Aldol Reactions 2 Mechanistic Considerations

The stereochemistry outcome of the aldol additions is an issue of paramount importance in the synthesis of iminosugars. Based on mechanistic considerations of the DHAP aldolases [29, 30] it can be assumed that the absolute configuration at C-3 (i.e. the stereocenter arising from DHAP) is independent of the acceptor used in the reaction. Analysis of the stereochemistry at C-4 (i.e. the one generated from the aldehyde) can be used to infer the kinetic stereoselectivity of the aldolases towards each of the N-protected amino aldehydes (Figure 19.4). For the selected... 

The careful mechanistic studies that have been documented by Evans are a highly attractive aspect associated with these catalyst systems, and the work is well worth consulting for the practical and mechanistic insight it provides [152, 154, 155]. The investigations have permitted an understanding of the structural and coordination chemistry of the metal complexes, which is sure to have a positive impact on the evolution of enantioselective catalysts. For example, Evans has noted that the general addition of TMSOTf can lead to considerable acceleration in the aldol reaction. Thus, the addition reaction of pyruvate and trimethylsilyl tert-butyl thioketene acetal mediated by 2 mol % of copper(bisoxazoline) affords product in 97 % ee over the course of 14 hours when the same reaction is conducted with one equivalent of TMSOTf and Cu catalyst under otherwise identical conditions, reaction is observed to reach completion in 35 minutes, with no deterioration in enan-... 

Researchers fundamentally interested in C-C bond-forming methods for polyketide synthesis have at times viewed allylation methods as alternatives, and maybe even competitors, to aldol addition reactions. Both areas have dealt with similar stereochemical problems simple versus absolute stereocontrol, matched versus mismatched reactants. There are mechanistic similarities between both reaction classes open and closed transition states, and Lewis acid and base catalysis. Moreover, there is considerable overlap in the prominent players in each area boron, titanium, tin, silicon, to name but a few, and the evolution of advances in both areas have paralleled each other closely. However, this holds for an analysis that views the allylation products (C=C) merely as surrogates of or synthetic equivalents to aldol products (C=0). The recent advances in alkene chemistry, such as olefin metathesis and metal-catalyzed coupling reactions, underscore the synthetic utility and versatility of alkenes in their own right. In reality, allylation and aldol methods are complementary The examples included throughout the chapter highlight the versatility and rich opportunities that allylation chemistry has to offer in synthetic design. 

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