry, 1994, 5, 723. 53 A. Stolle, H. Becker, J. Salaun and A. Demeijere, Tetrahedron Lett., 1994, 35, 3521. 54 V. Bernardes, X. Verdaguer, N. Kardos, A. Riera, A. Moyano, M. A. Pericas and A. E. Greene, Tetra- hedron Lett., 1994, 35, 575. 55 J. Castro, A. Moyano, M. A. Pericas, A. Riera and A. E. Greene, Tetrahedron: Asymmetry, 1994, 5, 307. 56 H. Moon, N. E. Schore and M. J. Kurth, Tetrahedron Lett., 1994, 35, 8915. 57 A. G. M. Barrett, M. A. Seefeld and D. J. Williams, J. Chem. SOC., Chem. Commun., 1994, 1053. 58 K. Hiroi, J. Abe, K.Suya, S. Sat0 and T. Koyama, J. Org. Chem., 1994, 59, 203. 59 P. J. Edwards, D. A. Entwistle, C. Genicot, K. S. Kim and S. V. Ley, Tetrahedron Lett., 1994, 35, 7443. 60 B. C. B. Beiuidenhoudt, G. H. Castle and S. V. Ley, Tetrahedron Lett., 1994,35, 7447. 61 G. H. Castle and S. V. Ley, Tetrahedron Lett., 1994, 35, 7455. 62 B. C. B. Bezuidenhoudt, G. H. Castle, J. V. Geden and S. V. Ley, Tetrahedron Lett., 1994, 35, 7451. 63 D. A. Price, N. S. Simpkins, A. M. Macleod and A. P. Watt, J. Og. Chem., 1994, 59, 1961. 64 Y. Landais and P. Ogay, Tetrahedron: Asymmetry, 1994, 5, 541. 65 R. Shirai, K. Aoki, D. Sato, H. D. Kim, M. Murakata, T. Yasukata and K. Koga, Chem. Pham. Bull., 1994, 42, 690. 35, 3653. Tetrahedron: Asymmetry, 1994, 5, 337. Asymmetry, 1994,5, 1649. Asymmetry, 1994,5, 793.41 P. Mangeney, R. Gosmini, S. Raussou, 43 H. Waldmann, E. Blaser, M. Jansen and H. P. 66 M. Majewski and R. Lazny, Tetrahedron Lett., 1994, 67 D. M. Hodgson, J. Witherington and B. A. Moloney, 68 M. Asami, J. Takahashi and S. Inoue, Tetrahedron: 69 M. Asami, T. Ishizaki and S. Inoue, Tetrahedron: 18 Contemporary Oqanic Synthesis70 T. Kumamoto, S. Aoki, M. Nakajima and K. Koga, Tetrahedron: Asymmetry, 1994, 5, 1431. 71 E. Brunet, A. M. Poveda, D. Rabasco, E. Oreja, L. M. Font, M. S. Batra and J. C. Rodriguezubis, Tetrahedron: Asymmetry, 1994, 5, 935. P. Duhamel and L. Toupet, J. 0%. Chem., 1994,59, 2285. J. Am. Chem. SOC., 1994, 116,3231. Chem. SOC., 1994, 116,9755. SOC., 1994, 116, 2175. 59, 6517. 1994,33, 1888. Chem. SOC., 1994,116, 11 179.H. Yamamoto, Angew. Chem., Int. Ed. Engl., 1994,33, 107. 80 F. Cavelier, S. Gomez, R. Jacquier and J. Verducci, Tetrahedron Lett., 1994, 35, 2891. 81 T. Mukaiyama, I. Shiina, H. Uchiro and S. Kobayashi, Bull. Chem. SOC. Jpn., 1994, 67, 1708. 82 C. Gennari, A. Vulpetti and D. Moresca, Tetrahedron Lett., 1994, 35, 4857. 83 K. Fujimoto and T. Nakai, Tetrahedron Lett., 1994,35, 5019. 84 M. Hayashi, T. Inoue and N. Oguni, J. Chem. SOC., Chem. Commun., 1994,341. 85 T. Inoue, 0. Kitagawa, S. Kurumizawa, 0. Ochiai and T. Taguchi, Tetrahedron Lett., 1995,36, 1479. 86 H. Schafer and D. Seebach, Tetrahedron, 1995,51, 2305. 87 C. Bolm and P. Muller, Tetrahedron Lett., 1995, 36, 1625. 88 M. Hayashi, K. Ono, H. Hoshimi and N. Oguni, J. Chem. SOC., Chem. Commun., 1994,2699.89 A. B. Charette and H. Juteau, J. Am. Chem. Sac., 1994, 116, 2651. 90 A. B. Charette, S. Prescott and C. Brochu, J. 0%. Chem., 1995,60, 1081. 91 K. Maruoka, S. Saito and H. Yamamoto, J. Am. Chem. SOC., 1995, 117, 1165. 92 J. F. Larrow, E. N. Jacobsen, Y. Gao, Y. P. Hong, X. Y. Nie and C. M. Zepp, J. Org. Chem., 1994,59, 1939. Martinez, Tetrahedron, 1994, 50, 4323. Chem. SOC., 1994, 116,6937. hedron Lett., 1994, 35, 669. 1994, 116, 12129. R. Ramasseul, J. C. Marchon, I. Turowskatyrk and W. R. Scheidt, Angew Chem., Int. Ed. Engl., 1994,33, 220. 1994,59,4378. 197. 102. Sharpless, Tetrahedron Lett., 1994, 35, 543. 72 J. Vadecard, J. C. Plaquevent, L. Duhamel, 73 P. Beak, S. T. Kerrick, S. D. Wu and J. X. Chu, 74 S. Thayumanavan, S. Lee, C. Liu and P. Beak, J.Am. 75 E. Vedejs, N. Lee and S. T. Sakata, J. Am. Chem. 76 E. Vedejs and J. A. Garciarivas, J. 0%. Chem., 1994, 77 C. Fehr and J. Galindo, Angew. Chem., Int. Ed. Engl., 78 K. Ishihara, M. Kaneeda and H. Yamamoto, J. Am. 79 A. Yanagisawa, T. Kuribayashi, T. Kikuchi and 93 E. N. Jacobsen, L. Deng, Y. Furukawa and L. E. 94 S. B. Chang, J. M. Galvin and E. N. Jacobsen, J. Am. 95 S. Chang, R. M. Heid and E. N. Jacobsen, Tetra- 96 J. F. Larrow and E. N. Jacobsen, J. Am. Chem. Sac., 97 M. Veyrat, 0 . Maury, F. Faverjon, D. E. Over, 98 B. D. Brandes and E. N. Jacobsen, J. 0%. Chem., 99 T. Fukuda, R. Irie and T. Katsuki, Synlett, 1995, 100 A. C. Korn and L. Moroder, J. Chem. Res. ( S ) , 1995, 101 G. A. Crispino, A. Makita, Z. M. Wang and K. B. 102 K. P. M. Vanhessche, Z.M. Wang and K. B. Sharp- 103 P. J. Walsh, P. T. Ho, S. B. King and K. B. Sharpless, 104 M. S. Vannieuwenhze and K. B. Sharpless, Etra- 105 D. Q. Xu, C. Y. Park and K. B. Sharpless, Tetra- 106 2. M. Wang, K. Kakiuchi and K. B. Sharpless, J. 0%. 107 S. Takano, T. Yoshimitsu and K. Ogasawara, J. Org. 108 S. Takano, T. Yoshimitsu and K. Ogasawara, J. Org. 109 A. R. Bassindale, P. G. Taylor and Y. L. Xu, J. Chem. 110 H. Becker, M. A. Soler and K. B. Sharpless, Tetra- 111 K. J. Hale, S. Manaviazar and S. A. Peak, Tetrahedron 112 B. B. Lohray, E. Nandanan and V. Bhushan, Tetra- 113 Z. M. Wang and K. B. Sharpless, J. 0%. Chem., 1994, 114 Z. M. Wang, H. C. Kolb and K. B. Sharpless, J. 0%. 115 I. Henderson, K. B. Sharpless and C. H. Wong, J. Am. 116 Y. L. Bennani, K. P. M.Vanhessche and K. B. Sharp- 117 E. J. Corey, M. C. Noe and S. Sarshar, Tetrahedron 118 H. Becker, P. T. Ho, H. C. Kolb, S. Loren, P. 0. less, Tetrahedron Lett., 1994, 35, 3469. Tetrahedron Lett., 1994, 35, 5129. hedron Lett., 1994, 35, 843. hedron Lett., 1994,35, 2495. Chem., 1994, 59,6895. Chem., 1994,59,54. Chem., 1995,60, 1478 Sac., Perkin Trans. 1, 1994, 1061. hedron, 1995, 51, 1345. Lett., 1994, 35, 425. hedron Lett., 1994, 35, 6559. 59, 8302. Chem., 1994,59,5 104. Chem. SOC., 1994, 116,558. less, Tetrahedron: Asymmetry, 1994, 5, 1473. Lett., 1994, 35, 2861. Norrby and K. B. Sharpless, Tetrahedron Lett., 1994, 35, 7315. 119 H. C. Kolb, P. G. Anderson and K. B. Sharpless, J. Am. Chem. SOC., 1994, 116, 1278. 120 P. 0 . Norrby, H. C. Kolb and K. B. Sharpless, J.Am. Chem. SOC., 1994, 116,8470. 121 P. Pitchen, C. J. France, I. M. McFarlane, C. G. Newton and D. M. Thompson, Tetrahedron Lett., 1994, 35, 485. Tetrahedron: Asymmetry, 1994, 5, 549. hedron: Asymmetry, 1994,5, 545. Collington and D. M. Andrews, Tetrahedron Lett., 1994,35,9629. 125 A. S. Gokhale, A. B. E. Minidis and A. Pfaltz, Tetra- hedron Lett., 1995,36, 1831. 126 M. Kitamura, Y. Hsiao, M. Ohta, M. Tsukamoto, T. Ohta, H. Takaya and R. Noyori, J. 0%. Chem., 1994, 59, 297. H. Landert and A. Tijani, J. Am. Chem. SOC., 1994, 116,4062. 128 K. Mashima, K. H. Kusano, N. Sato, Y. Matsumura, K. Nozaki, H. Kumobayashi, N. Sayo, Y. Hori, T. Ishizaki, S. Akutagawa and H. Takaya, J. 0%. Chem., 1994,59,3064. 129 T. Ohkuma, H. Ooka, S. Hashiguchi, T. Ikariya and R. Noyori, J.Am. Chem. SOC., 1995, 117,2675. 130 C. A. Willoughby and S. L. Buchwald, J. Am. Chem. SOC., 1994, 116, 8952. 131 N. E. Lee and S. L. Buchwald, J. Am. Chem. SOC., 1994, 116, 5985. 132 M. B. Carter, B. Schiott, A. Gutierrez and S. L. Buchwald, J. Am. Chem. SOC., 1994,116, 11 667. 122 P. Diter, 0. Samuel, S. Taudien and H. B. Kagan, 123 S. L. Griffiths, S. Perrio and S. E. Thomas, Tetra- 124 P. C. B. Page, J. P. Heer, D. Bethell, E. W. 127 A. Togni, C. Breutel, A. Schnyder, F. Spindler, Regan: Asymmetric processes 19133 M. J. Burk, J. P. Martinez, J. E. Feaster and N. 134 T. Hayashi, H. Iwamura, M. Naito, Y. Matsumoto, Cosford, Tetrahedron, 1994, 50,4399. Y. Uozumi, M. Miki and K. Yanagi, J. Am. Chem. SOC., 1994, 116, 775. 135 T. Hayashi, H. Iwamura and Y.Uozumi, Tetrahedron Lett., 1994, 35, 4813. 136 Y. Z. Jiang, Y. Qin, A. Q. Mi and Z. T. Huang, Tetrahedron: Asymmetry, 1994, 5, 1211. 137 Y. P. Hong, Y. Gao, X. Y. Nie and C. M. Zepp, Tetrahedron Lett., 1994, 35, 6631. 138 C. Caze, N. Elmoualij, P. Hodge, C. J. Lock and J. B. Ma, J. Chem. SOC., Perkin Trans. 1, 1995, 345. 139 K. Mikami and S. Matsukawa, J. Am. Chem. Soc., 1994, 116, 4077. 140 G. E. Keck and D. Krishnamurthy, J. Am. Chem. SOC., 1995, 117,2363. 141 E. M. Carreira, R. A. Singer and W. S. Lee, J. Am. Chem. SOC., 1994, 116,8837. 142 E. H. Carreira, W. Lee and R. A. Singer, J. Am. Chem. SOC., 1995, 117, 3649. 143 S. Kiyooka, Y. Kid0 and Y. Kaneko, Tetrahedron Lett., 1994, 35, 5243. 144 M. Sawamura, Y. Nakayama, T. Kato and Y. Ito, J. 0%. Chem., 1995, 60, 1727.145 K. S. Soai, T. Hayase, K. Takai and T. Sugiyama, J. Org. Chem., 1994, 59, 7908. 146 M. Watanabe and K. Soai, J. Chem. SOC., Perkin Trans. I , 1994, 837. 147 E. Rijnberg, J. T. B. H. Jastrzebski, M. D. Janssen, J. Boersma and G. Vankoten, Tetrahedron Lett., 1994, 35, 6521. 148 J. Kang, J. W. Lee and J. I. Kim, J. Chem. SOC., Chem. Commun., 1994,2009. 149 M. Ishizaki and 0. Hoshino, Tetrahedron: Asymmetry, 1994, 5, 1901. 150 L. Schwink and P. Knochel, Tetrahedron Lett., 1994, 35, 9007. 151 C. Eisenberg and P. Knochel, J. 0%. Chem., 1994, 59, 3760. 152 S. Nowotny, S. Vettel and P. Knochel, Tetrahedron Lett., 1994, 35, 4539. 153 R. Ostwald, P. Y. Chavant, H. Stadtmuller and P. Knochel, J. Org. Chem., 1994, 59, 4143. 154 J. V. Allen, G. J. Dawson, C. G.Frost, J. M. J. Williams and S. J. Coote, Tetrahedron, 1994, 50, 799. 155 J. V. Allen, S. J. Coote, G. J. Dawson, C. G. Frost, C. J. Martin and J. M. J. Williams, J. Chem. SOC., Perkin Trans. 1, 1994, 2065. 156 C. G. Forst and J. M. J. Williams, Synlett, 1994, 551. 157 P. Sennhenn, B. Gabler and G. Helmchen, Tetra- hedron Lett., 1994, 35, 8595. 158 H. Kubota and K. Koga, Tetrahedron Lett., 1994,35, 6689. 159 J. Y. Kang, W. 0. Cho and H. G. Cho, Tetrahedron: Asymmetry, 1994,5,1347. 160 P. Gamez, B. Dunjic, F. Fache and M. Lemaire, J. Chem. SOC., Chem. Commun., 1994, 1417. 161 R. C. Larock and J. M. Zenner, J. 0%. Chem., 1995, 60, 482. 162 Y. Sato, S. Nukui, M. Sodeoka and M. Shibasaki, Tetrahedron, 1994, 50, 371. 163 Y. Koga, M. Sodeoka and M. Shibasaki, Tetrahedron Lett., 1994, 35, 1227.164 L. F. Tietze and R. Schimpf, Angew. Chem., Znt. Ed. Engl., 1994, 33, 1089. 165 S. Sakuraba, K. Awano and K. Achiwa, Synlett, 1994, 291. 166 F. Ozawa, Y. Kobatake, A. Kubo and T. Hayashi, J. Chem. SOC., Chem. Commun., 1994, 1323. 167 C. Moinet and J. C. Fiaud, Tetrahedron Lett., 1995, 36, 205 1. 168 K. Ishihara and H. Yamamoto, J. Am. Chem. SOC., 1994,116,1561. 169 S. Itsuno, K. Kamahori, K. Watanabe, T. Koizumi and K. Ito, Tetrahedron: Asymmetry, 1994, 5, 523. 170 Y. Motoyama and K. Mikami, J. Chem. SOC., Chern. Commun., 1994, 1563. 171 K. Mikami, Y. Motoyama and M. Terada, J. Am. Chem. SOC., 1994, 116, 2812. 172 E. P. Kundig, B. Bourdin and G. Bernardinelli, Angew. Chem., Int. Ed. Engl., 1994,33, 1856. 173 S. Kobayashi, M. Araki and I. Hachiya, J. 0%. Chem., 1994, 59,3758. 174 S. Kobayashi, H. Ishitani, I. Hachiya and M. Araki, Tetrahedron, 1994, 50, 11623. 175 M. Terada, Y. Motoyama and K. Mikami, Tetrahedron Lett., 1994, 35, 6693. 176 K. Mikami and A. Yoshida, Tetrahedron Lett., 1994, 35, 7793. 177 Y. Sato, T. Nishimata and M. Mori, J. 0%. Chem., 1994,59, 6133. 178 H. Sasai, T. Arai and M. Shibasaki, J. Am. Chem. SOC., 1994, 116, 1571. 179 M. Yarnaguchi, T. Shiraishi, Y. Igarashi and M. Hirama, Tetrahedron Lett., 1994, 35, 8233, 180 H. Nishiyama, Y. Itoh, H. Matsumoto, S. B. Park and K. Itoh, J. Am. Chem. Soc., 1994, 116, 2223. 181 S. Kanemasa, S. Hamura, E. Hatada and H. Yama- moto, Tetrahedron Lett., 1994,35, 7985. 182 K. B. Hansen, N. S. Finney and E. N. Jacobsen, Angew. Chem., Int. Ed. Engl., 1995, 34, 676. 183 N. Watanabe, M. Anada, S. Hashimoto and S. Ikegami, Synlett, 1994, 1031. 184 S. E. Denmark, N. Nakajima and 0. J. C. Nicaise, J. Am. Chem. SOC., 1994, 116, 8797. 185 M. Imai, A. Hagihara, H. Kawasaki, K. Manabe and K. Koga, J. Am. Chem. SOC., 1994, 116, 8829. 186 E. J. Corey and K. A. Cimprich, J. Am. Chem. SOC., 1994, 116, 3151. 187 R. W. Barnhart, X. Q. Wang, P. Noheda, S. H. Bergens, J. Whelan and B. Bosnich, J. Am. Chem. SOC., 1994, 116, 1821. 188 S. I. Ozaki and P. R. 0. Demontellano, J. Am. Chem. SOC., 1994, 116, 4487. 189 J. L. Reymond, J. L. Reber and R. A. Lerner,Angew. Chem., Int. Ed. Engl., 1994, 33, 475. 190 A. Koch, J. L. Reymond and R. A. Lerner, J. Am. Chem. Soc., 1994, 116, 803. 191 C. C. R. Allen, D. R. Boyd, H. Dalton, N. D. Sharma, I. Brannigan, N. A. Kerley, G. N. Sheldrake and S. C. Taylor, J. Chem. SOC., Chem. Commun., 1995, 117. 192 S. T. Chen, W. H. Huang and K. T. Wang, J. 0%. Chem., 1994, 59, 7580. 193 T. Fukui, T. Kawamoto and A. Tanaka, Tetrahedron: Asymmetry, 1994, 5, 73. 194 E. Kiljunen and L. T. Kanerva, Tetrahedron: Asymmetry, 1994,5,311. 195 B. Sellergren and K. J. Shea, Tetrahedron: Asymmetry, 1994, 5, 1403. 196 K. Ishihara, M. Kubota and H. Yamamoto, Synlett, 1994, 611. 197 I, Fleming and S. K. Ghosh, J. Chem. SOC., Chem. Commun., 1994, 99. 198 P. Diter, S. Taudien, 0. Samuel and H. B. Kagan, J. OF. Chem., 1994, 59, 370. 20 Contemporary Organic Synthesis199 T. Kawabata, T. Wirth, K. Yahiro, H. Suzuki and K. Fuji, J. Am. Chem. Soc., 1994, 116, 10809. 200 K. Soai, T. Hayase, C. Shimada and K. Isobe, Tetra- hedron: Asymmetry, 1994, 5, 789. 201 W. C. Shieh and J. A. Carlson, 1. OR. Chem., 1994, 59, 5463. 202 G. Zadel, C. Eisenbraun, G. J. Wolff and E. Breit- maier, Angew. Chem., Int. Ed. Engl., 1994, 33, 454. 203 B. L. Feringa, R. M. Kellogg, R. Hulst, C. Zondervan and W. H. Kruizinga,Angew. Chem., Int. Ed. Engl., 1994,33, 1458. Engl., 1994, 33, 1459. 1457. 204 G. Kaupp and T. Marquardt, Angew. Chem., Int. Ed. 205 P. Golitz, Angew. Chern., Int. Ed. Engl., 1994, 33, Regan: Asymmetric processes 21

ISSN:1350-4894    

DOI:10.1039/CO9970400001

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

160 P. Renaud and I. Betrisey, Synth. Commirn., 1995, 25, 3479. 161 J. P. Begue, D. Bonnctdelpon, D. Bouvet and M. H. Rock, J. Flirorirte Chem., 1996, 80, 17. 162 M. Rejzek, M. Zarevucka, Z. Wimmer, T. Vanek, R. Tykva, J. Kuldova, D. Saman and B. Bennettova, Collect. Czech. Chem. Comrnirn., 1996, 61, 605. I63 T. Constantieux and J. P. Picard, Organometallics, 1996, 15, 1604. 164 J. H. Lai, H. Pham and D. G. Hangauer,.I. Org. Chem., 1996, 61, 1872. 165 R. J. Fletcher, M. Kizil and J . A. Murphy, Tetruhedron Lett., 1995, 36, 323. 166 K. Ramalingam, W. Zeng, P. Nanjappan and D. P. Nowotnik, Synth. Cornmun., 1995, 25, 743. 167 R. Joseph; T. Ravindranathan and A. Sudalai, Tetra- hedron Lett., 1995, 36, 1903. 168 V. M. Paradkar, T. B. Latham and D. M. Demko, Synlett, 1995, 1059. 169 F.Palacios, D. Aparicio, J. M. Delossantos and E. Rodriguez, Tetrahedron Lett., 1996, 37, 1289. 170 B. P. Bandgar, S. M. Nikat and P. P. Wadgaonkar, Synth. Comnzun., 1995, 25, 863. 171 D. Barbry and P. Champagne, Synth. Commun., 1995, 25, 3503. 172 S. Negi, M. Matsukura, M. Mizuno, K. Miyake and N. Minami, Synthesis, 1996, 991. 173 L. Maier and P. J. Diel, Phosphorus Sulfur Silicon Relut. Elem., 1995, 107, 245. 174 A. Zaks, A. V. Yabannavar, D. R. Dodds, C. A. Evans, P. R. Das and R. Malchow, J. Org. Chem., 1996, 61, 8692. 175 F. P. Ballistreri, E. Barbuzzi, G. A. Tomaselli and R. M. Toscano, Synlett., 1996, 1093. 176 J. G. Lee and J. P. Hwang, Chem. Lett., 1995, 507. 177 T. Shinada and K. Yoshihara, Tetrahedron Lett., 1995, 178 I. M. Baltork and S. Pouranshirvani, Synth.Comrnirn., 179 B. P. Bandgar, S. I. Shaikh and S. Iyer, Synth. 180 M. Curini, 0. Rosati, E. Pisani and U. Constantino, 181 V. J. Majo, M. Venugopal, A. A. M. Prince and P. T. 182 A. I. Bosch, P. Delacruz, E. Diezbarra, A. Loupy and 36, 6701. 1996, 26, I . Commun., 1996, 26, 1163. Synlett, 1996, 333. Perumal, Synth. Commun., 1995, 25, 3863. F. Langa, Synlett, '1995, 1259 183 I. P. Andrews, R. J. J. Dorgan, T. Harvey, J. F. Hudner, N. Hussain, D. C. Lathbury, N. J. Lewis, G. S. Macaulay, D. 0. Morgan, R. Stockman and C. R. White, Tctruhedron Lett., 1996, 37, 481 1. 184 T. Kiguchi, K. Tajiri, I. Ninomiya, T. Naito and H. Hiramatsu, Tetruheclron Lett., 1995, 36, 253. 185 M. Tiecco, L. Tcstaferri, M. Tingoli, L. Bagnoli and C. Santi, Tetruhedron, 1995, 51, 1277. 186 M.Tiecco, L. I'estaferri, M. Tingoli and L. Bagnoli, J. Chem. Soc., Chem. Commrrn., 1995, 235. 187 H. Kusama, Y. Yamashita and K. Narasaka, Chem. Lett., 1995, 5. 188 S. Bourke and F. Heancy, Te~tiahedrort Lett., 1995, 36, 7527. 189 V. N. Komissarov, Zh. Org. Khim., 1995, 31, 1060 (Chent. Ahstr., 124:289438). 190 U. Chiacchio, A. Corsaro, V. Pistara, A. Rescifina, G. Romeo and R. Romeo, Tetrahedron, 1996, 52, 7875. 191 M. T. Mckiernan and F. Heaney, Tetrahedron Lett., 1996,37,4597. 192 J. Alcazar, M. Begtrup and A. de la Hoz, Hc~terocyfc~s, 1906, 43, 1465. 193 M. C. McMills, D. L. Wright, J. D. Zubkowski and E. J. Valente, Tetrahedron Lett., 1996,37, 7213. 194 D. Armesto, M. A. Austin, 0. J . Griffiths, W. M. Horspool and M. Carpintero, Chem. Commcrri., 1996, 2715. 195 U.Chiacchio, A. Corsaro, V. Librando, A. Rescifina, R. Romeo and G. Romeo, Tetrahedron, 1996, 52, 14323. C. Santi and A. Temperini, Heterocycles, 1996, 43, 2079. 197 S. Ahmed and R. C. Boruah, Tetruhedron Lett., 1996, 37, 823 1. 198 A. V. Tkachev, A. M. Chibiryaev, A. Y. Denisov and Y. V. Gatilov, Tetruheclron, 1995, 51, 1789. 199 J. Boivin, E. Pillot, A. Williams, W. Roger and S. Z. Zard, Tetruhedron Lett., 1995, 36, 3333. 200 K. Griesbaum, B. Ovez, T. S. Huh and Y. X. Dong, Liehigs Ann., 1095, 1571. 201 K. Miyashita, T. Toyoda, H. Miyabe and T. Imanishi, Synlett, 1995, 1229. 202 J. L. Boucher, S. Vadon, A. Tomas, B. Viossat and D. Mansuy, Tetrahedron Lett., 1996, 37, 31 13. 203 M. R. Iesce, F. Cermola, A. Guitto, F. Giordano and R. Scarpati, J.Org Chern., 1996, 61, 8677. I96 M. Tiecco, L. Testaferri, L. Bagnoli, F. Marini, Adams: Imines, enamines and oximes 543160 P. Renaud and I. Betrisey, Synth. Commirn., 1995, 25, 3479. 161 J. P. Begue, D. Bonnctdelpon, D. Bouvet and M. H. Rock, J. Flirorirte Chem., 1996, 80, 17. 162 M. Rejzek, M. Zarevucka, Z. Wimmer, T. Vanek, R. Tykva, J. Kuldova, D. Saman and B. Bennettova, Collect. Czech. Chem. Comrnirn., 1996, 61, 605. I63 T. Constantieux and J. P. Picard, Organometallics, 1996, 15, 1604. 164 J. H. Lai, H. Pham and D. G. Hangauer,.I. Org. Chem., 1996, 61, 1872. 165 R. J. Fletcher, M. Kizil and J . A. Murphy, Tetruhedron Lett., 1995, 36, 323. 166 K. Ramalingam, W. Zeng, P. Nanjappan and D. P. Nowotnik, Synth. Cornmun., 1995, 25, 743. 167 R. Joseph; T.Ravindranathan and A. Sudalai, Tetra- hedron Lett., 1995, 36, 1903. 168 V. M. Paradkar, T. B. Latham and D. M. Demko, Synlett, 1995, 1059. 169 F. Palacios, D. Aparicio, J. M. Delossantos and E. Rodriguez, Tetrahedron Lett., 1996, 37, 1289. 170 B. P. Bandgar, S. M. Nikat and P. P. Wadgaonkar, Synth. Comnzun., 1995, 25, 863. 171 D. Barbry and P. Champagne, Synth. Commun., 1995, 25, 3503. 172 S. Negi, M. Matsukura, M. Mizuno, K. Miyake and N. Minami, Synthesis, 1996, 991. 173 L. Maier and P. J. Diel, Phosphorus Sulfur Silicon Relut. Elem., 1995, 107, 245. 174 A. Zaks, A. V. Yabannavar, D. R. Dodds, C. A. Evans, P. R. Das and R. Malchow, J. Org. Chem., 1996, 61, 8692. 175 F. P. Ballistreri, E. Barbuzzi, G. A. Tomaselli and R. M. Toscano, Synlett., 1996, 1093.176 J. G. Lee and J. P. Hwang, Chem. Lett., 1995, 507. 177 T. Shinada and K. Yoshihara, Tetrahedron Lett., 1995, 178 I. M. Baltork and S. Pouranshirvani, Synth. Comrnirn., 179 B. P. Bandgar, S. I. Shaikh and S. Iyer, Synth. 180 M. Curini, 0. Rosati, E. Pisani and U. Constantino, 181 V. J. Majo, M. Venugopal, A. A. M. Prince and P. T. 182 A. I. Bosch, P. Delacruz, E. Diezbarra, A. Loupy and 36, 6701. 1996, 26, I . Commun., 1996, 26, 1163. Synlett, 1996, 333. Perumal, Synth. Commun., 1995, 25, 3863. F. Langa, Synlett, '1995, 1259 183 I. P. Andrews, R. J. J. Dorgan, T. Harvey, J. F. Hudner, N. Hussain, D. C. Lathbury, N. J. Lewis, G. S. Macaulay, D. 0. Morgan, R. Stockman and C. R. White, Tctruhedron Lett., 1996, 37, 481 1. 184 T. Kiguchi, K. Tajiri, I. Ninomiya, T.Naito and H. Hiramatsu, Tetruheclron Lett., 1995, 36, 253. 185 M. Tiecco, L. Tcstaferri, M. Tingoli, L. Bagnoli and C. Santi, Tetruhedron, 1995, 51, 1277. 186 M. Tiecco, L. I'estaferri, M. Tingoli and L. Bagnoli, J. Chem. Soc., Chem. Commrrn., 1995, 235. 187 H. Kusama, Y. Yamashita and K. Narasaka, Chem. Lett., 1995, 5. 188 S. Bourke and F. Heancy, Te~tiahedrort Lett., 1995, 36, 7527. 189 V. N. Komissarov, Zh. Org. Khim., 1995, 31, 1060 (Chent. Ahstr., 124:289438). 190 U. Chiacchio, A. Corsaro, V. Pistara, A. Rescifina, G. Romeo and R. Romeo, Tetrahedron, 1996, 52, 7875. 191 M. T. Mckiernan and F. Heaney, Tetrahedron Lett., 1996,37,4597. 192 J. Alcazar, M. Begtrup and A. de la Hoz, Hc~terocyfc~s, 1906, 43, 1465. 193 M. C. McMills, D. L. Wright, J. D. Zubkowski and E. J. Valente, Tetrahedron Lett., 1996,37, 7213. 194 D. Armesto, M. A. Austin, 0. J . Griffiths, W. M. Horspool and M. Carpintero, Chem. Commcrri., 1996, 2715. 195 U. Chiacchio, A. Corsaro, V. Librando, A. Rescifina, R. Romeo and G. Romeo, Tetrahedron, 1996, 52, 14323. C. Santi and A. Temperini, Heterocycles, 1996, 43, 2079. 197 S. Ahmed and R. C. Boruah, Tetruhedron Lett., 1996, 37, 823 1. 198 A. V. Tkachev, A. M. Chibiryaev, A. Y. Denisov and Y. V. Gatilov, Tetruheclron, 1995, 51, 1789. 199 J. Boivin, E. Pillot, A. Williams, W. Roger and S. Z. Zard, Tetruhedron Lett., 1995, 36, 3333. 200 K. Griesbaum, B. Ovez, T. S. Huh and Y. X. Dong, Liehigs Ann., 1095, 1571. 201 K. Miyashita, T. Toyoda, H. Miyabe and T. Imanishi, Synlett, 1995, 1229. 202 J. L. Boucher, S. Vadon, A. Tomas, B. Viossat and D. Mansuy, Tetrahedron Lett., 1996, 37, 31 13. 203 M. R. Iesce, F. Cermola, A. Guitto, F. Giordano and R. Scarpati, J. Org Chern., 1996, 61, 8677. I96 M. Tiecco, L. Testaferri, L. Bagnoli, F. Marini, Adams: Imines, enamines and oximes 543

ISSN:1350-4894    

DOI:10.1039/CO99704BX003

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

~~ ~~ Applications of stoichiometric organotransition metal complexes in organic synthesis TIMOTHY J. DONOHOE,* PAUL M. GUYO, PETER R. MOORE and CLARE A. STEVENSON Department of Chemistry, The University of Manchesteq Oxford Road, Manchester M13 9PL, UK Reviewing the literature published between 1 May 1995, and 30 April 1996 Continuing the coverage in Contemporary Organic Synthesis, 1996, 3, 1 1 2 2.1 2.2 2.3 2.4 3 3.1 3.2 3.3 4 4.1 4.2 4.3 4.4 5 5.1 5.2 5.3 6 6.1 6.2 7 7.1 7.2 7.3 7.4 8 8.1 8.2 8.3 8.4 9 9.1 9.2 9.3 10 Introduction Transition metal alkyl, alkenyl, alkynyl and acyl complexes Alkyl and alkenyl organozirconium based methodology Alkenyl chromium species in organic coupling reactions Alkyl titanium and manganese reagents Acyl transition metal complexes Transition metal carbene and vinylidene complexes Annulation reactions Spirocycle formation Miscellaneous reactions of carbene and vinylidene complexes q*-Complexes $-Complexes of titanium y2-Complexes of iron q2-Complexes of cobalt q'-Complexes of rhenium q'-Complexes $-Complexes of titanium $-Complexes of iron $-Complexes of cobalt q4-~omplexes q4-Iron-diene complexes q4-Nickel-diene complexes $-~omplexes Stoichiometric ferrocene complexes $-1ron complexes $-Titanium complexes q5-Rhenium complexes $-Complexes $-Chromium complexes #-Iron complexes $-Manganese complexes $-Ruthenium complexes Transition metal mediated cycloadditions Pauson-Khand type reactions Nickel promoted [2 + 2 + 21 cyclotrimerisations Palladium promoted cycloalkenylation References 1 Introduction This article is a review of the literature published between 1 May 1995 and 30 April 1996, and is designed to be a selective account of recent developments in the field of stoichiometric organotransition metals in organic synthesis.The manner in which the field has been subdivided follows precedent,' with preference being given to methods which will be of use to the practising organic chemist. 2 Transition metal alkyl, alkenyl, alkynyl and acyl complexes This area of chemistry is dominated by the organometallic chemistry of zirconium, which continues to prove itself as a versatile and useful partner for organic substrates. 2.1 Alkyl and alkenyl organozirconium based methodology Recent work by Tietze directed towards a synthesis of the anticancer antibiotic CC-1065 utilised an elegant zirconocene mediated cyclisation as the key step (Scheme 1).2 The cyclisation of 1+2 is based upon methodology championed by Buchwald, and is presumed to occur via transformation of a putative zirconium-didehydrobenzene complex into a Ph02S OMe 1 .NS02Ph 4 i.Bu'Li then - Cp&CICH3 I] ( r B N S o 2 P h I I I Ph02S OMe I + PhO& 2 Ph02S Scheme 1 22 Contemporary Organic Synthesiszirconacyclopentene (the regiochemistry of this process is noteworthy). A transition metal was also essential in forming the final ring of the target: the remaining allyl group within compound 2 was cyclised onto the arene ring by a Heck reaction. Insertion of novel electrophiles into the carbon- zirconium bond continues to be worthwhile, as each new reaction expands the scope of organozirconium chemistry.Takahashi’s group has succeeded in reacting a zirconacyclopentene (which can be prepared from either an alkene or diene) with acyl chlorides, in the presence of copper(1) salts, to yield a zirconium containing ketone complex (Scheme 2).3 In the absence of an external electrophile, intra- molecular reaction of the carbon-zirconium bond with the carbonyl group ensued and, after acid treatment (presumably to effect dehydration), this furnished a cyclic olefin in good yield. The identity of the initially formed complex was established by trapping the remaining carbon-metal bond with iodine; this gave compound 3. Et CuCCLiCl PhCOCl ~ phvEt a Et Et Cp2Zr phw Et Et P h a E t Et 3 1 - ( p P 2 --J c Cp2zrBu2 \”ra Li i.BFpOEt2 ArCH(NR’Z)(OBu) - - -zrcp* i. BF39Et2 I ii. NaHC03 R rj ,,OEt Ar u--CH3 = Ph; R, R = [CH2I5 (95%) (yJR “CHs R = Me (73%) R = Et (61%) R = OEt (71%) Scheme 3 A useful extension of Taguchi’s method for preparing allyl zirconium species from allylic alcohols has been reported by Clark.* Treatment of the disilyl ether 4 with ‘CpzZr’ and an aldehyde gave a series of homoallylic alcohols with good to excellent diastereoselectivity (favouring the anti isomer) (Scheme 4). 4 Scheme 2 The general theme of carbon-zirconium bond functionalisation has also been investigated by S. Kim and K. H. Kim who have shown that treatment of either alkenyl or alkyl zirconium species with BuzSn(OMe)z promotes a transmetallation to the corresponding tin compound^;^ this approach may prove to be useful in synthesis. Vinyl selenides may also be prepared from alkenyl zirconium compounds by reaction with aryl selenyl bromides.’ Srebnik has published an interesting route to boron enolates and a-halo ketones via treatment of a vinyl boronate with Schwartz’s reagent, followed by (copper catalysed) reaction of the alkyl zirconium bond with an acyl chloride.6 Whitby has continued to expand the range of electrophiles that may be used in conjunction with his cyclisation-insertion reaction of dienes (this involves treatment of a diene with ‘Cp,Zr’, followed by addition of an allyl halide and strong base, Scheme 3).Reactions of the allyl zirconium species formed during the above sequence with acetals, orthoesters, iminium ions and 173-dithenium tetra- fluoroborate all give impressively functionalised compounds in a succinct manner (Scheme 3).7 I I (+) \OTBS (+) \OTBS R = Ph (51%) de = 91% R = Me (51%) de = 86% R = Pr‘ (31%) de = >95% Scheme 4 2.2 Alkenyl chromium species in organic coupling reactions Two groups have utilised the reaction of vinyl iodides with aldehydes as promoted by excess chromium( 11) chloride and catalysed by nickel.Procter’s group reported an intramolecular version of this reaction during their studies towards a synthesis of solenolide F (Scheme 5).9 Although the reaction proceeded in 30% yield, this may be a consequence of reaction of only one of the vinyl iodide geometrical isomers. Presumably, a stereo- chemically controlled synthesis of the cyclisation precursor will solve this problem.In addition, a total synthesis of halicholactone was recently reported by Wills et al. which used an intermolecular coupling reaction as a crucial step in assembly of the target skeleton (Scheme S).” Donohoe e t al.: Applications of stoichiometric organotransition metal complexes in organic synthesis 232.4 Acyl transition metal complexes The reaction of acyl cobalt complexes with functionalised allenes has been reported by Bates (Scheme 7).16 The requisite acyl cobalt complexes were conveniently prepared from the reaction of alkyl halides with sodium tetracarbonylcobaltate and, upon reaction with an appropriately substituted allene, a cyclisation ensued. This process is presumed to occur via addition of the cobalt-acyl bond to the internal n system of the allene, to give an $-ally1 cobalt system.Intramolecular nucleophilic attack by a variety of functional groups (alcohols, acids etc.) all formed five membered heterocycles, substituted with an olefin. This process works particularly well when the nucleophile is a sulfonamide, thus constituting an attractive synthesis of the pyrrolidine nucleus. xs. CrCI2 cat. NC12 ____c 30% H 2 0 + xs. crc12 cat. NEI2 0 0 % OSiButPh2 1 halicholactone ------- (74%) ( de=33% Scheme 5 2.3 Alkyl titanium and manganese reagents The reagent Cp2TiMe2 has been reported to be a powerful methylenating reagent by Petasis, and applications of this compound are now beginning to appear. Olefination of 1,3-dioxan-4-ones with this reagent led to compounds which are precursors to substituted tetrahydropyrans (Scheme 6)." Petasis et al.have also utilised Cp2Ti(CH2TMS)* and its reaction with alkynes as a method for synthesising vinylsilanes" and also for methylenating squaric acids to give cx-methylene cyclobutenones." $. C&TiMe2 Rfi i.DlBAL Rb (90-98%) R' R OAR' OAR, X R = H, Me; R' = Bu', Pi, Ph (6586%) Scheme 6 Rieke has recently published a method for the direct formation of organomanganese bromides from alkyl halides (using lithium, naphthalene and MnX2).14 These derivatives will couple with acyl chlorides (without transition metal catalysis) to give ketones in good to moderate yields. Another group has also investigated these rather unusual organo- metallics and shown that they will couple with vinyl iodides to give substituted olefins in the presence of catalytic iron( 111) acetylacet~nate:'~ this coupling is stereospecific and proceeds in excellent yields.(80%) Scheme 7 3 lkansition metal carbene and vinylidene complexes 3.1 Annulation reactions The use of group VI carbenes in the construction of cyclic systems has proved to be a productive area of organometallic chemistry over recent years; the archetypal reaction within this area must be the Dotz reaction of vinyl carbenes with acetylenes." Work published by Quayle has extended this methodology to encompass the construction of a series of annulated quinone derivatives. l 8 Reaction of either a sulfone- or sulfide-stabilised vinyl carbene with an acetylene, under Kerr's dry state adsorption conditions, furnished the benzannulated compounds in moderate to good yields (after oxidative work-up), A clue to the mechanism of the annulation process was found in the detection and eventual isolation of an intermediate, namely the chelated tetracarbonyl complex 5 (Scheme 8).This complex readily undergoes annulation when resubjected to the reaction conditions, and appears to be a chelated (and 18-electron) form of the 16-electron intermediate formed by dissociation of CO from the vinyl carbene (this is postulated to be the rate determining step in the Dotz reaction). 24 Contemporary Organic SynthesisObservation i. (ii) CAN, R ' E HNOs Si02, heat * ( y 7 J - I 0 Ph I (-ypQ4 0 OEt 5 I R = S32Ph, R' = Ph (69%) R = SPh, R' = Ph (21%) R r R' 1 MeCN, rt *-OMe 7 L R = CH20Me, R' = 2-furyl(45%, ee = 86%) R = CH20Bn, R' = Ph (55%.ee = 72%) Scheme 8 The reaction of vinyl carbenes with dienes has also been exploited in the synthesis of seven membered carbocyclic corn pound^.^^ Enantio- merically enriched products were accessible via this chemistry, which involved treatment of a series of vinyl carbenes 6 with dienes (substituted with a chiral auxiliary) 7 at room temperature (Scheme 8). The ring forming reaction was presumed to occur from a divinylcyclopropane intermediate which arose from carbene ligand transfer to the diene: this compound, which was isolated, then underwent a Cope rearrangement. Work from Germany has also described the cycloaddition chemistry of alkynyl carbenes with cyclic enamines20 and that of p-amino vinyl carbenes with alkynes:2' in both cases, the products were usefully substituted cyclopent adienes.Mori has reported an interesting method for the formation of lactams (with sizes ranging from four to seven membered).22 This reaction was originally noticed as a by-product in the [2+2+2] cyclisation of diynes and carbenes: the mechanistic hypothesis that emerged and the subsequent development of a general cyclisation method is indeed impressive (Scheme 9). 3.2 Spirocycle formation The reaction of but-3-ynyl alcohols with coordina- tively unsaturated chromium and molybdenum carbonyls to yield cyclic carbenes has been studied (1 OYO) + Application TSyw' H TMS (43%) n=0(16%) .ts n = 1 (85%) n = 2 (82%) n = 3 (84%) Scheme 9 further, with a view to extending the scope of the methodology and allowing the preparation of natural products. Quayle has used this reaction as a key step in his synthesis of (+) muricatacin (8+9, Scheme Schmidt has also reported work in this area, describing the cyclisation of a series of functionalised but-3-ynyl alcohols, each of which provides useful information about the generality of this method of ring formation (Scheme i.Cr(CO)5*THF ii. CAN D (+)-tartaric acid -- - "doH - - - 8 0 -\ - - (+)-muricatacin OH 9 (68%) (48%) Scheme 10 3.3 Miscellaneous reactions of carbene and vinylidene complexes Helquist has published some interesting work concerning the potential of cationic iron carbene complexes as initiators for polycyclisations (Scheme 11).25 Compound 10 is a precursor to the transient cationic complex 11, which was generated by Donohoe et al.: Applications of stoichiometric organotransition metal complexes in organic synthesis 2513 l1 I 10 C02Me 12 Fe(CO)2Cp NH~PFG 1 Scheme 12 Scheme 11 reaction with Meenvein’s salt.The cyclisation that ensued furnished the iron-containing bicycle 12 in 65% yield; the iron unit was then decomplexed with ceric ammonium nitrate in methanol. Helquist mentions the intriguing possibility of a variant of this reaction which would utilise a chiral metal fragment (e.g. COCpLFe) as an initiator: the enantioselective version of this reaction is awaited with interest. Several papers have been published which concern the preparation and reactivity of chromium cyclopropyl carbenes: Barluenga and Concellon report that vinylmethoxy carbenes undergo cyclopropanation when treated with chloroiodo- methane and methyllithium.26 The complexes thus formed may be transformed to the corresponding cyclopropyl esters by reaction with pyridine N-oxide.The authors point out that the reaction may be used as an indirect route to these esters as the direct transformation of x,B-unsaturated esters to their corresponding cyclopropyl derivatives, using identical conditions, led to a complex mixture of products. Herndon has published a careful study on the rearrangement of vinyl cyclopropyl carbenes to cyclopentenone~.’~ The mechanism of this stereo- specific two carbon ring expansion is thought to be related to the Cope rearrangement of divinyl cyclopropanes, alluded to earlier: in this case the conformational requirements of the vinyl group and the carbene unit were probed and it was shown that both must be positioned endo to the cyclopropane unit before rearrangement could occur.Finn and co-workers have published preliminary results regarding the cycloaromatisation of a ruthenium vinylidene complex formed from an enediyne (Scheme 12).2* Indeed, conversion of the terminal acetylene within 13 into an organometallic complex 14, served to increase its rate of cyclo- aromatisation relative to the parent hydrocarbon. The asterisks indicate the position of deuterium in the product when the cycloaromatisation is performed in deuteriocyclohexadiene. This approach to activation of the enediyne system represents a starting point for the construction of C02Me I derivatives which have controllable cyclo- aromatisation rates.4 q2-CompIexes 4.1 $-Complexes of titanium Sat0 and co-workers have been almost solely responsible for the publication of a large body of work regarding the synthesis and reactivity of olefin and alkyne complexes of Ti(OR)2. These complexes are formed by reacting a suitable olefin (or alkyne) with the propene-Ti(OPr’), complex 14: this reagent (which is easily prepared from titanium tetraiso- propoxide and isopropylmagnesium chloride) behaves as a ‘Ti(OPri)z’ equivalent, in a manner reminiscent of the zirconium chemistry described earlier.29 A simple example involves the reaction of 14 with alkynes (Scheme 13) which proceeds to give an addition complex.3o This complex may be reacted with a series of electrophiles (RCHO, D20 etc.) to furnish substituted olefins.The regiochemistry of reaction with an electrophile is difficult to control unless the alkyne is substituted with a TMS group; in this case reaction with two different electrophiles allows sequential replacement of each carbon-metal bond to form stereochemically defined vinylsilanes. Reactivity of the complex 14 with dienes, diynes and eneynes has also been explored: cyclisation gave a series of titanabicycles which were subsequently TMS TMSCECR $Ti(0Pt)2 + - bTi(OPr)2 - Ti(oPSl4 PiMgCl / 14 R’ I CeHilCHO r 1 I OH Scheme 13 26 Contemporary Organic Synthesisi. BnO 14 BnO ii. HCI ii. HCI (77%) OBn % (87%) TMS B n 0 - h ii.CO OBn (51%) OBn 2p2 c OBn 15 OBn i. PhCHO ii. I2 I TMS OBn I Ph OBn (66%) Scheme 14 reacted with electrophiles such as HC1, I2 or CO (Scheme 14).3' Such chemistry puts titanium on an equal footing with both zirconium and cobalt and will have manifold uses in organic synthesis.Even more elaborate reactivity was discovered when complex 14 was treated with dieneyne 15, as the complex resulting from cyclisation had both a vinyl- and an allyl-titanium bond, each of which could be substituted separately.32 cyclopropylamines from amides has been recently published by de Meijere.33 This reaction involves treatment of a series of N,N-dialkyl amides with the titanium complex of an alkene (prepared from a Grignard and Ti(OPri)4, Scheme 15). The inspiration for this work came from the related procedure for the synthesis of cyclopropanols.34 Presumably, the mechanism of the reaction involves attack at the amide by a metal n complex to give a titanaoxacyclopentane; this is unstable with respect to cleavage to form a titanium oxygen double bond, thus ejecting a cyclopropylamine.An interesting and useful preparation of 4.2 q2-Complexes of iron Enders has continued to explore the synthetic applications of enantiopure iron alkene complexe~.~~ EtMgBr, Ti(OPi), C HNR R = Me (56%) R=Bn(60%) EtMgBr, Ti(0Pt')d JNBn2 b via Scheme 15 Complexation of vinyl sulfone 16 with Fe2(C0)9 under an atmosphere of CO gave the q2-complex in good overall yield: a crystallisation was necessary to ensure that the complex was stereochemically homogeneous. Ionisation of the allylic ether with acid led to an $-cationic iron-ally1 system, which was subsequently treated with a series of Knochel- type organozinc-copper reagents (Scheme 16).Nucleophilic attack was both stereo- and regio- selective: having performed its task, the iron carbonyl fragment was decomplexed with ceric ammonium nitrate (CAN), thus allowing the formation of enantiopure y-substituted vinyl sulfones. Of course, participation by the transition metal means that overall the substitution had occurred with retention (via double inversion), ii. crystallisation A OBn A OBn (9-16 (65%) de, ee >99% S02Ph \ so2ph i. FG(CH2),Cu(CN)ZnX 'ke(C0) BF4- 7 ;.CAN4420 (CH2)fFG (3340%) ee = 96-99% FG = functional group Scheme 16 4.3 q2-Complexes of cobalt In forming the dicobalt hexacarbonyl complex of an acetylene, the reactivity and steric environment of the acetylene is altered dramatically." By far the most important reaction of these complexes involves the formation of a carbocation o! to a complexed acetylene (which is accelerated many times by the transition metal) and subsequent trapping of this Donohoe et a1 .: Applications of stoichiometric organotransition metal complexes in organic synthesis 27reactive intermediate by a nucleophile: this process is known as the Nicholas reaction.In order that a cation may be generated in the Nicholas reaction, it is clearly essential that a leaving group is attached in the prop-Zynyl 1-position. Most studies make use of an alcohol or ether group (ionised by treatment with acid, vide infra). Green, however, has shown that prop-2-ynyl chlorides may be successfully complexed, ionised and trapped in the Nicholas rea~tion.~’ Unfortu- nately, the prop-2-ynyl chloride-dicobalt hexacarbonyl compounds, which are precursors to stabilised cations, could not be isolated due to competing dehalogenation reactions: a solution to this problem was found, however, by performing the complexation, ionisation and trapping experiments without isolation of any intermediates.As part of a study directed towards the synthesis of marine toxins, Martin has investigated the Nicholas reaction for the formation of cyclic ethers (Scheme 17).38 By using a diol precursor to a cobalt stabilised cation, Martin was able to make the trapping reaction an intramolecular one: this approach proved to be rather powerful for the construction of six to nine membered ethers. Zn (+ 28) 1 Scheme 18 OH I r PH 1 ry OTBDPS n= 1 (85%) I Scheme 17 To complete this section, we would like to draw the reader’s attention to a paper by Nicholas on the formation of cyclic eight membered diynes and cobalt complexed enediynes (Scheme 18).’9 These motifs are important constituents of a range of highly topical natural products.Construction of such highly strained (and potentially reactive) species was achieved by reduction of a dication with zinc or sodium to yield diradical 17. Radical coupling ensued to form the cyclic compounds with extremely high diasteroselectivity in favour of the trans isomer. Decomplexation of the transition metal to form cyclic diynes was also accomplished: however, liberation of the cyclic enediynes remained elusive! 4.4 y*-Complexes of rhenium Rhenium complexes of the type Cp(NO)(PPh,)(ClCH,Cl)Re+ BF4- (18) are known to complex to both alkenes and alkynes.Bearing in mind that the above complexes can also be resolved, they provide an interesting method of achieving asymmetric synthesis. Guillemin has extended the work of Gladysz by investigating the reactivity of unsaturated alcohols with this organometallic fragment (Scheme 19).40 Reaction of 18 with a series of unsaturated alcohols provided the q’-complexes in good yields. These complexes could then be oxidised (without decomposition of the transition metal moiety) and even olefinated using Wittig chemistry. The products of such manipulation have potential as selectively protected enones or dieneones for more standard synthetic transformations. 5 q3-~omplexes 5.1 q3-~omplexes of titanium A method for the selective functionalisation of pinene derivatives using allyl titanium chemistry has been reported recently (Scheme 20).41 Treatment of nopadiene 19 with a titanium(rr1) complex resulted in the regioselective formation of an $-ally1 complex which was able to react further with a series of aldehydes.The outcome of these reactions was quite interesting: in each case the aldehyde attacked the endocyclic position of the allyl system from the endo face. The remaining (exocyclic) olefin was always formed with a cis configuration; indeed, relative configuration at the new hydroxy-substituted centre was the only facet of the reaction which was not completely controlled, and even in this case, use of a bulky aldehyde resulted in the formation of essentially one diastereoisomer.28 Contemporary Organic SynthesisI ON’* 1 PPh3 CICH2CI OH BF4- ,Re+, R=H(69%) R - \ R = CH20H (54%) 18 R = Me (81%) iodoxybenzoic acid (6 1 -92%) (79%) -OH I iodoxybenzoic acid - ON-= I ‘PPh3 I Ph3P=CHCOCH3 BF4- I+ BF4- 4 ON*-’Re, PPh3 I (76%) 7 0 H (73%) Scheme 19 19 Scheme 20 k p 2 1 RcHo OH R = Et (52%) de = 28% R = P i (62%) de = 4% R = Bur (47%) de = 90% 5.2 q3-Complexes of iron In our review of last year’s work, we commented upon the synthesis of iron-diene complexes via n-allyltricarbonyliron lactone complexes. This work had an advantage over previous methodology in that the precursors to the organometallic complexes could be prepared in an enantiomerically enriched form by the Sharpless epoxidation.Ley has (CH2)oOTBDPS >95% ee 20 AIBu‘~ 1 HOOC P-dimorphecolic acid (53%) cl 0 R = Me (76%) >95% de R = Ph (26%) >%yo de Scheme 21 subsequently used this chemistry to report the first enantioselective synthesis of P-dimorphecolic acid (Scheme 21).42 A key step was the diastereoselective reduction of ketone complex 20 (prepared in 95% ee via Sharpless chemistry) with Bu\Al, which duly formed the alcohol centre in the final product. Ley has also examined the addition of allyl- stannanes to ketone complexes similar to 20, and found that the reaction proceeds with extremely high levels of stereo~ontrol.~’ In each case, conversion of the n-allyltricarbonyliron species to a stereochemically defined iron-diene compound is possible, thus providing a concise route to these versatile organometallic complexes. Addition of organometallics to l-formyl- substituted iron-diene complexes is not normally a highly stereoselective process, and mixtures of diastereoisomers are to be expected.Addition of organoaluminium reagents to formyl-substituted n-ally1 t ricarbonyliron complexes (eg. 2 1 ), however, gives good levels of stereo~electivity.~~ If the resulting compounds were to be transformed into iron-diene complexes, then this route obviates the need to use formyl substituted iron-diene complexes at all. 5.3 q3-Complexes of cobalt An interesting study on the synthesis and reactivity of n-allylcyclopentadienyl cobaltolactone complexes has been reported by Kerr.45 These compounds are made by photolysis of the corresponding vinyl epoxides in the presence of dicarbonylcyclopenta- dienyl cobalt, in a manner reminiscent of the Donohoe et al.: Applications of stoichiometric organotransition metal Complexes in organic synthesis 29preparation of the analogous iron systems.Once prepared, these compounds are likely to exhibit a wide range of interesting and useful chemistry: they are air stable and appear to be even more resistant to oxidation than the iron complexes mentioned earlier. Initial studies have concentrated on the reaction of these complexes with CAN in the presence of a nucleophile so as to produce function- alised olefins (eg. 22, Scheme 22). R = H, Me, Ph; R'= H; R2=H, Me, Ph; R3= H Yields (2243%) CAN, MeCN 1 R X - O 0 A3 Scheme 22 6 q4-Complexes 6.1 q4-Iron-diene complexes Interest in the use of iron-diene complexes has continued throughout the last twelve month period.The synthesis and reactivity of tricarbonyl(viny1- ketene)iron(O) complexes has received further attention from Gibson (nee Thomas). Recently published results have illustrated that these vinyl- ketene complexes can react with anions of diethyl N-alkyl(aryl)phosphoramidates, to provide tri- carbonyl(vinylketenimine)iron(O) complexes 23 (Scheme 23).46 The yield of vinylketimine complex was found to be dependent on the steric bulk of the phosporamidate substituent R' and the vinylketene complex substituent R2. The use of phosphorami- date anions derived from chiral amines may provide access to enantiomerically enriched vinylketene complexes. 23 R1 R2 x vield Et Bur 1.0 50% Et Bu' 1.5 92% Ph Pr' 1.5 87% Scheme 23 30 Contemporary Organic Synthesis This group has also investigated the synthesis and reactivity of iron carbonyl complexes of p-silyl substituted a,P-unsaturated ketones (Scheme 24).47 Reaction of vinylketene complex 24 with methyllithium gave the a-substituted diketone 26.Less bulky silyl substituents were shown to be more labile during this reaction, giving rise to desilylated products . In contrast, when the trimethylsilyl deriv- ative 25 was treated with methyllithium under an atmosphere of carbon monoxide, the silylated vinylketene complex 27 was isolated in 68% yield. Bu'MePSi / i. MeLi, 24 ii. Bu'Br -+ 0 26 38% I \ Fe .O (Ca3 \ MeLi, 25 CO c M e 3 S i y ' 24 R = Bu'Me2Si 68% 25 R = Me3Si 27 Fe W ) 3 Scheme 24 Previous difficulties encountered during oxidation of the organic ligand within tricarbonyl(triene)iron complexes, caused by competitive oxidative decom- plexation of the transition metal, have been overcome r e ~ e n t l y .~ ~ Donaldson has shown that (polyene)Fe( CO)3 complexes such as 28 (Scheme 25) were stable to a two step osmylation-periodate cleavage sequence, and provided (dienal)Fe( CO)3 complexes in reasonable overall yield.49 This oxida- tion procedure provides a convenient route for the creation of unsaturated sites adjacent to the diene ligand, which can then undergo further transforma- tions. The generality of this method was demon- strated through its application to the oxidation of a series of related tricarbonyl(triene)iron complexes.Scheme 25 The use of iron-diene chemistry in stereoselective organic synthesis has continued to provide interesting results. Recent examples include the diastereoselective synthesis of metal-bound 2,3,3a,7a-tetrahydroindoles, using a single electron transfer-mediated oxidative cycli~ation.~~ Highdiastereoselectivities have also been achieved in the formation of heterobicyclic compounds, through the application of an intramolecular cyclisation of iron- diene complexes bearing amino acid derivatives." Chiral4-piperidones have been prepared by Troin (Scheme 26), using the Fe(CO)3unit as both a protecting and directing group during a diastereo- selective intramolecular Mannich The stereochemistry of the key cyclisation step has been rationalised in terms of the formation of the enol ethers 30 and 31, with the former being the less stable of the two rotamers due to an increase in steric hindrance .Addition of the enol ether occurs (within 31) from the face opposite to the bulky tricarbonyliron unit to yield the protected piperi- done 32 as the major product (9: 1 mixture of stereoisomers at C-2). Decomplexation followed by acid hydrolysis yielded the optically pure piperidone 33. H \ A 29 n Me02C 4 H Fe (CQ3 I 32 68% overall yield I Fe*,H+ 33 H Scheme 26 c- 6.2 q4-Nickel-diene complexes Nickel-promoted intramolecular oligomerisation of 1,3-dienes provides a valuable method for the formation of regio- and stereo-chemically defined rings.53 Earlier reports from Mori et al. had outlined the use of a remarkably stereoselective cyclisation of 1,3-dienes (Scheme 27).54 In this process, dienes such as 34 were treated with the nickel hydride complex 35; the cyclised product 38 was produced stereoselectively through the intermediacy of x-allyl- nickel complex 36.In all cases examined, cyclised products having an internal olefin on the side chain (as opposed to a terminal one) were formed predominantly. Recently published results have shown that the regiochemistry of this reaction can be altered through the addition of a stoichiometric amount of cyclohexa-l,3-diene to the nickel complex 100 mol% Ni(aca~)~-2OO mot% PPh3 DIBAL-H (2equiv.) OBn H-NP-X 35 toluene, 0 "C 36 (69%) 34 (EZ=8:1) I O"i-X hydrolysis '-OBn 38 '-OBn 37 H-Ni'I-X 35 V 1 ,Scyclohexadiene (1 50 mol%) toluene, 0 "C 39 40 (70%) Scheme 27 35, before addition of the diene substrate." Under these modified reaction conditions, cyclisation of diene 39 provided the terminal olefin 40 in a stereo- selective fashion.Preferential formation of the terminal olefin was discovered in all cases examined. These contrasting results were interpreted mechanistically as being a consequence of reaction via the cationic Ni" complex 41 (Scheme 28), which is formed in the presence of cyclohexa- 1,3-diene (or other dienes that can adopt an s-cis conformation). Insertion of H 41 H carbonyl group insertion Scheme 28 Donohoe et al.: Applications of stoichiometric organotransition metal complexes in organic synthesis 31the olefin into the hydride-nickel bond gives complex 42, which then undergoes carbonyl inser- tion and hydrolysis to provide the cyclised product 44.7 $-~ornplexes 7.1 Stoichiometric ferrocene complexes Investigation of the chemistry of ferrocene continues to be an extremely active and varied area of research, confirming the key role that this organometallic plays in many important synthetic transformations. Much of the focus of this work has been concerned with the preparation of chiral ferro- cene derivatives, which may then be used as catalysts or ligands in a host of asymmetric transformation^.^^ Knochel has recently communicated a novel approach to C,-symmetric 1,l '-ferrocenyl diols 47, using the readily available ferrocenyl diketones 45 (Scheme 29).57 Asymmetric reduction of the ketones was achieved through the use of borane in the presence of the oxazaborolidine catalyst 46. Use of this catalyst provided the reduced products in excel- lent yield and >98% ee.The diols so obtained were then elaborated further to provide ligands of interest for potential asymmetric catalysis. Thus, in one example, the bis(dimethy1arnino) ferrocenyl diphosphine 50, could be obtained in 55% overall yield from the chiral diol 48 via a directed metal- 46: 60 mol% R = Me, pi, ~ 5 ~ 1 1 , Ph or (CH2)&02Me e C 5 H 1 1 &C!iH11 ii. HNMe2 -c5H1 1 I i. Ac20, pyridine I A 48 OH A NMe2 49 (1 00%) i. Bu'Li ii. CIPPh2 A 50 (55%) NMe2 Scheme 29 32 Contemporary Organic Synthesis lation of the dimethylamine derivative 49. As can be seen, this method provides an extremely efficient entry to C2-symmetric ferrocenyl diols and aids the further development of asymmetric catalysts.Enantiomerically enriched ferrocenyl derivatives have also been prepared by Nicolosi et al. using a lipase-mediated resolution (Scheme 30).58 In this procedure, a racemic mixture of 2-hydroxymethyl- 1 -methylthioferrocene ( & )-51 was resolved with Novozym 435 in the presence of vinylacetate, providing the chiral ester (+)-52, in 47% yield and 84% ee. If the reaction was allowed to proceed to 60% conversion, then the unreacted enantiomer (+)-51 could be isolated in 95% ee. The configura- tion of ester (+)-52 was established through its conversion to the known amino alcohol (-)-54 via a four step sequence. During this procedure, the amino group was used to control the direction of lithiation, and this protocol provided amino alcohol (-)-53.Subsequent reduction gave compound (-)-54 of known absolute configuration. Fe CH20H Novozym-AcV * Fe (+51 (+)-52 (47%) 84% ee i. NH(CH3))TMeOH ii. Buti iii. C3H603 t (-)-54 (-)-53 -E Fe (+)-51 Scheme 30 Finally, Kagan has recently published the successful synthesis of a variety of chiral carbo- cations, which are o! to a ferrocene ~ystem.'~ The Lewis acidity of these carbocations with regard to initiating a variety of reactions, including the Diels- Alder reaction, was also investigated. The synthesis of these cationic species (Scheme 31) commences with the reaction of aldehyde 55 with p-tolyl- magnesium bromide, to provide the alcohol 56 as a single epimer, in yields ranging from 54 to 90%. The (S) configuration at the newly formed stereogenic centre was assumed through ex0 attack at the carbonyl group, with the carbonyl oxygen adoptingIHX 57 58 R = Me3Si, I, Bu3Sn, Me2Bu'Si or Ph 59 Scheme 31 an arrangement anti to the R group. Conversion to the carbocation 57 was then accomplished in 16% (R = Me2Bu'Si) to 68% (R = Ph) yield, through reaction with strong acid and acetic anhydride or trifluoromethanesulfonic anhydride.These carbo- cations were shown to adopt (as expected) the least sterically hindered conformation 58, and this was proved by hydrolysis to alcohol 59. In most cases, these cations acted as efficient catalysts in the Diels-Alder reaction between cyclopentadiene and methacrolein. Unfortunately, the product mixtures were shown to be racemic. Further investigations using these versatile cations are being undertaken and these should reveal other opportunities for asymmetric synthesis.7.2 $-Iron complexes As part of a continuing programme to explore the scope of transition metal-diene complexes in organic synthesis," Knolker et al. have recently published a high yielding, convergent synthesis of the marine alkaloid hyellazole (Scheme 32)." The key step in this sequence required the electrophilic aromatic substitution of an appropriately substituted arylamine with the tricarbonyliron-complexed cyclo- hexadienylium cation 60, to provide a substituted iron complex in almost quantitative yield. Subse- quent oxidation with ferricenium hexafluorophos- phate provided the target alkaloid in 59% yield. Complex 61, which was formed as a side product during this oxidation, could also be readily converted to hyellazole via a demetallation- O-methylation sequence.This approach provided an extremely short (three steps) and efficient (83% ,OMe I Ph . .. hyellazole (98%) Ph 61 Scheme 32 overall yield based on 60) method for the synthesis of carbazole alkaloids. 7.3 $-Titanium complexes A recent communication by Ernst et al. has highlighted the discovery of a new class of coupling reactions, involving the reaction of a novel half-open titanocene complex 62 with aldehydes and ketones (Scheme 33).62 The reaction proceeded with unusual 1,4-syn addition of the ketone or aldehyde, and was used to create up to five new stereocentres with very high or complete stereoselectivity. Simple modifica- tion of the reaction conditions, through exposure to air after addition of the substrate, resulted in forma- tion of the trio1 63, in which the third hydroxy group was orientated anti to the existing 1,4-substituents.The origin of the stereochemistry has been rational- ised through the generation of an q4-diene complex 64 in which the second ketone initially coordinates to titanium prior to coupling. The exceptional regio- and stereo-control exhibited by this reaction bodes well for its application to the synthesis of poly- oxygenated carbocycles. 7.4 $-Rhenium complexes The application of rhenium complexes to the asymmetric synthesis of organosulfur compounds has recently been investigated by Gladysz (Scheme 34).63 The key reaction proceeded via the [2,3] rearrangement of ylides derived from di(ally1) and di(prop-2-ynyl) sulfide complexes.Thus, treatment of the di(ally1) sulfide complex 66 with potassium tert-butoxide gives the rearranged complex, which wag then methylated and decomplexed to provide the chiral ( S ) sulfide and rhenium complex 67 [this may be recycled in three steps to the di(ally1) sulfide Donohoe et al.: Applications of stoichiometric organotransition metal complexes in organic synthesis 335Q ,Ti- f) . . 62 R' = Me, Et, Ph, Pr', Bu', or But; R2 = Me, Et or H; R1,R2 = [CH& or (CH2l4 64 Scheme 33 66 H' MeOTf, 1 4o0C ON PPh3 - -Re- - - 1 PPh3 (S)-ee=84% EN 67 Scheme 34 661. The starting material for this desymmetrisation process is prepared from commercially available Rez(CO),,], using a resolution.The ready availability of starting materials, coupled with the air stability of all the compounds depicted in Scheme 34, provided an ideal process for the synthesis of chiral sulfides on a multi-gram scale. 8 #-Complexes 8.1 q6-Chromium complexes additions.@ This type of reaction has been shown to provide efficient routes to highly substituted polycyclic compounds, which may otherwise prove difficult to construct. Rigby has developed this methodology to encompass the generation of optic- ally active cycloadducts using diastereoisomerically enriched tricarbonyl(cycloheptatriene)chromium(O) complexes 68 (Scheme 35).65 Reaction of these complexes with ethyl acrylate gave the expected cycloadducts as a 1 : 1 mixture of regioisomers in diastereoisomerically pure form.Further examples have confirmed the complete stereocontrol exhibited by this reaction in a variety of [6n + 4x1 and [6n + 2x1 cycloadditions. HQH R @COPE1 hv, 82% ,C02Et H-Q-H R > 98% de > 98% de R = (+)/(-)-2,lO-~amphorsultam Scheme 35 Planar tricarbonylchromium complexes have also been used to good effect in stereoselective hetero- Diels-Alder and 1,3-dipolar cycloadditions.66 One recent example involved the synthesis of indolizi- dines and quinolizidines (Scheme 36).67 In this sequence, the chiral aldimine complex 69 underwent a smooth aza-Diels-Alder reaction with Danish- efsky's diene, in the presence of tin(1v) chloride, to provide diastereoisomerically pure 2,3-dihydro- pyridin-4-one. Simple tributyltin mediated radical cyclisation proceeded with excellent stereo- selectivity, which was accounted for in terms of a transition state conformation that minimised A['%rain between the aryl methyl group and the dihydropyridinone ring." The use of $-chromium complexes in the synthesis of natural products and their derivatives has been of substantial interest.6X One recent (formal) synthesis of the antileukaemic lactone (-)-steganone by Uemura et al., employed a stereo- selective cross-coupling of a planar chiral (arene)- chromium complex (Scheme 37).69 The success of this sequence relied on two key transformations.Initially, ortho-lithiation of complex 70, proceeded in a diastereoselective manner, allowing access to the chiral intermediate 71. Subsequent reduction, Much effort has been focused on the use of chromium(0) complexes in higher order cyclo- followed by palladium catalysed cross-coupling with 2-formyl-4,5-methylenedioxyphenylboronic acid 72, 34 Contemporary Organic SynthesisMe H Me H i. reduction ii.72, Pd(PPh)o (cat.) Ar = CsHsBr I T O T M S 67% 0 light, air, MeCN 1 i BuaSnH c--- AIBN, 63% 0 & A 95% ee > 98% Scheme 36 de > 95% MeOy!p \ i. BuLi, toluene ii. brornination then Cr(C0)3 / bMe 70 \ hydrolysis 47% \ Br 88 90% M e o p C H 2 C H ( C 0 2 M e ) 2 CH20H Me0 73 Me0 c~(co)~ OMe OMe gave a single biaryl product, the stereochemistry of which was assigned on the basis of previous results reported by this Further elaboration gave the demetallated product 73. Efficient access to chiral tricarbonylchromium(0) complexes is of prime importance if they are to be utilised in asymmetric synthesis. One method by which this may be achieved involves the enantio- selective deprotonation of a prochiral complex using a chiral base, followed by quenching with an appro- priate ele~trophile.~' Schmalz has described the enantioselective deprotonation-silylation of mono- and 1,2-dimethoxybenzene(tricarbonyl)chromium derivatives, using the chiral lithium amide 74 (Scheme 38).72 As expected, best results were obtained when an in situ quench was employed, providing the silylated products in high enantio- meric purity.Scheme 37 Scheme 38 CHO 72 TMS Me Me a 1 \ 74 8.2 q6-Iron complexes $-Iron complexes have recently been used in the synthesis of polyhydroxylated nortropane derivatives (Scheme 39).73 Interest in this area was stimulated by the discovery of a new class of natural products (the calystegines), possessing the 1-hydroxynortropane structure. The approach described here relies on efficient formation of the substituted cyclohepta- diene 75, using the method originally described by P e a r ~ o n .~ ~ Subsequent hetero-Diels-Alder reaction of this cycloheptadiene with the appropriate acyl nitroso compound, occurred with complete stereo- selectivity. Further transformations provided the target 1-hydroxynortropane. This route should provide ready access to the calystegines and deriva- tives possessing similar bicyclic structures. 8.3 q6-Manganese complexes It has been shown previously that the benzene ring in the $-manganese complex 76 (Scheme 40), can Donohoe et a1 .: Applications of stoichiometric organotransition metal complexes in organic synthesis 35Alto' 75 I Scheme 39 a K * [ m ] - .L a I I co OC - - ;M n; co oc'- i"n: OC 77 I OC 76 i.20=C=CPh2 ii. [PhpNPPh&I 1 H oc. oc \ , Mn- CO [Ph3PNPPhJ Scheme 40 undergo reductive activation with naphthalenide, thus allowing further functionalistion of the aromatic ring.75 The chemistry of this system has now been extended to include an interesting [2 + 2 + 21 addition with di~henylketene.~~ Reduction of 76 with potassium anthracenide provided the postulated 18-electron transition metal complex 77 which, by virtue of the uncoordinated double bond, underwent a formal [2 + 2 + 21 cycloaddition with two equivalents of diphenylketene, and gave the bicyclic lactone complex. Oxidative decomplexation gave the highly functionalised dihydroisochroman- 3-one.Further investigation should uncover other applications for this unusual cycloaddition. 8.4 $-Ruthenium complexes Recent interest in the area of arene-ruthenium chemistry has been primarily concerned with the synthesis of cyclic biphenyl ethers as they form a key structural element in many biologically important peptides, including piperanomycin, bouvardin and the vancomycin family of antibiotic^.^^ Rich has developed a macrocyclisation procedure for the synthesis of these cyclic biphenyl ether peptides (Scheme 41).78 This protocol constructs the biphenyl ether linkage as one of the final synthetic steps, after initial formation of the peptide skeleton. The 0 D O H 78, EDCI, HOBt, DMF, 0 "C CpRu' ?H /sodium 2,6 65% \ CpRu' pFPci HN*co~H I Boc 70 di-tert-butyl MF, 24 h Scheme 41 ruthenium n-complex of the Boc-protected amino acid 78 was initially converted to the tripeptide 79, using standard peptide chemistry.Macrocyclisation was then achieved via an intramolecular SNAr reaction of this activated 7r-complex. Subsequent photolysis gave the target cyclic tripeptide in 65% overall yield. This method should allow for the generation of diverse libraries of variously substi- tuted aromatic peptides. 9 Wansition metal mediated cycloadditions 9.1 Pauson-Khand type reactions Application of the Pauson-Khand reaction to the synthesis of enantiomerically enriched cyclo- pentenones has been investigated recently by K e ~ r . ~ ~ Although the use of brucine N-oxide as a chiral promoter of this reaction provided cyclised products with moderate enantioselectivity, much greater success was achieved using the optically pure (a1kyne)pentacarbonyldicobalt complexes 80 (Scheme 42) and anhydrous N-methylmorpholine N-oxide (NMO).These complexes, containing the chiral ligand (R)-( + )-glyphos, were readily prepared from the corresponding cobalt alkyne complex and 36 Contemporary Organic SynthesisH NMO (6 equiv.), CH2C12,O to 20 "C XTPPh2 toluene, 70 "C, 3 h. 78% 1 (76%) ee >99% Scheme 44 Scheme 42 the individual diastereisomers separated by HPLC. Reaction with norbornene in the presence of anhydrous NMO prevents racemisation of the chiral cobalt complexes, giving the cyclopentenones in good yield (65-90%) and in good to excellent enantioselectivity (ees range from 64 to 99%).A stereoselective Pauson-Khand cyclisation has been used as the key step in the synthesis of linearly fused triquinanes (Scheme 43).*" The hirsutene type skeleton was constructed using the monocyclic precursor 81, which was formed in three steps and 40% overall yield from the known cyclopentanone. Conversion into the corresponding dicobalt hexa- carbonyl complex used conventional procedures, and this was followed by an intramolecular [2 + 2 + 11 cycloaddition which gave the required tricyclic compounds. The yields of the diastereo- isomers 82 and 83 were found to depend heavily on the conditions employed for the cyclisation process, which included thermolysis in solution and oxidative initiation in the presence of NMO.The advent of mild methods for promotion of the Pauson-Khand reaction has led to the development of a novel procedure for the intermolecular co- cyclisation of alkynes and allenes, resulting in formation of 4-alkylidenecyclopent-2-enones OH 3 steps Z Z , ~ 40% overall yield i. Co2(CO)*, ii. Si02, 50 "C, 3 h CH2C12, rt / 80% M e w + OH Me' Me' H H H 82 83 82:83 = 3 5 1 84 (56%) (Scheme 44)." Use of an allene as the ethylenic partner, with NMO as promoter, gave cyclised products such as the enone 84 in good yield. The generality of this reaction was also demonstrated through the successful use of aromatic and silylated allenes. Use of the Pauson-Khand reaction in this manner provided a much improved alternative to the previously described Fe2(C0)9 mediated reaction.*2 9.2 Nickel promoted [2 + 2 + 21 cyclotrimerisations It has been shown that nickel(0) promotes a host of co-cyclisation reactions between a, o-diynes and monoynes to provide bicyclic aromatics.83 However, reports regarding the use of nitrogen-containing alkynes in such reactions are limited.This deficiency of information has prompted Smith to undertake an in-depth investigation of the reactivity of alkynyl- amines and alkynylamides (Scheme 45).84 It was NR'R~ "">c' NiCI,(PPh& Et02C 2 BuLi, 2 PPh3, EO2C THF . . .. * R' = R2 = Et (60V0) R' = R2 = Me (62%) + NR' R~ -2 - R' = H, R2 = Me (72%) R' = H, R2 = MeCO (40%) R' = H, R2 = PhCO (42%) 0 RN h N%(PPh3)2, 2 BuLi, 2 PPh3, THF, reflux h 0 RN a l o M e R = H (59%) R = PhCH;! (4%) R = Ph2CH (63%) R = Me (34%) Scheme 43 Scheme 45 Donohoe e t a].: Applications of stoichiometric organotransition metal complexes in organic synthesis 37found that both secondary and tertiary amino groups, in the monoyne or diyne unit, were amenable to cyclisation, whilst amides in the diyne required heating to effect reaction.Unfortunately, the cyclisation of medium length diynes under these conditions proved unsuccessful, probably as a conse- quence of an unfavourable entropic effect. 9.3 Palladium promoted cycloalkenylation The stereoselective construction of the complex skeleton of an important family of plant growth regulators, known as the gibberellins, has been achieved using a palladium promoted cycloalkenyla- tion (Scheme 46).R5 Treatment of the corresponding silyl enol ether of enone 85 with palladium(i1) acetate, gave the required enone 86 as the sole product in 92% yield. Application of semiempirical Hamiltonian calculations subsequently showed that this em-olefin (AH,= -93.99 kcal mol-I; 1 cal=4.184 J) was more stable than the corre- sponding endo-olefinic enone 88 (AHf= - 92.61 kcal mol-').The enone 86 was transformed to the penta- cyclic compound 87, which may be used as a key intermediate in the preparation of the gibberellin GA12. 0 i. LDA, THF, -30-c; TMSCI, -78 "C to rt R ii. Pd(OAc)2, MeCN R 85 \\ q 2 87 3 steps 86 \ R = (CH2)20CH20Me Scheme 46 Acknowledgements The authors would like to thank Rh8ne-Poulenc Rorer for support. 10 References 1 T. J. Donohoe, Contemp. Org. Synth., 1996,3, 1. 2 L. F. Tietze and W.Buhr, Angew. Chem., Int. Ed. Engl., 3 T. Takahashi, M. Kotora and Z. Xi, J. Chem. SOC., 1995,34, 1366. Chem. Commun., 1995, 1503. 4 S. Kim and K. H. Kim, Tetrahedron Lett., 1995, 36, 3725. 5 X. Huang and L.-S. Zhu, J. Chem. SOC., Perkin Trans. 1, 1996, 767. 6 B. Zheng and M. Srebnik, Tetrahedron Lett., 1995,36, 5665. 7 T. Luker and R. J. Whitby, Tetrahedron Lett., 1995, 36, 4109. For reactions of the C-Zr bond with other electrophiles see: G . D. Probert, R. J. Whitby and S. J. Coote, Tetrahedron Lett., 1995,36, 4113; D. F. Taber and Y. Wang, Tetrahedron Lett., 1995, 36, 6639; S. Pereira, B. Zheng and M. Srebnik, J. 0%. Chem., 1995,60,6260; T. Takahashi, D. Y. Kondakov, Z. Xi and N. Suzuki, J. Am. Chem. SOC., 1995,117,5871; J. Barluenga, R. Sanz and F. J. Fananas, J.Chem. SOC., Chem. Commun.. 1995, 1009. Lett., 1995, 36, 7137. Lett., 1995, 36, 8103. 8 A. J. Clark, I. Kasujee and J. L. Peacock, Tetrahedron 9 M. B. Roe, M. Whittaker and G. Procter, Tetrahedron 10 D. J. Critcher, S. Connolly and M. Wills, Tetrahedron 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Lett., 1995, 36, 3763. N. A. Petasis and S.-P. Lu, Tetrahedron Lett., 1996, 37, 141. N. A. Petasis, J. P. Staszewski and D.-K. Fu, Tetra- hedron Lett., 1995, 36, 3619. N. A. Petasis, Y.-H. Hu and D.-K. Fu, Tetrahedron Lett., 1995, 36, 6001. S.-H. Kim, M. V. Hanson and R. D. Rieke, Tetra- hedron Lett., 1996, 37, 2197. G. Cahiez and S. Marquais, Tetrahedron Lett., 1996, 37, 1773. R. W. Bates. T. Rama-Devi and H.-H. KO, Tetrahedron, 1995, 51, 12939. K. H. Dotz and J.Pfeiffer, Chem. Commun., 1996, 895; J. Barluenga, F. Aznar and S. Barluenga, J. Chem. Suc., Chem. Commun., 1995, 1973; A. Rahm and W. Wulff, J. Am. Chem. Soc., 1996, 118, 1807; see also A. D. Reed and L. S. Hegedus, J. 0%. Chem., 1995, 60, 3787. J. E. Painter, P. Quayle and P. Patel, Tetrahedron Lett., 1995,36, 8089. J. Barluenga, F. Aznar, A. Martin and J. T. Vazquez, J. Am. Chem. SOC., 1995, 117, 9419. J. G. Meyer and R. Aumamm, Synlett, 1995, 1011. B. L. Flynn, F. J. Funke, C. C. Silveira and A. de Meijere, Synlett, 1995, 1007. N. Ochifuji and M. Mori, Tetrahedron Lett., 1995, 36, 9501. P. Quayle, S. Rahman and J. Herbert, Tetrahedron Lett., 1995, 36, 8087. B. Schmidt, P. Kocienski and G. Reid, Tetrahedron, 1996, 52, 1617; see also F. E. McDonald, C. C.Schultz and A. K. Chatterjee, Organometallics, 1995, 14, 3628. C. T. Baker, M. N. Mattson and P. Helquist, Tetra- hedron Lett., 1995,36, 7015. J. Barluenga, P. L. Berna Jr., J. M. Concellon, Tetra- hedron Lett., 1995,36, 3937; see also B. C. Soderberg, D. C. York, E. A. Harriston, H. J. Caprara and A. H. Flurry, Organometallics, 1995, 14, 3712. D. K. Hill and J. W. Herndon, Tetrahedron Lett., 1996, 37, 1359. 28 Y. Wang and M. G. Finn, J. Am. Chem. SOC., 1995, 117,8045. 29 A. Kasatkin, T. Nakagawa and F. Sato, J. Am. Chem. SOC., 1995, 117, 3881. 30 K. Harada, H. Urabe and F. Sato, Tetrahedron Lett., 1995,36,3203: see also Y. Gao, K. Harada and F. Sato, Chem. Commun., 1996,533; Y. Gao, K. Harada and F. Sato, Tetrahedron Lett., 1995,36, 5913; Y. Hori- 38 Contemporary Organic Synthesiskawa, T.Nomura, M. Wantanbe, I. Miura, T. Fujiwara and T. Takeda, Tetrahedron Lett., 1995,36, 8835. 31 H. Urabe, T. Hata and F. Sato, Tetrahedron Lett., 1995, 36, 4621. 32 H. Urabe, T. Takeda and F. Sato, Tetrahedron Lett., 1996, 37, 1253; see also P. K. Zubaidha, A. Kasatkin and F. Sato, Chem. Commun., 1996, 197. 33 V. Chaplinski and A. de Meijere, Angew. Chem., Int. Ed. En&, 1996,35,413; see also A. Kasatkin and F. Sato, Tetrahedron Lett., 1995,36, 6079; A. Kasatkin, S. Okamoto and F. Sato, Tetrahedron Lett., 1995,36, 6075. 34 0. G. Kulinkovich, S. V. Sviridov, D. A. Vasilevski and T. S. Prityskaya, Zh. 0%. Khim, 1989, 25, 2245; see ref 33. 35 D. Enders, S. von Berg and B. Jandeleit, Synlett, 1996, 18. 36 For a review, see: C. Mukai and M.Hanaoka, Synlett, 1996, 11. 37 C. S. Vizniowski, J. R. Green, T. L. Breen and A. V. Dalacu, J. Org. Chem., 1995, 60, 7496. 38 J. M. Palazon and V. S. Martin, Tetrahedron Lett., 1995, 36, 3549; see also E. Tyrrell, S. Claridge, R. Davis, J. Lebel and J. Berge, Synlett, 1995, 714. 39 G. G. Melikyan, M. A. Khan and K. M. Nicholas, Organometallics, 1995, 14, 2170. 40 S. Legoupy, C. CrCvisy, J.-C. Guillemin and R. GrCe, Tetrahedron Lett., 1996, 37, 1225. 41 J. Szymoniak, D. Felix, J. BesanGon and C. Moise, Tetrahedron, 1996, 52, 4377. 42 S. V. Ley and G. Meek, J. Chem. SOC., Chem. Commun., 1995, 1751. 43 S. V. Ley and L. R. Cox, Chem. Commun., 1996,657. 44 S. V. Ley and G. Meek, Chem. Commun., 1996,317. 45 S. D. R. Christie, C. Cosset, D. R. Hamilton, W. J. Kerr and J.M. O'Callaghan, J. Chem. SOC., Chem. Commun., 1995, 2051. 46 S. A. Benyunes, S. E, Gibson (n6e Thomas) and J. A. Stern, J. Chem. SOC., Perkin Trans. 1, 1995, 1333. 47 S. E. Gibson (nee Thomas) and G. J. Tustin, J. Chem. SOC., Perkin Trans. I , 1995, 2427. 48 K. Nunn, P. Mosset, R. GrCe and R. W. Saalfrank, J. Org. Chem., 1992,57,3359; C. Tao and W. Donaldson, J. 0%. Chem., 1993, 58, 2134. 1996, 37, 423. 1995,669. and L.-C. Row, Organometallics, 1995, 14, 3396. Tetrahedron Lett., 1995, 36, 6675. eds. G. Wilkinson, F. G. Stone and E. W. Abel, Pergamon, New York, 1982, vol. 8, p 613. 54 Y. Sato, M. Takimoto, K. Hayashi, T. Katsuhara, K. Takagi and M. Mori, J. Am. Chem. SOC., 1994, 116, 9771. 55 Y. Sato, M. Takimoto and M. Mori, Tetrahedron Lett., 1996, 37, 887.56 R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994. 57 L. Schwink and P. Knochel, Tetrahedron Lett., 1996,37, 25. 58 D. Lambusta, G. Nicolosi, A. Patti and M. Piatelli, Tetrahedron Lett., 1996, 37, 127. 59 S. Taudien, 0. Riant and H. B. Kagan, Tetrahedron Lett., 1995, 36, 3513. 49 W. A. Donaldson and L. Shang, Tetrahedron Lett., 50 A. McKillop, G. R. Stephenson and M. Tinki, Synlett, 51 M.-C. P. Yeh, L.-W. Chuang, C.-C. Hwu, J.-M. Sheu 52 I. Ripoche, J. Gelas, B. GrCe, R. Gree and Y. Troin, 53 P. W. Jolly, Comprehensive Organometallic Chemistry, 60 H.-J. Knolker, M. Bauermeister, J.-B. Pannek and M. Wolpert, Synthesis, 1995, 397. 61 H.-J. Knolker, E. Baum and T. Hopfmann, Tetrahedron Lett., 1995, 36, 5339. 62 A. M. Wilson, F. G. West, A. M. Arif and R. D. Ernst, J. Am. Chem. SOC., 1995, 117,8490. 63 P. C. Cagle, 0. Meyer, K. Weickhardt, A. M. Arif and J. A. Gladysq J. Am. Chem. SOC., 1995, 117, 11730. 64 J. H. Rigby, Acc. Chem. Res., 1993, 26, 579; J. H. Rigby, S. Scribner and M. J. Heeg, Tetrahedron Lett., 1995,36, 8569. 65 J. H. Rigby, P. Sugathapala and M. J. Heeg J. Am. Chem. SOC., 1995, 117, 8851. 66 C. Baldoli, P. Del Buttero, M. Di Ciolo, S. Maiorana and A. Papagni, Synlett, 1996, 258; C. Baldoli, P. Del Buttero, E. Licandro, S. Maiorana and A. Papagni, Tetrahedron: Asymmetry, 1995, 6, 171 I. 67 E. P. Kiindig, L. H. Xu, P. Romanens and G. Bernardi- nelli, Synlett, 1996, 270. For radical additions to ($-arene)(tricarbonyl)chromium complexes mediated by samarium(I1) iodide see H . G . Schmalz, S. Siege1 and J. W. Bats,Angew. Chem., Int. Ed. Engl., 1995, 34, 2383. hedron Lett., 1995, 36, 6695.; H.-G. Schmalz, A. Majda- lani, T. Geller, J. Hollander and J. W. Bats, Tetrahedron Lett., 1995,36, 4777. 69 M. Uemura, A. Daimon and Y. Hayashi, J. Chem. SOC., Chem. Commun., 1995, 1943. 70 M. Uemura and K. Kamikawa, J. Chem. SOC., Chem. Commun., 1994,2697. 71 E. L. M. Cowton, S. E. Gibson (nee Thomas), M. J. Schneider and M. H. Smith, Chem. Commun., 1996, 839. 72 H.-G. Schmalz and K. Schellhaas, Tetrahedron Lett., 1995,36, 5515. 73 J. SouliC, J.-F. Betzer, B. Muller and J.-Y. Lallemand, Tetrahedron Lett., 1995, 36, 9485. 74 A. J. Pearson and K. Srinivasan, J. 0%. Chem., 1992, 57, 3965. 75 R. L. Thompson, S. Lee, A. L. Rheingol and N. J. Cooper, Organometallics, 1991, 10, 1657. 76 S. Lee, S. J. Geib and N. J. Cooper, J. Am. Chem. Soc., 1995, 117,9572. 77 A. J. Pearson and K. Lee, J. 0%. Chem., 1995, 60, 7153; A. J. Pearson and G. Bignan, Tetrahedron Lett., 1996, 37, 735. 78 J. W. Janetka and D. H. Rich, J. Am. Chem. SOC., 1995, 117, 10585. 79 A. H. May, W. J. Kerr, G. G. Kirk and D. Middlemiss, Organometallics, 1995, 14, 4986; W. J. Kerr, G. G. Kirk and D. Middlemiss, Synlett, 1995, 1085. Strelenko, Tetrahedron Lett., 1995, 36, 4651. 1995,36,4417. 120, 23. Trans. I , 1992, 2163; E. C. Colthup and L. S. Meriwether, J. Org. Chem., 1961,26,5169. E. H. Smith and D. J. Williams, J. Chem. SOC., Perkin Trans. 1, 1996, 815. 85 M. Toyota, T. Wada, Y. Nishikawa, K. Yanai, K. Fuku- mot0 and C. Kabuto, Tetrahedron, 1995,51,6927 68 T. Watanabe, K. Kamikawa and M. Uemura, Tetra- 80 A. L. Veretenov, D. 0. Koltun, W. A. Smit and Y. A. 81 M. Ahmar, F. Antras and B. Cazes, Tetrahedron Lett., 82 R. Aumann and H. J. Weidenhaupt, Chem. Ber, 1987, 83 P. Bhatarah and E. H. Smith, J. Chem. SOC., Perkin 84 D. M. Duckworth, S. Lee-Wong, A. M. Z. Slawin, Donohoe et al.: Applications of stoichiometric organotransition metal complexes in organic synthesis 39

ISSN:1350-4894    

DOI:10.1039/CO9970400022

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Contemporary Organic Synthesis Editorial Board Professor P. J. Kocienski, FRS (Chairman), University of Glasgow Professor P. D. Bailey, Heriot- Watt University Dr S. E. Gibson (nke Thomas), Imperial College of Science, Technology, and Medicine Professor R. F. W. Jackson, University of Newcastle Professor C. J. Moody, University of Exeter Professor G. Pattenden, FRS, University of Nottingham Professor R. J. K. Taylor, University of York International Advisory Board Professor E. J. Corey, Harvard University Professor S. Hanessian, Universitk de Montrkal Professor M. Julia, Universitk de Paris XI (Paris-Sud) Professor P. D. Magnus, University of Texas at Austin Professor G. Mehta, University of Hyderabad Professor K. C. Nicolaou, The Scripps Research Institute and University of Professor R.Noyori, Nagoya University Professor L. E. Overman, University of California, Irvine Professor L. F. Tietze, University of Gottingen California at Sun Diego, La Jolla Contemporary Organic Synthesis is a bimonthly journal which aims to review and provide perspective in all aspects of methodology, selectivity and efficiency in contemporary synthesis. As well as covering all the principles and methods in functional group chemistry and interconversions, organometallic chemistry and asymmetric synthesis will feature prominently; so too will modern aspects of strategy and computer aided design, biotransforrnations and protecting group protocols. Special methods and techniques, such as sonochemistry, FVP, electroorganic synthesis and supported catalysis will be included as occasional articles, and the manner in which synthesis addresses problems and provides solutions in biology, medicine, agriculture, the environment and new materials, will also be encompassed.Contemporary Organic Synthesis aims to be proactive, drawing attention to new opportunities and new directions, providing timely information to the synthetic chemist who needs to keep abreast of developments in the field. Although the majority of articles are intended to be specially commissioned, the Society is always prepared to consider offers of articles for publication. In such cases a short synopsis, rather than the completed article, should be submitted to Dr Sheila R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemisty, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK.Deputy Editor: Dr Roxane Owen. Production Editor: Nicola Coward. Technical Editor: Dr Helen Saxton. Tel +44 (0) 1223 420066 Fax +44 (0) 1223 420247 E-mail perkin@rsc.org RSC Server http://chemistry.rsc.org/rsc/ Members of The Royal Society of Chemistry may subscribe to Contemporary Organic Synthesis by placing their orders on the Annual Subscription renewal forms in the usual way. All other orders accompanied with payment should be sent directly to The Royal Society of Chemistry, The Distribution Centre, Blackhorse Road, Letchworth, Herts SG6 lHN, England. 1997 annual subscription rate: E199.00; US$358.00. Customers in Canada will be charged the sterling price plus a surcharge to cover GST. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December.Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices. Periodicals postage is paid at Rahway, NJ. USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. (0 The Royal Society of Chemistry, 1997. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photographic, recording or otherwise, without the prior permission of the publishers.Typeset in Great Britain by Unicus Graphics Ltd, Horsham, West Sussex Printed in Great Britain by Whitstable Litho Ltd, Whitstable, KentContemporary Organic Synthesis Editorial Board Professor P. J. Kocienski (Chairman), Universiy sf Glasgow Professor P. D. Bailey, Heriot- Watt University Dr S. E. Gibson (nee Thomas), Imperial College of Science, Technology, arid Medicine Professor R. F. W. Jackson, University of Newcastle Professor C. J. Moody, University of Exeter Professor G. Pattenden, FRS, University of Nottingham Professor R. J. K. Taylor, University qf York International Advisory Board Professor E. J. Corey, Haward University Professor S.Hanessian, Universitt de Montrtal Professor M. Julia, Universitk de Paris X I (Paris-Sun) Professor P. D. Magnus, University qf Texas at Austin Professor G. Mehta, University of Hyderahud Professor K. C. Nicolaou, The Scripps Research Institute and Uniivrsiy of Professor R. Noyori, Nagoya University Professor L. E. Overman, Universiq of California, Inine Professor L. F. Tietze, University of Ciittingen California at Sun Diego, La Jolla Contemporary Organic Synthesis is a bimonthly journal which aims to review and provide perspective in all aspects of methodology, selectivity and efficiency in contemporary synthesis. As well as covering all the principles and methods in functional group chemistry and interconversions, organometallic chemistry and asymmetric synthesis will feature prominently; so too will modern aspects of strategy and computer aided design, biotransformations and protecting group protocols.Special methods and techniques, such as sonochemistry, FVP, electroorganic synthesis and supported catalysis will be included as occasional articles, and the manner in which synthesis addresses problems and provides solutions in biology, medicine, agriculture, the environment and new materials, will also be encompassed. Contemporary Organic Synthesis aims to be proactive, drawing attention to new opportunities and new directions, providing timely information to the synthetic chemist who needs to keep abreast of developments in the field. Although the majority of articles are intended to be specially commissioned, the Society is always prepared to consider offers of articles for publication.In such cases a short synopsis, rather than the completed article, should be submitted to Dr Sheila R. Buxton, Managing Editor, Organic Publications, The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK. Deputy Editor: Dr Roxane Owen. Production Editor: Nicola Coward. Technical Editor: Dr Helen Saxton. Tel +44 (0) 1223 420066 Fax +44 (0) 1223 420247 E-mail perkin@rsc.org RSC Server http://chemistry.rsc.org/rsc/ Members of The Royal Society of Chemistry may subscribe to Contemporary Organic Synthesis by placing their orders on the Annual Subscription renewal forms in the usual way. All other orders accompanied with payment should be sent directly to The Royal Society of Chemistry, The Distribution Centre, Blackhorse Road, Letchworth, Herts SG6 1 HN, England.1997 annual subscription rate: i199.00; US$358.00. Customers in Canada will be charged the sterling price plus a surcharge to cover GST. Contemporary Organic Synthesis is published 6 times a year in February, April, June, August, October and December. Airfreight and mailing in the USA by Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey, NJ 07001, USA and at additional mailing offices. Periodicals postage is paid at Rahway, NJ. USA Postmaster: Send address changes to Contemporary Organic Synthesis, c/o Mercury Airfreight International Ltd, 2323 Randolph Avenue, Avenel, New Jersey 07001. All other dispatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. Q The Royal Society of Chemistry, 1997. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photographic, recording or otherwise, without the prior permission of the publishers. Typeset in Great Britain by Unicus Graphics Ltd, Horsham, West Sussex Printed in Great Britain by Whitstable Litho Ltd, Whitstable, Kent

ISSN:1350-4894    

DOI:10.1039/CO99704FX025

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

160 P. Renaud and I. Betrisey, Synth. Commirn., 1995, 25, 3479. 161 J. P. Begue, D. Bonnctdelpon, D. Bouvet and M. H. Rock, J. Flirorirte Chem., 1996, 80, 17. 162 M. Rejzek, M. Zarevucka, Z. Wimmer, T. Vanek, R. Tykva, J. Kuldova, D. Saman and B. Bennettova, Collect. Czech. Chem. Comrnirn., 1996, 61, 605. I63 T. Constantieux and J. P. Picard, Organometallics, 1996, 15, 1604. 164 J. H. Lai, H. Pham and D. G. Hangauer,.I. Org. Chem., 1996, 61, 1872. 165 R. J. Fletcher, M. Kizil and J . A. Murphy, Tetruhedron Lett., 1995, 36, 323. 166 K. Ramalingam, W. Zeng, P. Nanjappan and D. P. Nowotnik, Synth. Cornmun., 1995, 25, 743. 167 R. Joseph; T. Ravindranathan and A. Sudalai, Tetra- hedron Lett., 1995, 36, 1903. 168 V. M. Paradkar, T. B. Latham and D. M. Demko, Synlett, 1995, 1059. 169 F.Palacios, D. Aparicio, J. M. Delossantos and E. Rodriguez, Tetrahedron Lett., 1996, 37, 1289. 170 B. P. Bandgar, S. M. Nikat and P. P. Wadgaonkar, Synth. Comnzun., 1995, 25, 863. 171 D. Barbry and P. Champagne, Synth. Commun., 1995, 25, 3503. 172 S. Negi, M. Matsukura, M. Mizuno, K. Miyake and N. Minami, Synthesis, 1996, 991. 173 L. Maier and P. J. Diel, Phosphorus Sulfur Silicon Relut. Elem., 1995, 107, 245. 174 A. Zaks, A. V. Yabannavar, D. R. Dodds, C. A. Evans, P. R. Das and R. Malchow, J. Org. Chem., 1996, 61, 8692. 175 F. P. Ballistreri, E. Barbuzzi, G. A. Tomaselli and R. M. Toscano, Synlett., 1996, 1093. 176 J. G. Lee and J. P. Hwang, Chem. Lett., 1995, 507. 177 T. Shinada and K. Yoshihara, Tetrahedron Lett., 1995, 178 I. M. Baltork and S. Pouranshirvani, Synth.Comrnirn., 179 B. P. Bandgar, S. I. Shaikh and S. Iyer, Synth. 180 M. Curini, 0. Rosati, E. Pisani and U. Constantino, 181 V. J. Majo, M. Venugopal, A. A. M. Prince and P. T. 182 A. I. Bosch, P. Delacruz, E. Diezbarra, A. Loupy and 36, 6701. 1996, 26, I . Commun., 1996, 26, 1163. Synlett, 1996, 333. Perumal, Synth. Commun., 1995, 25, 3863. F. Langa, Synlett, '1995, 1259 183 I. P. Andrews, R. J. J. Dorgan, T. Harvey, J. F. Hudner, N. Hussain, D. C. Lathbury, N. J. Lewis, G. S. Macaulay, D. 0. Morgan, R. Stockman and C. R. White, Tctruhedron Lett., 1996, 37, 481 1. 184 T. Kiguchi, K. Tajiri, I. Ninomiya, T. Naito and H. Hiramatsu, Tetruheclron Lett., 1995, 36, 253. 185 M. Tiecco, L. Tcstaferri, M. Tingoli, L. Bagnoli and C. Santi, Tetruhedron, 1995, 51, 1277. 186 M.Tiecco, L. I'estaferri, M. Tingoli and L. Bagnoli, J. Chem. Soc., Chem. Commrrn., 1995, 235. 187 H. Kusama, Y. Yamashita and K. Narasaka, Chem. Lett., 1995, 5. 188 S. Bourke and F. Heancy, Te~tiahedrort Lett., 1995, 36, 7527. 189 V. N. Komissarov, Zh. Org. Khim., 1995, 31, 1060 (Chent. Ahstr., 124:289438). 190 U. Chiacchio, A. Corsaro, V. Pistara, A. Rescifina, G. Romeo and R. Romeo, Tetrahedron, 1996, 52, 7875. 191 M. T. Mckiernan and F. Heaney, Tetrahedron Lett., 1996,37,4597. 192 J. Alcazar, M. Begtrup and A. de la Hoz, Hc~terocyfc~s, 1906, 43, 1465. 193 M. C. McMills, D. L. Wright, J. D. Zubkowski and E. J. Valente, Tetrahedron Lett., 1996,37, 7213. 194 D. Armesto, M. A. Austin, 0. J . Griffiths, W. M. Horspool and M. Carpintero, Chem. Commcrri., 1996, 2715. 195 U.Chiacchio, A. Corsaro, V. Librando, A. Rescifina, R. Romeo and G. Romeo, Tetrahedron, 1996, 52, 14323. C. Santi and A. Temperini, Heterocycles, 1996, 43, 2079. 197 S. Ahmed and R. C. Boruah, Tetruhedron Lett., 1996, 37, 823 1. 198 A. V. Tkachev, A. M. Chibiryaev, A. Y. Denisov and Y. V. Gatilov, Tetruheclron, 1995, 51, 1789. 199 J. Boivin, E. Pillot, A. Williams, W. Roger and S. Z. Zard, Tetruhedron Lett., 1995, 36, 3333. 200 K. Griesbaum, B. Ovez, T. S. Huh and Y. X. Dong, Liehigs Ann., 1095, 1571. 201 K. Miyashita, T. Toyoda, H. Miyabe and T. Imanishi, Synlett, 1995, 1229. 202 J. L. Boucher, S. Vadon, A. Tomas, B. Viossat and D. Mansuy, Tetrahedron Lett., 1996, 37, 31 13. 203 M. R. Iesce, F. Cermola, A. Guitto, F. Giordano and R. Scarpati, J.Org Chern., 1996, 61, 8677. I96 M. Tiecco, L. Testaferri, L. Bagnoli, F. Marini, Adams: Imines, enamines and oximes 543160 P. Renaud and I. Betrisey, Synth. Commirn., 1995, 25, 3479. 161 J. P. Begue, D. Bonnctdelpon, D. Bouvet and M. H. Rock, J. Flirorirte Chem., 1996, 80, 17. 162 M. Rejzek, M. Zarevucka, Z. Wimmer, T. Vanek, R. Tykva, J. Kuldova, D. Saman and B. Bennettova, Collect. Czech. Chem. Comrnirn., 1996, 61, 605. I63 T. Constantieux and J. P. Picard, Organometallics, 1996, 15, 1604. 164 J. H. Lai, H. Pham and D. G. Hangauer,.I. Org. Chem., 1996, 61, 1872. 165 R. J. Fletcher, M. Kizil and J . A. Murphy, Tetruhedron Lett., 1995, 36, 323. 166 K. Ramalingam, W. Zeng, P. Nanjappan and D. P. Nowotnik, Synth. Cornmun., 1995, 25, 743. 167 R. Joseph; T.Ravindranathan and A. Sudalai, Tetra- hedron Lett., 1995, 36, 1903. 168 V. M. Paradkar, T. B. Latham and D. M. Demko, Synlett, 1995, 1059. 169 F. Palacios, D. Aparicio, J. M. Delossantos and E. Rodriguez, Tetrahedron Lett., 1996, 37, 1289. 170 B. P. Bandgar, S. M. Nikat and P. P. Wadgaonkar, Synth. Comnzun., 1995, 25, 863. 171 D. Barbry and P. Champagne, Synth. Commun., 1995, 25, 3503. 172 S. Negi, M. Matsukura, M. Mizuno, K. Miyake and N. Minami, Synthesis, 1996, 991. 173 L. Maier and P. J. Diel, Phosphorus Sulfur Silicon Relut. Elem., 1995, 107, 245. 174 A. Zaks, A. V. Yabannavar, D. R. Dodds, C. A. Evans, P. R. Das and R. Malchow, J. Org. Chem., 1996, 61, 8692. 175 F. P. Ballistreri, E. Barbuzzi, G. A. Tomaselli and R. M. Toscano, Synlett., 1996, 1093.176 J. G. Lee and J. P. Hwang, Chem. Lett., 1995, 507. 177 T. Shinada and K. Yoshihara, Tetrahedron Lett., 1995, 178 I. M. Baltork and S. Pouranshirvani, Synth. Comrnirn., 179 B. P. Bandgar, S. I. Shaikh and S. Iyer, Synth. 180 M. Curini, 0. Rosati, E. Pisani and U. Constantino, 181 V. J. Majo, M. Venugopal, A. A. M. Prince and P. T. 182 A. I. Bosch, P. Delacruz, E. Diezbarra, A. Loupy and 36, 6701. 1996, 26, I . Commun., 1996, 26, 1163. Synlett, 1996, 333. Perumal, Synth. Commun., 1995, 25, 3863. F. Langa, Synlett, '1995, 1259 183 I. P. Andrews, R. J. J. Dorgan, T. Harvey, J. F. Hudner, N. Hussain, D. C. Lathbury, N. J. Lewis, G. S. Macaulay, D. 0. Morgan, R. Stockman and C. R. White, Tctruhedron Lett., 1996, 37, 481 1. 184 T. Kiguchi, K. Tajiri, I. Ninomiya, T.Naito and H. Hiramatsu, Tetruheclron Lett., 1995, 36, 253. 185 M. Tiecco, L. Tcstaferri, M. Tingoli, L. Bagnoli and C. Santi, Tetruhedron, 1995, 51, 1277. 186 M. Tiecco, L. I'estaferri, M. Tingoli and L. Bagnoli, J. Chem. Soc., Chem. Commrrn., 1995, 235. 187 H. Kusama, Y. Yamashita and K. Narasaka, Chem. Lett., 1995, 5. 188 S. Bourke and F. Heancy, Te~tiahedrort Lett., 1995, 36, 7527. 189 V. N. Komissarov, Zh. Org. Khim., 1995, 31, 1060 (Chent. Ahstr., 124:289438). 190 U. Chiacchio, A. Corsaro, V. Pistara, A. Rescifina, G. Romeo and R. Romeo, Tetrahedron, 1996, 52, 7875. 191 M. T. Mckiernan and F. Heaney, Tetrahedron Lett., 1996,37,4597. 192 J. Alcazar, M. Begtrup and A. de la Hoz, Hc~terocyfc~s, 1906, 43, 1465. 193 M. C. McMills, D. L. Wright, J. D. Zubkowski and E. J. Valente, Tetrahedron Lett., 1996,37, 7213. 194 D. Armesto, M. A. Austin, 0. J . Griffiths, W. M. Horspool and M. Carpintero, Chem. Commcrri., 1996, 2715. 195 U. Chiacchio, A. Corsaro, V. Librando, A. Rescifina, R. Romeo and G. Romeo, Tetrahedron, 1996, 52, 14323. C. Santi and A. Temperini, Heterocycles, 1996, 43, 2079. 197 S. Ahmed and R. C. Boruah, Tetruhedron Lett., 1996, 37, 823 1. 198 A. V. Tkachev, A. M. Chibiryaev, A. Y. Denisov and Y. V. Gatilov, Tetruheclron, 1995, 51, 1789. 199 J. Boivin, E. Pillot, A. Williams, W. Roger and S. Z. Zard, Tetruhedron Lett., 1995, 36, 3333. 200 K. Griesbaum, B. Ovez, T. S. Huh and Y. X. Dong, Liehigs Ann., 1095, 1571. 201 K. Miyashita, T. Toyoda, H. Miyabe and T. Imanishi, Synlett, 1995, 1229. 202 J. L. Boucher, S. Vadon, A. Tomas, B. Viossat and D. Mansuy, Tetrahedron Lett., 1996, 37, 31 13. 203 M. R. Iesce, F. Cermola, A. Guitto, F. Giordano and R. Scarpati, J. Org Chern., 1996, 61, 8677. I96 M. Tiecco, L. Testaferri, L. Bagnoli, F. Marini, Adams: Imines, enamines and oximes 543

ISSN:1350-4894    

DOI:10.1039/CO99704BX027

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Saturated and unsaturated hydrocarbons DAVID A. ENTWISTLE Department of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK reduction, especially in the incorporation of deuterium into organic molecules, was raised in a study of the selectivity of deoxygenation of nucleoside 2'-phenoxythiocarbonates using tributyltin deuteride (Scheme l).' The highest selectivity was elicited with tributyltin deuteride and Reviewing the literature published between January 1995 and May 1996 Continuing the coverage in Contemporay Organic Synthesis, 1995, 2, 441 1 2 2.1 2.2 2.3 2.4 2.5 2.6 3 3.1 3.2 3.2.1 3.2.2 3.2.3 3.3 3.3.1 3.3.2 3.3.3 3.3.4 3.4 3.5 4 4.1 4.2 5 Introduction Saturated hydrocarbons Deoxygenat ion Dehalogenation Desulfurisation Deamination Hydrogenation Miscellaneous Alkenic hydrocarbons Carbonyl olefinations Alkene sp2-sp2 coupling reactions Heck reaction Stille reaction Suzuki reaction Rearrangements Cope rearrangement Claisen rearrangement Wittig rearrangement Miscellaneous rearrangements Alkene metathesis Miscellaneous Alkynic hydrocarbons Alkyne met at hesis Miscellaneous References 1 Introduction In this review particular emphasis has been placed on reductive techniques in the synthesis of saturated hydrocarbons, and on the selective synthesis and connection of the multiple bonds in unsaturated hydrocarbons.Wherever possible novel or improved methods have been emphasised as opposed to an exhaustive list of all the synthetic procedures published in the area. 2 Saturated hydrocarbons 2.1 Deoxygenation triethylborane at - 78 "C leading-to a 99: 1 mixture of 2'R : 2's deuteriated 2'-deoxy[2'-~]uridines. Sonochemical tributyltin deuteride activation with azoisobutyronitrile (AIBN) gave a 96: 1 ratio, this being only slightly more selective than standard thermal conditions.BzO OC(S)OPh BzO D BZO yield (%) 2'R : 2"s Bu3SnD, AIBN, @,-7l "C 78 96 : 4 Bu3SnD, Et3B, -78 O C 90 99 : 1 U = uridyl Scheme 1 Titanium has been widely used stoichiometrically in deoxygenation reactions and carbon-carbon bond forming reactiom2 Furstner et al. have detailed the first catalytic use of titanium to effect these types of reaction. The key observation for successful reaction was found to be the addition of trimethylsilyl chloride (TMSCl) which activates the metal surface by removal of the inert oxide layer.' The same research group have also used stoichiometric amounts of commercial titanium powder as a reagent for reactions previously thought to be poorly mediated by this inactive form of the metal.These reactions, which include pinacol couplings (Scheme 2), McMurry couplings and epoxide deoxygenations (vide infiu), also use trimethylsilyl chloride activation.3 and ketone reduction of acyl resorcinols and A variation of a one pot hydroxy group protectio coumarins has been rep~rted.~ In this method the phenolic hydroxy groups are masked as methyl carbonates and then sodium borohydride reduction in a mixture of water and THF provided alkyl The well documented use of tributyltin hydride still dominates the methods of deoxygenation used in synthesis. The important issue of selectivity of resorcinols and coumarins bearing no ortho hydroxy group protection (Scheme 3).Water was found to be vital for the reduction to proceed as desired. 40 Contemporay Organic SynthesisPh ?h eo Ti, TMSCI, DME. reflux 60% -OH Ph Ph OMe i. Ti preheated for 40 h with TMSCI in DME ii. Add substrate ~ p h q P h PhAOMe 88% OMe meso : DL 1 :1 Scheme 2 i. Me02CCI, E13N, DMAP ii. NaBH4, H20, THF. 0 "C I OH Scheme 3 a, p-Unsaturated enones and allylic alcohols have been reduced successfully to the corresponding alkenes using a boron trifluoride-diethyl ether and sodium cyanoborohydride mixture (Scheme 4).' These potentially useful reactions tend to give mixtures of isomerised alkene products. such as boron trifluoride-sodium cyanoboro- hydride,6 titanium tetrachloride-, aluminium trichloride-, boron trifluoride- and iron trichloride- borane dimethylamine complex have been used for the complete reduction of aryl ketones to alkylben~enes.~ A reductive elimination of y-alkoxy-a, p-unsatur- ated esters using ethanolic activated zinc has been Various Lewis acid-hydride reagent mixtures, 0 C02Et Na(CN)BHs, BFs*Et20,65 "C D 50% A Scheme 4 developed which yields p, y-unsaturated esters.These synthons are of potential use in the stereospecific synthesis of natural products (Scheme 5).8 Zn. EtOH, OH C02Et Et02(: . CO2Et Zn, EtOH, \ reflux Scheme 5 2.2 Dehalogenation Chatgilialoglu et al. have reported the dehalo- genation of a wide variety of halides including alkyl, aryl, benzyl and a-alkoxy chlorides, bromides and iodides using catalytic amounts of palladium( I I) chloride in triethylsilane (Scheme 6).9 The reactions occur in high yield at ambient temperature with the exception of 1 - and 2-bromoadamantane which both require heating at 80 "C.PdC12, Et3SiH, ph-I rt, 10 min, 95% * Ph- PdC12, Et3SiH, Phsr rt, 40 min, 95% PhH PdCI2, Et3SiH, PhC, rt, 60 min, 95% PhH Scheme 6 Lithium aluminium hydride is often used for dehalogenations and a recent report has identified that when the cyclopropane acid 1 was reduced under strictly anaerobic conditions a dehalogenation product 2 was obtained (Scheme 7).'" When 'loosely' anaerobic conditions were applied no debromina- tion was observed.'" In fact, an excess of lithium aluminium hydride and elevated temperatures were required to reduce the bromides 1 and 3 under the non-rigorous anaerobic conditions.Even small quantities of oxygen are thought to retard the dehalogenation, by inhibiting the formation of key Hydrogenolysis of the chlorine-carbon bond in C02Et C02Et 20: 1 1 : l radical intermediates. the cyclopropane 4 has proved difficult under Q i : Entwistle: Saturated and unsaturated hydrocarbons 41been reduced to give fluoroalkenes by irradiating in electron donors (Scheme 9).17 LiAIH4, Et20, r.igorous P h B 0, exclusion p h q the presence of decamethy1ferrocenel6 and other COPH 1 2 OH 2.3 Desulfurisation When incorporated into organic molecules, sulfur is a versatile element allowing, amongst others, many novel carbon-carbon bond forming reactions to take place." In many cases the sulfur-containing functional group is not required in the final product Saito et al.have described a hetero Diels-Alder annulation reaction using the thioketone 5 (Scheme Treatment of the cyclised product 6 with Raney nickel was found to selectively hydrogenate the thioenol ether to the thioether 7 which was subsequently desulfurised to reveal the nine LiAIH4, Et20, rigorous O2 exclusion, rt 3 OH and requires removal. Scheme 7 either xz:ph NaBH4, HMPA c H)+Lz:ph CI or Lindlar, H2 membered cyclic ether 8. 4 H Scheme 8 standard catalytic hydrogenolytic conditions due to the lability of the strained three membered ring (Scheme S)." Successful dehalogenation has now been brought about by either sodium borohydride reduction in hexamethylphosphoramide (HMPA) or by hydrogenolysis over Lindlar's catalyst.' ' found to effectively dehalogenate bromo- and chloro-thiazoles that were poorly reduced by a number of other reagents." to remove when unactivated." Heterogenous methods for the hydrogenolysis of the carbon- fluorine bond are in general harsh and un~elective,'~ but recently inroads have been made towards mild defluorination techniques using homogeneous transition metal catalysts." (Me3P)&hC6H5 and (Me3P)3RhH have been used as catalysts for the monohydrogenation of a carbon- fluorine bond in hexafluorobenzene in the presence of triethylamine and potassium carbonate under 85 psi hydrogen (Scheme 9).15 Perfluoroalkanes have Hydrogenolysis over palladium on carbon was Of the halogens, fluorine can be the most difficult THF, hv + hv, N, Ntetramethyl- benzene-1,ediamine .- F H H Ob" / al Fe I F8 5 6 RaneyNi,TH+l I Raney Ni, PhMe, rt, 85% 110 oc, 62% 7 8 Scheme 10 Raney nickel is the most common way of reductively removing sulfur from organic molecules, but ytterbium in HMPA has also been shown to reduce thioketones selectively to either the thiol or the fully reduced methylene compound (Scheme 11).20 Work has also progressed to trap the intermediate radical anion with electrophiles.Substituted and fully deuteriated phenyl- propionoic acids have been synthesised by the action D SH i. 1 equiv. Yb. HMPA, THF, 0 OC ii. D20, H30+ w PhXPh 80% i. 2 equiv. Yb, HMPA, THF, 0 OC 9 P S ii. D20, H30+ w PhXPh II 69% !: 1 equiv. Yb, HMPA, THF, 0 OC 11. acetone PhAPh / 72% PhA Ph i 1 equiv.Yb. HMPA, THF, 0 OC Et SH ii. EtBr c PhXPh 84% Scheme 9 Scheme 11 42 Contemporaly Organic Synthesisof Raney alloy on perhalogenated benzofurans and 10% sodium deuteroxide in deuterium oxide (Scheme 12).21 Interestingly a cobalt-aluminium alloy in the same solvent (or Raney alloy in 10% sodium carbonate in deuterium oxide) has been shown to selectively cleave the sulfur and bromine atoms from some unsubstituted benzofurans but give no extra incorporation of deuterium on the aromatic nucleus (Scheme 12).*' O D C02H Ni-AI, NaOD, D20 &Dco2H c'w CI CI C-AI, NaOD, D20 Br b &C02H Scheme 12 WD Ni-AI, Na2C03, 40 i. SnC14, CH2C12 ii. KOH. N2H4 I 1 Raney Ni, H2. THF I Scheme 14 TiCI3, Li, THF i. PhNH2 Ar ii. NaBH,, MeOH - )-NHPh R R *')=O R >90% Ar R yield(%) eHO-CeH4 H 48 2-naphthyl Me 48 CeH5 (CH&JCO~H 67 During studies towards the synthesis of natural polyethers Nicolaou et al.published a method for the selective reduction of thioesters and thiolactones to ethers using triphenyltin hydride (Scheme 13).22 This method has proved to be high yielding and extremely general. 79% Go+ AIBN. 5 equiv. PhMe, PhSSnH, 110 OCW 94% Scheme 13 Scheme 15 2.5 Hydrogenation Asymmetric homogeneous catalytic hydrogenation by optically active transition metal complexes is now a vitally important area of organic synthesis and has recently been re~iewed.~' A recent development in this field has been the use of supercritical carbon dioxide as reaction solvent.26 heterogeneous partial reduction of alkynes to alkenes, has been used to selectively hydrogenate the double bond of a, P-unsaturated carbonyl compounds (Scheme 16).27 Esters, ketones and aldehydes are left unreduced, as are non-conjugated alkenes.Similarly, a water soluble rhodium catalyst The Lindlar catalyst, more commmly used for the has been developed for the homogeneous saturation of a,P-unsaturated aldehydeS,28 and metallic samarium and iodine in ethanol has been used to hydrogenate tl, P-unsaturated carboxylic acid derivative^.^^ In the Same vein, sodium borohydride and bismuth trichloride mixtures have been used to In their synthesis of niphatesine C, Bracher et al. used a Friedel-Crafts reaction to couple an acyl pyridine to a substituted thiophene (Scheme 14). After Wolff-Kishner reduction of the ketone, the thiophene was exhaustively hydrogenated to give the saturated product.2' selectively reduce not only alkenes conjugated to 2.4 Deamination Benzylic phenylamines are readily reduced to alkylbenzenes and aniline when treated with low valent convenient titanium two (Scheme step method 15).24 for This the is exhaustive also a I";.Lzzr QHO reduction of aromatic ketones and aldehydes, as they are readily converted into benzylic phenyl- amines by reductive amination with aniline and sodium borohydride. Scheme 16 Entwistle: Saturated and unsaturated hydrocarbons 4310 equiv. NaBH4, 0.5 equiv. BiCl3, EtOH, rt ~ P h m R R yield(%) H 80 Me 78 CH20H 97 fury1 60 Scheme 17 carbonyl groups,3o but also alkenes conjugated to aromatic groups (Scheme 17).”’ The cationic Crabtree iridium hydrogenation catalyst has been shown to selectively reduce alkenes that have a tethered 2-pyridyl group (Scheme 18).’* When the reductions of the tethered 2-pyridyl and phenylalkenes are performed in separate flasks the phenyl alkene is reduced the most rapidly.When a competition reaction is performed in one pot however the tethered 2-pyridyl alkene is reduced up to 100 times more quickly. The proposed pyridine complexation to the iridium complex and intramolecular hydrogen delivery accounts well for these observations. Scheme 18 X Y reaction time yield(%) CH CH 15 min 78 N N 17h 14 N CH E H } 17h{;=& 2; 2.6 Miscellaneous A recent review of transition metal catalysed carbo- cyclisations listed by the metals covers cobalt, iron, molybdenum, nickel, palladium, rhodium, ruthenium, titanium and zirconium examples.’3 In a novel nickel catalysed process Knochel et al.brought about the coupling of two sp3 hybridised carbon centres (Scheme 19).’4 This mode of reactivity is dependent on the alkyl iodide having unsaturation at either the 4- or 5-position to facilitate a nickel R = (CH2)4Me 72% R = (CHp)30Piv 70% R Zn 7% Ni(a~ac)~ R = (CH2)4Me 83% R = (CHp)3OPiv 79% * rCozEt CO,Et 23 THF, NMP, -35°C Scheme 19 centred reductive elimination. Absence of unsaturation leads to the predominance of a transmetallation and the formation of alkylnickel halides. Molander et al. have used samarium diiodide promoted tandem intramolecular Barbier type reactions to synthesise a large range of bi- and tri- cyclic hydrocarbons (Scheme 20).35 Metal halide exchange occurs giving an organosamarium reagent which adds initially to the ester or lactone to give a ketone which is then attacked further by the second organosamarium giving various polycyclic alcohols on work up.X X n m yield(%) I 2 2 8 8 Br 1 1 84 I 1 2 8 6 X n rn p yield(%) H 1 1 1 9 1 H 2 1 1 8 3 Me 2 0 2 80 Scheme 20 In their enantioselective synthesis of (-)-strychnine Overman et al. used an aza-Wittig rearrangement to construct the enantiomerically pure tricyclic portion 9 from a bicyclic precursor 10 (Scheme 21).36 The free amine 10 was treated with formaldehyde to give the iminium ion 11 which underwent a [3,3] sigmatropic rearrangement revealing the enol 12 which then attacked the newly formed iminium ion intramolecularly to give the tricycle 9.Similarly, in their work towards pungalandine IV, Florent et al. performed an aza-Cope rearrangement on the ally1 enamimium salt 13 giving the transient iminium ion 14 which became trapped to form (after amine elimination) a spirocyclopentenone (Scheme 22).37 Another highly selective ring forming reaction type, a [3 + 41 annulation, has been published by Takeda et al. (Scheme 23).38 Reaction of tert- butyldime t hyl[ p-( trime thylsilyl)acryloyl] silane 15 44 Contemporary Organic SynthesisBnO 7 __c HO Ar 10 B n O T HO $ Ar 11 c- c- B n 0 7 Ar 12 / OBn 9 (-) Strychnine Reagent; i. HCHO, TsOH, heat, 98%. Scheme 21 13 2:l Z:E 40% from parent enamine 2:l mix of diastereoisomers Scheme 22 L OMOM 14 SiMe2Bu' TMS 15 \ -a0 I ; I F , to -30 "C & * TBSO \ TMS OLi 9 15, THF, ~ M S Scheme 23 Entwistle: Saturated and unsaturated hydrocarbons with various enolates of unsaturated methyl ketones led to high yields of highly functionalised cycloheptane rings. Rare earth binaphthols have been used successfully in the first asymmetric nitro-aldol reaction, europium binaphthols in general giving the best asymmetric induction (Scheme 24).'9 The same rare earth binaphthols when prepared under halide free conditions made excellent catalysts for asymmetric Michael reactions of enones and malonates (Scheme 24).39 A review of asymmetric catalysis, by Noyori, lists many reactions catalysed by chiral transition metal complexes.40 OH * d-""' PrC13, (SBINOL)Li2, CHo NaOH, H20, MeN02, THF.-50 "C 91% 90% ee 0 0 C02Bn pr(opi),, SBINOL, THF, 60 h, -20 "C <CO2Bn 97% Bn02C' 'C02Bn 95% ee Scheme 24 3 Alkenic hydrocarbons 3.1 Carbonyl olefinations Recent modifications made to the Julia olefination procedure have allowed more efficient syntheses of trisubstituted alkenes from ketones.41 This was achieved firstly by trapping intermediate alkoxides in situ to form either P-sulfonyl benzoates or P-hydroxy sulfones and by using samarium diiodide and 1-5% HMPA in THF to perform the reductive elimination step (Scheme 25).42 Magnesium in ethanol with a catalytic amount of mercuric chloride has also been employed successfully for the reductive elimination of P-sulfonyl b e n z o a t e ~ .~ ~ 9 i. a, BuLi; b, PhCOCl or TMSCl y1 R2-S02Ph RKR1 ii. Sm12, 5% HMPA, THF, reflu: R &R* OBz(H) R' SOpPh Scheme 25 In 1993 Sylveser Julia published a major variation of the Julia olefination procedure employing lithiated benzothiazolyl sulfone~.'~,~~ The one step method gives E-vicinal disubstituted alkenes in an extremely stereoselective fashion, and has more recently been used successfully by Kocienski et al.in their synthesis of herboxidiene (Scheme 26).46 One of the most common methods of alkene synthesis, the Wittig reaction, has been performed 45i. LDA, THF. -80 "C Scheme 26 .* in the presence of silica gel in he~ane.~' The method was found to accelerate the rates of reaction? give slightly improved E : 2 selectivities and also greatly improve isolation and purification of the products by simply filtering off the silica adsorbed phosphine oxide by-product.Activated alumina has been used similarly as an additive in the analogous reactions with much the same effects.48 Wittig and Horner- Emmons olefinations have also been achieved with immobilised aldehydes.49 Standard Wadsworth- Emmons phosphonate anion olefination of the ketone 16 with the phosphonate 17 gave poor yields of the desired trisubstituted alkene (Scheme 27). In this case silica gel and molecular sieve additives enhanced reaction yields and gave higher stereoselectivitites over more standard methodologies. 50 16 17 BuLi, DME, silica gel, 4 A mot. sieves, -78 "C, then reflux, I MeO*OMe 54% E:Z >16:1 (cf. standard Wadsworth conditions 20%) Scheme 27 Selective homologations of aldehydes to E,E-dienyl aldehydes have been achieved by the Wittig-like reaction with formylmethylene- (tripheny1)arsane formed in situ from the arsonium bromide salt (Scheme 28).5' The reaction is most selective with a-oxygenated aldehydes, with no triene formation? and also has been employed successfully on alcohols in a one pot Swern- homologation process (Scheme 2Q5' '7c0 2 equiv.oAcHo (plus 21% 75% monoalkene) i. (COCI)p, DMSO, THF, EtsN, -70 "C iI, ii 2 equiv. [Ph&sCH2CHO)+Br-, 1 0 0 Et3N,-2O0C , 9 ? 66% Bu Bu Scheme 28 Developments in the asymmetric Wittig and Wittig variant reactions have recently been reviewed.52 To date kinetic and dynamic resolution of racemates and desymmetrisation of meso substrates have been achieved (Scheme 29). In the majority of cases the Wittig reaction fails when attempted on ester substrates? but by heating with met hoxycarbonyl( trip heny1)p hosp horane in a sealed tube some carbohydrate lactones have been olefinated (Scheme 30).53 0 Ir (CF3CH20) HryC02R* KHMDS, 18-crown-6, (CF3CH20) THF -78 "C 8 Z o w Scheme 29 Scheme 30 de 84% R' = (R)-menthyl (Ph3P)=CHC02Me, PhMe, 140 O C , w~~ sealed tube, 4 h D 58% -0' E:Z 1.6:l 0 (Ph3P)=CHC02Me, PhMe, 140 "C, >6$oy sealed tube, 24 h / C02Me c 90% F-! O X E:Z 1.6:l In a variant of the Peterson olefination reaction, ethyl a-(trimethylsily1)acetate when treated with non-enolisable aldehydes and a catalytic amount of caesium fluoride in dimethyl sulfoxide (DMSO) was shown to form silyl ethers.On heating these silyl ethers selectively furnished ethyl trans-prop- 2-enoates in good yields (Scheme 31).54 Ethyl a-(trimethy1silyl)acetate can be replaced with ethyl P-(trimethylsily1)ethylimines giving a,P-unsaturated imine products.54 46 Contemporary Organic SynthesisUnsymmetrical ketones, where one chain bears an ethereal oxygen atom can be olefinated using a 10% rt CSF, ,35 DMSO, mn c [ $c02Et] molybdenum alkylidene complex 36 (vide infra) with extremely high stereoselectivities (Scheme 34).58 The attached alkylidene group resides trans to the chain bearing the directing group. ThFSnC02Et 91% isolated yield 1100 OC, 60 min C02Et 93% overall yield (one pot) Ph 36, PhH.rt ~ 88% E : Z >99: 1 Scheme 31 Scheme 34 The use of dimethyltitanocene as a less reactive alternative to the Tebbe reagent has been reviewed." This versatile reagent is able to olefinate aldehydes, ketones, esters, thioesters, selenoesters, acylsilanes, carbonates, anhydrides, amides and imides in toluene at 70 OC." In a related reaction tris( trimethylsily1)titanacyclobutene has been shown to be an effective and mild reagent for the formation of vinyltrimethylsilanes from ketones, aldehydes, thioesters, esters and lactones at room temperature (Scheme 32)." TMS Dithioacetals of diary1 ketones are smoothly converted into alkenes by treatment with the I X , X magnesium-zinc reagent 19 under nickel catalysis with poor selectivities (Scheme 39'" Dithioacetals of aryl-alkyl ketones, or aryl aldehydes can be transformed similarly with a stoichiometric amount of nickel in the presence of a copper(1) salt.n @::: - 19 19,5% NiCWdppe), PhH, 77% 19, 1 equiv. NiCI~(dppe).CuCN, PhH. 77% svs c Nap ht h A Me Naphth JY Z:E 3:4 X = OR, OAr, OCOR, OCOOR, OTBS, SPh, SePh, SiPh, NRR' Scheme 35 Scheme 32 Methylenation of aliphatic, a,P-unsaturated and aromatic aldehydes using Knochel's (dialkoxy- bory1)methylcopper reagent (18, R = H) and boron trifluoride-diethyl ether in THF at reflux has recently been reported (Scheme 33)." This reaction has been repeated using a related reagent (18, R = Me) forming methyl substituted alkenes in good yields and with moderate E : 2 selectivity. 18, BF3.0Et2, THF. heat, 57% PhCHO R=Me P h w E:Z 6:l Scheme 33 Entwistle: Saturated and unsaturated hydrocarbons 3.2 Alkene sp2-sp2 coupling reactions 3.2.1 Heck reaction The Heck reaction is now a widely used synthetic method for the assembly of polyenes and has been extensively reviewed.60 Due to the size of the subject area, even during the present period of coverage, attention has been focused on only the use of new catalysts, regioselect ive react ions, enan t ioselect ive reactions and modified reactions.of three equivalents of tri-o-tolylphosphine on palladium diacetate is an extremely active catalyst for the Heck reaction at levels as low as 0.005% (Scheme 36).6' The catalyst is extremely stable at temperatures of 130 "C with no evidence of phosphorus-carbon bond cleavage which occurs with reactions using palladium diacetate and tri- o-tolylphosphine mixtures. The addition of tetrabutylammonium bromide (TBAB) or alkali metal salts increases the stability of the catalyst in The isolated palladacycle 20 formed by the action 47occurrence of alkene regioisomers, due to competing palladate reductive elimination pathways. This problem has been successfully avoided by the incorporation of an allylsilane into the starting material, so that final reductive elimination ejects trimethylsilane (Scheme 39).68 0.005% 20 Bu4NBr, DMF, 130 "C, 81% p C 0 2 B u CI CO~BU 7 mot% (R)~JN?IP, Ag3PO3, 2.5 mol% Pd2(dba)3CHC13, Me0 M e q T z J 1-70 Scheme 36 the presence of aryl chlorides and allow the Heck reaction of 4-chlorobenzaldehyde (Scheme 36).6' The same authors have developed the carbene palladium catalyst 21 which is not as active as the extremely active palladacycle catalyst 20 but is however very stable against heat, hydrolysis and oxidation (Scheme 37)" As with the palladacycle catalyst the carbene catalyst also promotes the Heck reaction of chloroarenes in the presence of TBAB.Scheme 39 The Heck reaction is usually performed with vinylic or aromatic halides or trifluoromethanesulfonates and, to a much lesser extent, aromatic diazonium salts. Two recent reports have successfully used the latter, the first employing heterogeneous palladium on carbon and the second using an in situ method of diazonium salt formation and subsequent Heck reaction (Scheme 40).70 2 [G$ Me r- Pd(0Ac)p 70% OMe OMe Scheme 37 i. NaN02, 42% HBF4. 0 "C ii. 1% P~(OAC)~, MeOH, 50 "C A N H 2 then The usual exo-selectivity witnessed in the Heck reaction has becn reversed to endo-selectivity in two cases of intramolecular reaction^^"^^ using the Jeffery catalyst system.6s The same reversal of regioselectivity was observed in intramolecular Heck reactions using catalytic palladium( 11) salts and the water soluble tris(m-sulfonopheny1)phosphine (TSPPS) ligand in aqueous acetonitrile (Scheme 38).66 C02Me P R C02Me A NHC02Et R yield(%) I NHC02Et C02Me 80 CN 75 Ph 64 Scheme 40 10 rnol%, PdC12, E Cascades involving Heck-Friedel-Craft~,~' Heck- aldoI7* and Heck-Michael reactions72 have found synthetic utility.Solid phase Heck reactions have also been reported which have been used to build libraries of cinnamate derivative^.^^.^^ Finally, vinylboronate esters have been selectively converted into dienylboronate esters in a Heck fashion in the presence of silver or thallium acetate avoiding the competing Suzuki reaction, albeit in poor yields (Scheme 41).74 The method holds promise for polyene synthesis as the dienylboronate products have then been further used in Suzuki couplings to form conjugated trienes stereo~electively.~~ BnNT 65% endo : ex0 5 mol%, PdCI2, 93 : 7 PhBP, Pr'zNEt, Ag&03,90 "C * 14 : 86 cf.60% TPPTS = [m-S03H-(CcH4)]3P Scheme 38 The asymmetric Heck reaction has become an extremely efficient met hod for the construction of chiral sp3 carbon centre^.^"".^^ In the 'standard' and asymmetric Heck reactions where a tertiary sp3 centre is formed there is always the potential for 3.2.2 Stille reaction Like the Heck, the Stille reaction has enjoyed widespread use in organic synthesis and the area has 48 Contemporary Organic Synthesis1- Bu Pd(OAc)p, PPh3, AgOAc. Et3N. MeCN, heat 9% c Scheme 41 Pd(MeCN)&, DMF, -1 0 to +5 OC.40 min P Br 56% Heck product \\/\\/\ Bu 0% Suzuki product been reviewed exten~ively.~' Here again the focus will be on new or unusual aspects of the reaction. The first case of a Stille reaction of q4 tricarbonyl iron complexed cyclohexadienyl trifluoromethane- sulfonate and vinylstannane has been reported (Scheme 42).76 The same complex has also been coupled to an alkynyl fragment. OTf // Scheme 42 Poor yields of dienyl sulfoxides were obtained under many of the modified Stille conditions, and only when the radical inhibitor 2,6-di-tert-butyl- 4-methoxyphenol (BHT) was included was the product obtained in 70% yield (Scheme 43)." R yield(%) H 89 Bu 75 Scheme 43 An extremely interesting accelerated Stille reaction of the more hindered vinylstannane 23 over the vinylstannane 22 is reported to be controlled by the chelation of a palladium intermediate species to a proximal imino functional group (Scheme 44).7s Fully aqueous versions of the Stille reaction have been reported using aryl and vinyl trichlorostan- nanes and 3 mol% palladium chloride in degassed 10% aqueous potassium hydroxide.79 The Stille reaction has been performed in the solid phase49 yielding benzodiazepine libraries8" and also biaryls." Heterogenous catalysis with palladium on charcoal has also been realised.s2 antibiotic natural products such as macrolactin A and anhydropristinamycin IIB have been achieved successfully using the Stille reaction (Scheme 45).83 Solution phase macrocyclic ring closure of several Ph Ph Scheme 44 /I OMOM MeO" I Me0 / / Pdp(dba)3, Ph3As, DMF, 50 "C, 50% I OMOM 9 M e O u / / MeO'.Scheme 45 3.2.3 Suzuki reaction As for the Heck and Stille reactions, this coverage of the Suzuki reaction summarises novel and unusual variations on the well precedented ~eaction.'~ An in situ method for the synthesis of vinylboronate esters from vinylsilanes for subse- quent Suzuki reaction gives moderate yields of arylated alkenes (Scheme 46)" Another in situ vinylboronate synthesis has been employed to effect a one pot Shapiro-Suzuki reaction.s6 A series of aromatic and aliphatic hydrazones have been converted into vinyl aromatics in reasonable yields (Scheme 46). In the borane variant of the Suzuki reaction, geminal vinyl dibromides have been reacted with 3, to-diborylalkanes, derived from a, a-dienes, under palladium(0) catalysis to give carbocycles with exocyclic double bonds (Scheme 47).x7 The water soluble catalyst system previously described for use in the Heck reaction (Scheme 38) has also been used successfully in the Suzuki cross- Etitwistle: Saturated and unsaturated hydrocarbons 491 Ph/\\/ B(OW2 Pd(PPh3)4, NaOH aq, PhH, ArX, 80 OC i.BCl3, CH2C12,O OC -SiMe3 ii. EtOH,PhH Ph \ J Ph/\\/ Ar ArX yield(%) PhI 50 2-bromothiophene 45 i. BuLi, TMEDA, hexane, -78 to 0 O C , then B(OPr')3 PPh3, PhBr, PhMe, 100 OC NNHT,~~ ii. Na2C03, Pd(OAc)2, c Scheme 46 Pd(PPh3),,, NaOH aq, THF w &.. i; R yield(%) 3.3 Rearrangements 3.3.1 Cope rearrangement The oxy-anion Cope rearrangement has been used most noticeably by Paquette et aZ.in the stereo- selective construction of a whole host of densely packed polycyclic hydrocarbons." The example depicted here involves a [3,3] Cope rearrangement followed by p elimination of the acetonide to give the tricyclic diene 24 (Scheme 49).91a This fragment has been further elaborated to a pentacyclic struc- ture which is closely related to the kaurane diter- penoid natural products. x KH, 18-crownd, OH THF, 25 "C, 80% I - Bu 44 Ph 56 Scheme 49 - $j$ 0 X 1 0 I , H H ?PH / 24 Scheme 47 The synthesis of chromium tricarbonyl complexed 1,2-dioxobenzocyclobutene 25 has recently been described by Butenschon et aZ.92 Addition of excess vinyllithium to this complex at - 78 "C gives, after acidic work up, the complexed benzocyclooctadione 26 which is readily decomplexed (Scheme 50).The reaction is postulated to pass through a syn divinyl coupling reations of vinylboronate esters with vinyl iodides in the presence of Hiinig's base yielding a variety of functionalised dienes and trienes (Scheme 48).88 C02Me 10 mol%, P~(OAC)~, MeCN, H20. r l TPPTS, Pt'2NEt, 70% C02Me pd Scheme 48 mo -!- &(CO), 0 TPPTS = [~-HO~S-(CGH~)]~P 25 Similarly the palladacycle catalyst described previ- ously for use in the Heck reaction6' has also been used in the Suzuki reaction in the synthesis of biaryls in 0.05 m01%.~~ The use of potassium tert- butoxide in the tetrakis(tripheny1phosphine)palla- dium(0) coupling of bulky boronic acids and aryl halides has been found to give much improved yields of biaryls.gO Suzuki reactions have also been performed successfully in the solid phase.49 ii r 1 YLi 26 Reagents: i, vinyllithiurn, THF, -78 "C; ii, a, vinyllithiurn, b, propenyllithium Scheme 50 50 Contemporary Organic Synthesiscomplex which then undergoes a double anionic oxy-Cope rearrangement giving the product.This reaction is of particular note as the same reaction of uncomplexed 1,2-dioxobenzocyclobutene gives only traces of the desired product. The majority of the product subsequently undergoes an undesired trans- annular aldol reaction. Reactions where there is branching on one or more of the reacting alkenes have also been reported but in much poorer yields. 3.3.2 Claisen rearrangement The Claisen rearrangement is an extremely powerful method for the construction of carbon-carbon bonds and has been used extensively in the synthesis of a number of natural products.Here again the synthesis of unusual terpenes by Paquette et al. has demonstrated the applicability of the rearrangement for the production of medium ring Two other applications of the Claisen rearrange- ment for the synthesis of medium ring lactams have been reported."-" The first employed an in situ preparation of the diene 28 from the selenoxide 27. The diene 28 subsequently rearranged to give the eight membered lactam 29 containing a cis double bond (Scheme 51).94 The addition of a soft nucleo- phile trap, such a silyl ketene acetal, was found to be crucial in preventing further reactions of selenic by-products. Bn02CN 0 OTBS, heat 27 'Se(0)Ph 28 180% Scheme 51 OMe Scheme 52 29 OMe The enolate aza-Claisen rearrangement depicted in Scheme 52 gives access to medium ring lactams with the thermodynamically more unstable trans double bond.9s An asymmetric variation of the Claisen reaction has been developed using (s)-( - )-2-(methoxy- methy1)pyrrolidine (SAMP) hydrazone as a chiral auxiliary for the synthesis of contiguous quaternary and tertiary centresY6 The same approach has also been successfully applied to the Wittig rearrange- ment (vide infra)."' Good to excellent ees have also been obtained from the use of chiral Lewis acids such as the binaphthol derivative 30 (Scheme 53).97 R ee% yield (%) But 91 70 CY 86 85 Ph 97 76 TMS 92 78 30 Scheme 53 Corey et al.have used a highly enantioselective Claisen rearrangement of chiral boron enol ethers derived from the diazaborolidine 31 in their total synthesis of fl-elemene and fuscol (Scheme 54).9R A more recent synthesis of dolabellatrienone describes substantial increases in yield using pentaisopropyl- guanidine in the formation of the boron enol ether.99 1.1 equiv.31, Et3N, 4 "C, 36 h, 85% 4 Scheme 54 phxph . . Ar02S"xB/NIS02Ar Br -4 The bulky Lewis acid complex of diethylalu- minium chloride and triphenylphosphine has given moderate levels of diastereoselectivity in the rearrangement of an ally1 vinyl ether from a remote .asymmetric centre.'('(' A urea soluble in organic solvents has given up to 22-fold acceleration of simple rearrangements. A stabilised bis-hydrogen Entwistle: Saturated and unsaturated hydrocarbons 51bonded transition state is suggested to be the cause of the rate increase.'"' Chelation control has played an important part in directing the stereochemical outcome of the Claisen rearrangement.P-Oxygenation in the ester enolate variant has allowed efficient '1,6chirality tran~fer',''~ whereas oxygenation on the allylic position has allowed the highly E-selective synthesis of alkenes.'"' Reactions involving amino acid derivatives have led to the stereoselective synthesis of alkylated amino acidsIo4 which have been made enantioselective in the presence of quinine (Scheme 55).'n4h LiN(SiMe3)2, THF, -78 "C to rt, *=A Scheme 55 1,2 Asymmetric induction has been witnessed in the rearrangement of allylamine derived zwitterionic species 32 giving good des of the tertiary centres formed (Scheme 56).OTBS 0 K2CO3, Me3AI, CH2Cl2, 73% 1 32 Scheme 56 Cyclic enol ether Claisen substrates, made in situ by the action of trifluoroacetic acid, rearrange in the presence of palladium(i1) salts to give products with extremely high anti selectivity (Scheme 57). '06*107 Interestingly this palladium catalysed process gives the opposite stereochemical bias to that of the syn selective thermal rearrangement. Homogeneous palladium catalysed 'vinylogous acetylenic Claisen rearrangements' have also been reportedIo8 as well as immobilised rhodium catalysed rearrangements followed by intramolecular a1 kene hydroacylation. Claisen rearrangement to a one pot procedure promoted by triisobutylaluminium has been imple- mented by Rychnovsky (Scheme 58)."03 Yields and E : Z selectivities are high.In contrast to the thermal 'reaction""' this low temperature (0 "C) procedure A modification of the thermal acid catalysed ketal 10molX 10 md% F A , PdCl2(PhCN)2, PhMe. rt ~ - Et / 96% anti, 68% + 96% syn, 80% Scheme 57 Pr ' L P h P F b P h linear branched Conditions yield(%) linear : branched i, PPTS, ii, Et3N, iii, Bu'& 0 "C. 94 : 6 PPTS, 79 9 : 91 58 Scheme 58 gives predominantly linear products when unsymmetrical ketals are used. The Claisen rearrangement has been incorporated successfully into a tandem Claisen-hetero-ene reaction yielding a tetrahydro-5H-fluorene derivative 33 (Scheme 59)."' OMe L OMe OMe 33 Scheme 59 3.3.3 Wittig rearrangement Trialkylsilanes have been used as an alternative to using the potentially toxic stannanes in the Wittig- Still rearrangement.' I 2 (Trimethylsily1)methyl ethers have been transmetallated successfully with excess butyllithium to give lithiomethylallyl ethers which then undergo the [2,3] sigmatropic rearrangement (Scheme 60).52 Contemporary Organic SynthesisII YH BuLi, THF, -5 to +5 "C 68% I A Scheme 60 The Wittig-Still rearrangement of E-alkenes, in general, is moderately selective in favour of the production of E-disubstituted alkenes."'*"4 When either a benzyloxy or (methoxymethy1)oxy moiety is placed p to the (tributylstanny1)methoxy group, however, the reaction becomes 95-100% 2 stereo- selective (Scheme 61)."' The choice of 1,Zdimeth- oxyethane (DME) as solvent was found to be crucial in obtaining high yields of products in these reactions.BuLi, DME, -60 "C OH R1 R2 cis: trans yield(%) Et Hx 57:43 84 BnOCH2 Hx 100: 0 76 Scheme 61 The aza-Wittig rearrangement of N-[(tert-butoxy- carbony1)met hyllvinylaziridines is a highly selective method f a - the synthesis of unsaturated czs- 2,6-disubstituted piperidines (Scheme 62)."' The selectivity is reversed leading to trans-2,6 substitu- tion when N-prop-2-ynyl(vinyl) aziridines are used."6 Wittig olefination of keto N-[(tert-butoxy- carbonyl)methyl]aziridines with two equivalents of ylide also yields cis-piperidines with total selectivity and in good yield; here the excess ylide acts as base for the [2,3] rearrangement of the vinyl aziridine intermediate (Scheme 62)."' LDA, THF, -78 "C Me 63% Ph3PMeBr. BuLi, DME, rt 100% cis 57% Me Ph trans : cis : pyrrolidine = 1.8 : 1.2 : 1 Scheme 62 Entwistle: Saturated and unsaturated hydrocarbons Several chiral auxiliaries have been appended to the carbanionic carbon atom, rendering the rearrangement diastereoselective.Notable among these approaches are the chiral 173,2-oxazaphos- phorinane method of Denmark"* and the prolinol derived hydrazone method of Ender~,"~ both of which, after auxiliary cleavage, give products of >99% ee. Glucose has also been used as a chirality transfer agent, where the attachment is an acetal linkage at the anomeric centre and the allylic carbon. Rearranged products are obtained in > 99% de and the auxiliary is readily cleaved by ozonolysis giving alk-2-ynyl alcohol 34 in high ee (Scheme 63). ' 2o OBn BnO BuLi, THF, 92% -78 "C I I OR TBDPS-CI, imidazole CH2C12, 92% R = H ~r R=TBDPS 03.MeOH, -78 "C; NaBH4 80% I HOJTMS I OTBDPS 34 Scheme 63 3.3.4 Miscellaneous rearrangements Extensive studies by Trost into the transition metal catalysed Alder-ene type coupling of alkynes and alkenes have shown that CpRu(C0D)Cl is in general the most efficient catalyst (Scheme 64).'?' The reaction tolerates a number of functional groups such as alcohols, silyl ethers and esters, and gives excellent stereochemical control at the newly formed double bonds. Regiochemical selectivities between branched and linear type coupling are in general of the order of 4: 1. Bu Bu CpRu(C0D)CL H20, 100 "C, 56% DMF, uc6H 13 branched branched:linear 5.2: 1 Bu h C 6 H 1 3 linear Scheme 64 53Br WOC14, PhMe, 110 OC Qo, ,cl+ cI'w'o \ / @OH -HCI Br Br Br 37 The [3,3] sigmatropic rearrangement of allyl- (viny1)zincs is known to be highly diastereoselective when coordinating atoms such as oxygen are attached to the carbon backbone.I2* Normant et al.have recently shown that a neighbouring alkene can act as a chelating group by 7c-donation to the zinc centre resulting in excellent diastereomeric induc- tion (Scheme 65). M e c I cf identical reaction conditions I 50% anti, 72% Scheme 65 3.4 AIkene metathesis Since the early 1990s ring closing metathesis, 'the metal catalysed exchange of the alkylidene of two olefins', has enjoyed increasing popularity in organic synthesis.'23 The most frequently used catalysts 35 and 36 devised by Schrock and Grubbs respectively (Scheme 66), have been exploited to great effect in many natural product syntheses.'24 Ph pcY3 35 Schrock's catalyst 36 Grubbs' catalyst Scheme 66 Although extremely versatile, the Schrock and Grubbs catalysts have to be made in the laboratory in multistep sequences.The use of a catalyst readily made from commercially available materials in a single step is therefore an attractive goal that has been realised in the synthesis of the tungsten complex 37 (Scheme 67).12' The catalyst is made simply by heating tungsten(v1) oxychloride and 2,6-dibromophenol in toluene, followed by evapora- tion of solvent and recrystallisation. Tetraethyllead and 2 mol% of 37 catalyses ring closing metathesis of dienes in good ~ie1ds.I~~ Scheme 67 Nicolaou et al. have adapted the earlier work of Grubbs and reported that a fourfold excess of the Tebbe reagent brings about olefination of esters which on further heating in situ undergo ring closing metathesis to give cyclic enol ethers (Scheme 68).'26 Some Lewis acid promoted hydrolysis of the products was noted but this was prevented by the use of dimethyltitanocene in place of the Tebbe reagent.BnO 0 BnO 1 4 equiv., THF;;flux Tebbe, Scheme 68 Grubbs has reported the first instancelL' of kinetic resolution of racemic substrates by a metathesis reaction with the chiral molybdenum catalyst 38 (Scheme 69).12' This preliminary report quotes low to moderate ees of recovered uncyclised material. Monosubstituted allylsilanes have been syn- thesised by metathesis of terminal alkenes with tri- PS QP+ 28% yield 72% yield 84% ee Scheme 69 54 Contemporary Organic SynthesisOSiEt, methyl(ally1)silane in the presence of the Shrock catalyst (Scheme 70).'29 The reaction is tolerant of a ,p< 3 mol% 36, CH&- ply wide range of functionality and is moderately trans selective.A similar synthesis of a, /I-unsaturated cyanides has been brought about by the cross metathesis of terminal alkenes with the usually x y yield(%) OSiEt, unreactive acrylonitrile (Scheme 70)."" In contrast this reaction is quite selective for the formation of cis-a1 kenes. R Z: E yield(%) ~ ~~ 8.5:l 72 %$MS 3:l 76 (CH2),0Bn 7.6:l 60 Scheme 70 P R 2 mol% 35, q = SiMe3 R dsiMe3 R E : Z yield(%) pTol 8.5:l 72 (CH2),Br 3:l 76 (CH2),0Bn 3.8:l 60 1 1 95 2 2 88 Scheme 72 continues to be a scientific and socially very important area of research.'"".'4 Dodecacarbonyltri- iron supported on zeolite ZSM-5 has been shown to be a very active catalyst for the conversion of carbon dioxide into methane and light alkenes with a high selectivity for ethene.''4 There are numerous methods for the deoxy- genation of 1,2-diol derivative^."^ A method has recently been described for the stereospecific synthesis of alkenes by the treatment of cyclic sulfates and thiocarbonates with a catalytic amount of telluride (Scheme 73).'36 The telluride is regen- erated by the action of a stoichiometric amount of either sodium hydride or lithium triet hylborohydride.0 2 o~s;o 10% Te', NaH, DMF, * E t 0 2 C 6 c 0 2 E t 0 OC to rt, 30 min Et0& %02E t 90% ( d l o 10% Te'. LiEtgBH, THF, rt, 5 min * Ph/=\Ph With carefully controlled reaction conditions the cross metathesis of bicyclic cyclobutenes and terminal alkenes catalysed by the Schrock catalyst 81% Ph has been realised (Scheme 71).'" The reaction gives a mild excess of &-substituted alkenes.Scheme 73 Deoxygenation has also been reported to be @C6H13 ($ 1 mol% 35, PhH. 68%- ,, facilitated by titanium metal activated by trimethyl- silyl chloride.' This activation procedure, described in Section 2.1 for the pinacol reaction, has also been used in the deoxygenation of epoxides and in the McMurry reaction.' H cis : trans = 3.2 : 1 Scheme 71 The Grubbs catalyst 36 has been used successfully in the intramolecular metathesis of non-conjugated dieneynes to give [n.m.O] fused bicyclic hydro- carbons (Scheme 72).132 The reaction allows the formation of five, six and seven membered rings but fails with halogen, trimethylsilyl and tributylstannyl substituted alkynes.3.5 Miscellaneous Attempts to form vinyl anions by treatment of vinyl sulfones with lithium naphthalenide have been shown to give the undesired phenyllithium~."~~ In a communication by Fuchs et al. the problem was circumvented by adding a silyl anion in a Michael sense to vinyl sulfones and trapping the a-lithio sulfone with an electrophile. The double bond is then regenerated simply by treating the /I-silyl sulfone with fluoride (Scheme 74).137b If the substrate has a potential leaving group /I to the silane, such as a protected hydroxy group, some p-elimination can arise to give allylic sulfones. Terminal alkynes bearing a nitrogen-containing The need for petrochemical feedstocks from non- hydrocarbon sources such as carbon dioxide functional group at the 3-position have been stannylcuprated and silylcuprated selectively using Entwistle: Saturated and unsaturated hydrocarbons 55OTBDPS TBAF, THF, reflux, 98% 1 T 6 D p s 0 7 ) 7 OTBDPS Reagents: i, PhMe2SiLi, THF; ii, TPSO(CH2)7CHCHCH2Br, HMPA, -78 "C, 69% 10% (R) BINOL-TiX2, 4 A mol sieves,CH&lp m x = CI, 97% 00 X = Bf, 98% 88 10% (R) BINOL-TiX2, 4 A rnol sieves,CHpCl2 x = CI, 53%, >99% ee D OSiMe2Thx 10% (R) BINOL-TiX2, 4 A mol sieves.CH2Clp x = CI, 54%.>99% 80 c OSiMe2Thx C02Me OJ w C02Me 6SiMe2Thx p++J C02Me OSiMe2Thx Scheme 74 Scheme 76 the appropriate metallocuprate to give the syn- metallocuprate in a highly regioselective manner (Scheme 75)."' These intermediates react smoothly with a broad range of carbon electrophiles and the products have been used as partners in Heck and Stille type reactions.( Me3Si)&u(CN)Li. or ( Bu3Sn)(Bu)Cu(CN)Li, //N(TMS), THF*-78 OC c THF, -78 "C M T N ( T M S ) , ] 1 R-X M y N ( T M S ) , R M R yield(%) M R yield(%) Me3Si ally1 85 Bu3Sn all I 82 Me$ C02Me 83 Bu3Sn d 2 M e 87 Me3Si vinyl 76 Bu3Sn COMe 76 Me3Si H 92 Bu3Sn H 95 Scheme 75 Novel titanium binaphthol dihalides have found use as chiral catalysts in the highly enantioselective glyoxalate-ene reaction."' The reaction is highly dependent on the presence of molecular sieves and exhibits a strong positive non-linear effect. The catalysts have also been used to desymmetrise meso substrates and kinetically resolve racemic substrates with high ees (Scheme 76).The catalysts have also been used successfully in the asymmetric carbonyl- ene cyclisation, Mukaiyama aldol condensation, hetero Diels-Alder and allylic stannanehilane addition to glyoxaldehyde.'39 Tankeshita and Kato used three interesting reactions for the formation of double bonds in their enantioselective synthesis of cotylenol.'") The first reaction used the increasingly popular NozakiI4' chromium catalysed addition of an ally1 chloride to aldehyde to give the alcohol 39 in 54% yield (Scheme 77). In this case the addition to the aldehyde was highly diastereoselective and also Y \OMe Scheme 77 <OMe 39 regioselective, reacting on the most hindered end of the allylchromiurn species.Multistep elaboration of the allylchromium addition product 39 gave the epoxy methanesulfo- nate 40 which when subjected to sodium and iron(ri1) chloride in liquid ammonia gave the alkene 41 in 72% yield (Scheme 78).14" Addition of the iron salt was found to be vital, over-reduction being seen otherwise. \OMe 40 Na, FeC13, NH3, -78 OC, 72% * Ho \oMe 41 Scheme 78 Finally, after protecting group manipulation of 41 and primary hydroxy group oxidation the key ring closing ene reaction was successfully achieved by heating the aldehyde 42 in xylene, giving the core tricyclic ring system 43 in 90% yield (Scheme 79).14' 4. Alkynic hydrocarbons 4.1 Alkyne metathesis The rapidly expanding area of alkene metathesis has been described previ~usly."~,'~~ A mixture of molyb- 56 Contemporary Organic SynthesisTMSO X O M e 42 43 Scheme 79 Scheme 82 denuni hexacarbonyl and p-chlorophenol in boiling toluene has been shown to be an effective catalyst for cross alkyne metathesis (Scheme reaction is brought about by shifting the reaction equilibrium towards products by the use of an excess of one alkyne component.This 11 equiv. Pr-Pr i 80% Ph - Et 11 equiv. ph-ph Reagents: i, MO(CO)~, pCI-C6H40H (1 equiv.), PhMe, 110 "C, 20 h Scheme 80 N2 The reaction of diethyl trichloromethyl- phosphonate with two equivalents of butyllithium and trimethylsilyl chloride gives the silylphospho- nate anion 40.'46 Peterson type reaction of 40 with aldehydes then gives a-chlorovinylphosphonates which after isolation are cleanly eliminated with lithium bis(trimethylsily1)amide (LHMDS) to give phosphonate substituted alkynes in very high yields (Scheme 83).146 0 P(OEt)2 I I LHMDS, THF, -78 "C * ,kOEtl2 - R CI R yield (%) The Ti(OPri)2 equivalent ( q2-propene)Ti(OPr')2 formulated by sat^'^^ has been used to form alkynes and allenes from prop-2-ynyl bromides and carbon- ates by cyclisation onto ketones and aldehydes (Scheme 81).Iu The low yields of alkynes are improved if the carbonyl function is masked as a cyclic a~eta1.l~~ 40 RCHO.THF, -78 "C I 4.2 Miscellaneous Ph 89 TMS, V i)C02Me 8 12% Scheme 81 A high yielding one step procedure for the conversion of aldehydes into terminal alkynes that avoids the use of strong alkyllithium bases or inert atmosphere has been adapted by Bestmann et al. (Scheme 82).14' O.F-CgH4 92 ptolyl 87 2-pyridyl 96 2-futyl 89 Scheme 83 1,2-Diarylalkenes have been oxidised directly to 1,2-diarylalkynes by treatment with Bu'OK in DMF under air although no yields were ~ e p 0 r t e d .l ~ ~ Unsymmetrical diynes have been constructed successfully by the cross coupling of a terminal alkyne with an iodoalkyne catalysed by copper(1) iodide in pyrrolidine at room temperature (Scheme 84).14' Addition of palladium salts improved the yields of the sluggish reactions with bromoalkynes. The area of enediyne natural products constantly brings to the fore new methods for the construction and joining of alkynes and alkenes. Cyclic enediynes have been constructed by the joining of two prop- 2-ynyl bromides in the presence of LHMDS and HMPA (Scheme 85).'49 In the synthesis of dynemicin analogues an improved route for the coupling of the dienyne portion has been published involving the intra- Entwistle: Saturated and unsaturated hydrocarbons 5710 mol% Cul, pyrrolidne, 20 "C R-I -R1 R Y = R 1 R R1 yield(%) C5H11 Ph 95 C5H1 1 (CH2)3C1 61 C5Hl1 CH20H 95 Ph CH2OH 95 Scheme 84 P B r LiN(SiMe&, HMPA, THF, 4 5 o c , 93 % ~TBDPS OTBDPS Scheme 85 molecular caesium fluoride catalysed addition of a trimethylsilylalkyne to an aldehyde (Scheme 86)."' The addition of an in situ alkoxide trap such as an anhydride, acyl halide or chloroformate was found to be crucial in obtaining high yields avoiding the formation of other by-products.TMS P : a = 2 : 1 Scheme 86 5 References 1 E. Kawashima, Y. Aoyama, T. Sekine, M.Miyahara, M. F. Radwan, E. Nakamura, M. Kainosho, Y. Kyogoku and Y. Ishido, J. 0%. Chem., 1995,60, 6980. 2 (a) J. E. McMurry, Chem. Rev., 1989,89, 1513; (b) See also A. Furstner and G. Seidel, Synthesis, 1995, 63, and the references therein. 1995, 117,4468. 3 A. Furstner and A. Hupperts, J. Am. Chem. SOC., 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 D. Mitchell, C. W. Doecke, L. A. Hay, T. M. Koenig and D. D. Wirth, Tetrahedron Lett., 1995, 36, 5335. A. Srikrishna, R. Viswajanani, J. A. Sattigeri and C. V. Yelamaggad, Tetrahedron Lett., 1995, 36, 2347. A. Srikrishna, J. A. Sattigeri, R. Viswajanani and C. V. Yelamaggad, Synlett, 1995, 93. E. V. Dehmlow, T. Niemann and A. Kraft, Synth. Commun., 1996,26, 1467. J.S. Yadav and D. K. Barma, Tetrahedron, 1996,52, 4457. B. Boukherroub , C. Chatgilialoglu and G. Manuel, Organometallics, 1996, 15, 1508. E. Ptralez, J.-C. Ntgrel and M. Chanon, Tetrahedron Lett., 1995, 36, 6457. C. Cativiela, M. D. Diaz-de-Villegas and A. L. Jimhez, Tetrahedron: Asymmetry, 1995, 6, 2067. F. A. J. Kerdesky and L. S. Seif, Synth. Commun., 1995,25,4081. J. L. Kiplinger, T. G. Richmond and C. E. Osterberg, Chem. Rev., 1994,94, 373. M. Hudlicky, Chemistry of Organic Fluorine Compounds, 2nd edn., Prentice-Hall, New York, 1992, p. 175. M. Aizenberg and D. Milstein, J. Am. Chem. SOC., 1995, 117, 8674. J. Burdeniuc and R. H. Crabtree, J. Am. Chem. SOC. 1996, 118, 2525. N. A. Kaprinidis and N. J. Turro, Tetrahedron Lett., 1996,37( 14), 2373. C. M. Rayner, Contemp.0%. Synth., 1995,2,409 and the references therein S. Moriyama, T. Karakasa, T. Inoue, K. Kurashima, S. Satsumabayashi and T. Saito, Synlett, 1996, 72. Y. Makioka, S.-Y. Uebori, M. Tsuno, Y. Taniguchi, K. Takaki and Y. Fujiwara, J. 0%. Chem., 1996, 61, 372. M. Mukumoto, H. Tsuzuki, S. Mataka, M. Tashiro, T. Tsukinoki, Y. Nagano and I. Hashimoto, J. Chem. Res. (S), 1996, 6. K. C. Nicolaou, M. Sato, E. A. Theodorakis and N. D. Miller, J. Chem. SOC., Chem. Commun., 1995, 1583. F. Bracher and T. Papke, J. Chem. SOC., Perkin Trans. I , 1995, 2323. S. Talukdar and A. Banerji, Synth. Commun., 1996, 26(6), 1051. (a) For a review of ruthenium catalysts see R. Noyori, Acta Chem. Scand., 1996, 50, 380; (b) For a very concise review of rhodium and iridium catalysts and for other leading references see J.Albrecht and U. Nagel, Angew Chem., Int. Ed. Engl., 1996,35, 407. For leading references see M. J. Burk, S. G. Feng, M. F. Gross and W. Tumas, J. Am. Chem. SOC., 1995, 117,8277. G. Righi and L. Rossi, Synth. Commun., 1996, 26, 1321. D. J. Darensbourg, N. W. Stafford, F. Joo and J. H. Reibenspies, J. Organomet. Chem., 1995,488, 99. R. Yanada, K. Bessho, Y. Yanada, Synlett, 1995,443. P.-D. Ren, S.-F. Pan, T.-W. Dong and S.-H. Wu, Synth. Commun., 1995, 25, 3395. P.-D. Ren, S.-F. Pan, T.-W. Dong and S.-H. Wu, Synth. Commun., 1996, 26, 763. A. D. Westwell and J. M. J. Williams,J. Chem. SOC., Perkin Trans I , 1996, 1. I. Ojima, M. Tzamarioudaki, Z. Li and R. J. Donovan, Chem. Rev., 1996,96,635. A. Devasagayaraj, T. Studemann and P.Knochel, Angew. Chem., Int. Ed. Engl., 1995, 34, 2723. G. A. Molander and C . R. Harris, J. Am. Chem. SOC., 1995, 117, 3705. 58 Contemporary Organic Synthesis36 S. D. Knight, L. E. Overman and G. Pairaudeau, J. Am. Chem. SOC., 1995, 117,5776. 37 C. Kuhn, G. Le Gouadec, A. L. Skaltsounis and J.-C. Florent, Tetrahedron Lett., 1995,36, 3137. 38 K. Takeda, M. Takeda, A. Nakajima and E. Yoshii, J. Am. Chem. Soc., 1995,117,6400. 39 M. Shibasaki and H. Sasai, Pure Appl. Chem., 1996, 68, 523. 40 R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994. 41 I. E. Mark6, F. Murphy and S. D o h , Tetrahedron Lett., 1996, 37, 2089. 42 G. E. Keck, K. A. Savin and M. A. Weglarz, J. Org. Chem., 1995, 60, 3194. 43 G. H. Lee, H. K. Lee, E. B. Choi, B. T.Kim and C. S. Pak, Tetrahedron Lett., 1995, 36, 2865. 44 J. B. Baudin, G. Hareau, S. A. Julia, R. Lorne and 0. Ruel, Bull. Soc. Chim. Fr:, 1993, 130, 336. 45 J. B. Baudin, G. Hareau, S. A. Julia, R. Lorne and 0. Ruel, Bull. SOC. Chim. Fr:, 1993, 130, 856. 46 N. D. Smith, P. J. Kocienski and S. D. A. Street, Synthesis, 1996, 652. 47 V. J. Patil and U. Mavers, Tetrahedron Lett., 1996, 37, 1281. 48 D. D. Dhavale, M. D. Sindkhedkar and R. S. Mali, J. Chem. Res. (S), 1995, 414. 49 P. H. H. Hermkens, H. C. J. Ottenheijm and D. Rees, Tetrahedron, 1996, 52, 4527. 50 X. Yue and Y. Li, Synthesis, 1996, 736. 51 Z.-H. Peng, Y.-L. Li, W.-L. Wu, C.-X. Liu and Y.-L. 52 T. Rein and 0. Reiser, Acta Chem. Scand., 1996, 50, 53 M. Lakhrissi and Y. Chapleur, Angew. Chem., Znt. Ed. 54 M.Ballassoued and N. Ozanne, J. Org. Chem., 1995, 55 N. A. Petasis, S.-P. Lu, E. I. Bzowej, D.-K. Fu, J. P. Wu, J. Chem. Soc., Perkin Trans. 1, 1996, 1057. 369. Engl., 1996, 35, 750. 60, 6582. Staszewski, I. Akritopoulou-Zanze, M. A. Patane and Y.-H. Hu, Pure Appl. Chem., 1996, 68, 667. 56 N. A. Petasis, J. P. Staszewski and D.-K. Fu, Tetra- hedron Lett., 1995, 36, 3619. 57 M. Sakai, S. Saito, G. Kanai, A. Suzuki and N. Miyaura, Tetrahedron, 1996, 52, 915. 58 0. Fujimura, G. C. Fu, P. W. K. Rothemund and R. H. Grubbs, J. Am. Chem. Soc., 1995, 117,2355. 59 €I.-R. Tseng and T.-Y. Luh, Organometallics, 1996, 15, 3099. 60 For the most recent reviews with leading references see ( a ) T. Jeffery, Advances in Metal-Organic Chemistry, ed. L. S. Liebeskind, JAI Press, Greenwich, 1996, 5, 149-256; (b) W.Cabri and I. Candiani, Acc. Chem. Res., 1995, 28, 2; (c) A. Ilemeijere and F. E. Meyer, Angew. Chem., Znt. Ed. Engl., 1994, 33, 2379. 61 W. A. Herrmann, C. Brossmer, K. Ofele, C.-P. Keisinger, T. Priermeier, M. Beller and H. Fischer, Angew. Chem., Int. Ed. Engl., 1995, 34, 1844. 62 W. A. Herrmann, M. Elison, J. Fischer, C. Kocher and G. R. J. Artus, Angew. Chem., Int. Ed. Engl., 1995,34, 2371. 63 J. H. Rigby, R. C. Hughes and M. J. Heeg, J. Am. (:hem. Soc., 1995, 117, 7834. 64 S. E. Gibson and R. J. Middleton, J. Chem. SOC., (:hem. Commun., 1995, 1743, 65 T. Jeffery, Synthesis, 1987, 70. 66 S. Lemaire-Audoire, M. Sauvignac, C. Dupuis and J.-P. Genet, Tetrahedron Lett., 1996, 37, 2003. 67 For selected examples of asymmetric Heck reactions with leading references see (a) A.Pfaltz, Acta. Chem. Scand., 1996, 50, 189; (b) 0. Loiseleut, P. Meier and A. Pfaltz,Angew. Chem., Znt. Ed. Engl., 1996, 35, 200; (c) K. Kondo, M. Sodeoka and M. Shibasaki, J. Org. Chem., 1995,60,4322 (and corrigendum, 1996,61, 1554; (d) Y. Sato, M. Mori and M. Shibasaki, Tetra- hedron Asymm., 1995, 6, 757; (e) s. Nukui, M. Sodeoka, H. Sasai and M. Shibasaki, J. Org. Chem., 1995,60,398. 68 L. F. Tietze and T. Raschke, Synlett, 1995, 597. 69 M. Beller and K. Kuhlein, Synlett, 1995, 441. 70 S. Sengupta and S. Bhattacharyya, Tetrahedron Lett., 1995,36, 4475. 71 D. Brown, R. Grigg, V. Sridharan and V. Tambyr- ajah, Tetrahedron Lett., 1995, 36, 8137. 72 G. Dyker and P. Grundt, Tetrahedron Lett., 1996, 37, 619. 73 M. Hiroshige, J.R. Hauske and P. Zhou, Tetrahedron Lett., 1995, 36, 4567. 74 S. K. Stewart and A. Whiting, Tetrahedron Lett., 1995, 36, 3925. 75 V. Farina, Pure Appl. Chem., 1996,68,73 and the references therein. 76 M. R. Attwood, T. M. Raynham, D. G. Smyth and G. R. Stephenson, Tetrahedron Lett., 1996,37, 2731. 77 R. S. Paley, H. L. Weers and P. Fernandez, Tetra- hedron Lett., 1995,36, 3605. 78 G. T. Crisp and M. G. Gebauer, Tetrahedron Lett., 1995,36,3389. 79 R. Rai, K. B. Aubrecht and D. B. Collum, Tetrahedron Lett., 1995, 36, 3111. 80 M. J. Plunkett and J. A. Ellman, J. Am. Chem. SOC., 1995, 117,3306. 81 F. W. Forman and I. Sucholeiki, J. Org. Chem., 1995, 60, 523. 82 G. P. Roth, V. Farina, L. S. Liebeskind and E. Pefia- Cabrera, Tetrahedron Lett., 1995,36, 2191. 83 (a) D.A. Entwistle, S. I. Jordan, J. Montgomery and G. Pattenden, J. Chem. Soc., Perkin Trans. 1, 1996, 1315; (b) R. J. Boyce and G. Pattenden, Tetrahedron Lett., 1996, 37, 3501. 1991, 63, 419; (h) A. R. Martin and Y. Yang,Acta Chem. Scand., 1993,47, 221. 85 G. M. Farinola, V. Fiandanese, L. Mazzone and F. Naso, J. Chem. Soc., Chem. Commun., 1995, 2523. 86 M. S. Passafaro and B. A. Keay, Tetrahedron Lett., 1996, 37, 429. 87 J. A. Soderquist, G. Leon, J. C. Colberg and I. Martinez, Tetrahedron Lett., 36, 3119. 88 J.-P. GenGt, A. Linquist, E. Blart, V. Mouriks and M. Sauvignac, Tetrahedron Lett., 1995, 36, 1443. 89 M. Beller, H. Fischer, W. A. Herrmann, K. Ofele and C. Brossmer,Angew. Chem., Int. Ed, Engl., 1995,34, 1848. 90 H. Zhang and K. S. Chan, Tetrahedron Lett., 1996,37, 1043.91 (a) L. A. Paquette and H.-C. Tsui, Synlett, 1996, 129; (b) L. A. Paquette and S. Bailey,J. 0%. Chem., 1995, 60, 7849; ( c ) L. A. Paquette and S. W. Elmore, J. Org. Chem., 1995, 60, 889; (d) L. A. Paquette, Z. A. Su, S. Bailey and F. Montgomery, J. 0%. Chem., 1995, 60, 897; (e) L. A. Paquette, D. Koh, X. Wang and J. C. Prodger, Tetrahedron Lett., 1995, 36, 673. 92 M. Brands, H. G. Wey, J. Bruckmann, C. Kruger and H. Butenschon, Chem. Eur: J., 1996,2, 182. 93 For a representative example see S. Borrelly and L. A. Paquette, J. Am. Chem. Soc., 1996, 118, 727. 94 P. A. Evans, A. B. Holmes, R. P. McGeary, A. Nadin, K. Russell, P. J. O’Hanlon and N. D. Pearson, J. Chem. Soc., Perkin Trans 1, 1996, 123. 84 For reviews see (a) A. Suzuki, Pure Appl.Chem., Entwistle: Saturated and unsaturated hydrocarbons 5995 Y.-G. Suh, J.-Y. Lee, S.-A. Kim and J.-K. Jung, Synth. Commun., 1996,26, 1675. 96 D. Enders, M. Knopp, J. Runsink and G. Raabe, Angew. Chem., Int. Ed. Engl., 1995,34, 2278. 97 K. Maruoka, S. Saito and H. Yamamoto, J. Am. Chem. SOC., 1995, 117, 1165. 98 E. J. Corey, B. E. Roberts and B. R. Dixon, J. Am. Chem. SOC., 1995, 117, 193. 99 E. J. Corey and R. S. Kania, J. Am. Chem. SOC., 1996, 118, 1229. Tetrahedron Lett., 1995, 36, 803. 36, 6647. 5035. and the references therein. J.Org. Chem., 1995,60, 5093. 941; (b) U. Kazmaier and A. Krebs, Angew. Chem., Int. Ed. Engl., 1995, 34, 2012; (c) U. Kazmaier and S. Maier, J. Chem. SOC., Chem. Commun., 1995, 1991, 100 R. K. Boeckman Jr., M. J. Neeb and M. D.Gaul, 101 D. P. Curran and L. H. Kuo, Tetrahedron Lett., 1995, 102 D. Kim and J. I. Lim, Tetrahedron Lett,, 1995, 36, 103 M. E. Krafft, 0. A. Dasse, S. Jarrett and A. Fievre, 104 (a) U. Kazmaier and S. Maier, Tetrahedron, 1996, 52, 105 U. Nubbemeyer, J. OR. Chem., 1995, 60,3773. 106 M. Sugiura, M. Yanagisawa and T. Nakai, Synlett, 107 M. Sugiura and T. Nakai, Chem. Lett., 1995, 8, 697. 108 H. Bienaymt, Bull. SOC. Chim. FK, 1995, 132, 696. 109 D. P. Dygutsch and P. Eilbracht, Tetrahedron, 1996, 52, 5461. 110 (a) S. D. Rychnovsky and J. L. Lee, J. Org. Chem., 1995, 60,4318; (b) G. W. Daub, M. G. Sanchez, R. A. Cromer and L. L. Gibson, J. Org. Chem., 1982,47, 745. 111 S. Lambrecht, H. J. Schafer, R. Frohlich and M. Grehl, Synlett, 1996, 283. 112 J. Mulzer and B. List, Tetrahedron Lett., 1996, 37, 2403.113 K. Fujii, 0. Hara and Y. Sakagami, Tetrahedron Lett., 1996, 37, 389. 114 M. M. Midland and Y. C. Kwon, Tetrahedron Lett., 1985,26,5013. 115 ( a ) I. Coldham, A. J. Collis, R. J. Mould and R. E. Rathmell, Tetrahedron Lett., 1995, 36, 3557; (b) J. Ahman and P. Somfai, Tetrahedron, 1995, 51, 9747. 116 J. Ahman and P. Somfai, Tetrahedron Lett., 1996, 37, 2495. 117 I. Coldham, A. J. Collis, R. J. Mould and R. E. Rathmell, J. Chem. SOC., Perkin Trans I , 1995, 2739. 118 S. E. Denmark and P. C. Miller, Tetrahedron Lett., 1995,36, 6631. 119 D. Enders, D. Backhaus and J. Runsink, Tetrahedron, 1996,52, 1503. 120 K. Tomooka, Y. Nakamura and T. Nakai, Synlett, 1995, 321. 121 B. M Trost, A. F. Indolese, T. J. J. Muller and B. Treptow, J.Am. Chem. SOC., 1995, 117, 615. 122 I. Marek, D. Beruben and J.-F. Normant, Tetrahedron Lett., 1995, 36, 3695. 123 ( a ) R. H. Grubbs, S. J. Miller and G. C. Fu, Acc. Chem. Res., 1995, 28, 446; (b) H.-G. Schmalz, Angew. Chem., Int, Ed. Engl., 1995, 34, 1833. 124 For selected reactions using Grubbs’ and Schrock’s catalysts see (a) S. F. Martin H.-J. Chen, A. K. 1995,447. Courtney, Y. Liao, M. Patzel, M. N. Ramser and A. S. Wagman, Tetrahedron, 1996, 52, 7251; (b) C. M. Huwe, 0. C. Kiehl and S. Blechert, Synlett, 1996, 65; (c) G. W. Coates and R. H. Grubbs, J. Am. Chem. SOC., 1996, 118,229; ( d ) H. S. Overkleeft and U. K. Pandit, Tetrahedron Lett., 1996, 37, 547; (e) S. Holder and S. Blechert, Synlett, 1996, 505. 125 W. A Nugent, J. Feldman and J.C. Calabrese, J. Am. Chem. SOC., 1995, 117, 8992. 126 K. C. Nicolaou, M. H. D. Postema and C. F. Clair- borne, J. Am. Chem. SOC., 1996, 118, 1565. 127 For an example of a chiral catalyst used in a stereo- regular ring opening polymerisation see R. O’Dell, D. H. McConville, G. H. Hoffmeister and R. R. Schrock, J. Am. Chem. SOC., 1994, 116, 3414. 128 0. Fujimura and R. H. Grubbs, 1. Am. Chem. SOC., 1996, 118, 2499. 129 W. E. Crowe, D. R. Goldberg and Z. J. Zhang, Tetra- hedron Lett., 1996, 37, 2117. 130 W. M. Crowe and D. R. Goldberg, J. Am. Chem. SOC., 1995, 117,5162. 131 M. L. Randall, J. A. Tallarico and M. L. Snapper, J. Am. Chem. SOC., 1995, 117,9610. 132 S.-H. Kim, W. J. Zuercher, N. B. Bowden and R. H. Grubbs, J. 0%. Chem., 1996, 61, 1073. 133 W. M. Ayers, Catalytic Activation of Carbon Dioxide, American Chemical Society, New York, 1988. 134 Y. Huang, X. Meng, Z. Dang, S. Weng and C. Zhang, J. Chem. SOC., Chem. Commun., 1995, 1025. 135 (a) E. Block, 0%. React., 1984,30, 457; (b) See refer- ence 136 and the references therein. 136 B. Chao, K. C. McNulty and Donald C. Dittmer, Tetrahedron Lett., 1995, 36, 7209. 137 (a) D. Guijarro and M. Yus, Tetrahedron Lett., 1994, 35, 2965; (b) S. H. Kim, Z. Jin, S. Ma and P. L. Fuchs, Tetrahedron Lett., 1995, 36, 4013. 138 A. Ricci, E. Blart, M. Comes-Franchini, G. Reginato and P. Zani, Pure Appl. Chem., 1996, 68, 679. 139 K. Mikami, Pure Appl. Chem., 1996, 68, 639. 140 N. Kato, H. Okamoto and H. Takeshita, Tetrahedron, 141 Y. Okude, S. Hirano, T. Hiyama and H. Nozaki, 142 N. Kaneta, K. Hikichi, S.-I. Asaka, M. Uemura and 143 ( a ) A. Kasatkin, T. Nakagawa, S. Okamoto and 1996, 52,3921. J. Am. Chem. SOC., 1977, 99, 3179. M. Mori, Chem. Lett., 1995, 1055. F. Sato, J. Am. Chem. SOC., 1995, 117, 3881; (b) Also see reference 144 and the references therein. 437. Synlett, 1996, 521 1783. K. Abiru and M. Watanabe, Bull. Chem. SOC. Jpn., 1995, 68,2043. 148 M. Alami and F. Ferri, Tetrahedron Lett., 1996, 37, 2763. 149 G. B. Jones, R. S. Huber and J. E. Mathews, J. Chem. SOC., Chem. Commun., 1995, 1791. 150 P. A. Wender, S. Beckham and D. L. Mohler, Tetra- hedron Lett., 1995, 36, 209. 144 Y. Toshida, T. Nakagawa and F. Sato, Synlett, 1996, 145 S. Muller, B. Liepold, G. J. Roth and H. J. Bestmann, 146 R. Dizere and P. Savignac, Tetrahedron Lett., 1996,37, 147 S. Akiyama, K. Tajima, S. Nakatsuji, K. Nakashima, 60 Contemporary Organic Synthesis

ISSN:1350-4894    

DOI:10.1039/CO9970400040

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Synthetic developments in host-guest chemistry JUSTIN J. B. PERRY? and JEREMY D. KILBURN Department of Chemistry, University of Southampton, Southampton SO1 7 IBJ, UK ?Current address: Department of Chemistry, University of Durham, Durham DHl 3LE, UK Reviewing the literature published between January and December 1995 Continuing the coverage in Contemporary Organic Synthesis, 1995, 2, 289 1 2 2.1 2.2 2.3 2.4 3 3.1 3.1.1 3.1.2 3.1.3 3.2 3.3 3.4 3.5 4 4.1 4.2 4.3 5 5.1 5.2 6 7 Introduction Crowns, cryptands and podands Crown ethers Azacrown ethers and related compounds Crypt ands Podands Calixarenes Calix[4]arenes Modifications to the lower rim Modifications to the upper rim Calix[4]resorcinarenes and other ‘calix’ tetramers Calix[S]arenes Calix[6]arenes Calix[7]arenes and calix[8]arenes Multiple-calixarene structures Cyclophanes All carbon cyclophanes He t eroat om-con t aining cyclop hanes Cage-type cyclophanes Clefts, bowls and other morphologies Cleft-type receptors Molecular bowls and other receptors Self-assembling receptors References 1 Introduction Nature’s host-guest systems achieve very impressive levels of selectivity and utility.Since the discovery of dibenzo-18-crown-6 and its ability to form stable complexes with alkali metals by Pedersen in 1967,’ the synthesis and testing of the properties of artificial receptors have become regular features in the literature. While, not surprisingly, most emphasis is placed upon the actual recognition properties of these receptors, the development of efficient syntheses is always an important considera- tion.The transfer of a receptor from a figment of its designer’s imagination to reality often involves far from trivial work and so the dissemination of the tricks of the synthetic supramolecular chemist’s trade is a necessary task. The purpose of this article is to review synthetic developments in host-guest chemistry over the period January 1995 to December 1995.2 As before, the review is divided into sections using the conventional categories of receptor type but due to the increasing ‘cross- pollination’ between these subspecies with features of one occurring in another, the categorization can be somewhat arbitrary. 2 Crowns, cryptands and podands Two general reviews have appeared this year dealing with the design and synthesis of macrocyclic structures. One concentrates on the use of Schiff bases as linking moieties,3 and the other on hosts for lanthanides and actinides4 2.1 Crown ethers One of the constant problems in the synthesis of crown ethers and macrocycles in general is the macrocyclization step.One method of obtaining high yields of cyclic oligomers in preference to polymer is to use a template. Tris(2-methoxy- pheny1)bismuthane has been reported to work as both a mild dehydrating agent and a good template in macrocyclic ester ~ynthesis.~ The synthesis of macrocyclic esters has previously been reported to proceed in only low yields (1-30%) using high- dilution condensations of diacid dichlorides and glycols. The bismuthane templated the reaction of dicarboxylic acid anhydride and glycols at higher concentration, giving higher yields of the 1 : 1 adduct Preorganization of reactants is also a common strategy for efficient macrocyclization.Using this idea, Jenneskens and co-workers have reported the formation and isolation of huge cyclic oligomers from an untemplated ester polycondensation in ca. 30% overall yield.6 The reaction of 1,5-bis- (l-hydroxy-3,6,9-trioxanonyl)naphthalene and terephthaloyl chloride gave crownophanes with 30n (n = 1-5) atom perimeters. The authors suggest favourable pre-orientation of the rigid diol as the reason for the relatively high degree of intra- molecular ring closure. If triptycene is used as a structural component of crown ethers, there is the possibility of it acting not only as a rigid spacer but also as a donor for cation- En-interactions with guests.The synthesis of the first triptycenocrown ethers 3 was achieved in a two-step (13-83%). Peny and Kilburn: Synthetic developments in host-guest chemistry 61procedure which comprised condensation of 9,10-bis(chloromethyl)anthracene 1 with poly- ethylene glycols to yield intermediate 9,lO-anthra- cenocrown ethers 2 followed by cycloaddition of benzyne to the anthracene moiety (Scheme l).7 CH2CI 1 y 0Ijb A 2 3 Reagents: (i) HO(CH2CH20),H (n = 5 or 6), KOH, Bu'OH, reflux 6-8 h; (ii) @H2NC6H4COOH, (CH3)2CHCH2CH20N0, CH2CI2, reflux 6 h Scheme 1 Crown-type cavities can be prepared by metal- assisted organization of linear oligo(oxyethy1ene). Both tropolonoid moieties8 and P-diketones' have been used at the terminal, metal-binding ends of the prehost. Two groups have reported the use of double or quadruple cycloadditions as a method of macro- cyclization of crown ethers.Thus the reactions of alkyne dipolarophiles with azides have been described," and Kim and co-workers have reacted dihydroximoyl chlorides prepared from dialdehydes with divinyl ethers or acrylates." When using tetraethylene glycol diacrylate as dipolarophile, a para-related bifunctional dipole provided the 12 + 21 cycloadduct 4, and a meta-related bifunctional dipole yielded the [1+ 11 cycloadduct 5 (Scheme 2). Chiral crown ethers are of interest because of their potential as enantioselective hosts. An optically active crown ether that relies solely on cis- cyclohexane-1,2-diol for its chirality has been reported.I2 This diol was desymmetrized by conversion of one of the hydroxy groups to a benzyloxy group and the resulting racemate 6 was enantioselectively acylated by lipase YS (from Pseudomonas fluorescens) with vinyl acetate as acylating agent.The two products of this reaction could be separated by chromatography providing easy access to large quantities of both 2-benzyloxy- cyclohexanol enantiomers 7 and 8 and, after several steps, both enantiomers of the azophenolic crown ether e.g. 9 (Scheme 3). Chiral crown ethers have also been prepared using D-glucose as structural units, for instance the bis-gluco-crown ether 10 (Scheme 4).13 CHO CIvNOH 0 (i) 96%- +J ononono i (iii) 27% 6 4 (ii) 87% CIANO, CHO ono-ono 5 CHO NOH 4 5 Reagents: (i) NH20H*HCI; (ii) NCS; (iii) Et3N, EtOH (10 mM) Scheme 2 6 7 '=yiii) (ii) 1 ArLN5 N 9 Ar = 2,&C&(N02)2 Reagents: (i) lipase YS, CH -CHOAc; (ii) mnc HCI, MeOH; (iii) MeSO20CH2CH20CH2&I2OSO2Me, NaH Scheme 3 62 Contemporary Organic Synthesis10 R = OCH2Ph Scheme 4 The palladium-catalysed Heck arylation of alkenes has proved a valuble synthetic method for the elaboration of moieties on the periphery of a crown ether though removal of homogeneous catalyst can some times be problematic.The use of polymeric palladium catalysts however has been reported to effect the vinylation of 4'-iodobenzo- crown ethers in good yields (45-85%) with the catalyst being completely removed by fi1trati0n.l~ 2.2 hacrown ethers and related compounds There are several common, general procedures for the synthesis of azacrowns and the use of tosylated synthons in azacrown construction is a popular one.Such tosylated synthons played a pivotal role in the first unequivocal syntheses of 1- and 8-N-mono- substituted 1,4,8,12-tetraazacyclopentadecane which has been reported by Granier and Guilard.'' Gu and Bowman-James have used a tosylated synthon strategy to prepare a series of new macrocycles containing four pendant arms and ranging in size from 18- to 24-membered rings.I6 Their strategy, which also entails the [1+ 11 addition of two different halves, enables the construction of symmetrically and asymmetrically N-substituted polyazaoxamacrocycles. Wu and co-workers have reported the use of 1,3-dichloropropan-2-ol with bis- N-tosylamides with sodium ethoxide in ethanol acting as base, as a facile method for the prepara- tion of hydroxyl-N-tosylcyclams in moderate yields (31-57%).'7 New conditions for rapid and high- yielding detosylation of linear and macrocyclic tosylamides have been described by Lazar.'* The use of 50% concentrated sulfuric acid solution at 170-180 "C produced detosylated product in only five to eight minutes. This compares favourably with the common conditions involving the use of 10% sulfuric acid solutions at 100-110 "C which require reaction times of the order of days.Picard and co-workers have described methods for construction of polyoxa- and polyaza- macrocycles via tetralactam formation using stepwise amide bond-forming reactions" while Reinhoudt and co-workers have used Schiff-base formation for the synthesis of host 13 which combines a crown ether-like interior with linking salen units.20 Cyclization of the dialdehyde 11 with diamine 12 in the presence of barium cations as -X N' \ / X 13 (ca.70%) X = 1,2-phenyIene = CH2CH2 = transcyclohexa-l,2-diyl Scheme 5 templates gave 13 in approximately 70% yield (Scheme 5). The syntheses of the two nonacyclic structures 14 and 15 were reported by Dale and co-workers." These interesting structures were formed in one-pot procedures, 14 by reaction of an aqueous solutions of pentane-1,3,5-triamine with formaldehyde, and 15 by reaction of 1 ,l-bis(2-aminoethyl)hydrazine and formaldehyde under similar conditions followed by reflux in dioxane. Macrocyclic 14 precipitated from the reaction mixture in 100% yield (Scheme 6).(i) HCHO-H20 (ii) for X = N, reflux in dioxane LPN-NJ LLJ 14X=CH 15X=N Scheme 6 A bimolecular cyclization process using nucleo- philic substitution of an aryl fluoride has been used to form naphtho- and biaryl-fused 1,g-diaza- 14-crown-4 macrocycles.22 The ability of fluoride to direct ortho-metallation enabled preparation of, for instance, 1,5-difluoronaphthalene-2-carboxylic acid 17 from 1,5-difluoronaphthalene 16 in 74% yield. Acid 17 was then converted to hydroxyamide 18 and bimolecular cyclization with NaH in DMF at Perry and Kilburn: Synthetic developments in host-guest chemistry 63q-+ c 0 3+ co 3 0 (iii) F OH 18 (57%) F 19 (76%) Reagents: (i) (a) TMEDA, Bu'Li, -78 "C; (b) solid COP, Et20, -78 "C; (ii) (a) SOC12, reflux; (b) H2NCH2CH20H, CH2CI2, NaOH, H20; (iii) NaH, DMF Scheme 7 ambient temperature provided the bis-naphtho- fused macrocycle 19 (Scheme 7) in good yield.An interesting series of macrocycles which provide a rigid ring of oxygen- and nitrogen- containing functionality analogous to azacrowns are the cyclic oliogosaccharides 22 which were constructed from two a,a'-trehalose units connected by thiourea bridges.23 These macrocycles were assembled by reaction of 6,6'-diamino derivative of a,a'-trehalose 20 with a 6,6'-diisothiocyanate derivative 21 in 40-65% yield (Scheme 8). Fuchs and co-workers have built receptors using the 1,3,5,7-tetraoxadecalin diacetal The synthesis begins with the condensation of rac- or D-threitol 23 with hydroxyacetalaldehyde, and the conversion of the bis(hydroxymethy1) derivative 24 so produced to the diamine 25.This precursor was then used to form macrocyclic dilactams 26 using tri- and tetra-glycolic acid dichloride, and diaza- crown 27 and cryptand 28 using respectively one and two equivalents of triethyleneglycol bis(trifluor0- methanesulfonate) (Scheme 9). has been shown to be an effective method for the synthesis of a variety of nitrogen-containing macro cycle^.^^ Electroreduction or chemical reduction with zinc has produced various ring sizes of P74-diazacrown ethers from bis(iminoethers)(e.g. 29 +30), macrocyclic bislactones from bis( imino- esters) (e.g. 31 +32) and macrocyclic bislactams from bis(iminoamides) (e.g. 33+34) in mostly good yields (26-90%) (Scheme 10). photocyclization reactions of N-[(a-trimethylsilyl- methoxy)polyoxalkyl]phthalimides 35 gave azacrown The intramolecular coupling of aromatic diimines Yoon and co-workers have shown that N H2 + Ncs I 22 (40-65%) R = Ac or TMS R' = H, Ac or TMS Scheme 8 roH 24 (98%) 25 (49%) 23 (iii) (iv) fR,OMs 1 OMS - f OMS 26a n = 1 (26%) 26b n = 2 (41%) 28 (1 7%) 27 (17%) Reagents: (i) HOCH2CH0, HCI 1 M, 15 min; (ii) (a) CH2SO,CI, NEt,, DMF; (b) DMF, NaN3; (c) MeOH, Pd/C, H2; (iii) DMF, K2CO3, 90 OC, 7 d; (iv) CH3CN, K2CO3,80 'C, 5 d; (v) CH3CN, KzcO3, 80 *C Scheme 9 64 Contemporary Organic Synthesis2 Ph+N *UX R Y 29 R = H,,Y = H2, X = O 30 R = H, Y = H2, X = 0, (90%) 31 R=Pt',Y=O,X=O 33 R = H, Y = 0, X = NH 32 R = Pr', Y = 0, X = 0, (53%) 34 R = H, Y = 0, X = NH, (41%) Scheme 10 35 hv MeOH, 4-6 h n = 1 to 5 (50-99%) 37 n = l t o 5 Scheme 11 ethers.26 Irradiation of compounds 35 in methanol solution (3-9 mM) by Pyrex glass-filtered light for up to six hours provided cyclized products 36 in 50-99% yield.Compounds 36 underwent slow dehydration in solution to generate unsaturated azacrown ethers 37 (Scheme 11). Black and co-workers have proposed that 3,7-diazabicyclo[3.3.l]nonan-9-one or 'bispidinone' may be useful as structural elements of receptor^.^' Symmetrically N-substituted bispidinones can be readily prepared by Mannich condensations between a propanone, formaldehyde and primary amine. The initial substituents on the bispidinone can be controlled by varying the amine or propanone employed. For instance, a reaction between ketone 38, diamine 39 and formaldehyde gave the macrocycle 40 in 48% yield (Scheme 12).30 + 6 ) 0 39 Scheme 12 9 40 (48%) Linked macrocycles that bind two cations in close proximity provide the potential for generating unusual physical and chemical properties. Lindoy and co-workers have prepared spiro-linked receptors using a pentaerythrityl core.2* The reaction of a salicylaldehyde derivative 41 with pentaerythrityl bromide 42 produced linking unit 43. Schiff base formation followed by reduction yielded two-ring receptors such as 44a-c (Scheme 13). But ' o \ ^ O B d e ' ' b B u t OH KZco3 \ / 0 0 41 DMF. 120 O C - + Br Kr Br 0 0' 43 (92%) .~ 42 /HzNXNH*, NaBH4 44a X = CH2CH2 (39%) 44c X = CH2CH2NH6H2CH2 (60%) 44b X = CH2CH2CH (54%) Scheme 13 While the complexation properties of polyaza- macrocycles are fundamentally determined by ring size, N-functionalization can be used to 'tune' selectivity.Sherry has reported the addition of phosphonic and phosphinic moieties in efficient syntheses of 1,4,7-triazacyclononane-tris( met hylene- phosphonic acid) and -tris(methylenephosphinic acid) ester derivatives from the unsubstituted azac~own.*~ Direct attachment of aromatic rings to the nitrogens of azacrowns using high pressure SNAr reactions has been described.3o The synthesis of azacrown hosts with a pattern of N-functionalization is commonly achieved by the selective addition of N-substitution of pre-formed macrocycles. The metal complexes of 174,7,10-tetraazacyclododecanes and its derivatives are widely used in diagnostic and therapeutic medicine and so the regioselective N-functionalization of the parent azacrown has received some attention.Kovacs and Sherry have reported a general synthesis of 1,7-disubstituted derivatives which relies on the regiospecific addition of chloroformates in acid solution to give 1,7- diprotected compounds (yields ranging from 66 to 98%).3' The same authors have reported a general synthesis of mono- and di-substituted 1,4,7-triaza- Perry and Kilbum: Synthetic developments in host-guest chemistry 65cycl~nonanes.~~ Their method relies on the fact that the unsubstituted macrocycle reacts with exactly two equivalents of Boc-ON or Z-ON in anhydrous chloroform to form the appropriate disubstituted derivatives in over 90% yields. The reaction of l74,7,10-tetraazacyclododecane with methyl- trichlorosilane was reported to produce a hypervalent silicon bonded to the four azacrown nitrogens and its methyl group.'" This structure was then used in high-yielding synthesis of N-mono- alkylated and N',N7-symmetrically and dissymmetrically dialkylated compounds (yields 6045%).The regioselective preparation of 7-substi tut ed 1,4,7,10- tet raazacyclododecane- 1-carbaldehydes 47 (in yields 67-86%) has been described, and used ring opening of orthoamide protected derivatives 46 prepared by reaction of the mono-N-substituted compound 45 with dimethyl- formamide diethyl acetal (Scheme 14)." 45 46 (ca. 100%) 47 (6746%) Reagents: (i) Me2NCH(0Et)*, C6H6, reflux 2-4 h; (ii) EtOH-H20 or THF-H20 Scheme 14 Mono-N-alkylation and -N-acylation of two tetraazacrowns has also been achieved in 35-90% yield by reaction of either their chromium or molybdenum tricarbonyl complexes with enolisable aldehydes or acid chloride^.,^ The conversion of azacrowns 174,7,10-tetraaza- cyclododecane 48 and 1,4,8,1 l-tetraazacyclotetra- decane 50 to macrocyclic diureas has been reported.'6 The azacrown, selenium and LiHBEt, were suspended in THF, in an atmosphere first of carbon monoxide then of oxygen.Thus 48 produced 49 in 85% yield and 50 gave the two isomers 51 and 52 in 66% and 22% respectively (Scheme 15). 48 n = l 50 n = 2 Scheme 15 49 n = 1 (85%) 51 n = 2 (6670) 52 (22%) Thiacrown ethers are an important variation on crown ethers due to the 'soft' nature of their ligating sites. Troyansky and colleagues have reported a stereoselective free radical cycloaddition-macro- cyclization which enables the facile synthesis of trans-cyclohexane-fused 12-membered crown thioether~.,~ Their method involved the one-step cycloaddition of a,co-dithiols to alkynes initiated by a tripropylborane-oxygen system.Using the trans- dithiol53, cycloaddition of 54 afforded a mixture of stereoisomeric trans-cyclohexane-fused crown thialactones with a significant predominance of the isomer 55 shown (3.1 : 1, overall yield 28%) (Scheme 16). In contrast use of the cis-dithiol resulted in equal quantities of the two possible stereoisomers in 21% yield. 0 s-7 + =-I OMe 54 Scheme 16 a- 0 55 (28%) Gleiter and co-workers have produced a range of strained, conjugated thiacrowns.38 Reacting 2,7-dimethyl-2,7-dichloroocta-3,5-diyne 56 with aliphatic and or,to-dithiols gives 1 : 1 or 2: 2 products with the proportions of each macrocycle dependent on the chain length of the dithiol.The reaction is proposed to occur via a S', reaction with a reactive [4]cumulene as an intermediate. Thus hexane- 1,6-dithiol 57 formed the [1+ 13 product 58, while propane-173-dithiol 59 gave the [2+2] and [1+ 11 products 60 and 61 (Scheme 17). Aromatic dithiols yielded solely a [2 + 21 product. 9-t + SH A A X SH CI 56 57 X = [CH2]4 59 X = CH2 I Scheme 17 58 X = [CH& (60%) 61 X = CH2 (42%) Another heteroatom used in the construction of crown ether analogues is phosphorus and Majoral and co-workers have extended their work on the synthesis of phosphorus-containing macro cycle^^^ and multimacr~cycles~~ by the reaction of 66 Contemporary Organic Synthesisfunctionalized phosphodihydrazides with dialdehydes.Novel diphosphazacrown 65 and phosphacrown 66 have been prepared from hexachlorocyclotriphosphazatriene 62 after reaction with oligo(ethy1ene glycols) (producing 63 and 64) and subsequent reaction with phenol or 2-naphthol (sodium hydride acting as base in both reactions) (Scheme 18).41 NH TsN U 67 68 R = BOC (75-80%) (ii) n 0 0 n 0 0 CI CI cl\\p/N+CI Nxp5N 1 CI' b II I (i) 62 II I R 63 R = CI N, ,,N R - ' " 4 R R/p*N/p, R 64 R=CI (ii) 6 6 5 R = OAr (ii) 6 5 6 R = OAr 71 (81%) 70 (55%) Reagents: (i) HO[CH2CH20I5H, NaH; (ii) NaH, ArOH Scheme 18 Finally, silicon-containing macrocycles have been prepared using a catalytic amount of bis(tert-butyl isocyanide)palladium(O) to induce oligomerization of 1.1,2,2-tetramethy1-1,2-disilacyclopentane through Si-Si bond metathesis.Cyclic oligomers up to the 40-membered octamer were prepared using this meth~dology.~~ 2.3 Cryptands Guilard and co-workers have reported the synthesis of the tricyclic host molecule 71.43 The tris-protected azacrown 67 was reacted with a dibromo-aromatic linker to form 68. After the removal of the Boc protection, the bimacrocycle 69 was reacted with an aromatic diacid dichloride at high dilution. The amide bonds in the resulting compound 70 were then reduced with diborane to yield host 71 (Scheme 19). A similar reaction sequence produced the In-phenylene-linked variant. Due to the multi-bridged nature of cryptands, stepwise syntheses of this type of compound can become a lengthy process. Clark and co-workers have described a remarkable one step condensation, requiring neither high dilution conditions nor a metal template, which assembled six fragments in a tetrapode capping reaction.44 Two moles of tetraaldehyde 72 and four moles of triamine 73 formed eight imine links which, after reduction of these bonds by sodium borohydride, gave the cryptands 74 in 32 to 50% yield (Scheme 20).Supercryptands have been defined as spherical macrotricyclic ligands with at least ten ligating atoms. Krakowiak and Bradshaw have reported an efficient six-step synthesis of these relatively Reagents: (i) pBrCH2C6H4CH2Br, K2CO3, CH3CN, reflux; ii) TFA-H20; (iii) pCICOC6H4COCI, NEt3, THF; (iv) LiAIH4 Scheme 19 72 R = H, CH3, CI, OCH3 (32-96%) hH2 73 f;Hp (2 equiv.) (ii) NaBH,.CH30H NH-NH-NH 74 R = H, CH3, CI, OCH3 (32450%) Scheme 20 Peny and Kilburn: Synthetic developments in host-guest chemistry 67inaccessible hosts starting from toluene-p-sulfon- a ~ l l i d e . ~ ~ The appropriate diamino ether 76 was treated with bis(to1uene-p-sulfonate) 75 (2.1 equiv.) to give the cryptand 77. The toluene-p-sulfonyl protecting groups were removed using LiAlH4, and the resulting cryptand 78 reacted with an excess of the appropriate diiodo compounds 79 to form supercryptands 80 in yields of 30 to 40% (Scheme 21). -u H2N+0TNH21 76 79 C3H&N. Na2C03 or K2C03 78n=1 b 80 m = 2-3 (33-37%) Scheme 21 Bradshaw and co-workers have also published a paper detailing a one-step method for the synthesis of new phenol-containing cryptands and crypto- hemispherands by coupling N , N'-bis(methoxy- methy1)diazacrowns with the appropriate bis- and tris-phen~ls,~~ using a Mannich-type reaction.Reaction of 81 with trisphenol 82, for instance, gave cryptohemispherand 83 in 61% yield (Scheme 22). A rigid cryptand which incorporates alkynes and thus offers the possibility of establishing 71-71 interactions with potential guests, has been described by Gleiter.47 The reaction of 1,4-dibromo- but-2-yne 84 with diazacyclodecadiyne 85 resulted in bicyclic triyne 86 (10%) and macrotricycle 87 (6%) (Scheme 23). 2.4 Podands A macrocyclic structure is not necessarily a prerequisite for host properties as the required degree of preorganization can be obtained from an acyclic podand morphology. De Sousa and Hancock have shown that cyclohexene oxide 88 reacted diastereoselectively with polyamines to give good 81 82 Scheme 22 Br yBr + - - HN NH 85 - - 83 (69?!) 87 (6%) Scheme 23 yields of podands such as 89, 90 and 91 (Scheme 24).48 Rodriguez-Franco and colleagues have synthesized podands 94 and 95 which include 1,3-bis( 1H-pyrazol-1-y1)propane The key step in their synthesis was a regioselective lipase- catalysed transesterification of the dipyrazolic tetraethyl ester 92 with monomethyl ether poly- ethylene glycols 93 (Scheme 25).Hovorka and co-workers have reported that binapthols 96 and 98 reacted with poly(ethy1ene glycols) using chlorinated silica gel as a Lewis acid to afford podands 97 and 99 respectively in good to excellent yields (37-99%) (Scheme 26)" Several tripodal receptors have been described. Three squarimide moieties supported by a triaryl benzene spacer were used to provide a receptor for polyalkylammonium salts," and Moran and co-workers have reported tripodal receptors comprising three chromenone fragments on a cyclo- hexane supportS2 and three ureas or chromenone units arranged on tri~(2-aminocthyl)amine.~~ Poly- podands comprising a cyclophosphazenic ring and six N , N'-bis[oligo(oxyalkylene)] amine chains have also been ~ynthesized.'~ 68 Contemporary Oganic Synthesisn 3 Calixarenes EtOH, heat 89 only meso form observed (80%) 91 only diastereoisomer (57%) observed *"'OH HO 90 only diastereoisomer observed (83%) Scheme 24 92 93 n = 0 to 3 Et02C M M Lipase 94 R = Et, R'= vke + 95 R = R'= v ? n n n = 0 to 3 (1 8-37%) n = 0 to 3 (4-27%0) Scheme 25 98 R' = CHZOH, R2 = C(CH3)s R2 = C(CH3)3(37-88%) ' Scheme 26 3.1 Calix[4]arenes Bohmer has published a very comprehensive review of calixarene chemistry." Takeshita and Shinkai have reviewed recent topics on functionalization and recognition ability of calixareness6 and a review has also been published on calixcrowns and related m01ecules.~' 3.1.1 Modifications to the lower rim Modifications to the phenolic hydroxy groups of calixarenes by alkylation are well known.One drawback to this functionalization is that it removes the intramolecular hydrogen bonding which favours the cone conformation and as a result tetraalkylated calix[4]arenes tend to be formed as a mix of different conformers. However, Bitter and co-workers have described a set of liquid-liquid phase-transfer catalysis conditions which afford calix[4]arene tetraethers in the cone conformation in good yield.58 Gutsche has also published a full paper describing selective arylmethylation, arylmethenylation and aroylation of mono- and tetra-p-cyanomet hyl~alix[4]arene.~~ the lower rim of the calixarene.Examples of this reported include a 1,3 distal link consisting of a 1,8-bis(ethyleneoxy)anthraquinone bridge,6o and a 1,3 distal link containing a bithiophene (which enabled the manufacture of a polythiophene funct ionalized with calk[ 41 arene ionop hores) .61 Shinkai and co-workers have synthesized a chromogenic Na+ selective ionophore from a 1,3 distal crown strapped calix[4]arene Alkylation of one of the remaining hydroxy groups to form 101 was followed by the conversion of the last phenol unit of the calix[4]arene to a quinone, making 102.Finally condensation of 102 with 2,4-dinitrophenyl- hydrazine produced the receptor 103 with a remarkably high selectivity for Na' over K+ ions (Scheme 27). De Mendoza and colleagues found that the 1,3-bis(trifluoromethanesulfonate) and 1,3-bis- (methanesulfonate) derivatives of calix[4]arene underwent a facile intermolecular rearrangement of sulfonyl groups in the presence of both a palladium catalyst and chloride anion, leading to 1 : 1 mixtures of the mono- and tri-substituted derivatives that cannot be prepared directly from calix[4]arene by sulfonylation reactions.63 Employment of the Newman-Kwart method to replace the phenolic hydroxy groups of calixarenes with thiol groups has been used by Hosseini and co-workers in the synthesis of a 1,3-dihydroxy- 2,4-disulfonylcalix[4]areneh" and Gutsche and co-workers have published a detailed account of the use of the Newman-Kwart method to produce tetra- thiol, trithiol, 1,3-dithiol and the monothiol deriva- tives of ~alix[4]arene.~~ The attachment of phosphorus to the lower rim gives a calixarene novel properties and the synthesis Alkylation can also be used to put a strap across Peny and Kilburn: Synthetic developments in host-guest chemistry 69L o J Lo 100 \" N I 103a R = Et (67%) 103b R = CH2Ph (39%) (iii) - 101a R = Et (65%) 101 b R = CH2Ph (46%) 102a R = Et (63%) 102b R = CH2Ph (80%) Reagents: (i) RBr (1 equiv.), NaH, DMF, 0 OC, 4 h; (ii) TI(N03)3.3H20, MeOH, EtOH, CHCI,, 10 min; (iii) 2,4-(N02)2C6H3NHNH2, H2S04, EtOH, CHCi3, rt, 2 h Scheme 27 of calixarene phosphine oxides has been reported.66 Reduction of the known ethyl acetates 104 to primary alcohols 105, conversion to toluene-p-sulfo- nates 106, introduction of diphenylphosphino residues through reaction with sodium diphenyl- phosphide and oxidation of the resulting phosphines 107 using dimethyldioxirane or hydrogen peroxide in acetone produced phosphine oxides 108 (Scheme 28).These compounds were shown to be highly efficient in extraction of actinides from simulated nuclear waste. @ /O 104 OAOEt \X 105 X =OH R = Bu'or H, n=4, 6 or8 Reagents: (i) DIBAL in toluene; (ii)TsCl in pyndine; (iii) NaPPh2 in dioxane-THF; (IV) dimethyldioxirane or H202 in acetone Scheme 28 Phosphine groups have been attached indirectly to the lower rim so that the calixarene provides a scaffold for novel transition metal ~ a t a l y s t s .~ ~ ~ ~ ~ The reaction of the lower rim hydroxy groups with various chlorophosphorinanones has also been used to produce a bifunctional ligand for metal coordina- tiod9 and metals such as molybdenum have also been connected directly to the hydroxy groups of the lower rim.7o Other phosphorus-containing calix- arenes formed by reaction of the calixarene hydroxy groups which have been reported this year include monofluorophosphites and mono- and bis- difluoroph~sphites.~~ 3.1.2 Modifications to the upper rim One method of obtaining a particular pattern of substituents on the upper rim of a calixarene is by condensation of the appropriate calixarene fragments.No and co-workers have reported a synthesis of calixarenes with substituents in an ABAC att tern.^' This was achieved by a (3 + l} condensation reaction between a trimer of para- substituted phenol 109 (the ABA segment) and a 2,6-bishydroxymethylated para-substituted phenol 110 (the C fragment) to give calix[4]arenes 111 in 30-40% yield (Scheme 29). R' R2 R' R3 110 O9 1 TiCl.,, dioxane reflux 111 (3040%) Scheme 29 Sartori and co-workers have synthesized the o-(tert-buty1)phenol-derived calixarene 113, which has the hydroxyls arranged in an extraannular fashion, by condensation of 2,2'-dihydroxy-3,3'-di- tert-butyldiphenylmethane 112 with formaldehyde using BF3 - Et20 catalysis (Scheme 30).72 Kanamathareddy and Gutsche have reported the syntheses of a variety of calix[4]arenes carrying two types of functional groups on the upper rim.73 This pattern of functionality was achieved by selective aroylation of a tetraol followed by removal of tert- butyl groupspara to the phenol groups and subse- quent use of the quinomethane procedure to effect substitution.The same publication described the use 70 Contemporary Organic SynthesisHO 112 (70%) Reagents: (i)(a) EtMgBr-Et20; (b) CH20-toluene, 80 OC, 10 h; (ii) CH20-BF3*Et20-H2CI2, I (ii) 25 OC, 3 h 113 (30%) Scheme 30 The cross coupling of calix[4]arene dialdehydes 117 using low-valent titanium produced highly distorted calixarenes in approximately 30% yield bridged by either a (CHOH);? unit (as in 118) or a CH=CH unit (as in 119) depending on the reaction time (Scheme 32).of intramolecular oxidative coupling of prop-2-ynyl subst ituents to yield bridged calixarenes.'? Pochini and co-workers have also described the synthesis of calix[4]arenes diametrically bridged with a hexa- 2,4-diynyl The selective chloromethylation of a diol dimethoxy calix[4]arene has been reported and involved nucleophilic substitution with, for instance, alcohols or thiols, to give calixarenes with ether and thioether moieties para to their lower-rim hydroxy Scheme 32 119 (ca30%) R = CH2CH20CH2CH3 R' = H or CHO R2 = H or CHO groups. Attachment of a hydrophilic cyclodextrinto the calix[4]arene's upper rim has been used to produce a water-soluble ~alix[4]arene.~~ Kubo and colleagues have introduced a chromogenic function to the upper rim of a ~alix[4]arene,~~ by effecting a condensation of aniline derivative 115 with calix- crown 114 in an alkaline solution of 1,8-diazo- bicyclo[5.4.0]undecene (DBU) and potassium hexacyanoferrate, to give receptor 116 in 34% yield, capable of recognition of butylamines (Scheme 31). Pochini and co-workers have reported the regio- selective formylation of tetraalkoxycalix[4]arenes in the cone formation, including conditions for mono-, di-, tri- and tetra-f~rrnylation.~~ The 1,3-dialdehyde was used in the preparation of highly distorted cone calix[4]arenes using a McMurry coupling reaction.79 The persubstitution of the meta-position of calix- arenes has the effect of radically reducing their conformational freedom.Mascal and co-workers perbrominated the meta-position of calix[4]- and calix[8]-hydroquinone using a variety of conditions for electrophilic bromination in 32-67% yields." Reinhoudt and co-workers have monosubstituted the meta-position of mono( acetamido)calix[4]arenes to give inherently chiral calix[4]arenes. Thus, bromination or nitration selectively introduced a substituent adjacent to the acetamido moiety in 58-98% yield.*' Chiral calix[4]arenes were also produced by dibromination or dinitration of bis(acetamido)calix[4]arenes in 10 and 53% yields respectively. 3.1.3 Calix [4] resorcinarenes and other 'calix' Calix[4]resorcinarenes are readily synthesized by acid-catalysed cyclocondensation of resorcinols with aliphatic or aromatic aldehydes. However the presence of an electron-withdrawing group on the 2-position of the resorcinol deactivates it towards electrophilic attack. Konishi and Iwasaki have discovered that deactivated 2-butyrylresorcinol 120 formed a calix[4]resorcinarene 121 with para- formaldehyde under basic conditions in 58% yield R tetramers X X 114 115 11 6 (34%) CH3 N o (Scheme 33).82 X = 8-u non:g " R = { - N O 0 There are several positions on the calix[4]- resorcinarene skeleton where derivatization is possible.The hydroxy groups can be used to add further functionality and have been selectively Scheme 31 Peny and Kilbum: Synthetic developments in host-guest chemistry 71121 (58%) Scheme 33 acylated to give a tetrasubstituted compound (yields 30-50%).83 All eight phenolic hydroxy groups have been used to form four dioxaphosphocine rings, the different diastereoisomers of which were separated by chromatography (total isolated yields 50-80%).84 reaction to add aza-18-crown-6 to the 2-position to form calix-azacrowns in 99% yield.85 The use of the Mannich reaction to effect a regio- and diastereo- selective addition of primary amines to calix[4]- resorcinarene (e.g.122 + 123) has also been widely reported (Scheme 34),’”8’ and using a-amino alcohols rather than primary amines led to the formation of 173-oxazolidine moieties rather than 1,3-oxazine rings.” Linnane and Shinkai have used a Mannich \ R. RNH2,CHzO EtOH-toluene \ reflux ’R 123a R1 = C1 H23 R = (R)-(+)- 1-phenylethylamine (87%) R = CH2CH2CH2CH3 (89%) 123b R1 = C11H23 Scheme 34 Novel lantern-shaped molecules with large cavities and shielded intra-cavity functionality were synthesized by Okazaki and colleagues by combining a rn-terphenyl fragment and a calix[4]resorcin- arene.90 The link was via a substituted benzyloxy ether appended to the 2-position of the resorcinol units. Another position for calix[4]resorcinarene elaboration is at the methine linker between the aryl units.Reinhoudt and co-workers reported the synthesis of calix[4jresorcinarenes which self- assemble on a gold surface via four bis(decy1 sulfide) chains attached to the methine linker.” Schilling and co-workers have reported the synthesis of persubstituted calix[n]arenes 125 comprising 4 to 13 aryl units by acid-catalysed reaction of 3,4,5-trimethoxytoluene 124 with para- formaldehyde (Scheme 35).92 Separation of the different oligomers was accomplished by chroma- tography.The substitution of calix[n]arenes 125 was adopted to force what the authors term an ’inverse’ conformational behaviour wherein the alkyl groups formed the base of the calix shape rather than the rim. CH20 HPSO~-THF, 24 h 125b-j, n = 5-13 (1- 2.6% yield each) Scheme 35 Other aromatic units have been used to construct calix-type structures. Syntheses of four isomeric calix[4]naphthalenes from 1-naphthol have been described providing four novel supramolecular building blocks with different cavity morph~logies.~’ The monosodium salt of 4-amino-5-hydroxynaphtha- lene-2,7-disulfonic acid has been used to form a cyclic tetramer which was water-soluble and provided a hydrophobic binding cavity able to bind polyaromatic hydrocarbon^.^^ Black and co-workers have reported the formation of calix[4]indoles 128 in 25% yield from the reaction of the 7-hydroxy- methylindole 126 in hydrochloric acid as the minor component to a trimer 127 (Scheme 36).95 prepared by the reaction of dibromo compound 129 with triazinone 130 (Scheme 37) and its conforma- tional behaviour compared to that of ~alix[4]arene.~~ An analogue of calix[4]arene7 131, has been 3.2 Calix [S] arenes Gutsche and co-workers have synthesized a variety of ethers and esters of p-tert-buty1calix[5]arene7 and assessed their conformational behaviour, deter- 72 Contemporary Organic SynthesisBut CH30 127 n= 1 (60%) 128 n = 2 (25%) Scheme 36 /-Br + 129 + NaH-THF 130 -A 131 (54%) Bu ' 132a n=2 133a n =2 (63%) 133b n = 3 (52%) But r I 1 .But OCH3 134a m = 1 (48%) 134b m = 2 (61%) -But Scheme 37 Scheme 38 mining those derivatives with limited or no confor- mational m~bility.~' Beer and colleagues have reported the preparation of a 1,3,4-trisferrocenoyl ester of p-tert-b~tylcalix[5]arene~~ which exhibited an interesting change in redox activity on addition of potential guests which may reflect host-guest association.In an extension to their work on calix[4]arenes, Biali and co-workers reported a method for intra- annular incorporation of an amino group, or an azo group, in a calix[5]arene skeleton by reaction of amino nucleophiles with the monospirodienone derivatives 133a of ~alix[5]arene.~~ The mono- spirodienones 133a and 133b were formed by the reaction of the appropriate calixarene 132a or 132b with a mild oxidizing agent, Me3N+PhBr3-.In addition, both the monospirodienone derivatives 133a and 133b underwent an acid-catalysed rearrangement leading to calixarene systems 134a and 134b incorporating a xanthene unit (Scheme 38).w has followed developments in calix[4]arene chemistry. Bohmer and co-workers have reported the synthesis of a bis(arylazo)calix[5]arene crown in 36% yield from the starting unsubstituted calix- Derivatization of the upper rim of calix[5]arenes [5]a~ene.~'' The calix[5]arene receptor 140 which bears two benzoic acid moieties was shown to bind imidazolium ions. lo' The initial calix[5]arene super- structure with two types of upper-rim functionality was synthesized by a [1+ 11 cyclization of 135 and 136.After removal of the tert-butyl groups under retro-Friedel-Crafts conditions from 137, protection of its hydroxy groups and bromination, the calix- [5]arene 138 underwent a Suzuki coupling reaction to produce 139. Removal of protecting ether and ester functionality yielded the target molecule 140 (Scheme 39). novel ethylene-bridged analogues of calix[5]- and calix[6]-arene resulting from the base-catalysed condensation of suitable tetrahydroxyphenyl fragments . lo2 Yamato and co-workers reported the synthesis of 3.3 Calix[6]arenes The larger cavity dimensions of calix[6]arenes are of increasing interest because of their use in receptors for larger guests. Most work in this area has been based around functionalization of the lower rim.Thus, Shinkai and co-workers have reported the syntheses of all the possible calix[6]arene derivatives Peny and Kilbum: Synthetic developments in host-guest chemistry 73BU' Bu ' YH 135 yH pp$ \ But But 136 137 (19%) (ii) I 138 (65%) OR' OR' J (iv) 6 1 3 9 R = R' = Me (65%) 140 R = R' = H (69%) Reagents: (i) xylene, reflux; (ii) (a) phenol, AICIrtoluene; (b) CH31, BubK; (c) NBS, butan-2-one; (iii) Pd(PPh3)4, Na,CO,; (iv) (a) LiOH-MeOH-H,O; (b) BBr3-CH2Ci2 Scheme 39 with Me0 and EtOCOCH20 substituents,Io3 as well as syntheses of calix[6]arenes bridged with a xylenyl unit or capped with a mesitylenyl group.Io4 Reinhoudt and co-workers have added pendant ureas from the lower rim of a calix[6]arene to form a receptor for anion^'"^ while Ungaro and co-workers have synthesized 1,4-calix[6]crown ethers from the parent calix[6]arene and tetraethylene glycol bis( toluene-p-sulfonate) in 36-42% and Ross and Luning have added 1,4-pyridine- containing bridges which create concave reagents for base-catalysed reactions.Io7 The calix[6]arene 141 bridged by m-phenylene supporting an azide group underwent an unusual reaction in which the azide was converted to a nitrene by photolysis followed by a transannular addition reaction to produce the fused azepine 142 (41% yield) as the major product (Scheme 4O).Ios The partial functionalization of the upper rim by selective nitration, formylation, halogenation, chloromethylation and Claisen rearrangement has been reported,"' and the same paper described the formation of di- and tri-quinones of calix[6]arene.But- I But I But 141 ITHF, hv, 13 h, -78 "C But But But- BU' 142 (41%) Scheme 40 Konishi and co-workers have described the synthesis of the first examples of calix[6]resorcin- arenes."' Refluxing 2-propylresorcinol and 173,5-trioxane in ethanol-conc. HC1 (4: 1 v/v) for three hours, produced the hexamer (as a minor product to the tetramer) in 22% yield. 3.4 Calix [ 71 arenes and calix [S] arenes A one-step synthesis of p-tert-butylcalix[7]arene has been described."' The optimum conditions for base- catalysed cycloaddition of p-tert-butylphenol were established and gave an isolated 11% yield ofp-tert- butylcalix[7]arene. Neri and co-workers have studied the alkylation of p-tert-butylcalix[8]arene by p-methylbenzyl bromide in the presence of weak bases.'12 They have determined that substitution proceeds by an 'alter- nate alkylation' mechanism, i.e.the reaction path goes mainly via mono-, 173-di-, 173,5-tri-, 1,3,5,7-tetra-, 172,3,5,7-penta-, 1,2,3,4,5,7- and 172,3,5,6,7-hexa- and hepta-substitution. They have also described a synthesis of l73,5,7-tetrarnethyl ether of p-tert-butylcalix[8]arene (previously unreported as synthesis by standard alkylation reactions was very much hampered by the target compound being insoluble in most organic 74 Contemporary Organic Synthesissol~ents),"~ and of doubly-crowned p-tert- b~tylcalix[X]arenes."~ 3.5 Multiple calixarene structures One strategy to obtain larger cavities is to form a receptor from several calixarene units. Shinkai and co-workers have described a biscalix[4]arene which, though formed by a single methylene connection between the upper rims of the constituent calix- arenes, is conformationally-immobile and serves as a receptor for N-methylpyridinium i~dide."~ Reinhoudt and colleagues have synthesized a bis- calix[4]arene 145 which incorporated a zinc- porphyrin moiety between its two calixarene units."6 The calixarene 144 was used to template the synthesis of the porphyrin unit in the product 145 (Scheme 41).The same research group has also continued its studies into receptors built from upper-rim-functionalized calix[4]arenes and partly bridged re~orcinarenes,"~ and have described a novel calix[4]arene-based carceplex.' Beer and co-workers have reported the synthesis of a neutral fluoride ion selective biscalix[4]arene receptor in which the upper rim of one calix[4]arene segment was linked by amide bonds to the lower rim of the other."' Ether links formed between lower rim phenolic oxygens have been used to assemble X o-x- 143 X \ 145 (5%) Reagents: (i) pyrrole, TFA, 0.5 h, rt; 11) (a) 143, BF *Et 0 CHCIs, 1 h, rt; (b) DDQ, CHC13, 1 h, rt; (c) Z~(&AC)~*~H~O, 8HCfgMeOH (2:l) reflux, 3 h Scheme 41 biscalixarenes joined by calixarene-type segments,12' and oligocalixarenes (containing up to five mono- mers) linked by aliphatic chains,12' while Pochini and co-workers have reported the synthesis of the macrocavitand 148'22 by the head-to-tail four-point capping of p-tert-butylcalix[8]arene 146 with tetra- met hoxy-p-tetrakis( chloromet hyl)calix[ 41 arene 147.In the presence of CsF and NaI, in refluxing acetone, at high dilution, the reaction gave a 30% yield of biscalixarene 148 (Scheme 42).1 46 1 47 ICsF, Nal, acetone, reflux, 3 d 148 (30%) Scheme 42 4 Cyclophanes 4.1 All-carbon cyclophanes An ionophore which is selective for the larger alkali metals has been prepared by incorporating an oligo(oxyethy1ene) bridge into a rigid 'paddlane' unit.'23 The dihydroxycyclophane 150 was prepared by Birch reduction of 149 followed by ether cleavage with HBr-AcOH (Scheme 43) and the crowno- phane 151 was then synthesized by standard Williamson ether methodology. new calix[4]arene-type cyclophane using syn- dihydroxy[2.n]metacyclophane 152 as the building b10ck.I~~ Dimerization of 152 using CsOH and para- formaldehyde yielded cyclophane 153.The cyclo- butane rings of 153 could be opened by Birch reduction producing cyclophane 154 (Scheme 44) and the phenolic hydroxy groups of 153 and 154 were derivatized to produce a variety of pendant ethers. Related cyclophanes with ether substituents bearing chiral pendants were shown to selectively extract and transport amino acids.125 Nishimura and co-workers have also developed a Peny and Kilbum: Synthetic developments in host-guest chemistry 751 49 150 (87%) (ii) 1 Fob e, .4 n=1-3 151 (3843%) Reagents: (i) (a) liq. NH3, Na, Bu'OH-THF, -60 OC to rt; (b) HBr-AcOH, reflux; (ii) TsO(CH2CH20),Ts (rn = 4-6), NaH-THF, reflux Scheme 43 1 52 HO OH HO OH 153 (78%) I(ii) HO OH HO OH 154 (55%) Reagents: (i) CH20, CsOH, diglyme 140-150 OC, 12 h; (ii) (a) CICH20CH3, NaH, THF-DMF; (b) Na, EtOH, liq.NH3, THF; (c) aq. HCI-dioxane platinum-linked porphyrin trimer has also been r e ~ 0 r t e d . l ~ ~ Diederich and co-workers have made a series of chiral receptors (157a, 157b and 158) for pyranosides derived from a 3,3'-diethynyl-l,1 '-bi- naphthyl-2,2'-diol spacer 155.l3' The monomer 155 was cyclized by oxidative Glaser-Hay coupling to give trimer 156a and tetramer 156b, both in 20% yield. Removal of benzyl protection (giving 157a and 157b) and conversion of 157b to tetraphosphate 158 were accomplished in good yield (Scheme 45). BnO MH BnO OBn t yR:&oBn '0 OBn 156an=l,R1 =R2=Bz(20%) n = 2, R1 = R2 = Bz (20%) (ii) (92%) 57an=l,R1 =R2=H 1 57b n = 2, R' = R2 = H n = 2, R',R2 = PO,- (iii) (67%) Ll 58 Reagents: (i) air, CuCI2, TMEDA; (ii) KOH, MeOH-THF; (iii) (a)P0Cl3, NEt3, CH2CI2; (b)THF-H20, 12 h, 40 OC Scheme 45 Scheme 44 The use of diyne units to give rigidity to cyclo- phanes is common.Hoger and Enkelmann have prepared large ambiphilic macrocycles by coupling of oligo(aryla1kyne) units.'26 Sanders and co-workers have published several full papers detailing their syntheses of various porphyrin cyclophanes which use d i ~ n e ' ~ ~ and even tetrayne12' links with the aim of creating spacious cavities able to bind two or more substrate molecules in such a manner that homogeneous catalysis could occur. A related 4.2 He teroa tom-con taining cyclop hanes A simple method of formation of [3.3] azacyclo- phanes by dialkylation of cyanamide has been described by Shinmyozu and colleagues."' In the presence of a phase-transfer catalyst, in a mixture of toluene or CH2C12 and water, in mildly alkaline conditions, the addition of cyanamide to a range of bromomethyl compounds produced N, N'-di- cyano[ 3.3]azacyclophanes and their higher homologues in good to moderate yields.Molina and 76 Contemporary Organic Synthesisco-workers have reported a method of preparation of macrocyclic bis(guanidines) using the high yielding reaction (74-98%) of readily available bis(carb0diimides) with ammonia, primary or secondary amines and a,~-diamines.'~~ Hart, Rajakumar and co-workers have used the tandem aryne reaction of aryl Grignard reagents 160 with 1,2,3-trihalobenzenes 159 followed by electrophilic quenching to produce m-terphenyl units 161 with the electrophile attached to the 2'-position (Scheme 46).Substitution on the outer aryl groups of the terphenyl provided linking moieties e.g. bromination of 161 gave 162 followed by displacement to form dithiol 163. Structures of this type have been used to build a variety of oxa-and thia-cyclophanes with intraannular f~nctionality.'~~-'~~ I V (ii) electrophilic 1 59 reagent \ / -t' - E = H, Hal, C02H, CN, COCl etc CH3 161 (5575%) ,CH2SH p (i) NH2CSNH2. THF. 50 "C GE (ii) KOH, THF-H20 CH2SH 163 (3042%) Scheme 46 Q CH2Br 162 Inouye and colleagues have used a sterically similar terpyridine moiety to provide an intra- annular hydrogen bonding functionality in their macrocyclic receptor for fi-ribofuranosides,'36 while Shinkai and co-workers have continued their research on oxacyclophanes describing a triamide ionophoric deri~ative'~~ and a C3-symmetrically- capped host for primary ammonium ions.'38 Konig and co-workers have described the synthesis of silicon-bridged macrocycles such as 164 and 165.'",'40 Furan, thiophene and N-methylpyrrole were deprotonated at the 2- and 5-positions with two equivalents of BuLi-TMEDA-KOBu' (1 : 1 : 1) in hexane and after slow addition of Me2SiC12, macrocyclic tetramers 164 and hexamers 165 were formed in yields up to 35% (Scheme 47).139 The BUL-TM EDA-KOBU Me2SiC12 164 n = 1, X = 0, S, NMe (12-18%) 165 n = 3, X = 0, S (10-17%) Scheme 47 same group has also used the addition of dianions to biselectrophiles to form silicon-substituted deriva- tives of calix[4]arene, an octamethoxysila- [l.l.l.l]paracyclophane and tin or phosphorus analogues of 164 and 165 by using Me2SnC12 or PhPClz rather than MezSiCI2.l4' Heterophanes have also been constructed using heterocyclic betaine The trisheterocyclic fragment 167 was obtained by a three-step procedure from 1,2,4-triazole 166.Condensation of 167 with bis(chloromethy1) derivative 168 afforded the macrocycle 169 in 63% yield. After reflux of 169 with trifluoroacetic acid (TFA) and phenol for an hour, the resultant compound was treated with an anion exchange resin producing 170 in 95% yield from 169 (Scheme 48). Other novel, charged hetero- phanes assembled by reaction of alkyl halide with amine include Xie and co-workers' imidazolium ~yclophane,'~~ Menger and Catlin's octacationic 1,4-diazabicyclo[ 2.2.2loctane (DABC0)-based macr~cycle'~~ and Skog and Wennerstrom's macro- cyclic host constructed with four nicotinamide N-N 167 (56%) 2 168 (65%) N-N /CHPh2 % O y 6 9 H (63%) Reagents: (i) dry MeCN, reflux, 48 h; (ii) (a) TFA, phenol, reflux, 1 h; (6) anion exchange resin IRA-401 (OH- form) Scheme 48 Perry and Kilbum: Synthetic developments in host-guest chemistry 77Amino acids are useful 'building blocks' for molecular receptors.Ishida and co-workers have synthesized a series of neutral cyclic hexapeptides containing the non-natural amino acid 3-amino- benzoic acid which serves to orient the amide groups correctly for interaction with phosphoester Flack and Kilburn's macrocyclic receptor for peptides was assembled from a diaminopyridine unit, succinic acid, phenylalanine and a non-natural amino acid spacer unit with the formation of four amide bonds (Scheme 49).147 First, monoprotected succinic acid 171 was reacted with N-phenylalanine via the formation of the acid chloride, giving 172 which was coupled with 2,6 diaminopyridine using 1,3-dicyclohexylcarbodiimide-4-dimethylamino- pyridine (DCC-DMAP) forming 173.Addition of a large spacer unit using ethyl 1,2-dihydro-2-ethoxy- quinoline-1-carboxylate (EEDQ) created 174 which, after deprotection and activation, was cyclized to form 175. 4.3 Cage-type cyclophanes Diederich and colleagues have described the first examples of 'dendrophanes' which are composed of // II HA0 H02C 171 Ph /-( COpH H2N yJ"bb 172 (98%) 173 (72%) 1 (iii) 175 (24%) Reagents: (i) (a) (COCI)2, cat.DMF, CH2Cl ; (b) L-phenylalanine, Na2C03, H20; (ii) 2,bdiaminopyridine, DC8, DMAP, CH2C12; (iii) non-natural amino acid spacer unit, EEDQ, THF; (iv) (a) Pd(PPh3)4, H 0, dioxan; (b) C6F50H, DCC; (c) 20% HCI, dioxane; (d) DMAP, h3N, DMF Scheme 49 a [6.1.6.1] paracyclophane embedded in first-, second- and third generation dendritic poly(ether amide) shells.'48 The construction of spherical hydrocarbons which can act as silver ion receptors has been described by Vogtle and co-w~rkers.'~~ For instance, the tripodal unit 176 was reacted with sodium sulfide at high dilution, to produce the thia-bridged compound 177. Subsequent oxidation to 178 and pyrolytic desulfur- ization gave hydrocarbon host 179 in overall 5% yield from 177 (Scheme 50). 176 Br = S (14%) = SO2 (96%) = - (38%) Reagents: (i) Na2S*9H20, Cs2C03, benzene-EtOH, reflux; (ii) MCPBA, CHCI,; (iii) lo4 Torr, 580 "C Scheme 50 Cram has continued his programme of study on hemicarcerands and carcerands and their com- plexes"" and has described new linking elements such as a diphenylmethane derivative which provides hemicarcerands with large interiors of the same scale as [60]f~llerene,l~~ and the synthesis and properties of a hemicarcerand-corand able to complex both a cation and an anion simultane- 0us1y.'~~ Sherman has reviewed the field of carce- plexes and hemicarceplexe~,'~~ and has also described the templated synthesis of both covalently-linked and self-assembled carceplexe~.'~~ 5 Clefts, bowls and other morphologies 5.1 Cleft-type receptors The cleft is an attractive overall design for a receptor as it can generate a high degree of pre- organization of binding moities in a relatively short synthesis. For instance, cleft 183 was produced in three steps from a-tetralone 180 in 55% yield (Scheme 51).155 The cleft 181 was synthesized by heating 180 in sulphuric acid at 100 "C for 4-5 h.Chlorination of the sulfonates with chlorosulfonic 78 Contemporary Organic Synthesis(iii) L 183 R =SOpNHBu (55% from 180) Reagents: (i) H2S04, 100 OC, 4-5 h; (ii) HSOsCI, rt; (iii) BuNH2, EtOAc Scheme 51 acid yielded 182 and then reaction with butylamine gave 183. A synthetically accessible cleft has been reported by Hamilton and co-workers and consists of a rigid bicyclo[3.3.0]octane framework holding two guani- dinium units parallel and 4-5 A apart.It has proved capable of selectively binding aspartate residues separated by two amino acids on an a-helical ~eptide.'~' Zimmerman and co-workers have published a full paper describing the syntheses of heterocyclic compounds containing three contiguous hydrogen bonding sites in all the possible arrange- ments of donor and ac~eptor.''~ These heterocycles can be used as modules in the construction of more specific clefts. For instance, the fused pyridine framework of receptor 187 was built up from benzylidene ketone 184.'58 Construction of the lower pyridine ring was achieved through addition to CH3CH20CH=C(CN)2 and cyclization, giving 185. After removal of the benzylidene group by ozono- lysis, addition of the upper naphthyridine unit to 186 was achieved by a Friedlander addition of 4-aminopyrimidine-5-carbaldehyde, acid hydrolysis of the resultant pyrimidine ring and reaction with malononitrile (Scheme 52).The resultant cleft 187 has an arrangement of hydrogen bond donors and acceptors which tightly docks with guanine deriva- tives. The related syntheses of highly preorganized polyheterocyclic hosts for creatinine has also been described.159 Porphyrin analogues of Troger's base have been synthesized (in 70% yield from 2-aminoporphyrin derivatives) to produce chiral clefts with large cavities containing two metal centres for binding guests.''" Chiral clefts have also been fabricated using 9,9-~pirobi[9H-fluorene],'~' l,l'-binaphthyll6' and 2,6-diarylbenzoic acid units.163 The use of peptides as a source of chirality in clefts or tweezer-like molecules has been reported by Kelly who has constructed a host by coupling dibenzofuran-2,8-dipropanoic acid with two tetra- pep tide^.'^^ The two peptides are hence arranged such that a peptide guest can bind between them in a three-stranded antiparallel /3-sheet.Related tweezer-like receptors for peptides have also been Q 0 4 (i),(ii),(iii) - 184 ' 185 (39% from 184) ' FN I (iv) H2 % N \ H2Nm NC H2N NC 186 (76%) 1 87 (28%) I Reagents: (i) pyrrolidine, benzene, reflux, 24 h; (ii) CH3CH20CH=C(CN)2, THF, -20 OC, 30 min; (iii) conc. aq. NH3, THF, reflux, 4 h; (iv) CH2CITCH30H, 03, -78 OC; (v) 4-amino-l ,Spyrimidine- 5-carbaldehyde, CH30H-toluene. KOH, reflux, 30 h; (vi) (a) 0.2 M HCI, reflux, 12 h; (b) CH2(CN)*, CH30H-toluene, piperidine, reflux, 24 h Scheme 52 constructed with two vinylogous sulfonyl peptides arrayed on a benzene-1,3,5-tricarbolrylate spacer, the third position on this unit being used to attach a dye molecule to facilitate screening with a library of potential guests.16' The use of peptidic frameworks as the basis of molecular receptors has been reviewed by Voyer and Lamothe.'66 5.2 Molecular bowls and other receptors The use of 2,6,10-triaminotrioxatricornan 188 as a C3-symmetric, bowl-shaped keystone for the construction of cyclophanes has been rep~rted."~"'~ A (metal1o)macrocyclophane 189 assembled with a ferric tris(catecho1amide) phane 190 capped with a phloroglucinol unit'68 have been described (Scheme 53). Kilburn and co-workers have constructed a series of macrobicyclic receptors for amino acid derivatives which have a bowl-like They used amino acid subunits to impart chirality and incorporated either thiourea or diamidopyridine units as carbovlic acid binding sites.The macrobicycles were generally assembled by stepwise formation of amide bonds with a double macrocyclization as the key step. For instance,'69 the biarylmethane unit 191 (prepared by a Suzuki coupling) which rigidifies the upper rim was coupled with DCC-HOBt to a suitably protected glutamic acid. After removal of and a cage cyclo- Peny and Kilburn: Synthetic developments in host-guest chemistry 79Scheme 53 the ally1 protecting group, two equivalents of 192 were reacted with bis(L-phenyla1anine)-derived amidopyridine unit 193 yielding macrocycle precursor 194.The benzyl esters of 194 were hydro- lysed and the resulting diacid converted to a bis(pentafluoropheny1 ester). Removal of the amine protecting groups with trifluoroacetic acid and slow addition of the resulting bis(trifluor0acetate salt) to a solution of DIPEA in acetonitrile gave the desired macrobicycle 195 in -30% yield (Scheme 54). Still and his group have extended their studies of peptide-binding &B6 macrotricycles. The synthesis of an &B;B4 variant 196 (Scheme 55) and Still’s method of ascertaining its binding selectivity for di- and tri-peptide sequences using an encoded combi- natorial library has been the subject of a full paper.’72 They have also reported a water soluble analogue 197 which exhibited sequence-selective binding of peptides in ~ a t e r .” ~ It was constructed with trimesic acid for the A motif and two derivatives of a chiral diaminocycloazaheptane for the B portions; a hydro- philic ammonium salt as B and a rhodamine dye- substituted azaheptane as B’ (Scheme 56). Further research has been aimed at finding the minimal structural element of the A2BSB4 receptor system which functions as a sequence-selective binding Interestingly, whilst fragments 198 and 199 show no evidence of binding, partial receptor 200 showed greater selectivity than the parent structure 196 (Scheme 57). 192 (51%)/) C02CH2P h CO2CH2P h 194 (50-70%) 1 (iii) NH I 195 (30%) Reagents; (i)(a) Boc-L-glutamic acid yallyl ester, DCC, HOBt, DIPEA, DMF; (b) Pd(PPh3)4, pyrrolidine, CH2CI2; (ii) PyBOP, Pi2NEt, DMF; (iii) (a) 10°/oPd/C, NH4C02H, DMF; (4 syringe pump addition to DIPEA, CH3CN.HOBt = 1 -hydroxybenzotriazole; PyBOP = benzotriazol-1 -yl- oxytripytrolidinophosphonium hexafluorophosphate (b) CGFSOH, DCC, DMAP, THF; (c) 50% TFA, CH2C12; DIPEA = PrJ2NEt Scheme 54 6 Self-assembling receptors The use of non-covalent bonds to construct host molecules is an increasingly popular and easy method of receptor manufacture because the greater the degree of self-assembly in the host, the less work for the synthetic chemist, in theory at least! A review on self-assembling supramolecular complexes has appeared,175 and the self-assembly of 80 Contemporary Organic SynthesisH O 0 0 O H 1 96 Scheme 55 H O 0 H2Nt 0 O H 1 97 Scheme 56 B' Ac. 199 1 B /AB Scheme 57 42+ &AB 200 y 2 Scheme 58 molecular-sized boxes has been reviewed by Hunter.'76 driving force for the self assembly of receptors.Self- assembling ionophores based on isog~anosine'~~ and deoxyg~anosinel'~ have been reported. Isoguanosine mononucleoside 201 (Scheme 58) formed cyclic tetramers in nonpolar organic solvents which on addition of metal ion guest could be either stabi- lized, destabilized so that monomer was favoured or even further assembled into octamers, all depending on the identity of the metal ion. Deoxyguanosine derivative 202 formed a receptor able to extract alkali metal picrates by a similar mode of self assembly. Hamilton and his group have published further work on metal-templated receptor^^^^^'^^ and they have described the preparation of a small library of bifunctional receptors using such an assembly procedure.'" Thus terpyridyl ligands substituted at the 5-position with binding moieties such as a thiourea or a crown ether were prepared and coordinated to a Ru" centre to form a library of fifteen receptors.These were then assessed for their selectivity towards various bifunctional guests. Stang and his group have published further work on macrocyclic squares assembled with either metal or iodonium corner pieces.Ix2 The use of guest-induced assembly to create a host has been described by Ogura and co-workers.183 Thus, a three-dimensional cage 205 was formed when the tridentate ligand 203 and Pd(en)(NO,), 204 were mixed in the presence of sodium 4methoxyphenylacetate, in water (Scheme 59). Without the correct guest present, only oligomers were formed.Bilyk and Harding have described the guest-induced assembly of a chiral [2+2] me tallomacrocycle. Rebek and his group have continued their research into self-complementary molecules that assemble into dimeric capsules using hydrogen bonding and can act as size-selective hosts. For instance, 206 dime.rized to encapsulate xenon (Scheme 60).Ifi5 Other monomer units have been synthesized generally by reaction of an appropriate Metal chelation has been used to provide the Peny and Kilburn: Synthetic developments in host-guest chemistry 81il H H I 204 guest (sodium 4-methoxy- phenylacetate), D20, R guest included in 6(N03)- cavity 205 Scheme 59 0 0 0 R=CO*Et 0 206 Br I I OBn 208(30%) OBn B; Br 207 (i) TiCI4, LiAIH4 (ii) HBr, AcOH Br Br 210(82%) Br Br 209(65%) Br R' = CO2Et 0 0 Scheme 60 tetrabromide with a glycol~ri1.'~~~'~~ One of the new monomers 212 has a bridged anthracene spacer which was synthesized via tandem benzyne additions to furan 207.The reaction produced a mixture of isomeric syn- and anti-endoxides 208 which were both reduced with Tio and after replacement of the benzyl oxyether groups with bromides gave 209. A subsequent Diels-Alder reaction with diethyl acetylenedicarboxylate yielded the ethenoanthra- cene tetrabromide 210. Reaction of 210 with glyco- luril211 produced a mixture of 212 and two stereoisomers. However the target compound 212 was the only isomer soluble in nonpolar organic solvents and could be separated by extraction with chloroform (Scheme 60).Reinhoudt and co-workers have reported a self- assembled bifunctional receptor which uses hydrogen bonding in its construction. 188 The receptor 213 contained a calix[4]arene unit to recog- nize sodium cations and a tetraphenylporphyrin unit to coordinate to anions such as thiocyanate. The two halves of the receptor 213 assembled via a diamidopyridine-thymine interaction (Scheme 61). Scheme 61 7 References 1 C. J. Pedersen, J. Am. Chem. SOC., 1967,89, 2495. 2 Continuing the coverage in J. Dowden, J. D. Kilburn and P. Wright, Contemp. Org. Synth., 1995, 2, 289. 3 P. Guerriero, S. Tamburini and P. A. Vigato, Coord. Chem. Rev., 1995, 139, 17. 4 V. Alexander, Chem. Rev., 1995,95,273. 5 T. Ogawa, A. Yoshikawa, H. Wada, C. Ogawa, N. Ono and H. Suzuki, J. Chem. SOC., Chem. Commun., 1995, 1407.A. C. van der Kerk-van Hoof, J. W. Zwikker, W. J. J. Smeets and A. L. Spek, J. Chem. SOC., Chem. Commun., 1995, 1621. 7 A. A. Gakh, R. A. Sachleben, J. C. Bryan and B. A. Moyer, Tetrahedron Lett., 1995, 36, 8163. 8 T. Kato, A. Hiraide, M. Suda, T. Kanbe and T. Nozoe, Bull. Chem. SOC. Jpn., 1995, 68, 3145. 6 I. J. A. Mertens, L. W. Jenneskens, E. J. Vlietstra, 82 Contemporary Organic Synthesis9 Y. Kobuke, K. Kobuko and M. Munakata, J. Am. Chem. SOC., 1995, 117, 12751. SOC. Chim. Belg., 1995, 104, 629. SOC., 1995, 117, 6390. T. Kaneda and Y. Sakata, J. Chem. SOC., Perkin Trans. 1, 1995, 213. Commun., 1995,25,3777. Commun., 1995, 25, 595. 1197. 1995,36,1977. Commun., 1995,25, 1427. 10 G, L'abbk, G. Van Wuytswinkel and W. Dehaen, Bull.11 B. H. Kim, E. J. Jeong and W. H. Jung, J, Am. Chem. 12 K. Naemura, S. Takeuchi, K. Hirose, Y. Tobe, 13 P. P. Kanakamma, N. S. Mani and V. Nair, Synth. 14 L. Yi, Z. Zhuangyu and H. Hongwen, Synth. 15 C. Granier and R. Guilard, Tetrahedron, 1995, 51, 16 K.-J. Gu and K. Bowman-James, Tetrahedron Lett., 17 M. Wu, G. Cheng, Y. He and C. Wu, Synth. 18 I. Lazar, Synth. Commun., 1995, 25, 3181. 19 N. Amaud, C. Picard, L. Cazaux and P. Tisnks, Tetra- hedron Lett., 1995, 36, 5531. 20 W. T. S. Huck, F. C. J. M. van Veggel and D. N. Reinhoudt, Red. Trav. Chim. Pays-Bas, 1995, 114, 273. 21 (a) J. Dale, C. Rgmming and M. R. Suissa, J. Chem. SOC., Chem. Commun., 1995, 1631; (b) J. Dale, C. Rgmming and M. R. Suissa, J. Chem. SOC., Chem. Commun., 1995, 1633. 22 A. G. Shultz and Z.Guo, Tetrahedron Lett., 1995, 36, 659. 23 J. M. Garcia Fernandez, J. L. Jimenez Blanco, C. Ortiz Mellet and J. Fuentes, J. Chem. SOC., Chem. Commun., 1995, 57. Lemcoff, S. Abramson, L. Golender and B. Fuchs, Tetrahedron Lett., 1995, 36, 9193. 25 N. Kise, H. Oike, E. Okazaki, M. Yoshimoto and T. Shono, J. 0%. Chem., 1995,60, 3980. 26 U. C. Yoon, S. W. Oh and C. W. Lee, Heterocycles, 1995, 41, 2665. 27 D. St C. Black, M. A. Horsham and M. Rose, Tetra- hedron, 1995, 51, 4819. 28 J. Kim, L. F. Lindoy, 0. A. Matthews, G. V. Meehan, J. Nachbaur and V. Saini, Aust. J. Chem., 1995, 48, 1917. 24 K. Frische. M. Greenwald, E. Ashkenasi, N. G. 29 I. Lazar and A. D. Sherry, Synthesis, 1995,453. 30 ( a ) K. Matsumoto, K. Fukuyama, H. Iida, M. Toda and J. W. Lown, Heterocycles, 1995, 41, 237; (b) K.Matsumoto, S. Okuno, H. Iida and J. W. Lown, Heterocycles, 1995, 40, 521; (c) K. Matsumoto, M. Hashimoto, M. Toda and H. Tsukube, J. Chem. SOC., Perkin Trans. 1, 1995, 2497. Commun., 1995, 185. 36, 9269. and H. Handel, J. Chem. SOC., Chem. Commun., 1995, 1233. 34 P. L. Anelli, L. Calabi, P. Dapporto, M. Murru, L. Paleari, P. Paoli, F. Uggeri, S. Verona and M. Virt- tuani, J. Chem. SOC., Perkin Trans. 1, 1995, 2995. 35 V. Patinec, J. J. Yaouanc, J. C. Clement, H. Handel and H. des Abbayes, Tetrahedron Lett., 1995, 36, 79. 36 W. Ferraz de Souza, N. Kambe, Z. J. Jin, N. Kane- hisa, Y. Kai and N. Sonoda, J. Org. Chem., 1995, 60, 7058. Y. A. Strelenko, D. V. Demchuk, G. I. Nikishin, S. V. 31 Z. Kovacs and A. D. Sherry, J. Chem. SOC., Chem.32 Z. Kovacs and A. D. Sherry, Tetrahedron Lett., 1995, 33 A. Roignant, I. Gardinier, H. Bernard, J. J. Yaouanc 37 E. 1. Troyansky, R. F. Ismagilov, V. V. Samoshin, Lindeman, V. N. Khrustalyov and Y. T. Struchkov, Tetrahedron, 1995,51, 11 431. Lett., 1995,36, 1835. Synthesis, 1995, 952. dieu and J.-P. Majoral, J. Am. Chem. SOC., 1995, 117, 1712. 41 K. Brandt, I. Porwolik, T. Kupka, A. Olejnik, R. A. Shaw and D. B. Davies, J. 0%. Chem., 1995,60, 7433. 42 M. Suginome, H. Oike and Y. Ito, J. Am. Chem. SOC., 1995,117, 1665. 43 M. Lachkar, B. Andrioletti, B. Boitrel and R. Guilard, New J. Chem., 1995, 19,777. 44 B. P. Clark, J. R. Harris, G. H. Timms and J. L. Olkowski, Tetrahedron Lett,, 1995, 36, 3889. 45 K. Krakowiak and J. S. Bradshaw, J. Org. Chem., 1995, 60,7070.46 A. V. Bordunov, N. G. Lukyanenko, V. N. Pastushok, K. Krakowiak, J. S. Bradshaw, N. K. Dalley and X. Kou, J. 0%. Chem., 1995,60,4912. 47 R. Gleiter, K. Hovermann, J. Ritter and B. Nuber, Angew. Chem., Int. Ed. Engl., 1995,34, 798. 48 A. S. de Sousa and R. D. Hancock, J. Chem. SOC., Chem. Commun., 1995, 415. 49 M. Fierros, S. Conde, A. Martinez, P. Navarro and M. I. Rodriguez-Franco, Tetrahedron, 1995, 51, 2417. 50 M. Hovorka, I. Stibor, R. Scigel and I. Smiskova, Synlett, 1995, 251. 51 S. Tomas, M. C. Rotger, J. F. Gonzalez, P. M. Deyh, P. Ballester and A. Costa, Tetrahedron Lett., 1995,36, 25 23. C. Cabellero and J. R. Morin, Tetrahedron Lett., 1995, 36, 3255. 53 C. Raposo, M. Almaraz, M. Martin, V. Weinrich, L. Mussons, V. Alcazar, C. Cabellero and J.R. Moran, Chem. Lett., 1995, 759. 54 L. Corda, G. Delogu, A. Maccioni, E. Maccioni and G. Podda, Gazz. Chim. Ital., 1995, 125, 491. 55 V. Bohmer, Angew. Chem., Int. Ed. Engl., 1995,34, 713. 56 M. Takeshita and S. Shinkai, Bull. Chem. SOC. Jpn., 1995, 68, 1088. 57 Z. Asfari, S. Wenger and J. Vicens, Pure Appl. Chem., 1995, 67, 1037. 58 I. Bitter, A. Griin, B. Agai and L. TBke, Tetrahedron, 1995, 51, 7835. 59 S. K. Sharma, I. Alam and C. D. Gutsche, Synthesis, 1995, 1089. 60 D. Bethell, G. Dougherty and D. C. Cupertino, J. Chem. SOC., Chem. Commun., 1995,675. 61 M. J. Marsella, R. J. Newland, P. J. Carroll and T. W. Swager, J. Am. Chem. SOC., 1995, 117, 9842. 62 H. Yamamoto, K. Ueda, K. R. A. S. Sandanayake and S. Shinkai, Chem. Lett., 1995, 497. 63 J. J. Gonzalez, P.M. Nieto, P. Prados, A. M. Echavarren and J. de Mendoza, J. Org. Chem., 1995, 60, 7419. Cian and J. Fischer, J. Chem. SOC., Chem. Commun., 1995, 609. 65 C. G. Gibbs, P. K. Sujeeth, J. S. Rogers, G. G. Stanley, M. Krawiec, W. H. Watson and C. D. Gutsche, J. Org. Chem., 1995, 60, 8394. 66 J. F. Malone, D. J. Marrs, M. A. McKervey, P. O'Hagan, N. Thompson, A. Walker, F. Arnaud- Neu, 0. Mauprivez, M.-J. Schwing-Weill, J.-F. Dozol, 38 R. Gleiter, H. Rockel and B. Nuber, Tetrahedron 39 J. Mitjaville, A.-M. Caminade and J.-P. Majoral, 40 J. Mitjaville, A.-M. Caminade, J.-C. Daran, B. Donna- 52 C. Raposo, N. Perez, M. Almaraz, L. Mussons, 64 X. Delaigue, M. W. Hosseini, N. Kyritsakas, A. De Peny and Kilburn: Synthetic developments in host-guest chemistry 83H.Rouquette and N. Simon, J. Chem. SOC., Chem. Commun., 1995, 2151. 67 C. Loeber, C. Wieser, D. Matt, A. De Cian, J. Fischer and L. Toupet, Bull. SOC. Chim. Fr, 1995, 132, 166. 68 B. R. Cameron, F. C. J. M. van Veggel and D. N. Reinhoudt, J. Org. Chem., 1995, 60, 2802. 69 I. Neda, H.-J. Plinta, R. Sonnenburg, A. Fischer, P. G. Jones and R. Schmutzler, Chem. Ber, 1995, 128, 267. Elsegood, J. Chem. SOC., Chem. Commun., 1995, 2371. 1995,36,8453. Tetrahedron Lett., 1995, 36, 23 1 1. 1995, 60,6070. A. Secchi, A. R. Sicuri, R. Ungaro and M. Vincenti, Tetrahedron, 1995, 51, 599. 75 Z.-T. Huang, G.-Q. Wang, L.-M. Yang and Y.-X. Lou, Synth. Commun., 1995, 25, 1109. 76 E. van Dienst, B. H. M. Snellink, I. von Piekartz, J. F. J. Engbersen and D. N. Reinhoudt, J. Chem. SOC., Chem.Commun., 1995, 1151. 77 Y. Kubo, S. Maruyama, N. Ohhara, M. Nakamura and S. Tokita, J. Chem. SOC., Chem. Commun., 1995, 1727. R. Ungaro, A. R. Sicuri and F. Ugozzoli, J. 0%. Chem., 1995,60, 1448. 79 A. Arduini, S. Fanni, A. Pochini, A. R. Sicuri and R. Ungaro, Tetrahedron, 1995, 51, 7951. 80 M. Mascal, R. T. Naven and R. Warmuth, Tetra- hedron Lett., 1995, 36, 9361. 81 W. Verboom, P. J. Bodewes, G. van Essen, P.Timmerman, G. J. van Hummel, S. Harkema and D. N. Reinhoudt, Tetrahedron, 1995, 51,499. 82 H. Konishi and Y. Iwasaki, Synlett, 1995, 612. 83 0. V. Lukin, V. V. Pirozhenko and A. N. Shivanyuk, 84 T. Lippmann, H. Wilde, E. Dalcanale, L. Mavilla, 70 V. C. Gibson, C. Redshaw, W. Clegg and M. R. J. 71 K. No, J. E. Kim and K. M. Kwon, Tetrahedron Lett., 72 G.Sartori, F. Bigi, C. Porta, R. Maggi and R. Mora, 73 S. Kanamathareddy and C. D. Gutsche, J. 0%. Chem., 74 A. Arduini, M. Cantoni, E. Graviani, A. Pochini, 78 A. Arduini, S. Fanni, G. Manfredi, A. Pochini, Tetrahedron Lett., 1995, 36, 7725. G. Mann, U. Heyer and S. Spera, J. Org. Chem., 1995, 60, 235. 85 P. Linnane and S. Shinkai, Tetrahedron Lett., 1995, 36, 3865. 86 (a) R. Arnecke, V. Bohmer, E. F. Paulus and W. Vogt, J. Am. Chem. SOC., 1995, 117, 3286; (b) R. Arnecke, V. Bohmer, S. Friebe, S. Gebauer, G. J. Krauss, I. Thondorf and W. Vogt, Tetrahedron Lett., 1995,36,6221. Tetrahedron Lett., 1995, 36, 4905. 1463. 1995,36, 8969. R. Okazaki, Tetrahedron Lett., 1995, 36, 7677. Reinhoudt, Synthesis, 1995, 989. Patz, H. Irngartinger, C.-W. von der Lieth and R. Pipkorn, Liebigs Ann.Chem. , 1995, 1401. J. 0%. Chem., 1995, 60, 7284. Lett., 1995, 36, 3877. hedron Lett., 1995, 36, 8075. 87 M. T. El Gahani, H. Heaney and A. M. Z. Slawin, 88 W. Iwanek and J. Mattay, Liebigs Ann. Chem., 1995, 89 W. Iwanek, C. Wolff and J. Mattay, Tetrahedron Lett., 90 S. Watanabe, K. Goto, T. Kawashima and 91 E. Thoden van Velzen, J. F. J. Engbersen and D. N. 92 R. Shtz, C. Weber, G. Schilling, T. Oeser, U. Huber- 93 P. E. Georghiou, M. Ashram, Z. Li and S. G. Chaulk, 94 B.-L. Poh, L. Y. Chin and C. W. Lee, Tetrahedron 95 D. St C . Black, D. C . Craig and N. Kumar, Tetra- 96 P. R. Dave, G. Doyle, T. Axenrod, H. Yazdekhasti and H. L. Ammon, J. 0%. Chem., 1995,60,6946. 97 D. R. Stewart, M. Krawiec, R. P. Kashyap, W. H. Watson and C. D. Gutsche, J.Am. Chem. SOC., 1995, 117, 586. 98 P. D. Beer, Z. Chen, M. G. B. Drew and P. A. Gale, J. Chem. SOC., Chem. Commun., 1995, 1851. 99 0. Alegsiuk, S. Cohen and S. E. Biali, J. Am. Chem. SOC., 1995, 117, 9645. 100 J. L. M. Gordon, V. Bohmer and W. Vogt, Tetra- hedron Lett., 1995, 36, 2445. 101 T. Haino, T. Harano, K. Matsumura and Y. Fukazawa, Tetrahedron Lett., 1995, 36, 5793. 102 T. Yamato, M. Yasumatsu, L. K. Doamekpor and S. Nagayama, Liebigs Ann. Chem. , 1995, 285. 103 H. Otsuka, K. Araki and S. Shinkai, Tetrahedron, 1995, 51, 8757. 104 H. Otsuka, K. Araki, H. Matsumoto, T. Harada and S. Shinkai, J. 0%. Chem., 1995, 60, 4862. 105 J. Scheerder, J. F. J. Engbersen, A. Casnati, R. Ungaro and D. N. Reinhoudt, J. Org. Chem., 1995, 60, 6448. 106 A. Casnati, P. Jacopozzi, A.Pochini, F. Ugozzoli, R. Cacciapaglia, L. Mandolini, R. Ungaro, Tetra- hedron, 1995, 51, 591. 107 H. Ross and U. Liining, Angew. Chem., Int. Ed. Engl., 1995,34, 2555. 108 N. Tokitoh, T. Saiki and R. Okazaki, J. Chem. SOC., Chem. Commun., 1995, 1899. 109 A. Casnati, L. Domiana, A. Pochini, R. Ungaro, M. Carramolina, J. 0. Magrans, P. M. Nieto, J. L6pez-Prados, P. Prados, J. de Mendoza, R. G. Jannsen, W. Verboom and D. N. Reinhoudt, Tetra- hedron , 1995, 51, 12699. K. Kobayashi, J. Chem. SOC., Chem. Commun., 1995, 309. 11 1 F. Vocanson, R. Lamartine, R. Lanteri, R. Longeray and J. Y. Gauvrit, New. J. Chem., 1995, 19, 825. 112 P. Neri, C. Geraci and M. Piattelli, J. Org. Chem., 1995, 60,4126. 113 F. Cunsolo, G. M. L. Consoli, M. Piattelli and P. Neri, Tetrahedron Lett., 1995, 36, 3751.114 C. Geraci, M. Piattelli and P. Neri, Tetrahedron Lett., 1995,36,5429. 115 K. Araki, K. Hisaichi, T. Kanai and S. Shinkai, Chem. Lett., 1995, 569. 116 D. M. Rudkevich, W. Verboom and D. N. Reinhoudt, J. 0%. Chem., 1995, 60, 6585. 117 (a) P. Timmerman, K. G. A. Nierop, E. A. Brinks, W. Verboom, F. C. J. M. van Veggel, W. van Hoorn and D. N. Reinhoudt, Chem. Eul: J., 1995, 1, 132; (6) P. Timmerman, H. Boerrigter, W. Verboom and D. N. Reinhoudt, Red. Pav. Chim. Pays-Bas, 1995, 114, 103. W. Verboom and D. N. Reinhoudt, J. Chem. SOC., Chem. Commun., 1995, 1941. 119 P. D. Beer, P. A. Gale and D. Hesek, Tetrahedron Lett., 1995, 36, 767. 120 Z.-L. Zhong, Y.-Y. Chen and X.-R. Lu, Tetrahedron Lett., 1995, 36, 6735. 121 P. Lhotak and S. Shinkai, Tetrahedron, 1995, 51, 768 1.122 A. Arduini, A. Pochini, A. Secchi and R. Ungaro, J. Chem. SOC., Chem. Commun., 1995, 879. 123 S. Inokuma, S.-R. Gao and J. Nishimura, Chem. Lett., 1995, 689. 124 Y. Okada, Y. Kasai and J. Nishimura, Synlett, 1995, 85. 110 H. Konishi, K. Ohata, 0. Morikawa and 118 A. M. A. van Wageningen, J. P. M. van Duynhoven, 84 Contemporary Organic Synthesis125 Y. Okada, Y. Kasai and J. Nishimura, Tetrahedron 126 S. Hoger and V. Enkelmann, Angew. Chem., Znt. Ed. 127 (a) H. L. Anderson and J. K. M. Sanders, J. Chem. Lett., 1995,36, 555. Engl., 1995,34, 2713. SOC. Perkin Pans. 1, 1995, 2223; (b) S. Anderson, H. L. Anderson and J. K. M. Sanders, J. Chem. SOC. Perkin Trans. 1, 1995, 2247; (c) S. Anderson, H. L. Anderson and J. K. M. Sanders, J.Chem. SOC. Perkin Trans. 1, 1995, 2255; (d) D. W. J. McCallien and J. K. M. Sanders, J. Am. Chem. SOC., 1995, 117,6611. 128 H. L. Anderson, C. J. Walters, A. Vidal-Ferran, R. A. Hay, P. A. Lowden and J. K. M. Sanders, J. Chem. SOC., Perkin Trans. 1, 1995, 2275. 129 I,. G. Mackay, H. L. Anderson and J. K. M. Sanders, .I. Chem. SOC., Perkin Trans. 1, 1995, 2269. 130 S . Anderson, U. Neidlein, V. Gramlich and F. I>iederich,Angew. Chem., Int. Ed. Engl., 1995,34, 1596. 131 G. Wen, M. Matsunaga, T. Matsunaga, H. Takemura and T. Shinmyozu, Synlett, 1995, 947. 132 1'. Molina, M. Alajarin and P. Sanchez-Andrada, Tetrahedron Lett., 1995,36, 9405. 133 €3. Hart and P. Rajakumar, Tetrahedron, 1995,51, 1313. 134 T. K. Vinod, P. Rajakumar and H. Hart, Tetrahedron , 1995,51, 2267.135 A. Kannan and P. Rajakumar, Synth. Commun., 1995, 25, 3053. 136 M. Inouye, T. Miyake, M. Furusyo and H. Nakazumi, J . Am. Chem. SOC., 1995, 117, 12416. 137 €3. Matsumoto, S. Nishio, M. Takeshita and S. Shinkai, Tetrahedron, 1995, 51, 4647. 138 M. Takeshita, F. Inokuchi and S. Shinkai, Tetrahedron Lett., 1995, 36, 3341. 139 B. Konig, M. Rodel, P. Bubenitschek and P. G. Jones, Angew. Chem., Int. Ed. Engl., 1995,34, 661. 140 B. Kijnig, M. Rodel, P. Bubenitschek, P. G. Jones and I. Thorndorf, J. 0%. Chem., 1995, 60, 7406. 141 EL Alcalde, M. Alemany, M. Gisbert and L. Perez- Garcia, Synlett, 1995, 757. 142 E. Alcalde, M. Alemany, L. Perez-Garcia and M. L. Rodriguez, J. Chem. SOC., Chem. Commun., 1995, 1239. 1995,41, 1421. Ed. Engl., 1995, 34, 2147.36, 4629. J. Org. Chem., 1995, 60, 5375. 36, 3409. Acta, 1995, 78, 1904. K. Gloe, Angew. Chem., Znt. Ed. Engl., 1995,34, 481. Reviewed R. Faust, Angew. Chem., Znt. Ed. Engl., 1995, 34, 1429. Knobler and D. J. Cram, J. Chem. SOC., Chem. Commun., 1995, 1825; (6) R. G. Helgeson, C. B. Knobler and D. J. Cram, J. Chem. SOC., Chem. Commun., 1995, 307; ( c ) T. A. Robbins and D. J. Cram, J. Chem. SOC., Chem. Commun., 1995, 1515; ( d ) Y.-S. Byun, T. A. Robbins, C. B. Knobler and D. J. Cram, J. Chem. SOC., Chem. Commun., 1995, 1947; (e) S. K. Kurdistani, T. A. Robbins and D. J. Cram, J. Chem. SOC., Chem. Commun., 1995, 1259. 143 h4. Luo, S. Guo, C. Zhou and R. Xie, Heterocycles, 144 F. M. Menger and K. K. Catlin, Angew. Chem., Znt. 145 K. Skog and 0. Wennerstrom, Tetrahedron Lett., 1995, 146 H.Ishida, M. Suga, K. Donowaki and K. Ohkubo, 147 S. S. Flack and J. D. Kilburn, Tetrahedron Lett., 1995, 148 S. Mattei, P. Seiler and F. Diederich, Helv. Chim. 149 J. Gross, G. Harder, F. Vogtle, H. Stephan and 150 (u) Y.-S. Byun, 0. Vadhat, M. T. Blanda, C. B. 151 C. von dem Bussche-Hunnefeld, D. Buhring, C. B. Knobler and D. J. Cram, J. Chem. SOC., Chem. Cbmmun., 1995, 1085. 152 S. K. Kurdistani, R. G. Helgeson and D. J. Cram, J. Am. Chem. SOC., 1995, 117,1659. 153 J. C. Sherman, Tetrahedron, 1995, 51, 3395. 154 (a) J. R. Fraser, B. Borecka, J. Trotter and J. C. Sherman, J. 0%. Chem., 1995,60, 1207; (b) R. G. Chapman and J. C. Sherman, J. Am. Chem. SOC., 1995,117,9081. 155 F. de la Torre, L. Mussons, C. Raposo, J. L. Lbpez, J. Anaya, C. Caballero and J. R. Moran, J. Chem. SOC., Perkin Trans. 1, 1995, 2455. 156 J. S. Albert, M. S. Goodman and A. D. Hamilton, J. Am. Chem. SOC., 1995, 117, 1143. 157 T. J. Murray, S. C. Zimmerman and S. V. Kolotuchin, Tetrahedron, 1995, 51,635. 158 T. W. Bell, Z . Hou, S. C. Zimmerman and P. A. Thiessen,Angew. Chem., Znt. Ed. Engl., 1995,34, 2163. 159 D. L. Beckles, J. Maioriello, V. J. Santora, T. W. Bell, E. Chapoteau, B. P. Czech and A. Kumar, Tetra- hedron, 1995,51,363. 160 M. J. Crossley, T. W. Hambley, L. G. Mackay, A. C. Try and R. Walton, J. Chem. SOC., Chem. Commun., 1995, 1077. 161 J. Cuntze, L. Owens, V. Alcazar, P. Seiler and F. Diederich, Helv. Chim. Acta, 1995, 78, 367. 162 E. Martinborough, T. Mordasini Denti, P. P. Castro, T. P. Wyman, C. B. Knobler and F. Diederich, Helv. Chim. Acta, 1995, 78, 1037. Tetrahedron Lett., 1995, 36, 8403. 1995, 117, 1655. Angew. Chem., Int. Ed. Engl., 1995, 34, 1765. 163 C-T. Chen, R. Chadha, J. S. Siegel and K. Hardcastle, 164 S. R. LaBrenz and J. W. Kelly, J. Am. Chem. SOC., 165 C. Gennari, H. P. Nestler, B. Salom and W. C. Still, 166 N. Voyer and J. Lamothe, Tetrahedron, 1995,51, 9241. 167 M. Lofthagen and J. S. Siegel, Tetrahedron, 1995, 51, 168 M. Lofthagen and J. S. Siegel, J. 0%. Chem., 1995,60, 169 C. P. Waymark, J. D. Kilburn and I. Gillies, Tetra- 170 G. J. Pernia, J. D. Kilburn and M. Rowley, J. Chem. 171 R. S. Wareham, J. D. Kilburn, N. H. Rees, D. L. 6195. 2885. hedron Lett., 1995, 36, 3051. SOC., Chem. Commun., 1995,305. Turner, A. R. Leach and D. S . Holmes, Tetrahedron Lett., 1995, 36, 3047. 172 S.-S. Yoon and W. C. Still, Tetrahedron, 1995, 51, 567. 173 M. Torneiro and W. C. Still, J. Am. Chem. SOC., 1995, 117,5887. 174 H. Wennemers, S.-S. Yoon and W. C. Still, J. 0%. Chem., 1995, 60, 1108. 175 D. S. Lawrence, T. Jiang and M. Levett, Chem. Rev., 1995, 95,2229 176 C. A. Hunter, Angew. Chem., Znt. Ed. Engl., 1995,34, 1079. 177 J. T. Davis, S . Tirumala, J. R. Jenssen, E. Radler and D. Fabris, J. Org. Chem., 1995, 60, 4167. 178 G. Gottarelli, S. Masiero and G. P. Spada, J. Chem. SOC., Chem. Commun., 1995, 2555. 179 M. S. Goodman, A. D. Hamilton and J. Weiss, J. Am. Chem. SOC., 1995, 117,8447. 180 M. S. Goodman, V. Jubian and A. D. Hamilton, Tetrahedron Lett., 1995, 36, 2551. 181 M. S. Goodman, V. Jubian, B. Linton and A. D. Hamilton,J. Am. Chem. SOC., 1995, 117, 11611. 182 (a) P. J. Stang and K. Chen, J. Am. Chem. SOC., 1995, 117, 1667; (b) P. J. Stang, D. H. Cao, S. Saito and A. M. Arif, J. Am. Chem. SOC., 1995, 117,6273. Perry and Kilburn: Synthetic developments in host-guest chemistry 85183 M. Fujita, S. Nagao and K. Ogura, J. Am. Chem. SOC., 184 A. Bilyk and M. M. Harding, J. Chem. SOC., Chem. 185 N. Branda, R. M. Grotzfeld, C. Valdts and J. Rebek 186 C. ValdCs, U. P. Spitz, L. M. Toledo, S. W. Kubik and J. Rebek Jr, J. Am. Chem. SOC., 1995, 117, 12733. 187 C. Valdts, U. P. Spitz, S. W. Kubik and J. Rebek Jr, Angew. Chem. Int. Ed. En& 1995,34, 1885. 188 D. M. Rudkevich, A. N. Shivanyuk, Z. Brzozka, W. Verboom and D. N. Reinhoudt, Angew. Chem., Int. Ed. Engl., 1995, 34, 2124. 1995, 117, 1649. Commun., 1995, 1697. Jr, J. Am. Chem. SOC., 1995, 117, 85. 86 Contemporary Organic Synthesis

ISSN:1350-4894    

DOI:10.1039/CO9970400061

出版商:RSC    

年代:1997

数据来源: RSC