Total Synthesis of (+)-Methynolide Using a Ti-mediated Aldol Reaction of a Lactyl-Bearing Oxazolidin-2-one, and a Vinylogous Mukaiyama Aldol Reaction

A highly convergent total synthesis of (+)-methynolide, based on two types of stereoselective aldol reaction, was achieved. The C1-C8 and C9-C11 fragments of (+)-methynolide were prepared by a vinylogous Mukaiyama aldol reaction using a vinyl ketene silyl N,O-acetal, and a Ti-mediated aldol reaction of a lactyl-bearing chiral oxazolidin-2-one, respectively. Yamaguchi esterification of both fragments and ring-closing metathesis afforded (+)-methynolide.