Silylated aldols Subject

As with aldol and Mukaiyama addition reactions, the Mannich reaction is subject to enantioselective catalysis.192 A catalyst consisting of Ag+ and the chiral imino aryl phosphine 22 achieves high levels of enantioselectivity with a range of N-(2-methoxyphenyljimines.193 The 2-methoxyphenyl group is evidently involved in an interaction with the catalyst and enhances enantioselectivity relative to other A-aryl substituents. The isopropanol serves as a proton source and as the ultimate acceptor of the trimethyl silyl group. 

Hydrogen bond-promoted asymmetric aldol reactions and related processes represent an emerging facet of asymmetric proton-catalyzed reactions, with the first examples appearing in 2005. Nonetheless, given their importance, these reactions have been the subject of investigation in several laboratories, and numerous advances have already been recorded. The substrate scope of such reactions already encompasses the use of enamines, silyl ketene acetals and vinylogous silyl ketene acetals as nucleophiles, and nitrosobenzene and aldehydes as electrophiles. 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

Since the middle of the 198O s remarkable progress has been achieved in the development of asymmetric aldol reactions of silyl enolates. In the beginning of this evolution, chiral auxiliary-controlled reactions were extensively studied for this challenging subject [106]. As new efficient catalysts and catalytic systems for the aldol reactions were developed, much attention focused on catalytic enantiocontrol using chiral Lewis acids and transition metal complexes. Thus, a number of chiral catalysts realizing high levels of enantioselectivity have been reported in the last decade. 

In 1986, Reetz et al. reported that chiral Lewis acids (B, Al, and ll) promoted the aldol reaction of KSA with low to good enantioselectivity [115]. The following year they also introduced asymmetric aldol reaction under catalysis by a chiral rhodium complex [116]. Since these pioneering works asymmetric aldol reactions of silyl enolates using chiral Lewis acids and transition metal complexes have been recognized as one of the most important subjects in modern organic synthesis and intensively studied by many synthetic organic chemists. 

The use of these boryl complexes in catalytic, enantioselective additions to aldehydes by silyl ketene acetals has also been the subject of intense investigation by Yamamoto (Eq. 30) [108]. Although ethyl and benzyl acetate-derived enol silanes furnished racemic products, the phenyl acetate-derived trimethylsilyl ketene acetals proved optimal, giving adducts in up to 84% ee. Additionally, Yamamoto has documented the use of 184 in aldol addition reactions of propionate- and isobutyrate-derived enol silanes (Eqs. 31 and 32). Thus, the addition of the phenyl acetate derived (E)-enol silane afforded adducts as diastereomeric mixtures with the syn stereoisomer displaying up to 97% ee (Eq. 32). 

Imino aldol reaction of ketene silyl acetals with the chiral imine derived from tartaric acid 83 in the presence of a cation-exchange resin provided the corresponding /i-amino esters 84 in a good yield and high diastereose-lectivity [68]. The esters 84, thus obtained, were subjected to the Grignard reagent which promoted S-lactam formation. After a sequence of reactions compound 84 was transformed into the ester 85 [68] which in the past was... 

Brigaud and Portella et al. applied Yb(OTf)3 to aldol reaction of a,a-difluoroenol silyl ether (2) affording difluoromethylene ketones, a common structural motif of HlV-1 protease inhibitor [4], (2) was generated from acylsilane and trifluo-romethyltrimethylsilane and directly subjected to the aldol reaction with aldehydes with 10 mol% ofYb(OTf)3 in a one-pot procedure (Scheme 13.1). The same reaction with other Lewis acids such as TiCU or BF3-OEt2 required more than stoichiometric amount. 

Soon after the first report of the aldol reaction of silyl enol ethers was disclosed, allylsilanes were reported to show similar reactivity toward aldehydes and ketones when activated by a stoichiometric amount of TiCU (Scheme 3-85). This synthetically important reaction has subsequently become the subject of many synthetic chemists and was improved extensively using various kinds of Lewis acid catalysts. Acyclic transition states are proposed to explain diastereoselectivities of the reaction depending on a Lewis acid and reaction conditions. Particularly, synclinal orientation of reactants is suggested to be more preferable rather than an antiperiplanar one particularly for ( )-allylsilanes based on molecular model studies (Scheme 3-86). High diastereoselectivity observed in the reaction of chiral allylsilanes with aldehydes is understood in terms of this transition state model which is based on the Felkin-type induction (Scheme 3-87). ... 

Cyclohepta-3,5-dienone)iron complexes can be stereoselectively methylated and hydroxylated. The electrophile adds exclusively anti to the tricarbonyliron fragment. Double methylation or hydroxylation of the a and a positions is accomplished in high overall yield (Scheme 4-146). Silyl enol ethers adjacent to tricarbonyl(Ti -diene)iron units can be subjected to Mukaiyama aldol reaction with aldehydes to provide aldol adducts with varying diastereoselectivity. This methodology has, for example, been applied to the enantioselective synthesis of the dienetriols streptenol C and D (Scheme 4-147). ... 

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