5 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By B. V. SMITH Department of Chemistry King's College London Strand London WC2R2LS 1 Alcohols and Ethers A wide-ranging synthesis of polyfunctional secondary alcohols depends on efficient coupling of an aldehyde and a cuprate RCu(CN)ZnI; the functional groups within the reagent may include ester nitrile enoate or amide. High yields were obtained with for example AcO(CH,),Cu(CN)ZnI and PhCHO (86%).' The absolute and relative configuration of fluorohydrins established via use of a-phenylpropionic acid as a derivatizing reagent for n.m.r. studies was supported by X-ray measure- ments.2 An article summarizing the work on generation of simple enols has been pub- li~hed.~ High selectivity has been reported for the reduction of p-hydroxyketones to anti-diols by Me4N+BH(OAc)3-.4 Controlled 'Payne-type' rearrangement of 2,3-epoxyalcohols in aprotic media has been studied and the product ratio shown to depend on the reactivity of the nucleophile; thus (1) after lithiation may by interchange afford (2) and the products (3) (4) and (5) reflect nucleophilic capture OH Nu P~CHZO+~~ PhCH20+oH PhCHzO4Nu OH Nu OH a~cordingly.~ Thus the product ratio from MeCu was significantly different to that from Ph,CuLi.This method was applied to a short synthesis of (+)-exo-brevicomin (6) in 31% overall yield. The synthesis and reactions of optically active 1.3-diols ' M.C. P. Yeh P. Knochel and L. E. Santa Tetrahedron Lett. 1988 29 3887. * P.Bravo F. Ganazzoli G.Resnati S. DeMunari and A. Albinati J. Chem. Res. (S) 1988 216. B. Capon B.-Z.Guo F. C. Kwok,A. K. Siddhanta and C. Zucco Acc. Chem. Res. 1988 21 135. D. A. Evans K. T. Chapman and E. M. Carreira J. Am. Chem. Soc. 1988 110 3560. P. C. B. Page C. M. Rayner and I. 0. Sutherland J. Chem. SOC.,Chem. Commun. 1988 356. 105 106 B. V. Smith derived from methyl 3-hydroxyglutarate have been explored particularly with respect to the synthon (7) which was converted into pure (8) (68%) by reaction with vinylmagnesium bromide.6 Easy access to t-butyl ethers and esters is achieved by reaction of Cl,C(C=NH)OBu' (from C1,CCN-ButOH) with the alcohol or acid in the presence of BF3.0Et2 .7 Some selectivity was noted for PhCH20CH2CH(OH)CH20H in which the terminal group was etherified.Reaction with acids was equally easy and afforded good yields e.g. BrCH2C02H gave 71% of ester. An alternative approach applicable to a wide range of alcohols was the use of isobutene and an Amberlyst H15 catalyst to form the t-butyl ether; this could be smoothly cleaved by Ac,O-FeCl in ether to afford the acetate. The advantage of this two-step method was that no isomeriz- ation ring closure or destruction of sensitive groups occurred; by this route (9) formed (lo) and for (1 1) -+ (12) no isomerization could be detected.' Me Et m=J(CH2)60R (9) R = But (11) R = But (10) R = Ac (12) R = AC Asymmetric synthesis of functionalized homoallylic alcohols (in both configur- ations) has employed a-sulphinylepoxides as a starting point.' High diastereoselec- tivity (90%) was noted for the synthesis of homoallylic alcohols with a syn-P-methyl group (Scheme l)." The complementary reaction of the (E)-a-chlorocrotyl boronate Reagents i RCHO CH2C12 0 "C;ii RCHO light petroleum 0 "C Scheme 1 L.Rosslein and C. Tamm Helu. Chim. Acra 1988 71 47. ' A. Armstrong I. Brackenridge R. F. W. Jackson and J. N. Kirk Tetrahedron Lett. 1988 29 2483. A. Alexakis M. Gardette and S. Colin Tetrahedron Lett. 1988 29 2951. G. Solladii C. Hamdouchi and M. Vicente Tetrahedron Lett. 1988 29 5929. LO R. W. Hoffman S. Dresely and J. W. Lanz Chem. Ber. 1988 121 1501. 107 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds (13) with 2-methylbutanal gave (14) and (15) (ca.3 1) which by reduction gave the known compounds (16) and (17) respectively. Such methods thus afford useful building blocks. qJ+ WC1 Me Me c1 Me Me * Me Me A stereoselective preparation of (E)-ally1 alcohols has been reported in which elimination from (18) by AIBN-boiling toluene is a key step." A convenient one-pot preparation of 2-substituted ally1 alcohols by transformation of an acid halide RCOCl into (19) has been reported.12 The enediol (20) was prepared in RLOH "\(""" good yield and enantiomerically pure via a boration-oxidation sequence starting from a borol-3-ene and was further transformed into a protected aldehyde (21) with a quaternary chiral centre (78%).13 Among methods which have been used in the preparation of oxiranes the following are noted.Stereospecific and efficient oxidation of alkenes by (22) (from Me2CO-K,S05) was achieved in 16 cases; for trans-2,5-dimethylhex-3-ene, compet-ing allylic oxidation lowered the yield.14 An interesting efficient and enantioselective A. Kaminura and N. Ono J. Chem. SOC.,Chem. Commun. 1988 1278. l2 J. Barluenga J. M. ConceMn J. L. Fernlndez-Simon and M. Yus J. Chem. SOC.,Chem. Commun. 1988 536. l3 G. Zweifel and T. M. Shoup J. Am. Chem. Soc. 1988 110 5578. A. L. Baumstock and P. C. Vasquez J. Org. Chem. 1988 53 3437. 108 B. V. Smith Ph .. Ph PhCOCH2Cl -VCI -H OH H H Reagents i BH,THF 1 mol % ; ii NaOH-H20 6; H Scheme 2 route to (S)-(-)-phenyloxirane is shown in Scheme 2.” Bromohydrins with base and in the presence of an optically active cobalt complex gave oxiranes of modest optical purity.16 The epoxyether (23) (R = tritylmethoxy) has been prepared in a sequence from (R)-malic acid.” Raney Ni-induced deoxygenation of tertiary alcohols in toluene shows regioselec- tivity since remote halogen for example is unaffected; neopentyl-like alcohols react normally.18 P-Hydroxyselenides with MCPBA furnished either epoxides or ketones.” With cyclic structures ring expansion occurred.A method for selective protection of 1,n-diols with preferential reaction at the secondary group is depicted in Scheme 3.20 Stereospecific 0-benzoylation of propan- 1,2-diol at C2 proceeds with inversion of configuration and was affected by dibenzoyl Reagents i (MeO),CH D-camphorsulphonic acid r.t.; ii DIBAH hexane -78 “C Scheme 3 peroxide-PPh .21 It was suggested that a 1,3,2-A 5-dioxaphospholane (24) which underwent proton-assisted ring opening to an oxyphosphonium species could account for the observed selectivities [e.g.(24) -* (25)]. A selective mono-0-benzyla- tion of a meso-divinylglycol has been used to advantage in preparation of chiral precursors of some carbohydrate derivatives.22 15 E. J. Cbrey S. Shibata and R. K.Bakshi J. Org. Chern 1988 53 2861. 16 T. Takeichi T. Takakura M. Ishimori and T. Tsuruta Bull. Chem. Soc. Jpn. 1988 61 603. 17 R. DiFabio and D. Misiti Gazz. Chim. Ital. 1988 118 209. I8 M. E. Krafft and W. J. Crooks 111 J. Org. Chem. 1988 53 432.19 S. Uemura K. Ohe and N. Sugita J. Chem. SOC.,Chem. Cornmun. 1988 111. 20 M. Takasu Y. Naruse and H. Yamamoto Tetrahedron Lett. 1988 29 1947. 21 A. M. Pautard and S. A. Evans jun. J. Org. Chem. 1988 53 2300. 22 R. R. Schmidt and K. Frische Liebigs Ann. Chem. 1988 209. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Ph3P:) OR Palladium-catalysed phenylation of allylic alcohols showed a dramatic rate enhancement in the presence of tertiary amine~.,~ Thus but-3-en-2-ol-PhI-Pd gave 97% of phenylated butan-2-ones (principally the 4-isomer). The ring opening of oxiranes by SiF4 has been examined with respect to selec- ti~ity.,~ Alkene or ether functions are unaffected and the fluorohydrin formed has fluorine at the more substituted carbon atom; from (26) the major product (78%) was (27).Anti-opening of meso-oxiranes by B-halogenodiisopinocampheylboranes F Ph/y ‘\ H’ Me OH proceeds with high e.e.; thus MeCH(OH)CH(I)Me (lR 2R) from cis-but-2-ene epoxide had 78% e.e.25 For some cyclic examples 100% e.e. was observed. Variable e.e. was observed for a number of nucleophilic ring-opening reactions in the presence of metal(1r) tartrates.26 The regio- and chemoselectivity of oxirane ring opening by Me3SiN3 in the presence of Al(OPri)3 has been examined; 2-trimethylsilyloxy derivatives are produced in a stereospecific (anti) process.*’ Alcoholysis of oxiranes catalysed by an organotin phosphate condensate gave P-alkoxyalcohols; gem-dialkyloxiranes cleaved at the tertiary C-0 bond.28 Oxiranes carrying aryl alkenyl alkynyl or trimethylsilyl groups react with titanium acetylides at the more substituted carbon to afford 2-substituted b~t-3-yn-l-ols.~~ Yields were dependent on solvent ratio of reactants and structure.‘Reactive’ titanocene deoxygenated oxiranes in a stereoselective manner; thus trans-oxiranes gave E-alkenes and cis-isomers formed Z-alkene~.~’ Phenylsulphonyloxirane (28a) is a useful synthetic equivalent for the dipolar synthon (29); ring opening and elimination from (28b) by MgBr (ether-toluene) gave (30).” il\so2ph R (28) a; R = H b; R = D allyl Me,SiMe 23 R. Benhaddou S. Czernicki and G. Ville J. Chem. SOC.,Chem. Commun. 1988 247 24 M. Shimizu and H. Yoshioka Tetrahedron Lett.1988 29 4101. 25 N. N. Joshi M. Srebnik and H. C. Brown J. Am. Chem. SOC.,1988 110,6246. 26 H. Yamashita Bull. Chem. SOC.Jpn. 1988 61 1213. 27 M. Emziane P. Lhoste and D. Sinou Synthesis 1988 541. 2a J. Otero Y. Nubo N. Tatsumi and H. Nozaki J. Org. Chem. 1988 53 275. 29 N. Krause and D. Seebach Chem. Ber. 1988 121 1315. 30 F. Schobert Angew. Chem. Int. Edn Engl, 1988,27 855. 11 -A n I-xsr 1-t. r -1 -_. 31 %I A-I. ._,--* - 110 B. K Smith Wittig rearrangement of allyloxycarbanions is of interest as a method for stereoselective C-C bond formation and two examples of the transformation (31) -+ (32) with high asymmetric induction have been described.32 2 Alkyl Halides Amongst the reagents examined for the conversion of a trialkylborane into a chloroalkane nitrogen trichloride was the best.This method permits anti-Markov- nikov hydrochlorination of alkenes via hydroboration in 66-94% yields.33 Decar- boxylative chlorination of aliphatic (and aromatic) carboxylic acids gave chloro compounds in good yield; this method is based on prior formation of benzophenone oxime esters (33) and photolytic breakdown in CC14.34 Some by-products were R C9, N=CPh2 II found but for Me(CH2)16C02H the chloroalkane was formed in 82% yield. Conver- sion of tlcohols into chloro compounds was also effected by reaction with HC1-H20- C16H33NMe3 X-(catalyst) in micellar conditions and gave for C4 to c16 80-97% of the desired product.35 A convenient one-pot reductive halogenation of carbonyl compounds has been used for aralkyl bromides and iodides.36 Some papers from H.C. Brown and co-workers have continued the investigations into hydroboration- halogenation; thus bromination in the presence of sodium methoxide is particularly. effective since all three alkyl groups are utilized and very high or quantitative yields were rep~rted.~’ The role of bromine in an inert solvent was examined and a free radical chain mechanism was suggested.38 Hydroboration-iodination sequences furnish approximately 67% of iodoalkane normally; the reaction rate is accelerated by sodium hydroxide but the yield of for example 1-iododecane is still only 60%. However with Sia2BH 95% of the iodo compound was produced. It was further established that the base-induced reaction occurs with inversion of configuration at the reaction centre.39 32 R.Bruckner and H. Priepke Angew. Chem. Inr. Edn. Engf. 1988 27 278. 33 H. C. Brown and N. R. DeLue Tetrahedron 1988,44 2875. 34 M. Hasebe and T. Tsuchiya Tetrahedron Lett. 1988 29 6278. 35 B. JurSi6 Synthesis 1988 868. 36 C. Bilger R. Royer and P. Demerseman Synthesis 1988 902. 37 H. C. Brown and C. F. Lane Tetrahedron 1988,44 2763. 38 H. C. Brown C. F. Lane and N. R. DeLue Tetrahedron 1988,44 2773. 39 H. C. Brown M. W. Rathke M. M. Rogic and N. R. DeLue Tetrahedron 1988,44 2751. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Copper(I) iodide-assisted exchange of vinyl bromides gave iodo analogues with the same isomer ratio as starting material and in 54-89% yield.40 No exchange occurred with KI in the absence of the copper(1) salt.1,l-Dibromides gave 1,l- diiodides (74% 1-4 h) and 1,2-dibromides gave low yields of diiodides (4.5 h). Longer reaction time in the latter reaction gave elimination to alkyne. HMPT and N-methylpyrrolid-2-one were more effective than diglyme or DMF. Base-promoted elimination from Sfluorononane has been reported; alkoxide gave a cis trans ratio of ca. 1:3 whereas diisopropylamide formed almost pure trans-i~omer.~' Even with Schlosser's base (LDA-KOBu') reaction was slow. The same authors report on elimination from meso-and (*)-6,7-difluorodecane. Preparation of starting materials is also reported?2 Carbonylation of Bu'Br mediated by Cp2Sm gave at -40 "C a modest yield (46%) of Bu'CH(OH)CH(OH)BU'; the intermediacy of an acyl compound (34) was presumed since heptanal trapped it to form (35)."3 Bu'CSmCp, It 0 Bu'COCH( OH)C6H,3 (34) (35) The asymmetric induction consequent upon replacement of diastereotopic bromine atoms by lithium has been probed by Hoffmann and co-workers.u As shown in Scheme 4 the diastereoisomeric ratio is high and it is presumed that the carbenoid intermediates (36) and (37) must be configurationally stable enough at low temperature to permit stereospecific trapping.By oxidation of (38) and (39) (formed in 70% yield d.s. = 93:7 respectively) it was concluded that the pro-ul-bromine45 is preferentially replaced on lithiation. Although it was not established Me3Si0 Me3SuBr Br R H R = But or Pr' (36) ii I (37)I Me3Si0 E Me3Si0 Br H Reagents i BuLi hexane -120°C; ii E = Me2C0 Me,CHCHO or HO-B 'x -120°C 0 Scheme 4 H.Suzuki,M. Aihara H. Yarnamoto Y. Takarnoto and T. Ogawa Synthesis 1988 236. 41 S. Matsubara H. Matsuda T. Harnatani. and M. Schlosser. Tetrahedron 1988. 44. 2855. 42 S. Matsubara H. Matsuda T. Harnatani and M. Schlosser Tetrahedron 1988 44 2865 2875. 43 J. Collin and H. Kagan Tetrahedron Lett. 1988 29 6097. 44 R. W. Hoffrnann M. Brewersdofi K. Ditrich M. Kriiger and R. Stunner Angew. Chem Int. Edn. Engl. 1988 27 1176. 45 D. Seebach Angew. Chern. Int. Edn. Engl. 1982 21 654. 112 B. V. Smith beyond doubt the role of the trimethylsilyloxy group in co-ordinating to the lithium atom (see Scheme 4) is believed to be crucial.Iodoalkanes in the presence of an alcohol a metal carbonyl and a platinum complex form esters in good to excellent yields.& No reaction occurred without the catalyst or light. Acid halides were produced from ButX-CO-RSO3H-CCl4 in a process believed to involve cationic intermediates (cf Koch-Haaf process).47 A very effective reducing agent for alkyl halides is tris(trimethylsilyl)silane (Me3Si)3SiH.48 A free radical pathway is suspected as reduction may be photo- initiated and inhibited by scavengers. The authors advocate its use in place of Bu3SnH and claim better ecological acceptability of silicon -could this be a 'green' reagent? A~hby~~ has replied to criticismsSo of the SET pathway in reactions of alkyl halides (and ketones) and defends his position strongly.Bromochloromethane under the influence of sonication and in the presence of lithium rapidly reacts with carbonyl groups affording high yields of ~xiranes.~~ Samarium has achieved popularity again this year and in an interesting example of use of SmI it has been shown that drastically altered stereochemistry in cleavage of (cyclic) P-halogenoethers may be realized. Thus high E selectivity was found for formation of y,8-en01s.~~ Vinyl halides with PhSeCl in MeOH gave a-alkoxyacetals presumably via addition-elimination-addition sequences; some rearrangement apparently occurred since PhCH=C( D)Br gave (40) in addition to (41).53 3 Aldehydes and Ketones This section is once again the largest in the Report and of necessity it cannot give complete literature coverage.Work reported is hopefully of general interest and not mentioned for its novelty alone. 46 T. Kondo Y. Tsuji and Y. Watanabe Tetrahedron Lett. 1988 29 3833. 47 J.-J. Brunet P. Legars Y. Peres and I. Tkatchenko Tetrahedron Lett. 1988 29 4569. 48 C. Chatgilialoglu D. Griller and M. Lesage J. Org. Chem. 1988 53 3641. 49 E. C. Ashby Acc. Chem. Res. 1988 21 414. 50 M. Newcomb et aL J. Org. Chem. 1987 52 3275; J. Am. Chem. SOC.,1987 109 1195; D. Curran Tetrahedron Lett. 1986 27 5821. 51 C. Einhorn C. Allaveno and J.-L. Luche J. Chem. Soc. Chem. Commun. 1988 333. 52 L. Crombie and L. J. Rainbow Tetrahedron Lett. 1988 29 6517. 53 M. Tiecco L. Testaferri M.Tingoli D. Chianelli and D. Bartoli Tetrahedron 1988 44,2273. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 113 Controlled potential electrolysis of Fe(CO),-RX (EtI or PhCH,Br) is a novel route to aldehydes.54 Preparation of 2,2-dialkoxyethanals (RO),CHCHO which can be tedious has been achieved in 50-70% yield by using an excess of the alcohol and sufficient catalyst. The products are useful two-carbon synthons for ketoalde- hydes oximes nitriles and amine products.55 An easy access to P-acyl- and p-arylpropanols relies on a novel silylated organotin homoenolate equivalent as an umpolung reagent (see Scheme 5).56 Direct conversion of RCHO into RCHSe and RCHS (45-85% yields) was effected by reaction with (Me,Si),Se or (Me,Si),S in the presence of a catalytic amount of BuLi in THF; R was alkyl (including But) or aryl.The selenoaldehyde was trapped with cycl~pentadiene.~~ 0 1v iv SiMe3 HCECCH,OMe Bu3Sn&OMe iii 0 SiMe3 Reagents i Bu3SnH AIYN 110 "C; ii BuLi THF -78 "C then Me3SiC1; iii RCOCI PdC12(PPh3)2 THF 65 "C; iv Bu4N F-THF 0 "C; v ArBr Pd(PPh,), 110 "C Scheme 5 H. C. Brown has continued his elegant work on the preparation of compounds with very high enantiomeric purities uia boron compound^.^^ The preparation of chiral ketones was effected by three methods (a) carbonylation (b) cyanidation and (c) iodoalkynation as shown in Scheme 6. It is notable that in the examples shown the enantiomeric purities of (42) (43) and (44) were 100 99 and 96% respectively.This must surely be one of the most versatile routes to this type of compound. The preparation of a-chiral-a'-alkynylketonesof very high e.e. starting with organyl-( 1-alkynyl)borinic esters has been rep~rted.'~ Thus (45) was obtained in 65% yield but with e.e. >99%. Aldehydes with trimethylsilyldiazomethane gave trimethylsilylketones (46) after aqueous work up; dilute hydrochloric acid gave the 54 D. Vanhoye F. Bediou A. Martreux and F. Petit Tetrahedron Lett. 1988 29 6441. S5 A. Stambouli F. Hamedi-Sangsari R. Amoroux F. Chastrette A. Blanc and G. Mattioda Bull. SOC. Chim. Fr. 1988 95. 56 J. B. Verlhac J.-P. Quintard and M. Pereyre J. Chem. Soc. Chem. Commun. 1988 503. 57 M. Segi T. Nakajima S. Sugg S. Murai I. Ryn A. Ogawa and N.Sonoda J. Am. Chem. SOC.,1988 110 1976. 58 H. C. Brown R. K. Bakshi and B. Singaram J. Am. Chem. Soc. 1988 110 1529. 59 H. C. Brown A. C. Gupta J. V. N. V. Prasad and M. Srebnik J. Org. Chem. 1988 53 1391. 114 B. V. Smith (a> iy""2 I' (44) Reagents i ,0 "C THF; ii CO 1000 p.s.i.; iii [O],pH 8; iv NaCN THF; v TFAA -78 "C; vi IC_CMe EtzO -25 "C; vii NaOMe 25 "C Scheme 6 0 y.:C C(CH2) 3 C 1 &SiMe3 R desilylated product in 43-89% yield.60 Two papers dealing with the synthesis of a-fluoroketones (and polyfluoroketones) have been published. Homochiral a-fluoroketones have been prepared from racemic a-fluorocarboxylic esters and enan- tiomerically pure sulphoxides; by this route (47) [from PhCH(F)CO,Me and the lithiated sulphoxide (48)] yielded (S)-(49) (73Y0 optically pure).61 Extension of this method to polyfluoroesters gave polyfluoroketones.62 Iodination of ketones with I,-ceric ammonium nitrate (in AcOH or MeOH) was efficient; by this method pentan-2-one gave principally the 3-iodo derivative (97% ) the remainder being the primary Ketone hydrazones via reaction of dimagnesium salts and Se,C12 gave an intermediate (tetraselenide?) which when heated in tributylamine formed a 60 T.Aoyama and T.Shiori Synthesis 1988 228. 61 P. Bravo and G. Resnati J. Chem. SOC.,Chem. Commun. 1988 218. 62 P. Bravo E. Piovosi and G. Resnati Guzz. Chim. Ztul. 1988 118 115. 63 C. A. Horiuchi and S. Kiji Chem. Lett. 1988 31. 115 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds ~elenoketone.~~ By using two equivalents of RMgX to react with the hydrazone before selenation (instead of base) a yield of 51% of Bu\C=Se was formed (rather than 28%).An approach to optically active a-unsubstituted or a-anti-substituted-/3 -hydroxy- ketones was sought via Pd-catalysed asymmetric disilylation of a,P-enones followed by oxidative cleavage of the C-Si bond. As depicted in Scheme 7 the method gave reasonable success.65 (R2) -P 'iii iv PhTR' i ii hw~ ___ 0 '"WR' Me?PhSi OL1 OH R' = R2= Me 78% e.e. Reagents i PhSiCl,SiMe,; ii MeLi PdCl,.binap; iii R'X; iv HBF4-H,02 Scheme 7 A metallation-alkylation sequence with 4H-1,3-dioxin -a new p -acyl anion equivalent -is a practicable route to a$-unsaturated aldehydes.The reagent (50) [equivalent to (51)] by alkylation gave (52) which was cleaved by methanolic HCl to give a P-hydroxyacetal; thermolysis of this (boiling toluene) gave the product.66 Three-carbon homologation of a ketone was used to prepfre a p,?-unsaturated aldehyde; acrolein with Ph3P and HBr in Pr'OH gave Ph3PCH2CH2CH0 trans- formed into (53) by HC(OPr'),. The acetal (54) [71-96% from (53) R'COR' and base] was cleaved to the product in >93% yield.67 This method is a neat exploitation of reactivity and selectivity. A variation on this phosphorane chemistry is the preparation of 4-diethylphosphonobut-2-enaland its use to prepare a conjugated aldehyde. Thus (55) protected as an imine gave with hexanal a 78% yield of deca-2,4-dienal of predominantly E,E stereochemistry.Further purification of the reaction product from 4-MeOC6H4CH0 (93% E,E-isomer) allowed a pure sample to be obtained.68 + 64 A. Ishii R. Okazaki and N. Inamoto Bull. Chem. SOC.Jpn. 1988 61 861. 65 T. Hayashi Y. Matsumoto and Y. Ito J. Am. Chem. SOC.,1988 110 5579. 66 R. L. Funk and G. L. Bolton J. Am. Chem. Soc. 1988 110 1290. 61 J. Viala and M. Santelli Synthesis 1988 395. 68 T. Rein B. Akermark and P. Helquist Acta Chem. Scand. Ser. B,1988 42 569. 116 B. V. Smith 1,l-Diorganometallics of Mg and Zn' react with Me,SnCl to accord 'mixed' reagents oxidized by air to aldehydes and ketones.69 Thus (56),after stannylation and oxidation gave (57). With formation of aryl ketones (57; RS= Ph) reaction was rapid; the generation of aldehydes was slower.It was observed that the reaction rate was enhanced by added Me,SiCl but retarded by DMF or Me$. It was possible to adapt this reaction to form aldol-like products (see Scheme 8) with reasonable selection. f" i-iii+ EttcMgBr -Et:C EtfCH OEt Hex-iv,v Hex-H i-ZnBr H Hex 0 0 88 12 Reagents i Bu'Li -78 "C; ii ZnBr,; iii C6H,,CH=CHMgBr; iv 1 eq. Me,SnCl; v O, Me3SiC1 Scheme 8 Phosphorus-containing reagents have also been used in synthesis of unsaturated ketones by chain extension. As shown in Scheme 9 good yields of (58) were obtained by either route." Typically the 2:E ratio of (58) was 3 1. Lithiated N,N-dimethyl- hydrazones derived from CU,~ -unsaturated aldehydes are alkylated to afford 0 I1 ph2py?(;l /yo R2 R' vii ii x R3 \ R' Reagents i Ph2PO-; ii HO(CH,),OH H+; iii BuLi; iv R2R3CO; v NaH; vi H30+; vii Ph3P-Me,SiCI Scheme 9 69 P.Knochel C. Xiao and M. C. P. Yeh Tetrahedron Lett. 1988 29 6697. 70 H. J. Cristau E. Torreilles and C. Barois-Gacheriau Synth. Commun. 1988 18 185. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds rearranged a-alkylated P,y-unsaturated aldehyde dimethylhydrazones. Thus from (59) and PhCH2Br there was produced (60) (63'/0).~' This approach was used in the synthesis of 2,5,9-trimethy1-2-vinyldeca-4,8-dienal(61), a sesquiterpene occurring in the intriguingly named beefsteak plant. It was further shown that dimethylhy- drazones of (2E 4E)-alkadienals underwent the corresponding rearrangement to afford a-alkylated 3 E,5Z derivatives.A stereoselective synthesis of conjugated dienones was effected by treating an alkynylketone with RuH2(PPh3)4 (with or without solvent toluene); in this way (62) was obtained in 85% yield.72 Al kylidene malonaldehydes have been obtained from (63) by treatment with RMgBr or RLi followed by hydrolysis. Simple alkyl derivatives were unstable and were trapped by cycloaddition with CH,=CHOEt; alkynyl-substituted analogues showed greater stability.73 But-2-yn-l,4-dial has been prepared but is explosive even under nitrogen.74 1,2-Diketones were prepared from alkynes by reaction with Ru02-NaI04; the terminal alkyne Me(CH,),,C_CH gave myristic acid (47Y0).~' Oxidation of a hydroxycarbonyl system by N-chlorosuccinimide-Me2S gave a range of 1,3-dicar- bonyls in good to excellent yield.76 Some limitations were noticed with for example P-hydroxyesters which gave no carbonyl-containing product.The required starting materials were prepared via the usual aldol method. Selectivity in reduction of aldehyde groups in preference to ketones was shown (>95'/0) with sodium borohydride in 30% EtOH-CH,Cl at -78 0C.77 The anti-Cram reduction of acyclic ketones has been discussed in terms of a process initiated by electron tran~fer.~' An exceptionally efficient reducing agent for prochiral ketones is diisopinocam- pheylchloroborane; reduction at -25 "C in THF is rapid and gives extremely good selectivity. This approach is recommended as superior to other methods including 71 M.Yarnashita K. Matsurniya K. Nakano and R. Suernitsu Chem. Lerr. 1988 1215. 72 D. Mo Y. Lin X. Lu and Y. Lu Tetrahedron Lett. 1988 29 1045. 73 Z. Arnold G. V. Kryshtal V. Krll D. Dvoilk and L. A. Yanovskaya Tetrahedron Lerr. 1988,29,2861. 74 D. Stephen A. Gorques A. Belyasmine and A. LeCoq. J. Chem. SOC.,Chem. Commun. 1988 263. 75 R. Zibuck and D. Seebach Hefv. Chim. Acra 1988 71 237. 76 S. Katayama K. Fukudo T. Watanabe and M. Yarnaguchi Synthesis 1988 178. 77 D. E. Ward and C. K. Wee Synrh. Commun. 1988 18 1927. 78 Y. Yarnarnoto K. Matuoka and H.Nemoto J. Am. Chem. SOC.,1988 110 4475. 118 B. V. Smith use of Alpine-b~rane.'~ Reduction was significantly better in some cases with neat reagent; thus 3,3-dimethylbutan-2-one gave a modest yield of the S-alcohol (50% ) but in high e.e.(93%).The favoured transition state for reduction was considered as boat-like (64) and the preference for S selectivity was thus rationalized. However with PhCOCMe the R-alcohol (79% e.e.) was obtained which was surprising the alternative transition state (65) should on steric grounds be less favoured. A bonus I RS RL (64) (65) from this reaction was recovery of a-pinene of ca. 100% (>99.4%) e.e.; reaction of Ipc2BC1 and PhCHO led to rapid release of 2 equivalents of the pinene. Optically active Grignard reagents (derived from naturally occurring isoprenoids) gave little or no addition but some selectivity in reduction.80 Thus the Grignard reagent from (66) with PhCOPr' gave 67% reaction and the reduction to the R-alcohol proceeded with 66% selectivity.Selective activation of one enantioface of a methyl ketone was investigated via a-bonding to a chiral metal template. Formally the reduction occurs by hydride addition and the liberated alcohol has very high e.e. For reduction of butan-2-one the highest recorded e.e. achieved was 95%;with PhCOMe e.e. >99% .81 The key intermediate [(q5-C5H5)ReNO(PPh,){ ql-Me(R)C=O}]+PF,- (68) is derived from the chiral rhenium derivative (67). 79 H. C. Brown J. Chandrasekharan and P. V. Ramachandran J. Am. Chem. SOC.,1988 110 1539. 80 M. Falarni L. Lardicci G. Uccello-Baretta and G. Giamcomelli Gazz. Chim. Ztal. 1988 118 495. 81 J. M. Fernandez K. Emerson R.D. Larsen and J. A. Gladysz J. Chem. SOC.,Chem. Cornmun. 1988 37. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Chemoselectivity in reduction and alkylation of aldehydes and ketones has been achieved via a little MADness.82 This acronym for methylaluminium bis-( 2,6-di-t- butyl-4-methylphenoxide) is not connected with the irrational; on the contrary selectivity uia complexation is a useful approach to overcoming lack of discrimina-tion by Grignard reagents or alkyllithiums as between aldehydes and ketones. MAD activates an aldehyde but not a ketone such that a nonanal-di-t-butyl ketone mixture gave only decan-2-01(62%) in the presence of MAD. Conversely the reagent Me,AIN(Me)Ph reacts with an aldehyde to form (69); the uncomplexed ketonic carbonyl is thus free to react and alkylation of a nonanal-nonan-5-one mixture gave a secondary tertiary alcohol ratio of 1:9.R'CHX I OAlRz (69) 1,2-Diketones are usually reduced by baker's yeast with low selectivity; excep- tionally 1 -phenylpropane- 1,2-dione gave pure (S)-(-) -2- hydroxy- l-phenylpropan- 1-one in good yield.83 Benzil gave racemic benzoin; modest e.e. (56%) was achieved when SmI in THF-HMPA was used and in the presence of q~inidine.~~ High stereoselectivity was observed in the Ru"B1NAP-catalysed homogeneous hydroge- nation of 1,3-diketones; e.g. MeCOCH2COMe gave anti and syn-diols (98% ratio 99 :1 e.e. >99'/0).'~ Pentan-2-one was little affected under these conditions. Reduc- tion of 2-alkyl-3-hydroxyketonesuia silyl ethers has been used as a route to anti-anti-1,3-diols; typically (70; R' = R2 = Pr') gave 73% of (71) and (72) (ratio 98:2).R3SiO R&:H-R' The Bu'Me2Si group was chosen to prevent chelation; the favoured conformer was considered to be (73).86 Two articles dealing with reviews of enantioselective alkylation of carbonyl compounds have been published.",'' A route to C-monoalkylation of p -diketones 82 K. Maruoka Y. Araki and H. Yamamoto Tetrahedron Lett. 1988 29 3101. 83 R. Chinevert and S. Thiboutot Chem. Lett. 1988 1191. 84 S. Takeuchi and Y. Ohgo Chem. Lett. 1988 403. 85 H. Kawano Y. Ishii M. Saburi and Y. Uchida J. Chem. SOC.,Chem. Commun. 1988 87. 86 R. Bloch L. Gilbert and C. Girard Tetrahedron Lett. 1988 29 1021.87 R. Noyori S. Suga K. Kawai S. Okada and M. Kitamura Pure Appl. Chem. 1985 60 1597 88 M. T. Reetz Pure Appl. Chem. 1988 60 1607. 120 B. V. Smith which avoids 0-alkylation dialkylation and cleavage reactions has been estab- li~hed.~~ Controlled electrolytic reduction of pyrrolidone in the presence of Et,N+ OTs- in DMF gave (74) which with pentane-2,4-dione gave the tetraethylammonium enolate; the latter with 1-iodohexane gave 3-hexylpentane-2,4-dione(89%). This result was contrasted with conventional alkylation (NaH-DMF then C6H131) which gave 23% of the desired product 12% of the dihexyl derivative and 3% of 0-alkylated product. For 14 examples the preferred route gave yields between 64 and 92%. Studies of the Knoevenagel reaction of ArCHO and P-ketoacids have shown that the role of catalyst (secondary or tertiary amine) is in modifying product formation and reversibility?' Effective heterogeneous catalysis of reaction between PhCHO and CNCH,CO,Et by amino groups of aminopropylsilica was reported (98% yield).No Michael addition could be detected. Pentane-2,4-dione gave a low yield of condensation product perhaps owing to its adsorption as an enol." Stereoselective aldol reaction of (R)-and (S)-2-hydroxy- 1,2,2-triphenylethyl ace- tate (75) was achieved in high optical yields (Scheme lo) and for PhCHO for example the ratio of (76):(77) in THF at -78°C (88:12) increased to 98:2 in HO MO OM HO H RU*Xh-+o<22 'Rmox;h H Ph -Reagents i 2 eq. LDA THF-Me20 -135 "C; ii MgX,; iii RCHO Scheme 10 THF-Me20 (-135°C).Hydrolysis of (76) or (77) gave P-hydroxyacids of corre-sponding optical purity." Further very detailed work on this system has sought to probe the control in additions of (R)-and (S)-(75) to chiral aldehydes.93 The general Scheme 11 predicts the outcome of the addition of enolates from (R)-and (S)-(75) to RCHO; doubly deprotonated (R)-(75) gave with (R)-(78) at -125 "C (79) and (80) (90 lo) which were cleaved in turn to (81) and (82). With (S)-(75) opposite 89 T. Shono S. Kashimura M. Sawamura and T. Soejima J. Org. Chern. 1988 53 907. 90 M. Tanaka 0.Oota H. Hiramatsu and K. Fujiwara Bull. Chern. SOC.Jpn. 1988 61 2473. 91 E. Angeletti C. Camena G. Martinetti and P. Venturello Tetrahedron Lett. 1988 29 2261.92 R. Devant U. Mahler and M. Braun Chern. Ber. 1988 121 397. 93 U. Mahler R. M. Devant and M. Braun. Chem. Ber. 1988 121 2035. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Si OBn OH OBn OH 2 L R +Mej\/CR_li' Me Me (79) 90 10 OBn OH Me&OH Me=OH + (81) (82) Reagents i (R)-(75),2 eq. LDA THF-Me,O -125 "C; ii KOH Scheme 11 selectivity was observed i.e. (79) :(80) = 5 :95. It was deduced that reagent control was dominant in the reactions studied since the controlled and predictable synthesis of anti-(81) and syn-(82) could be realized. D-Glyceraldehyde acetonide and 2-trimethylsilylthiazole react to form a 'thiazole-masked' chiral butanal; with thiazole D-erythose for example a route to (83)was available.Additionally chiral hydroxy- epoxy- and azidobutanals were prepared.94 I OCHzPh (83) 1,3-Asymrnetric induction was observed in the coupling of 2-lithio-2-( l-methylalk- 2-enyl)-1,3-dithiane with RCHO; the product ratio syn-(84):anti-(85)was a function of the aldehyde structure so whereas PhCH2CH2CH0 showed syn preference the reverse was true for MeCECCHO. Addition of BF,.OEt diminished selectivity?' A remarkably high 1,3-anti selectivity was shown in the addition of organotitanium reagents to &substituted aldehydes carrying a dithioacetal group at the a-position e.g. (86) with MeTiCI gave a 72% yield of (87) (anti:syn = 98:2)?6 Horner olefination of aldehydes with N-acyl-(2-diethoxyphosphoryl)glycine ethyl ester proved a useful route to dehydroamino acids with 2 selectivity e.g.(88) (72%) had a 2 :E ratio of 6.3 :l.97 94 A. Dondoni G. Fantin M. Fogagnolo A. Medici and P. Pedrini Synthesis 1988 685. 95 Y. Honda E. Morita K. Ohshiro G. Tsuchihashi Chem. Lett. 1988 21. 96 Y. Honda and G. Tsuchihashi Chem. Lett. 1988 1937. 97 P. G. Ciattini E. Morera and G. Ortar Synthesis 1988 140. 122 B. V.Smith High diastereo- and enantioselection was found for the addition of 2-(y-alkoxyally1)diisopinocampheylboraneto aldehydes. Lithiated ally1 methyl ether with either enantiomer of (89) followed by BF3-OEt2 gave (90) (or enantiomer). As Scheme 12 shows for EtCHO 65% yield of product was obtained with threo selectivity of 94 6 and high enantioselectivities (>go%).As a means of introducing a masked hydroxy group the methoxymethyl ether borane (91) was useful. Taken together this group of chiral (2)-alkoxyallylboranes show the highest enantio- and diastereoselection of any compounds of this type reported to date.98 )2BOMe Reagents i BuLi THF-C6H,* =78"C; ii (89),THF -78 "C; iii BF,-OEt2 Et20 -78 "C; iv EtCHO -78 "C; v H,N(CH,),OH Scheme 12 As a means of probing the intermediates and key steps in addition of allylstannanes to aldehydes spectroscopic methods were used to investigate the complexes formed. Aldehydes formed a complex with SnCl quantitatively and no free aldehyde was detected; with BF3.0Et different behaviour was observed with complexation and free species being present. Complexed MeCHO and allyltrimethylstannane showed that at -80°C both components were present at -60°C redistribution took place H.C. Brown P. K. Jadhav and K. S. Bhat J. Am. Chem. SOC.,1988 110 1535. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 123 without reaction at -20 "C the first sign of pent-4-en-2-01 formation was detected and at 0°C only this product was present. With Bu'CHO however reaction with the stannane was immediate at -80 "C. A rationale for these reactions was available on the basis of these and other experiment^.^^ Addition of tetraallylstannane to aldehydes (or reaction with an acid chloride) was smoothly effected by CsF."' Montmorillonite clay has found application as catalyst in aldol reactions of silylenol ethers with aldehydes or acetals."' The diastereoselection was sensitive to the solvent of choice but little changed by replacing A1 in the clay by Ti or H+.Addition of (92) (E :2 = 83 :17) to MezCHCHO gave a threo :erythro ratio of 72 28 (toluene -3O"C -20 "C) 74 26 (DME -30 "C -20 "C) or 46 54 (CH,Cl,). Reaction of (93) and (94) with 'Almont' clay gave (95) :(96) = 93 :7 (-65 "C),and 92 8 with 'H-mont' at -50 "C. Triethylamine proved an effective catalyst poison. The selection in aldol reactions via P-silylketones has been utilized by Enders.'" h Me3Si0 PhxCHO \ PMe3Si0 b Ph Ph+Ph Phre3 (93) (94) (95) (96) The method as outlined in Scheme 13 and with high d.e. (92-98%) and e.e. 2 98% was applied to a synthesis of sitophilure an aggregation pheromone of the rice and maize weevil.I Bu' Me Si B u' iii + R Me Reagents i Bu2BOS02CF3 PrlNEt CH2C12 -10 "C;ii RCHO -78 "C then [O],flash chromatography; iii HBF, H20 20°C Scheme 13 99 S. E. Denmark T. Wilson and T. M. Willson J. Am. Chem. Soc. 1988 110 984. 100 D. N. Harpp and M. Gingrass J. Am. Chem. SOC.,1988 110 7737. 101 M. Kawai M. Onaka and Y. Izumi Bull. Chem. Soc. Jpn. 1988 61 1237. 102 D. Enders and B. B. Lohray Angew. Chern. Inr. Edn. En& 1988. 27 581. 124 B. V; Smith Although the lithium derivative of the allenic reagent (97; M = Li) showed low regioselectivity on addition to aldehydes the titanium analogue (97; M = TiOPr;) gave much better result^."^ The products from such additions were elaborated into 2,6-dideoxyhexoses of urubino-and xylo-configuration.Titanium (or niobium) com- plexes of aldehydes block aldol-type reactions; evidence for a compound MeCl,TiOCH( R)PPh3 was obtained.lW Competitive experiments demonstrated that the heptanal heptanone reactivity ratio was 25 1 but 1 :9 in the presence of the complexing agent. Addition of diethylzinc to an aldehyde showed reasonable-to- good e.e. when conducted in the presence of a chiral tertiary-amino alcohol e.g. (98); PhCHO in the presence of (98) (20.5% e.e.) gave 96% of the s-alcohol 88% e.e.'05 Germanium enolates (from Li enolates and Me3GeX) reacted with PhCHO to give predominantly erythro-aldol products; if the co-existing lithium halide was removed before condensation then threo-product formation was favoured.lo6 This was considered to account for differences between this work and that of Stille.'" A review of proline-catalysed enantioselective aldol reactions has been pub- lished.'08 An interesting enzymatic synthesis of glycosidase inhibitors was achieved by coupling dihydroxyacetone phosphate and (R S)-(99) with aldolase; following phosphatase-mediated cleavage of the intermediates and reduction l-deoxyman- nonojirimycin (100) and 1-deoxynojirimycin ( 101) were isolated.10g Alkoxyacetylide anions react with carbonyl groups to form adducts e.g.(102) which are transformed by acid into a$-unsaturated esters (e.g. Ph2C=CHC02Me 70%).'lo An interesting account of the Bayliss-Hillman process for coupling acti- vated vinyl carbanions with aldehydes has been published.' RZ R1jG -OR3 HO (102) 10.1 R.W.Hoffrnann J. W. Lanz and R. Metternich Liebigs Ann. Chem. 1988 161. I04 T. Kauffrnann T. Abel and M. Schreer Angew. Chem. Int. Edn. Engl. 1988 27 944. I05 N. Oguni Y. Matsuda and T. Kaneko J. Am. Chem. Soc. 1988 110 7877. I06 Y. Yarnarnoto and J. Yarnada J. Chem. Soc. Chem. Commun. 1988 802. 107 J. K. Stille et a/. Tetrahedron Lett. 1983 23 627; Tetrahedron 1984 40,2329. ion C. Agarni Bull. Soc. Chim. Fr.. 1988 499. I09 R.Ziegler A. Straub and F. Effenberger Angew. Chem. Int. Edn. EngL 1988 27 716. I10 G. A. Olah A. Wu 0. Farooq and G. K. S. Prakash Synthesis 1988 537. Ill S. E. Drewes and G. H. Roos. Tetrahedron 1988 44. 4653. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Michael addition can be catalysed efficiently by montmorillonite clay and silyl ketene acetals and silyl enol ethers have been used in this way.Modest selectivity was noted for (103) and MeCH=CHCO,Me the syn :anti ratio being 27 :73 (-78 "C OSiMe3 0.5 h 84%).'I2 Enantioselective Michael addition of tin( 11) enolates to a,p-unsatur- ated ketones with chiral diamine ligands (Scheme 14) depended on activation; thus Me3SiC1 was ineffective but Me3SiOTf gave 70% yield in the displayed reaction (>95 :5 anti :syn 80%optical yield) with diamine (1O4).ll3 A similar result followed for addition of methyl dithioacetate. It was also established that a catalytic cycle could be set up with a catalytic amount of Sn( OTf),-chiral diamine complex.' l4 Addition of allyllithium reagents containing polar groups (sulphoxides phosphine oxides phosphonates) has been studied.' l5 Reagents i Sn(OTf), EtN3; ii,pNs(lO4) CH2Clz -78 "C; iii TMSOTf; 0 iv v H+ 'e Scheme 14 Enones with t-butyl hydroperoxide yield y-hydroxy derivatives.lI6 An intensive study of the silicon-directed Nazarov reaction has concentrated on the influence of substituents and the anomalous cyclization of vinyl dienyl ketones."'*"* A number of functional groups are compatible with the reaction which proceeds with good specificity e.g.(105) +40% (106) (single isomer) and 'Iz M. Kawai M. Onaka and Y. Izumi Bull. Chem. SOC.Jpn. 1988. 61 2157. 113 T. Yura N. Iwasawa and T. Mukaiyama Chem. Lett. 1988 1021. I14 T. Yura N.Iwasawa and T. Mukaiyama Chem. Lett. 1988 1025. IIS M. R. Binns R. K. Haynes A. G. Katsifis P. A. Scholer and S. C. Vonwiller J. Am. Chem. SOC.,1988 110 5411. I I6 M. R. Sabol C. Wiglesworth and D. S. Watt Synth. Commun. 1988 18 1. 117 S. E. Denmark K. L. Habermas and G. A. Hite Helu. Chim. Am 1988 71 168. IIX S. E. Denmark and G. A. Hite Helc. Chim. Acta 1988 71 195. 126 B. V. Smith 0 (107) + (108) (single isomer). The mechanism of cyclization was discussed in terms of substituent effects and stabilization of the cationic intermediates. For rearrange- ment of (109) a 1,2-cationic shift was invoked; FeC1 in CH2C12 at -10 "C gave (1lo) probably via (1 11)+(1 12). SiMe3 I SiMe3 Me3Si, i"'I Finally the preference for thioaldehydes RCHS to give endo-Diels- Alder addi- tion with cyclopentadiene has been attributed to steric effects particularly at the a-position in R.l19 4 Carboxylic Acids Esters and Lactones a-Aminoacids have been used as chiral educts in the preparation of chiral a-alkylcarboxylic acids.N-(9-Phenylfluoren-9-yl)aminoketonesgave via regioselec-tive enolization and alkylation diastereoisomeric a'-alkyl-branched a-amino-ketones. Separation gave individual diastereoisomers of >99% enantiomeric purity; deprotonation and oxidation gave the desired product in very high enantiomeric purity e.g. from L-alanine in seven steps there was obtained (R)-a-methylpentanoic acid of >99% e.e.l2' Stereoselective alkylation of chiral imide enolates has been used for a high-yielding (in both senses) process leading to a-alkylsuccinates.'21 L-Valinol was converted into (113) by metallation (Li or Na) with hexamethyl- disilazide-THF at -78 "C; alkylation (BrCH,CO,Me) and cleavage of (114) gave (115) (84% 96% e.e.).121 Asymmetric catalytic transfer hydrogenation of a$-unsaturated acids in the presence of a rhodium catalyst [from {Rh(cod)Cl} and I19 E.Vedejs. J. S. Stults and R. G. Wilde J. Am. Chem. SOC.,1988 110 5452. lZo W. D. Lube11 and H. Rapoport J. Am. Chem. SOC.,1988 110 7447. ''I A. Fade1 and J. Salaun Tetrahedron Left.. 1988. 29 6257. 127 Aliphatic Compounds -Part (ii) Other Aliphatic Cornpounds M ph2ph N PPh2 I 1-CO~BU' (116) or (117)] gave good yields. In this way itaconic acid was reduced to MeCH(C02H)CH2C02H(93% e.e.).12*A similar approach was by reduction in the presence of a chiral ferrocene-based catalyst (118) (R = Et Bu or R = c-C5HI0); thus (1 19) gave (2S,3R)-( 120) 92% e.e.123 In addition to the expected reduction incorporation of deuterium occurred at other positions and (E)-(121) gave (2S,3S)-(122) and (2S,3R)-( 123) with the relative distributions shown.Two effective methods for esters depend on bromination-oxidation (or its reverse); in the first of these (the Kiliani method 1861) methyl ethyl and isopropyl esters were prepared by brominative oxidation of a hemiacetal. The method gave poor results in attempted preparations of t-butyl esters but was successful in the presence of other functional groups. The protected (124) gave esters smoothly (Me 95%; Et 85% ;Pr' 70%) and no elimination occurred with (125).124Swern oxidation of I22 H.Brunner and W. Leitner Angew. Chem. Int. Edn. Engl.. 1988 27 1180. 12' T. Hayashi N. Kawamura. and Y. Ito. Tetrahedron Lett. 1988 29. 5969. I24 D. R. Williams F. D. Klingler E. E. Allen and F. W. Lichtenthaler Teerrahedron Lett. 1988 29 5969. I25 F. W. Lichtenthaler. P. Jarplis and K. Lorenz. Svnrhetis 1988 790. 128 B. V. Smith O/OH (126) and bromination-oxidation in methanol gave (127) (84% ).125 Amberlyst-15 is a useful catalyst for preparation of methyl esters and no racemization epimeriz- ation or ketalization was observed in appropriate examples. Remote unsaturation was compatible e.g. (128) gave 90% of the expected methyl ester and some selectivity was observed with (129) which was esterified at the acid group shown in bold type (80%).126 Ester interchange without solvent was brought about under phase-transfer catalysis Me(CH2),,C02Me exchanged with C8H,,0H in the presence of K2C03- Bu,N+ HSO (55"C) to give 97% of product ester.12' CotH A mechanistic study of the Mitsunobu reaction for synthesis of esters has been undertaken in order to clarify the role of substituents and other variables.12' Asymmetric monoesterification of malonic acids using Cinchona alkaloids has been achieved by cleavage of 2,2,5-trimethyl-5-phenyl-4,6-dioxo-1,3-dioxane (130).'29 N-Benzyl-quinidinium and -cinchonidium salts (and their epimers) with sodium alkoxides gave BnAlk+ OR- (BnAlk = benzylalkaloid cation) which for example caused formation of Ph(Me)C*(C02H)C02Me from (130) at -50 "C (73% 34% e.e.pro-R selectivity). Selective reduction of the ester function in this product gave (S)-a-methyltropic acid of modest e.e. (38%). 126 M. Petrini R. Ballini E. Marcantoni and G. Rosini Synth. Commun. 1988 18 847. I27 J. Barry G. Bram and A. Petit Tetruhedron Lerr. 1988 29 4567. I28 D. L. Hughes R. A. Reamer J. J. Bergan and E. J. J. Grabowski J. Am. Chem. SOC. 1988 110 6487. 129 J. Hiratake K. Shibata N. Baba and J. Oda Synrhesis 1988 278. 129 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Esters of 2-methyl-3-oxopropanoic acid showed variable e.e. on reduction by baker's yeast due to variation in size bulk and hydrophobicity of the alcohol rn~iety.'~' Enolates from dioxanones e.g.(131) could be decomposed to a,P-unsaturated acids or reacted with RX and the alkylated compound cleaved to a P-hydr~xyacid.'~~ A new route to (2)-a$-disubstituted acrylates has been described reduction [Ca(BH,) in MeOH-THF] of (132) to syn-(133) an$ anti-(134) (syn anti = 96:4 82% yield) folhwed by reaction of (133) with C,H5NMe BF,-Et,N then LiI gave C,H,,CH=C(Me)C02Me with 98% 2 ~electivity.'~~ For the phenyl analogue RxMe 00 OH however E selectivity was observed. Pure E-or 2-isomers of unsaturated acids have been obtained from phosphine oxide precursors Ph,P( =O)CH2R.133 A route to a$-unsaturated acids via reaction of RCHO and (135) in the presence of ZnBr gave via RCH=CHCO,SiMe, good yields (R = Me 93%) of desired A palladium-catalysed coupling of PhBr and tin-masked dienolates gave unusually y-sub~titution.'~~ OSiMe3 Me3Siy OSiMe3 (135) A flow method has been used in preparation of ethyl 2,2-difluoropent-4-enoate a useful precursor for preparation of various fluoro compound^.'^^ Rearrangement of (136) at -50 "C (BuLi in hexane-THF) gave (137) which is easily ethanolysed to the desired product.Some interesting examples of the DABCO-induced coupling of aldehydes and acrylic esters have been uncovered. Whilst a more 'normal' coupling of RCH2CH0 and CH2=CHC02R' gives acylic hydroxyenoate with PhCHzCHO I30 K. Nakamura T. Miyai K. Ushio S. Oka and A. Ohno Bull. Chem. Soc. Jpn. 1988 61. 2089.131 J. Zimmerrnann D. Seebach and T.-K. Ha Helv. Chim. Acfa 1988 71 1143. 132 M. Shimagaki M. Shiokawa K. Sugai T. Teranaka T. Nakata and T. Oishi Terrahedron Lett. 1988 29 659.. 133 D. Levin and S. Warren J. Chem. SOC.,Perkin Trans. 1 1988 1799. I34 M. Bellassoued and M. Gaudernar Tetrahedron Lerr. 1988 29 4551. 135 Y. Yarnamoto S. Hatsuya and J. Yarnada J. Chem. Soc. Chem. Commun. 1988 86. I36 M. Kolb F. Gerhart. and J.-P. Franqois Svnthesis 1988 469. 130 B. V; Smith FF FF F-pO-P-+O F (137) a [2 + 2 + 21 cycloaddition occurred as well to give (138) in addition to the 'usual' product. Aldehydoester (139) gave (140) from partial lactonization of the acyclic product; with CH2=CHC02Bu' only the cyclized product was dete~ted.'~~ Thermolysis of (141) (R = mesityl) gave a ketene (142) and thence the enolate (143) in which E-and 2-isomers are in equlibrium; 2-isomers predominate in aprotic or moderately polar s01vents.l~~ The configurational stability of enolates from @-ketocarboxylates has been investigated with respect to deprotonation under kinetic control; depending on the medium temperature and counter-ion some equilibrium was found but conditions were defined for preparation of enol ethers and esters of the desired c~nfiguration.'~' O/H-R \ RQx OR RO/c=c=o R Monoalkylmalonates condensed readily with a,@-unsaturated aldehydes forming penta-2,4-dienoic esters of predominatly E stereochemistry." Two cyclization reactions of unsaturated acid derivatives have been reported.In the first CH2=CH(CH2)3CC12C02Et formed cyclopentanes (144) (trans :cis -1:1) with RuC12(PPh3)3.'41 An 'activating device' for an acid such as CH2=CHC02H anticipates the reactivity of an acyloxyborane (the intermediate in reduction of RC02H by BH3). The formed derivative thus undergoes Diels- Alder addition acrylic acid yielding (145) (72(%0).'~~ With a chiral acid such as (146) serving as the precursor of a chiral acyloxyborane the cycloaddition product had modest e.e. (35-78% ). This is a novel and interesting approach to the construction of such systems. W. Poly D. Schomburg and H. M. R. Hoffmann J. Org. Chem. 1988 53 3701. H. Meier H. Wengenroth W. Lauer and.W. Vogt Chem. Ber. 1988 121 1643. I39 H. Meier W.Lauer and V. Franse Chem. Ber. 1988 121 1109. 140 J. Rodriguez and B. Waegell Synthesis 1988 534. 141 T. K. Hayes R. Villani and S. M. Weinreb J. Am. Chem. SOC.,1988 110 5533. I42 K. Furuta Y. Miza K. Iwanaga. and H. Yamamoto. J. Am. Chem. Soc. 1988. 110 6254. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds OH i c1 o''cozH R Enantiomerically pure (2&3 S)-and (2S,3R)-3-hydroxy-2-methylbutanoateesters have been obtained from L-or D-threonine as illustrated in Scheme 15.'43 y,6-Alkylidenedioxy-a,P -unsaturated esters undergo cleavage with LiMe,Cu (to ketones and enolates) and ultimately form P,G-dihydroxy-P,y-unsaturatedesters e.g. (147) (R' = R2 = Me R3 = Et 76'/0).'~ Me OH OR Reagents i NaN02 KBr aq.HBr -15°C; ii KOH EtOH -30°C; iii R2SO4 18-crown-6 CH2C12 20 "C; iv Me2CuLi Et20 -25 "C Scheme 15 A combination of enzymic and chemical reactions has been used to prepare each stereoisomer of methyl 6-(4-chlorophenylthio)-3,5-dihydroxyhexan0ate.'~~ An asymmetric synthesis of dimethyl (R)-4-amino-4-methylpent-2-endioates has followed a bis-lactim route with high specificity; thus addition of (148)to (149) furnished after hydrolysis of the intermediate (150)(75% ).146 Yeast-mediated Li reduction was used in an efficient synthesis of (3S,4S)-4-amino-3-hydroxypentanoic acids; (151)gave the desired product (d.e. -92%) with Hansenula anomala whereas Candida boidinii showed opposite selection in formation of the (3&4S)-isomer (d.e. 143 Y. Petit C.Sauner and M. Larchevique Synthesis 1988 538. 144 S. Takano Y. Sekiguchi and K. Ogasawara J. Chem. Soc. Chem. Commun. 1988 449. 145 M. Christen and D. H. G. Crout J. Chem. Soc. Chem. Commun. 1988 264. 146 U. Schollkopf and J. Schroder Leibigs Ann. Chem. 1988 87. 132 B. V. Smith 90%). Amazingly this reaction was run with 50 g batches of (151) to afford 35 g of product (98% d.e.).I4' P-Propiolactones with K-18-crown-6 in THF suffer C-C scission to enolates and ultimately form esters.'48 00 Ph+OMe BocNH H R1a 0 0 a$-Unsaturated esters with a carbonyl component react in the presence of SmI to form y-lactone~.'~~ It was surmised that a ketyl intermediate was involved. Chiral methyl y-oxocarboxylates with R-metal form y-lactone~.'~' Enzymatic resolution of racemic lactones (using either PPL HLE or PLE) gave products with an optical activity of 60-90%.Thus (152) gave 72% e.e. R-isomer when R = Pr and 76% e.e. for R = C7H,5.151 3-Methyl- y- butyrolactone by extrusion of CO and replacement by OH groups using Criegee's reagent yielded polypropionate 'starter' units of high enantiomeric Stabilized Wittig reagents e.g. Ph3P=CHC0,Me with unsymmetrical maleic anhydrides show Z preference in product formation particularly if an alkoxy group is present. This was interpreted as arising from interaction between the phosphorus and alkoxy oxygen acting as a Lewis base. Thus with (153) no attack occurred at the P-site and the product (154) had E 2 = 28 72.'53 0 Meoco 0 0 Long-chain hydroxy acids with lipase form lactones but the process is complicated by (po1y)lactone formation e.g.10-hydroxydecanoic acid formed di- tri- tetra- and pentalactones but no monolactone. Progress was made in elucidating the stereochemical course of dilactone formati~n.''~ Stille has used palladium-catalysed cyclization of esters with vinyl triflate and vinyl stannone groups at their termini as a route to large ring 1act0nes.l~~ 147 P. Raddatz H.-E. Radurnz G.Schneider and H. Schwartz Angew. Chem. Inr. Edn. Engl. 1988,27,425. I48 2.Jedlinski M. KowalczLk and A. Misiolek J. Chem. Soc. Chem. Commun. 1988. 1261. I49 S. Fukuzawa A. Nakanishi T. Fujinami and S. Sakai J. Chem. Soc. Perkin Trans. 1 1988 1669. I50 T. Kunz and H.-U. Reissig.Angew. Chem. Inf. Edn. Engl. 1988. 27. 268. 151 L. Blanco E. Guibk-Jampel and G. Rousseau Tetrahedron Len. 1988 29 1915. F. E. Zeigler A. Kneisley J. K. Thottathil and R. T. Wester J. Am. Chem. Soc. 1988 110 5434. I53 M. M. Kayser and L. Brean Tetrahedron Lerr. 1988 29 6203. IS4 G. Zhi-wei T. K. Ngooi A. Scilimati G. Fulling and C. .I.Sih Terrahedron Lett. 1988 29 5583. 15' J. K. Stille and M. Tanaka. J. Am. Chem. Sor. 1988 110. 3785. 133 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 5 Amines and Amides A Review of the Leuckart reaction for preparation of amines has been p~blished."~ Synthesis of secondary allylic amines in good yield and giving principally the E-isomer follows Scheme 16.'57 An efficient route to blocked allylamines relies upon 0 NR3 N R3 NHR3 Reagents i R'NH,; ii (X = C1 or Br); iii base; iv NaBH, EtOH 0 Scheme 16 Pd-catalysed coupling of an allylic acetate and NaN( BOC),; subsequent deprotec- tion gives the free amine.'58 Masked 1,3-dicarbonyl compounds have been converted into primary or secondary amine~.'~~ Tertiary amine oxides were transformed into a-functionalized t-amines; the starting material with R3SiOS02CF3 gave (1 55) R1\+ /OSiMezR4 RZ/N\ CHzR3 which by sequential treatment with a base and an electrophile yielded the product e.g.PhCH2(Me),N-0-gave PhCH2N(Me)CH2CN (40%).'60A new synthesis of imines (and thence secondary amines) resulted from reaction of R'M (a Grignard reagent or a cuprate) with an N-silyl- N-alkyl- or N-arylformamide [HCON(R2)SiMe3,etc.] to form R'CH=NR2.'6' Oxidation of amino groups e.g.PhCH,NHPh +PhCH=NPh was effected by PhIO alone or with RuC~,(PP~~)~; the ethyl ester of phenylalanine gave PhCH,CN probably via the imine.16 Coupling of R'CH=NR2 is a route to a 1,2-di-s-amine and was effected by a low valent titanium species (from TiC14-Mg-HgC12) which gave some selectivity since MeCH=NPr gave 50% of diamine with (KR):(RS) ratio 85 15. For MeCH=NCH,Ph selectivity of 90 10 was achieved and debenzylation in the formed MeCH( NHCH,Ph)CH( NHCH,Ph)Me was p0ssib1e.l~~ The preparation of N-methyl-"-( R)-methyl-1,2-diaminoethanehas been described and its use as a chiral modifying reagent for LAH reduction of prochiral ketones was studied. I56 S.Ram and R. E. Ehrenkaufer Synthesis 1988 91. I57 N. De Kimpe E. Stanoeva R.Verhe and N. Schamp Synthesis,1988 587. I SX R. D. Connell T. Rein B. Akermark and P. Helquist J. Org. Chem. 1988 53 3845. 159 J. Barluenga E. Aguilar B. Olano arid S. Fustero. 1.Org. Chem. 1988 53 1741. I60 N. Tokitoh and R.Okazaki Bull. Chem. SOC.Jpn. 1988 61 735. 161 B. L. Feringa and J. F. G. A. Jansen Synfhesis 1998 184. I62 P. Miiller and D. M. Gilabert Tetrahedron 1988 44 7171. 1h3 P. Mangeney T. Tejero. A. Alexakis. F. Grosjean and J. Normant Smhesis 1988 255. 134 B. K Smith Selectivity was moderate (PhCOPr') and the product (R)-alcohol had 59% e.e.164 An improved optical resolution of (R,R)-N,N'-1,2-diphenylethylenediamineled to an estimated 95% optical purity.An n.m.r. method was used to estimate the enantiomeric purity of a chiral aldehyde by reaction with the diamine and measure- ment of differences in 'H and I3C spectra.165 The alleged preparation of a 1-acyl-2-alkylhydrazine by reaction of a hydroxamic acid and an amine in the presence of tosyl chloride has been shown to be incorrect.'66 Lossen rearrangement occurs and the isolated product (from isocyanate and amine) is the urea. Amides are formed from nitriles on silica gel. The reaction may be slow (2-48 h) and yields are variable (35-100% ) a quantitative yield being obtained from PrCN.'67 Penicillin acylase has been shown to catalyse formation of amide bonds. The method works for a range of structural types and esters of aminoacids and di- and tri-peptides can be used as the amine component.Titanium tetrachloride-mediated addition of isocyanides to aldehydes and ketones afforded a-hydroxyamides. No selection was found for chiral is~cyanides.'~~ If a stable cation can be formed from RNC some cyanhydrin results. A 2-functionalized allylstannane reacts with 2-bromo-N-benzoylglycine methyl ester (AIBN-toluene) to give an a-alkylated aminoacid derivative (156).17' Amidoesters have been obtained uia a Kolbe reaction in which diacid hemiesters and amidoacids are co-o~idized.'~~ HN AcO,Me I COPh Alkylation of amines by aralkyl Bi"' derivatives in the presence of Cu(OAc) is moderately successful; BuNH with (PhCH,CH,),Bi gave BuNH(CH,),Ph (24% Oxidation of primary amines by NaOCl in micellar conditions gave nitriles; the reaction can be run on a 0.1 mole scale and is accelerated markedly by the micellar agent (e.g.CTAB).'73 Direct regio- and stereoselective lithiation of secondary allyl- and methallylamines proceeds cleanly; from RLNHCH2C( R2)=CH2 there was obtained I hJ M. Falorni L. Lardicci and G. Giacomelli Gazz. Chim. Ira/. 1988 118 573. I h5 P. Mangeney F. Grosjean A. Alexakis and J. F. Normant Terrahedron Lett. 1988 29 2675; P. Mangeney A. Alexakis and J. F. Normant ibid. p. 2677. 166 W. Hartmann Synthesis 1988 807 and reference cited therein. 107 K.-T. Liu M.-H. Shih H.-W. Huang and C.-J. Hu Synthesis 1988 715. I hX A. Pessina P. Liithi P. L. Luisi J. Prenosil and Y.-S. Zhang. Helo. Chim.Acra 1988 71 631.I hV D. Seebach G. Adam T. Gees M. Schiess and W. Weigand Chem. Ber. 1988 121 507. I70 J. E. Baldwin R. M. Adlington C. Lowe I. A. O'Neil G. L. Sanders C. J. Schofield and J. B. Sweeney J. Chem. SOC..Chem. Commun.. 1988. 1030. 171 M. B. Abderrahman E. Laurent and B. Marquet Bull. SOC.Chim. Fr. 1988. 571. "' D. H. R. Barton N. Ozbalik and M. Ramesh Tetrahedron Lerr. 1988 29 857. ll\ B. JurSi6. J. Chem. Rex (S). 1988. 168. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds R'NHCH,C(R2)=CH-R3 in 70-90% by reaction of the lithiated species with R3X.174 2H n.m.r. has been used to analyse the stereodynamics of N-ethyl-N-methyl-2- aminobutane in the range 100-200 6 Other Nitrogen Compounds Aldehydes with HN in the presence of an alcohol and TiC14 catalyst yield a-azidoethers.In this way C9H19CH0 gave C9H,,CH(OMe)N3 (go0/,). Pyrolysis or photolysis of such compounds gave an iminoether further transformed into a nitrile (heat) or an amide (A1203).'76 The silicon-directed Beckmann fragmentation of silylated oximes led to a nitrile and an alkene; R'C(=NOH)CH2CH2SiR3 in acid or with F- gave R'CN + C2H4. Cyclic systems behaved ~imi1arly.l~~ Silyl amines as lithium or zinc salts are oxidized by dry air (-60 to 20 "C) to form ultimately an aldehyde or ketone; probable intermediates are a nitroso compound and thence the ~xime.'~' A substantial review of the uses of nitroalkanes as synthetic equivalents of alkyl anion synthons has been p~blished.'~~ Addition of nitroalkanes to a$-unsaturated carbonyl compounds in the presence of basic Al,03 gave rise to functionalized 1,4-diketone~.'*~ Typically R'CH,NO and R2CH=CHCOR3 gave R'COCH(R2)CH2COR3 from a sequence of reactions with (i) Al,03 (ii) 30% H202-K2C03 and (iii) MeOH.Yields were 50-90%. MeNO served as a carbonyl dianion synthon since 2 moles of enone in the presence of Al,03 gave a 1,4,7- triketone. This methodology was applied to a synthesis (60%) of dihydrojasmone. Aluminium trialkyls (and then etherates) add rapidly to a,P-unsaturated nitro compounds to give 1,3-a1kylation.''' A cyclic intermediate (157) was proposed as the vehicle for transferring an alkyl group selectively. Selective hydrolysis by PLE has been used to obtain monoacetates of nitrodiols.From meso-diacetates there was obtained for example (158) in 60% yield and 90-95% e.e. Elimination of water gave nitro unsaturated esters whose addition and substitution was further studied.'" I71 J. Barluenga F. J. Fahanas F. Foubelo and M. Yus J. Chem. Soc. Chem. Commun. 1988 1135. C. T. Danehey jun. G. L. Grady P. R. Bonneau and C. H. Bushweiler J. Am. Chem. Soc. 1988 110 7269. I76 A. Hassner R. Fiaiger and A. S. Amarasekera. J. Org. Chem. 1988 53 22. I71 H. Nishiyama K. Sakuta N. Osaka H. Arai M. Matsumoto and K. Itoh Tetrahedron 1988. 44 2413. I78 H. G. Chen and P. Knochel Tetrahedron Lett. 1988 29 6701. I79 G. Rossini and R. Ballini Synthesis. 1988 833. I xn R. Ballini M. Petrini E. Marcantoni and G. Rossini Svnthesis 1988 231.1x1 A. Pecunioso and R. Menicagli 1.Org. Chem. 1988 53 45. "'M. Eherle M. Egli. and D. Seebach. Hek. Chirn. Acta. 1988. 71. 1. 136 B. V. Smith 7 Phosphorus and Sulphur Compounds This section on phosphorus compounds is shorter than usual; reference to applica- tions involving phosphorus derivatives e.g. Wittig reagents have been listed under other functional groups. A route to optically active phosphanes has been described. Sharpless oxidation of an allylic alcohol and tosylation gave (159); ring opening and displacement (LiPPh,-THF) of (159) gave potentially (160) and (161). When R = Ph only (160) was formed; with R = Pr an inseparable mixture of (160) and (161) was formed. When (160; R = Ph) was used as a chiral ligand for preparation of a rhodium catalyst asymmetric hydrogenation of a-acetamidocinnamic acid gave (It)-(-)-N-acetylphenylalanine (83 % e.e.).lg3 A new route to 1,3-diphosphabutadiene deriva- tives has been described; nucleophilic addition of a carbanion Arc=P -R to ArCEP is a key A 1,2,3-triphosphabutadienewas not produced from ArPCl and (Me3Si),P-P=C(SiMe3) or from ArP(C1)(SiMe3) and CIP=C(SiMe,),; the product was assigned the structure (162).”’ Alkenes were converted into P-chlorosulphides in a regioselective manner by reaction with either Me2SO-PhOPOC12 or Me2SO-POCI3 (-20 “C -CH,Cl,); Me(CH2)&H=CH2 gave Me( CH2)15CH( Cl)CH2SMe.‘86 Tetra-n-butylammonium oxone (from aqueous oxone and Bu,N+HSO;) is a useful and selective reagent for converting sulphide into sulphone in the presence of amino keto ester alkene and alcohol group^.'^' A review of selective dealkylation of aryl alkyl ethers and thioethers (and selenoethers) has been published.18’ The structure of the t-butylsulphinyl( pheny1)methyl carbanion in THF has been examined. It exists as two diastereoisomeric dimeric forms in the presence of an equivalent concentration of counter-cation. An excess of base causes monomer formation. The meso-form is shown as (163).lg9 Reduction of sulphoxides to thioethers has been re~iewed.”~ An unusually facile cleavage of an S-C bond in in3 H. Brunner and A. Sichender Angew. Chem. Int. Edn. Engl. 1988 27 718. A. M. Arif A. Barron A. H. Cowley and S. W. Hall 1.Chem. Soc. Chem. Commun. 1988 171. I85 R. Appel B.Niemann and M. Nieger Angew. Chem. Int. Edn. Engl. 1988 27 957. I86 H.-J. Liu and J. M. Nyangulu Tetrahedron Lett. 1988 29 5467. I 87 B. M. Trost and R. Braslau 1.Org. Chem. 1988 53 532. I88 M. Tiecco Synthesis 1988 749. 189 A. Ohno M. Higaki and S. Oka Bull. Chem. SOC.Jpn.. 1988 61 1721. 190 M. Madesclaire Tetrahedron. 1988 44 6537. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds But H h R3 But@ / ph..?5:u* Bu' sterically crowded sulphoxides occurs on attempted oxidation of ArCR' R3CH2SR2 (Ar = 1,3,5-Bu\C,H2) to afford (164) (+R2SOH).19' 2-Phenylsulphonyl-l,3-dienescan be regioselectively epoxidized at either double bond by choice of reagent MeCH=CH-C(S02Ph)=CH2 gave the 3,4-epoxide with MCPBA and the 1,2-epoxide with alkaline H202.These products were useful in regio- and stereospecific reactions with nu~leophiles.'~~ Acyclic diastereocontrol has been found in the formation and reactions of y-hydroxysulphones. The dianion of methyallyl phenyl sulphone gave on alkylation with styrene epoxide y-hydroxy- sulphone (165) (71'/0 d.e. > 99 :1). The necessary structural requirements for such selectivity were considered to be a terminal epoxide and chain branching in the sulphone and adjacent to the ~ulphone.'~~ The protonation of the dianion (166) 2-JYYR PhOzS OH during quenching was envisaged as occurring from the topside consistent with product stereochemistry; single regio- and stereoisomers were formed in coupling of Grignard reagents (catalysed by CuCN) with substitution of the sulphone.(E)-MeCH=CHCH2S02Ph was converted into (167) and then with BuMgBr- CuCN-Et20 gave (168). Double control is thus exerted first in hydroxysulphone formation and then in its substitution. Many possible transformations can thus be +H -?p+H PhOzS OTBDMS H OTBDMS 191 R. Okazaki T. Ishida and N. Inamoto 1. Chem. SOC.,Chem. Commun. 1988 40. I92 J.-E. Backvall and S. K. Juntunen 1. Org. Chem. 1988 53 2398. 193 B. M. Trost and C. A. Medic 1. Am. Chem. Soc.. 1988. 110 5216. 138 B. V. Smith envisaged based on this methodology and by taking advantage of the availability of enantiomerically pure epoxides. Chiral y-arylsulphanylbutyrolactonesundergo a stereo-controlled intramolecular ring closure to form optically pure ring-fused y-butyrolactones uia a radical or cationic pathway.194 Trost has reviewed organosulphone chemistry drawing an intriguing parallel to the chameleon !195 Perhalogenated sulphines (thione oxides) and sulphenes (thione dioxides) have been reviewed.196 Some highly efficient and selective oxidations of methyl thioether substrates by the o-hydroxylase from Pseudomonas oleovorans have been rep01ted.l~' Although MeSCH,CH,Me gave the sulphoxide with 88% e.e.MeS(CH,),CHMe gave a product of very low (2%) e.e. An interesting example of selectivity was the clean sulphoxidation of MeS(CH,),CH=CHPr (86% e.e.) with no concurrent hydroxyla- tion. A general account of such chiral sulphoxidations by biotransformations of sulphides is a~ailable.'~~ Synthetically useful extrusion reactions of organo-sulphur -selenium and -tellurium compounds have been surveyed.'99 8 Miscellaneous Three useful general reviews have been published.The characteristics of the reactions of allylsilanes and their applications to versatile synthetic equivalents has been surveyed.200A full and interesting account of organosilicon chemistry in organic synthesis provides a comprehensive coverage.*" A multi-author review of 'emerging organic reactions' has summarized much work of novelty and importance.202 194 J. P. Marino E. Laborde and R. S. Paley J. Am. Chem. SOC.,1988 110 966. 195 B. M.Trost Bull. Chem. SOC.Jpn. 1988,61 107. 196 W. Sundermeyer Synrhesis 1988 349. 197 A. G.Katopodis H. A. Smith jun. and S. W. May J. Am. Cbem. Soc. 1988 110 897. H. L. Holland Chem. Rev. 1988 88 473. I99 F. S. Guziec jun. and L. J. Sanfilippo Tetrahedron 1988 44 6241. 200 A. Hosomi Acc. Chem. Res. 1988 21 200. 201 1. Fleming (ed.) Tetrahedron 1988 44 3761. 202 Chem. Rev. 1988 86 733.