One-Step Stereocontrol of Three Contiguous Stereogenic Centers in Acyclic Systems: The Tuning Effect of an Additive in a Tandem Asymmetric Michael Addition and Meerwein-Ponndorf-Verley Reduction

摘要

A significant amount of chemistry that involves chiral 1, 3-oxathianes derived from optically active 1,3-hydoxythiols has been developed for asymmetric synthesis. However, optically active 1,3-hydroxythiols are only available from natural sources, for example, as 10-sulfanylisoborneol (1) from camphor, and little attention has been focused on their synthesis. The stereoselective construction of contiguous stereogenic centers in acyclic compounds is generally difficult compared to that in cyclic systems. For example, the asymmetric synthesis of cyclic systems with three contiguous stereogenic carbon centers by tandem conjugate addition to bis (α, β-unsaturated ester)s and the tandem Michael-aldol cyclization of acyclic ω-oxo-α, β-unsaturated esters and ketones has been developed sufficiently. Despite the sophisticated methodology of double aldol reactions and of the catalytic hydrogenation of enamino ketones, one-step stereocontrol of three contiguous stereogenic centers in acyclic compounds still remains a challenge for asymmetric synthesis, and the one-step asymmetric conversion of acyclic α, β-unsaturated ketones into acyclic compounds with three contiguous stereogenic carbon centers was previously unknown. We report herein the highly stereoselective construction of three contiguous stereogenic centers in a tandem Michael addition and Meerwein-Ponndorf-Verley (MPV) reduction of the α, β-unsaturated ketones 2 with (-)-1 to give the alcohols 3, thus allowing the asymmetric synthesis of 1,3-hydroxythiols 4 (Scheme 1).