A Nitrone Dipolar Cycloaddition Strategy toward an Enantioselective Synthesis of Massadine

Abstract

An enantioselective route to the C,D-bicycle of massadine is reported. Enantiopure intermediates were generated by a single stereoselective reduction using the Corey-Bakshi-Shibata reagent. This initial stereoinduction was translated into the five contiguous stereocenters of the massadine D-ring by a synthetic route that features a diastereoselective and stereospecific Ireland-Claisen rearrangement of a trianionic enolate followed by a diastereoselective nitrone dipolar cycloaddition of a highly electron-poor oxime.

Scheme 1.

Retrosynthetic Analysis

Scheme 2.

Allylic Ester Synthesis

Scheme 3.

Synthesis of Oxime Substrates

Scheme 4.

Conversion to Functionalized Cyclopentane

Scheme 5.

Synthesis of C-Ring