Conjugate addition silyl enol ethers from

The preparation of silyl enol ethers from carbonyl compounds represents one of the major uses of TMSOTf. Recently, the stereochemistry and regiospeciflcity of such transformation has been addressed for aldehydes and Q -(lV-alkoxycarbonylamino) ketones, respectively. On the other hand, enantiopure silyl enol ethers can be formed by addition of TMSOTf to zinc enolates, which are obtained from the copper-catalyzed enantioselective conjugate addition of dialkyIzinc reagents to cyclic (eq 36) and acyclic enones. ... 

The scope of the conjugate addition reaction can be further expanded by use of Lewis acids in conjunction with enolate equivalents, especially silyl enol ethers and silyl ketene acetals. The adduct is stabilized by a new bond to the Lewis acid and products are formed from the adduct. 

A number of other chiral catalysts can promote enantioselective conjugate additions of silyl enol ethers, silyl ketene acetals, and related compounds. For example, an oxazaborolidinone derived from allothreonine achieves high enantioselectivity in additions of silyl thioketene acetals.323 The optimal conditions for this reaction also include a hindered phenol and an ether additive. 

An RCu(LiI)/TMSI combination13 promotes conjugate addition to a,/)-unsaturated ketones, leading directly to TMS enol ethers from a presumed organocopper-enone jr-complex, thus ruling out significant amounts of enolate as an intermediate on the reaction pathway (equation 2). However, these results do not allow discrimination between an a-cuprio ketone or a /i-silyl copper species. 

If the 1,5-diearbonyl compound is required, then an aqueous work-up with either acid or base cleaves the silicon-oxygen bond in the product but the value of silyl enol ethers is that they can undergo synthetically useful reactions other than just hydrolysis. Addition of the silyl enol ether derived from aeetophenone (PhCOMe) to a disubstituted enone promoted by titanium tetrachloride is very rapid and gives the diketone product in good yield even though a quaternary carbon atom is created in the conjugate addition, This is a typical example of this very powerful class of conjugate addition reactions. 

The silyl enol ether that is the initial product from conjugate addition of a silyl enol ether or silyl ketene acetal need not be hydrolysed but can also be used in aldol reactions. This example uses trityl perchlo-... 

First, chemoselective (Chapter 24) conjugate addition of the silyl ketene acetal on the enone is preferred to direct aldol reaction with the aldehyde. Then an aldol reaction of the intermediate silyl enol ether on the benzaldehyde follows. The stereoselectivity results, firstly, from attack of benzalde-hyde on the less hindered face of the intermediate silyl enol ether, which sets the two side chains trans on the cyclohexanone, and, secondly, from the intrinsic diastereoselectivity of the aldol reaction (this is treated in some detail in Chapter 34). This is a summary mechanism. 

A racemic, bichromophoric C70-pyrene conjugate showing intramolecular photo-induced energy transfer from the excited singlet state of the PAH to the fullerene has been reported by Daub and co-workers.383 Its chirality is based on the stereogenic center resulting from reduction of a fullerene-fused cyclohexanone, itself obtained by Diels-Alder addition of 2-[(trimethylsilyl)oxy]buta-1,3-diene to the C(l)-C(2) bond of C70 and subsequent hydrolysis of the formed silyl enol ether (cf. Section IV.C.l.d and Scheme 1.18). 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

A similar conjugate addition- silyl group transfer process was reported later by Danishefsky and co-workers for the synthesis of PGF2a (Scheme 52) (103). In this case, the silyl ketene acetal adds, under Hgl2 promotion, cis to the OTBS group in the optically pure enone 52.1 to provide silyl enol ether 52.2 as the exclusive product. The indicated aldol products are obtained from 52.2 in subsequent reactions with ( )- and (Z)-octenal using TiCl4 catalysis. 

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