Polypropionate asymmetric aldol reactions

Rutamydns. Rutamycins A (137) and B (138) are 26-membered macrolide antibiotics isolated from Streptomyces cultures (Scheme 9-43). They are closely related to the oligomycin family of natural products and more distantly to the 22-membered cytovaricin. Each of these macrocycles consists of a highly functionalized spiroacetal unit bridged by a polypropionate-derived chain. In the rutamycins, the asymmetric aldol reaction could be envisaged to play a key role in assembling the spiroacetal portion and the C4-C]4 polypropionate sector with various strategic disconnections possible. 

Due to the importance of polypropionate antibiotics, mainy chiral auxiliaries have been introduced on propionic add derivatives in order to perform asymmetric aldol reactions. The use of esters of chiral alcohols usually gives disappointing results [147, 209]. In an important exception, Braun and Sacha [149] recommended the propionate of a trimethylsilyloxyalcohol 1.12. The reaction of the derived dicyclopentylchlorozirconium enolate with aliphatic aldehydes at -105°C leads to anti aldols with an excellent fedal stereoselectivity (Figure 6.78). The selectivity is lower with benzaldehyde. The use of titanium enolates of N-tosyl-aminoephedrine 1.61 (R = Ts) propionate has recently been advocated [1262],... 

Class II aldolase mimics (Scheme 10.4) were the first small-molecule catalysts that were reported for the direct intermolecular aldol reaction. These catalysts are characterized as bimetallic complexes that contain both Lewis acidic and Brpnsted basic sites. Shibasaki et al. first reported on the use of such a catalyst in the aldol reaction in 1997, demonstrating its potential with the reaction of various acetophenones 52 and aldehydes 53 (Scheme 10.13). Aldols 55 were obtained in good yields and enantioselectivities. A similar approach was used in the direct catalytic asymmetric aldol-Tishchenko reaction.Nevertheless, for the moment, this method does not provide access to true polypropionate fragments. ... 

A synthesis of both the polypropionate and spiroacetal fragments of rutamycin B have been described by Panek and Jain [65]. The majority of stereocenters were introduced via asymmetric allylation and crotylation reactions however, an aldol... 

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