Trimethylsilyl asymmetric addition reaction

Several reports have employed a more traditional approach where the use of enantio-pure chiral amino auxiliaries, that, after the successful Strecker reaction, can be chemically modified to yield the free amino acids. For example, Chakraborty and co-workers have reported the highly diastereoselective addition of trimethylsilyl cyanide to a variety of a-phenylglycinol-derived benzaldimines [16]. (S)-a-Methylbenzylamine has been used as a chiral auxiliary for the asymmetric Strecker reaction [17]. (R)-Phenylglycinol has been utilized as a chiral auxiliary from the asymmetric Strecker reaction products of aldehydes in the synthesis of a,a-disubstituted amino acids [18]. (R)- and (S)-2-Amino-2-phenylethanol were used as chiral auxiliaries in the synthesis of optically pure a-arylglycines [19]. 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

The only known metal catalyst for the asymmetric catalytic Strecker reaction is the aluminum salen catalyst 465 (Sch. 65) recently reported by Sigman and Jacobsen [97]. They prepared 11 different chiral salen complexes from different transition and main group metals and screened these complexes for the addition of trimethylsilyl cyanide to imine 460 at room temperature. The aluminum catalyst 465 was optimum in terms both of asymmetric induction and rate. This constitutes the first aluminum salen complex successfully developed for an asymmetric catalytic reaction. 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

In 1988, Mukaiyama et al. reported the Sn(OTf)2-50d-catalyzed asymmetric Michael reaction of a trimethylsilyl enethiolate, CH2=C(SMe)SSiMej (up to 70% ee) [243]. It was proposed that the catalytic reaction proceeded via an Sn(II) enethiolate. They also demonstrated that a BINOL-derived oxotitaniurn catalyzes the Michael addition of ketene silyl thioacetals to a-enone with high enantioselectivity (up to 90% ee) [244]. After this pioneering work other research groups developed new reaction systems for enantioselective Mukaiyama-Michael reactions. 

Metal compounds possessing Lewis acid character are often used in the Michael addition reaction, and the methodology is reasonably applied to the asymmetric reaction in the presence of chiral ligands. The mechanism could involve either purely Lewis acidic activation of the Michael acceptor or generation of new orga-nometallic species by the transmetalation or C-H activation, although they were not clear in many cases. The system of Sn(OTf)2 and chiral (S)-diamine developed by Mukaiyama promoted the asymmetric addition of trimethylsilyl enethi-olate 68 to P-arylvinyl ketones (Scheme 13) [70, 71]. The diamine-coordinated tin enolate was considered to be involved, and slow addition of 68 was essential to inhibit the racemate formation process. 

The organocatalysed asymmetric cycloaddition reaction of a,p-unsaturated ketones and aldehydes is scarcely studied, especially for fluorine-containing substrates. In this area, Liu et al. have reported unusual inverse-electron-demand oxa-Diels-Alder reactions of a,p-unsaturated trifluoromethyl ketones with aldehydes catalysed by chiral a,a-diphenylprolinol trimethylsilyl ether. It was shown that the addition of pura-fluorophenol and silica gel along with this catalyst was necessary, otherwise the reaction was very slow and a poor yield was obtained. Under these optimal conditions, the expected cyclic adducts were obtained in good yields and high fl n-diastereo- and enantioselectivities, as shown in Scheme 6.11. 

In 2009, the North group found that bimetallic aluminium(salen) complex 4 was a highly effective catalyst for the asymmetric addition of trimethylsilyl cyanide to aldehydes (Scheme 19.2). In the presence of a phosphine oxide cocatalyst and 2 mol% of the catalyst (l ,l )-[(salen)Al]20 4, the corresponding adducts were obtained in 53-96% enantiomeric excess, which were comparable to those obtained using mononuclear (salen)AlCl complexes. An analysis of the reaction kinetics showed that the reactions exhibited first-order kinetics, with the reaction rate being independent of the aldehyde... 

In 1999, Shibasaki et al. reported on the direct catalytic asymmetric aldol reaction (Scheme 8.36), which was not necessary to preconvert the ketone moiety into the more reactive species such as an enolate ion and enol ether." The addition of bulky aldehyde 248 into the mixture of ethyl methyl ketone 249 and LaLi3tris(/ -binaphthoxide) [(/ )-LLB)] afforded aldol adduct 250 in excellent stereoselectivity. However, this reaction required a large amount of ketones (50 equiv), and catalyst (20 mol%) were required. They improved the conditions to reduce the amount of ketone (5 equiv) and catalyst (8 equiv) by using the hetero-polymetallic asymmetric catalyst (Scheme 8.37). The addition of the catalytic amount of potassium bis(trimethylsilyl) amide (KHMDS) and H2O was found to be effective to the catalysis. Adduct 253 was converted into ester 254 by the... 

The addition of HCN to aldehydes or ketones produces cyanohydrins. This is an equilibrium reaction. For aldehydes and aliphatic ketones the equilibrium lies to the right therefore the reaction is quite feasible, except with sterically hindered ketones such as diisopropyl ketone. However, ketones ArCOR give poor yields, and the reaction cannot be carried out with ArCOAr since the equilibrium lies too far to the left. With aromatic aldehydes the benzoin condensation (16-54) competes. With oc,p-unsaturated aldehydes and ketones, 1,4 addition competes (15-33). Ketones of low reactivity, such as ArCOR, can be converted to cyanohydrins by treatment with diethylaluminum cyanide (Et2AlCN see OS VI, 307) or, indirectly, with cyanotrimethylsilane (MesSiCN) in the presence of a Lewis acid or base, followed by hydrolysis of the resulting O-trimethylsilyl cyanohydrin (52). The use of chiral additives in this latter reaction leads to cyanohydrins with good asymmetric... 

The preparation of optically active analogues of the natural amino acids has proven reasonable using the reaction of tris(trimethylsilyl) phosphite with chiral aldimines prepared from optically active amines.225 The asymmetric induction has been observed to be as high as 80%, a significant competitive process compared to the multistep approaches available.226227 An alternative one-step approach involving asymmetric induction upon addition to an aldimine derived from a chiral N-substituted urea provided a product with less desirable optical purity.228... 

Tomioka et al. reported the asymmetric Michael addition of lithium thiolates catalyzed by chiral aminoether 31 (Scheme 8D. 18) [39]. Thus, in the presence of catalytic amounts of 31 (10 mol %) and lithium 2-(trimethylsilyl)thiophenolate 32-Li (8 mol %), thiol 32 (3 equiv.) reacted with a,p-unsaturated esters at -78°C in toluene-hexane solvent to give the Michael adduct with up to 97% ee. In the ahsence of 31, the reaction of thiophenol proceeded in only 0.5% yield at room temperature. A monomeric complex consisting of 31 and lithium is proposed as the key reactive species in this asymmetric reaction. The trimethylsilyl group at the ortho-po-sition of the thiol moiety in 32 contributes to the formation of the stereochemically defined monomeric chelated structure, wherein the lithium cation is coordinated with the three heteroatoms of the tridentate ligand 31. The reactions of acyclic /nmv-a,P-unsaturated esters (R1 = Me, Et, Pr, Bu, Bu, PhCH9 R2 = H) proceeds with high enantioselectivity in... 

Two other types of catalysts have been investigated for the enantioselective Strecker-type reactions. Chiral N-oxide catalyst 24 has been utilized in the trimethylsilyl cyanide promoted addition to aldimines to afford the corresponding aminonitriles with enantioselectivities up to 73% ee [14]. Electron-deficient aldimines were the best substrates, but unfortunately an equimolar amount of catalyst 24 was used in these reactions. The asymmetric Strecker addition of trimethylsilyl cyanide to a ketimine with titanium-based BINOL catalyst 25 gave fast conversions to quarternary aminonitriles with enantiomeric excesses to 59%... 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

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