Anti-Selective Asymmetric Aldol Reaction

The construction of the anti- and syn-3-hydroxy-2-methylcarbonyl structural units is important for the synthesis of polyketide natural products exemplified by macrolides. While the efficient construction of the syn unit can now be readily achieved through asymmetric aldol reactions, methods for the direct elaboration of the anti counterparts have met with limited success.

Recently, A. Abiko and S. Masamune et al. have developed a highly enantioselective anti-aldol reaction using the chiral ester 1 with dicyclohexylboron triflate and triethylamine¹⁾. The ester 1 is a superb stereocontrolling reagent in terms of both simple diastereo- and diastereofacial selectivities. The anti-aldol reaction can be carried out with a wide variety of aldehydes in high reaction yield and under mild condition. The anti-aldol products 3 are converted to the corresponding alcohols 4 by LiAlH₄ and/or carboxylic acids by LiOH without loss of the stereochemical integrity. The chiral auxiliary alcohols 2 can be recovered in nearly quantitative yield and reused.

An application to a natural product synthesis has been reported²⁾.