The Role of theα-Stereogenic Center in the Control of Stereoselection in the Reduction ofα-Alkyl-β-hydroxy Ketones: A Highly Diastereoselective Protocol for the Synthesis of 1,2-syn-2-Alkyl-1,3-diols

Abstract

Accurate investigations on the role played by an alpha-stereogenic center in controlling the reduction of various classes of beta-hydroxy ketones allowed us to set up a general and highly diastereoselective protocol for the synthesis of 2-alkyl-1,3-diols with 1,2-syn relationship. This methodology is based on the conversion of a beta-hydroxy ketone into the corresponding titanium alcoholate that permits us to organize the substrate in a stable and rigid structure, which stereofacially favors attacking hydride ions. The use of THF as solvent makes available a variety of hydride donors that cover a large spectrum of steric demand: the choice of the more appropriate one depends on the conformational stability of the cyclic intermediate. Excellent results are obtained also in the presence of an additional stereogenic center in the beta-position, even if it exerts a concordant or an opposite steric effect with respect to the alpha-substituent.

Asymmetric Syntheses of (Z)- or (E)-β,γ-Unsaturated Ketones via Silane-Controlled Enantiodivergent Catalysis

“…Grignard addition to 10 afforded tertiary alcohol 11 in 59% yield with 6:1 diastereoselectivity. 16 The stereochemistry of 11 was assigned by nOe analyses of acetonide derivative 12.…”