Step‐Economic and Protecting‐Group‐Free Total Synthesis of (+)‐Cardiobutanolide

Abstract

AbstractA short protecting‐group‐free synthesis of (+)‐cardiobutanolide is reported. We have modified a one‐pot conversion of D‐glucono‐δ‐lactone into the building block β‐hydroxy‐γ‐lactone. A series of cross‐metathesis reactions and dihydroxylations either under the Sharpless conditions or achiral 4‐methylmorpholine N‐oxide (NMO) conditions were used to synthesize (+)‐cardiobutanolide and its various diastereomers. In this endeavour, we have achieved a step‐economic and protecting‐group‐free synthesis of (+)‐cardiobutanolide in 22.4 % overall yield from D‐glucono‐δ‐lactone. A cross‐metathesis reaction that is compatible with hydroxy groups and a substrate controlled Upjohn dihydroxylation reaction are key steps in the synthesis. The synthesis is highly efficient and competitive with previous reports.