Asymmetric Synthesis of Dihydropyranones from Ynones by Sequential Copper(I)-Catalyzed Direct Aldol and Silver(I)-Catalyzed Oxy-Michael Reactions

摘要

Chiral dihydropyranones are versatile intermediates for the synthesis of tetrahydropyrans and spiroketals, which are ubiquitous structural motifs in biologically active molecules. The asymmetric hetero-Diels-Alder reaction between car-bonyl compounds and Danishefsky-type siloxy dienes is one of the most reliable methods of accessing optically active dihydropyranones [Scheme 1, Eq. (1)]. However, this method requires additional steps for the preparation of siloxy dienes, and the stereoselective synthesis of multisubstituted siloxy dienes is generally difficult. Considering the fact that enolates derived from ynones 2 are in the same oxidation state as Danishefsky-type dienes, we envisioned that a stepwise catalytic asymmetric direct aldol reaction of ynones, followed by an intramolecular oxy-Michael reaction would produce enantiomerically enriched dihydropyranones [Scheme 1, Eq. (2)]. This sequential pathway would be atom-economical and require fewer steps. Herein, we report the catalytic asymmetric synthesis of 2,6-disubstituted and 2,3,6-trisubstituted dihydropyranones by a sequential aldol-oxy-Michael reaction using stable and easily accessible ynones.