2 Synthetic methods Part (iv) Heteroatom methods Patrick J. Murphy Department of Chemistry University of Wales Bangor Gwynedd UK LL57 2UW 1 Introduction This report will focus on the organic chemistry of phosphorus sulfur silicon selenium and tellurium; the heterocyclic free radical and transition metal chemistry of these elements has been largely ignored as this will be covered elsewhere. 2 Organophosphorus chemistry The Baylis—Hillman reaction has attracted considerable attention and new methods for e.ecting this transformation are of current interest. Soai has reported the reaction of aldehydes 1 with acrylates using a range of chiral phosphines and has found that (S)-BINAP catalyses the reaction most e.ectively however only modest yields and ees are obtained (Scheme 1).The conjugate addition of LDA to vinylphosphonates 2 with in situ trapping of the enolate with an aldehyde and elimination of diisopropylamine leads to the formation of the Baylis—Hillman products 3 in good yields (Scheme 2). In a related process Warren has reported the addition of the amine 5 to vinylphosphine oxides 4 in the presence of TMSCl leading to the silylated intermediate 6 which on protodesilylation gave the -amino phosphine oxides 7 with excellent stereoselectivity (Scheme 3). TMSCl has also been reported to lead to improved yields for the addition of alkyl aryl and vinyl cuprates to -substituted vinylphosphine oxides. The phosphonium salts 8 have been shown to lead to predominantly E-alkenes in Wittig reactions with aromatic aldehydes;KHDMSwas found to be the base of choice for this process (Scheme 4). Tomioka and co-workers have reported an asymmetric HWE reaction mediated by the external chiral ligand 9; reaction of lithiated phosphonates 10 with 4-substituted cyclohexanones 11 in the presence of 9 led to the formation of the intermediate cis-alcohols 12 (together with the trans-isomers in 2—7% yield) which were eliminated to give the S-alkenes 13 in 51—84% ee (Scheme 5). Shibasaki has reported an interesting and potentially very useful Michael reaction of phosphonate ester 14 with enones 15 mediated by aluminium lithium bis(binaphthoxide) complex (ALB) in the presence of NaOtBu or n-BuLi leading to the adducts 16 59 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 —— CHCO R (S)-BINAP (20 mol%) CHCl 20 °C 62—327 h.RH Me; RMe Et i-Pr. Scheme 1 Reagents (i) CH CH 4-tert-butylcyclohexyl. Scheme 2 Reagents (i) RRC——O LDA THF 78 °C 30 min. R RH Me; REt Ph t-Bu PhCH Scheme 3 Reagents (i) 5 TMSCl (5 equiv.) THF,78 °C; (ii) TBAF THF. RPh p-MeOC H 2-furyl. with ees as high as 99% being obtained at the -position (Scheme 6). The combination of Sn(OTf) and N-ethylpiperidine in the HWE reaction of 2-.uoro-2-diethylphosphonoacetate with ketones has been reported to lead to high E-selectivities typically greater then 95 5 whereas the corresponding use of a magnesium based enolate system leads in some cases to the formation of Z-products (E:Z from 37 63 to 19 81). Nicolaou has reported the elaboration of a polymer supported methyl phosphonate to the precursors 17 which were cyclised to the macrocyclic lactones 18 by treatment with potassium carbonate.Further modi.cation of this methodology using 60 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 CH ; RPh 3,4,5-(MeO) C H . Scheme 4 Reagents (i) KHDMS 0 °C 2 h then 78 °C RCHO then rt 4 h. RMe Ph n-Bu PhCH Scheme 5 Reagents (i) n-BuLi hexane—PhMe,78—0 °C 1 h; (ii) NaOAc AcOH 30 min or KOH DMSO 50 °C 30 min. RPh vinyl aryl 1-naphthyl 2-naphthyl; RMe Ph t-Bu. Scheme 6 Reagents (i) ALB NaOt-Bu or n-BuLi THF rt—50 °C 72—140 h. a sort-pool combinatorial strategy led to a synthesis of ( )-muscone and a library of modi.ed muscones (Scheme 7).In two new variants of the HWE reaction the carbohydrate derived lactones 19 undergo reaction with the phosphonate 20 to give the ketene dithioacetals 21 (Scheme 8), whereas in a previously unprecedented reaction the phosphonate 23 undergoes reaction with the dithiocarbonate function of the substrate 22 leading to the TTF 24 in a reasonable yield (Scheme 9). 61 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 7 Reagents (i) K CO (5 equiv.) 18-crown-6 (5 equiv.) PhMe 65 °C 12 h. Scheme 8 Reagents (i) KHDMS THF,78—0 °C. Scheme 9 Reagents (i) 23 (10 equiv.) n-BuLi THF,78—0 °C. 62 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 10 Reagents (i) KHDMS 18-crown-6 (5 equiv.) THF RCHO 78 °C—rt 2h. RPh Bn PhCH—— CH C H i-Pr Cy.Scheme 11 Reagents (i) (EtO) (O)PCH Li (28) THF,78 °C 1 h; (ii) LDA RCHO 78 °C—rt 3 h. RAr 2-furyl cyclopropyl styryl. A new synthesis of Z-vinyl phosphonates has been reported using the bis(trifluoroethyl) phosphonate 25 which on reaction with aldehydes in the presence of KHMDS and 18-crown-6 leads to phosphonates 26 in excellent yields and moderate to good selectivity for the Z-isomer (Scheme 10). A related strategy has been reported for the synthesis of buta-1,3-dienyl phosphonates 30 in that bis-phosphonate 27 undergoes reaction with lithiated phosphonate 28 to give 29; reaction of this under standard HWE conditions leads to 30 as exclusively or predominantly the E,E-isomer (Scheme 11). Taillefer and Cristau have also reported the reaction of phosphonium diylide 31 with a range of electrophiles leading to the synthesis of styrylphosphines or the corresponding oxides or sul.des which depending on the electrophile used can be tailored to give either stereoisomer of the required compound (Scheme 12). A two step synthesis of -phosphonated cycloenones 33 can be e.ected by the alkylation of the dianion of -ketophosphonates 32 followed by ozonolysis and base-catalysed cyclisation (Scheme 13). Reaction of trimethylsilyl phosphites 34 with -haloacrylates has been reported to give the corresponding -phosphonoacrylates 35 in good yield under very mild conditions (Scheme 14). Tetramethylguanidine has been reported to be an e.ective catalyst for the 1,2-addition of dialkyl phosphites to imines aldehydes and ketones and 63 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 12 Reagents (i) Ph P(O)Cl then PhCHO; (ii) Ph PCl then PhCHO; (iii) Ph P(S)Cl then PhCHO; (iv) H O ; (v) S ; (vi) Si Cl . then Me S; (iii) NEt TsOH (65—88%). RRH Me Et. Scheme 13 Reagents (i) NaH THF then n-BuLi,CH ——CH(CH )Br (65—80% yield); (ii) O Scheme 14 Reagents (i) TMSCl NEt CH Cl 0 °C; (ii) 0 °C—rt 6 h. R REtO MeO Ph ()-menthyl; ZCN COMe CO Me; HalCl Br. the corresponding 1,4-addition to enones and acrylates. The presence of an electronwithdrawing group has also been shown to accelerate the uncatalysed addition of phosphites i-PrRPOH (Ralkenyl or alkynyl) to imines aldehydes and ketones and a Co(PMe ) mediated Reformatsky-type addition of -halomethylphosphonates to aldehydes and ketones has also been reported. Shioiri has reported that diethyl phosphorocyanidate [(EtO) P(O)CN] e.ects the homologation of carboxylic acids leading to the corresponding -hydroxycarboxylic acids 37 via the intermediates 36 (Scheme 15).64 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 15 Reagents (i) THF,20 °C (EtO) P(O)CN (2 equiv.) Et N; (ii) HCl (aq) 12h. Ralkyl aryl 2-naphthyl. Scheme 16 Reagents (i) n-BuLi THF,78 °C 1 h; (ii) electrophile (H O D O MeI allyl bromide TMSCl PhCHO). RMe Et i-Pr; RH Me alkyl; RRMe —(CH )— (n4 5); EH D Me CH —— CHCH TMS PhCH(OH).An unusual carbon to nitrogen migration observed during the reaction of lithiated alkyl phosphonates with N,N-dialkylcyanamides 38 leads to the formation of Nphosphorylamidines 39 (EH) in good yields; these products can be further modi.ed by reaction of the intermediate anion 40 with a range of electrophiles (Scheme 16). There continues to be interest in asymmetric organophosphorus chemistry including the appearance of a review on more recent aspects of the topic. The same author 65 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 17 Reagents (i) RCHO DBU; (ii) RCHO TMSCl; (iii) H. R()- menthyl ()-bornyl ()-1,2;5,6-di-O-isopropylidene--glucofuranosyl; Ri-Pr Ph Ar. has also reported the preparation of symmetric dialkyl 41 and trialkyl phosphites 42 which can be converted into the -hydroxyalkylphosphonic esters 43 with good des being obtained; the reaction is also applicable to aldimines with similar results being observed (Scheme 17).-Proline ethyl ester has also been reported to be useful as an auxiliary in the synthesis of chiral methyl p-nitrophenyl alkyl phosphonates [RP(O)(OMe)(pNOCH) Ralkyl Ph] via the corresponding N-prolinylphosphoramidates with des of 73¡X98% being obtained. Other reviews of note include reports on borane complexes of organophosphorus compounds and their use in the synthesis of chiral phosphine ligands and on the reaction of phosphorus acid halides with N-silylated organic compounds. 3 Organosulfur chemistry Kataoka has described a chalcogeno-variant of the Baylis¡XHillman reaction in which suldes and selenides act as catalysts for the reaction in the presence of a quantitative amount of titanium tetrachloride; for the example illustrated (Scheme 18) yields ranged from 69¡X85%.In a related process the thiolate or selenolate triggered tandem Michael/aldol reaction of acrylates with aldehydes leads predominantly to the synproducts 44 with modest stereoselectivity (Scheme 19). The regioselective opening of epoxides using (TIPS)SH in combination withDBUhas been reported to proceed with silyl migration to the oxygen oering a convenient synthesis of -silyloxythiols (9 examples 59¡X92%) (Scheme 20). The asymmetric Michael addition of thiols to ,-unsaturated ketones esters and thiolesters can be catalysed using (R)- LaNa tris(binaphthoxide) or the corresponding samarium complex; ees ranging from 56¡X90% were achieved.A controlled one-pot sequence of three Ad reactions can be initiated using ArSCl which after addition to an enol ether for example 45 undergoes reaction with a further enol ether substrate leading to the thiophanium ion intermediate 46 which is quenched with trimethylallylsilane to give 47 (Scheme 21). Other examples using silyl enol ethers and allylstannanes as quenches were also reported. 1,2-Dithiocyanates 66 Annu. Rep. Prog. Chem. Sect. B 1999 95 59¡X81Scheme 18 Reagents (i) Chalcogen TiCl CH Cl rt 1 h. XS Se; YS Se NBn; n0 1. Scheme 19 Reagents (i) RCHO PhSLi CH Cl 78 to 50 °C; (ii) (PhSe) MeLi—LiBr Et O 78 °C—rt.RMe Et t-Bu; RPh Ar 1-naphthyl 2-naphthyl C H C H ; XS Se. Scheme 20 Reagents (i) (TIPS)SH DBU THF 25 °C 12 h. Scheme 21 Reagents (i) p-TolSCl 78 °C CH Cl ; (ii) TiCl ; (iii) MeOCH——CH ; (iv) TMSCH CH——CH 0 °C 5 h. can be obtained from styrenes using CAN and ammonium thiocyanate in acetonitrile in good to moderate yields. A new method for the formation of silicon protected enethiols involves the deprotonation of thiirane S-oxides with LiHMDS leading to the rearranged intermediate lithium vinyl sulfenates which can be reduced in situ with 67 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 22 Reagents (i) 49 n-BuLi TMSCl; (ii) TMSOTf 2,6-lutidine,CH Cl ,78 to 25 °C.Scheme 23 Reagents (i) KHDMS 18-crown-6 THF,78 °C; (ii) BnBr. LiAlH and trapped with TBDMSCl (27—70% 7 examples). Magnus has reported that the benzylic sulfoxide 48 is an excellent substrate for the Pummerer reaction. For example the reaction with the -amino acid anion equivalent 49 led to the formation of 50 in quantitative yield o.ering an interesting synthetic strategy to the antibiotic gliovirin (Scheme 22). The addition of lithium bromide has been shown to lead to an increase in ee for the protonation of lithium enolates of ketones with chiral -sul.nyl alcohols. Treatment of bis-sulfoxide 51 with KHDMS has been found to lead to an e.cient desymmetrisation reaction leading to 52 a precursor in a total synthesis of the chitinase inhibitor allosamizoline (Scheme 23). A simple synthesis of chiral vinyl and dienyl sulfoxides can be e.ected by treatment of (S)-menthyl toluene-p-sul.nate 53 with two equivalents of methylenetriphenylphosphorane to yield the phosphorane 54 which on treatment with a range of aldehydes yields the E-Wittig products in reasonable yields and high ee (Scheme 24). An e.cient multi-gram resolution of p-tolyl vinyl sulfoxide has been reported based on the Michael addition of the sodium salt of menthol to the racemic material followed by separation of the two diastereoisomers and elimination of the menthol. Vinyl sulfoxides have been shown to be Michael acceptors in the reductive cyclisation of dienoates such as 55 (Scheme 25); stereoselectivity was high when the cis-derivatives were used and was less when trans-substrates were employed orHMPAwas used as an additive. 68 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 24 Reagents (i) PPh CH (2 equiv.) PhH rt 1 h; (ii) RCHO. RH vinyl E-CH CH——CH Ph Ar. Scheme 25 Reagents (i) Li(s-Bu) BH,30 °C 3 h then 10 °C 2 h. Scheme 26 Reagents (i) RLi or EtMgBr THF 78 °C 5 min. Rn-Bu t-Bu; RH PhCH CH Ar 1-naphthyl; RAr PhCH CH — 1-naphthyl alkyl. Sulfoxides have been employed in a new variant of the Julia—Lythgoe ole.nation whereby the -mesyloxy sulfoxides 56 (easily prepared from the corresponding sulfoxide and LDA followed by treatment with aldehyde RCHO and mesylation) undergo ligand exchange when treated with an alkylmetal (typically RLi) and elimination of the mesylate anion to give predominantly E-alkenes (Scheme 26). A modi.cation of the Julia reaction which employs 1-phenyl-1H-tetrazol-5-yl sulfones has been reported to give improved yields over the known benzothiazole variant when potassium or sodium hexamethyldisilazide are used as bases and DME is employed as the solvent. The intramolecular Michael addition of the carvone derived sulfone 57 leads to a stereoselective addition product 58 from which the sulfone functionality can be removed using samarium iodide leading to the overall formal addition of an acetate synthon via a temporary sulfur connection (Scheme 27). An interesting tandem reaction of the furan derived sultones 59 has been reported in which initial ring opening by an alkyllithium leading to 60 is followed by a 1,6-addition of a second equivalent of the base to give 61; subsequent alkylation and elimination leads to dienes 62 in good yields (Scheme 28). A convenient and high yielding synthesis of thiolesters involves the treatment of the corresponding alkyl thioacetylene with either tosic or tri.uoroacetic acid and silica in re.uxing dichloromethane. The coupling of thiols and acid chlorides mediated by activated zinc gives thiolesters directly in high yield and high purity. The conversion of secondary and tertiary amides to the corresponding thioamide can be e.ected by sequential treatment with tri.ic anhydride and hydrogen sul.de representing a useful alternative to traditional sulfuration methods. Symmetrical thiosulfonic S-esters 69 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 27 Reagents (i) DBU THF 0 °C; (ii) SmI THF MeOH. Scheme 28 Reagents (i) 2RLi THF 78—0 °C; (ii) ICH MgCl 70—25 °C. RH Me; RH n-Pr; RMe n-Bu. [RSO SR] can be prepared from the corresponding sulfonyl chloride by an acetyl chloride-activated zinc mediated reduction. Sul.nimines (thiooxime S-oxides) continue to attract attention indeed a recent review by Davis and co-workers details methods available for the synthesis of amino 70 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 29 Reagents (i) 63 (12 mol%) CuOTf PhMe 3Åmol. sieves 24 h. RPh 1-naphthyl 2-naphthyl ferrocenyl. acids using them as precursors. These intermediates readily undergo 1,2-addition reactions with a range of organometallics with recent examples including reactions with alkyllithiums, Grignard reagents and ester enolates. An indium metal mediated allylation of sulfonimines has also been reported. Other reviews of note include a comprehensive overview of the methods available for the synthesis of thiols selenols sul.des selenides sulfoxides selenoxides sulfones and selenones covering the literature published from mid 1997 to mid 1998. Reviews on the use of sulfur ylides in catalytic epoxidation and aziridation, the uses of sulfonyl 1,3-dienes in synthesis and the applications of 1,3-dithiane 1-oxide derivatives as chiral auxillaries have also appeared.4 Organoselenium and organotellurium chemistry It has been shown that the reductive coupling of selenocyanates can be e.ected using samarium diiodide in THF at low temperature the advantage of this method being that it tolerates substrates containing diverse functionality including esters ketones aldehydes cyanohydrins and enones. Catalytic asymmetric imidation of selenides is possible using TosN—— IPh in the presence of CuOTf and the bis(oxazoline) 63 with ees for the selenimides [RRSe——NTos] formed being in the range of 20—36% (5 examples).The reaction of allylselenides 64 proceeds with [2,3] rearrangement to give after aqueous hydrolysis the allylamines 65 in reasonable yield and with similar levels of enantiomeric enrichment (Scheme 29). Potassium 4-methylselenobenzoate acts as a selenating agent in the BF ·OEt mediated selenation of aliphatic or aromatic nitriles forming primary selenoamides [RC(Se)NH ] in high yields (11 examples 41—96% yield). ,-Unsaturated selenoamides 66 have been shown to react in a 1,4-fashion with alkyllithium reagents with diastereoselectivity of up to 94 4 at the -position; subsequent quenching of the intermediate adduct with allyl bromide gave 67 as the major diastereoisomer (Scheme 30). Reaction of corresponding saturated selenoamides with alkyllithiums leads to the net overall displacement of the amine function and deselenation to give ketones as products in high yields. Vinylselenides can be formed in reasonable yield by the Pd(..) catalysed hydroselenation of allenes, whilst 1-phenylthio-2-phenylselenation of alkynes can be e.ected using a (PhS) —(PhSe) binary system under photochemically generated free 71 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 30 Reagents (i) MeLi Et O 0 °C 10 min; (ii) allyl bromide 0 °C 1 h. Scheme 31 Reagents (i) DIBAH (PhSe) PhMe 50 °C 4 h; (ii) HCl (aq 1 M). RH Me Et n-Pr Ph vinyl; RH Me; RMe Et. Scheme 32 Reagents RNMe NHMe NEt pyrrolidin-1-yl NHCONMe ; RMe Et. radical conditions. The interesting allylselenides 69 have been prepared by treatment of the vinyl substituted acetals 68 with i-Bu AlSePh and are precursors to the - selenoaldehydes 70 (Scheme 31). Asymmetric oxyselenation of alkenes continues to attract considerable attention and the substrates 71, 72, and 73 all gave good yields in this reaction with reasonable to excellent selectivity being observed (Scheme 32).In addition oxyselenation of cycloalkenes with N-(phenylselenyl)phthalimide and (R,R)-or (S,S)-hydrobenzoin has been used in the synthesis of polyhydroxylated cycloalkanes however no stereoselectivity was observed in the addition step. Diselenide 74 has been found to be an e.ective mediator of arene—alkene cyclisation reactions giving excellent des; the presence of a catalytic amount of methanol was essential for the reaction to occur as it was found that the reaction proceeds via a -methoxyarylselenide intermediate (Scheme 33). An alternative method for the formation of -oxyarylselenides is the 72 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 AgOTf CHCl MeOH (3¡X5%),78¡X0 ¢XC 1 h. Scheme 33 Reagents (i) Br O¡Xpentane (4 1 1),100 ¢XC; (ii) RCHO; then RRC¡X¡XO; (iv) RCuMgBr THF 78 ¢XC 2¡X30 min. Rn-CH H n-CH Ph Tol aryl styryl; RPh Ar t-Bu i-Pr alkyl; RMe Scheme 34 Reagents (i) n-BuLi THF¡XEt (iii) CeCl n-C alkyl. BF¡POEt mediated ring opening of epoxides with tri-n-butylstannyl phenylselenoate which gives -hydoxyarylselenides in good to moderate yield. Transmetallation features heavily in organotellurium chemistry this year. Huang has reported that reaction of vinyltelluride 75a (XNHi-Bu) with two equivalents of n-BuLi leads to the intermediate organolithium species 76 which undergoes 1,2- addition reaction with aldehydes and ketones (on addition of cerium() chloride).The corresponding ester 75b (XOEt) has been shown to undergo 1,6-addition of organocuprates with concomitant elimination to give the E-products 77 in excellent yield (Scheme 34). The same group has reported that the organotellurium salts 78 undergo transmetallation with diethylzinc followed by addition to aldehydes ketones and esters in excellent yield. (Scheme 35) It has also been reported that aryltelluroesters [ArCOTeAr] undergo overall cis-1,2-addition to terminal alkynes on treatment with CuI in the presence of triethylamine followed by heating with trimethylamine hydrochloride. The reaction proceeds via an intermediate cuprous alkynylide which undergoes substitution at the telluroester function leading to an ,-alkynone which is susceptible to 1,4-addition of the arenetellurol formed in the second stage of the reaction; -aryltelluro-,-unsaturated ketones are thus formed in good yields.Telluroglycosides have been shown to be excellent glycosyl donors under neutral 73 Annu. Rep. Prog. Chem. Sect. B 1999 95 59¡X81 Scheme 35 Reagents (i) Et Zn RRC——O CH Cl rt. Rn-Bu i-Bu RH Ar vinyl; RAr alkyl; ECH —— CH TMSC—— — C Ph; XCl Br I BPh . conditions and it is possible to e.ect -or -selectivity through the choice of the C-2 sugar protecting group with benzyl leading to -selectivity and benzoyl to -selectivity. Reviews of note include monographs on the thioselenation of unsaturated C—C bonds using disul.de—diselenide binary systems, the synthesis of selenothioic and diselenoic acids, the isolation and stereochemistry of optically active selenium and tellurium compounds and the synthetic applications of organotellurium salts. 5Organosilicon chemistry Phenyldimethylsilyllithium [PhMe SiLi] 79 remains a versatile reagent for the introduction of a silyl group into organic moieties.Work of particular note has been performed by Fleming et al. who have investigated in detail the preparation and analysis of this reagent and its application in the cleavage of silyl enol ethers. They have also reported that the reagent will cleave the toluene-p-sulfonamides derived from secondary amines and indoles and also react with aziridine toluene-p-sulfonamides to give the products of ring opening in most cases. Their investigation of the reduction of -silyloxy ketones to ketones using this reagent has shown that the reaction proceeds via a Brook rearrangement leading to the formation of an intermediate silyl enol ether. Reaction of a slight excess of 79 with tertiary amides has been shown to lead to the formation of enediamines 80 in good yields; these intermediates are precursors to -amino ketones dienediamines and aminoenamines (Scheme 36). Investigations into the mechanism of this reaction have shown it to involve a carbene or carbenoid like intermediate. also e.ects 1,4-addition of the PhMe Si—group to enones (11 examples 35—100%). The metallation of the N-silylated benzyl carbamate 81 with a combination of In combination with a copper salt (typically CuCN) 79 has long been used for conjugate additions and epoxide ring openings however the need for a two fold equivalence of the reagent in forming (PhMe SiLi) CuCNLi and the use of stoichiometric amounts of copper have somewhat restricted its use.Lipshutz and co-workers have reported that the use of a stoichiometric amount of dimethylzinc in forming (PhMe Si)(Me) ZnLi followed by the addition of the higher order cuprate MeCu(CN)Li in a catalytic amount (3%) leads to e.ective formation of conjugate and ring opened products in high yields (9 examples 69—96%). In addition to this they found that Sc(OTf) had a remarkable catalytic e.ect on the reaction leading to an increase of rate to a level above that of the stoichiometric process. It has been reported that (PhMe Si) combined with a catalytic amount of (CuOTf) and P(n-Bu) n-BuLi and ()-sparteine leads to the formation of the corresponding -silylbenzyl- 74 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 36 Reagents (i) PhMe SiLi (79 1.1 equiv.) THF 78 to 20 ¢XC 1 h. Ralkyl aryl. Scheme 37 Reagents (i) s-BuLi ()-sparteine 78 ¢XC hexane or EtO. RMe i-Pr. Scheme 38 Reagents (i) RCHO CsF NaF or ZnBr DMSO DMF or THF 0.5¡X32 h. Ralkyl vinyl Ar Het-Ar. carbamate in excellent yield and with moderate ee (Scheme 37). The reduction of alkyl-1-(trimethysilyl)imine [n-PrC(¡X¡XNH)TMS] using lithium borohydride and -()- diethyl tartrate in THF leads to the formation of the corresponding -trimethylsilylamine [n-PrCH(NH )TMS] with a 60% ee.The tris-C,O,O-(trimethylsilyl)ketene acetal 82 reacts with aldehydes under Lewis acid or uoride catalysis to give E-alkenoic acids 83 in good to excellent yields and represents a mild alternative to more traditional methods for this transformation (Scheme 38). A Lewis acid catalysed [22] cycloaddition of crotylsilanes to methyl propiolate has been shown to be highly stereospecic leading cleanly to the cis-or transcyclobutene from the corresponding Z-or E-silane (Scheme 39). Allyl-tert-butyldiphenylsilane allyldiisopropylphenylsilane and allyltriisopropylsilane have been used in Lewis acid catalysed [32] cycloadditions to ,-unsaturated esters and ketones leading to silyl-substituted cyclopentenes which can be converted into the corresponding cyclopentanols using the Fleming¡XTamao oxidation protocol.The rst exclusive endo-dig carbocyclisation to be reported involves the HfCl catalysed allysilylation of the unactivated alkynes 84 which proceeds in moderate to excellent yields for a range of substrates (Scheme 40). The conjugate addition of allylsilanes to ,-unsaturated esters and ketones can be catalysed eciently using TMSN(OTf) generated in situ from HN(OTf) and the allylsilane employed. The bis-allylsilane 85 together with several related structures has been shown to be far superior in the TBAF mediated allylation of aldehydes than corresponding monoallysilanes; a stronger anity towards uoride ions leading to the chelate intermediate 86 is proposed (Scheme 41). Allylation of -hydroxyaldehydes with Z-crotyltrifluorosilane 87 in the presence of DIPEA leads predominantly to the formation of the 75 Annu.Rep. Prog. Chem. Sect. B 1999 95 59¡X81Scheme 39 Reagents (i) Methyl propiolate TiCl CH Cl ,78 to20 °C 19 h. Scheme 40 Reagents (i) HfCl (10 mol%) TMSCl (50 mol%) CH Cl 0 °C. RPh alkyl aryl; n0 1 2. Scheme 41 Reagents (i) TBAF. Scheme 42 Reagents (i) 87 (3 equiv.) DIPEA (3 equiv.),CH Cl 4Åmol. sieves 36 h. Rsubstituted alkyl. anti,anti-dipropionate stereotetrad 88 (Scheme 42). Allene 89 on treatment with t-BuLi undergoes -deprotonation followed by reverse Brook rearrangement to give enolate 90 which reacts with aldehydes leading to -hydroxy-,-unsaturated acylsilanes 91 in good yields (Scheme 43). Reaction of lithium enolates with -(2-pyridyl)acryloylsilanes 92 lead to the formation of the cyclopentenes 93 (major isomer) via a similar rearrangement process. A similar [43] annulation can be e.ected using lithium enolates of ,-unsaturated ketones 94 and -(trimethysilyl)acryloylsilanes 95 (Scheme 44). A [41] annulation of 76 Annu.Rep. Prog. Chem. Sect. B 1999 95 59—81 Scheme 44 Reagents (i) THF,80 to 30 °C. REt n-Pr i-Pr n-octyl. Scheme 45 Reagents (i) 96 97 98; 1.0 1.3 2.0 (C 78 °C 6 h. Scheme 43 Reagents (i) t-BuLi THF 78 °C 30 min; (ii) RCHO. Ralkyl vinyl styryl 1-naphthyl 1-furyl Ph Ar. F ) SnBr (0.2 equiv.) CH Cl 77 Annu. Rep. Prog. Chem. Sect. B 1999 95 59—81 30 ¢XC CHCl. Scheme 46 Reagents (i) SnCl Scheme 47 Reagents (i) TMSOTf Py CH CN,40 ¢XC¡Xrt; (ii) BF¡POEt.Ri-Pr Ph CH; n0 1. trialkylsilylvinylketenes with carbenoids providing a new route to cyclopentenones has also been reported. New methods for catalysing the Mukaiyama aldol coupling reaction continue to appear. The use of MgI SmI Bi(OTf) InCl (under aqueous conditions) polymer bound chiral Ti() complexes Sc(OSOCH) and bulky organoaluminium catalysts in combination with trialkylsilylsulfonates to mediate this reaction are all worthy of note. In addition Denmark has reported that readily prepared trichlorosilyl enolates react under chiral phosphoramide catalysis to give good levels of enantioselectivity. Otera has continued to investigate the strategy of ¡¥parallel recognition¡¦ in designing multi-component reactions and has demonstrated that discrimination between aldehydic and ketonic functions is possible in the one-pot reaction of substrate 96 with the ester 97 and ketone 98 derived silyl enol ethers catalysed by (CF)SnBr leading cleanly to the adduct 99 in 72% yield with no apparent cross over of reaction modes (Scheme 45).Anomeric silyl enol ethers for example 100 undergo rearrangement to give the -hydroxy ketones 101 in high yield and with moderate stereoselectivity 78 Annu. Rep. Prog. Chem. Sect. B 1999 95 59¡X81 (Scheme 46). In a process reminiscent of the Baylis—Hillman reaction enone 102 undergoes reaction with TMSOTf in the presence of pyridine to give the intermediate 103 which on treatment with cyclic acetals under Lewis acid catalysed conditions yields the enones 104 (Scheme 47). 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