Development of Stereodivergent Synthesis of Skipped Dienes and Application to Unified Total Synthesis of Madangamine Alkaloids

Abstract

A skipped diene (1,4-diene) is an important structural motif found in a variety of biologically active natural products. We report the stereodivergent method, consisting of hydroboration of allenes and the Migita-Kosugi-Stille coupling, which allows for access to all four possible stereoisomers of the skipped dienes. The hydroboration of allenes is especially useful because both E-allylic and Z-allylic alcohols are obtained by simply changing the organoborane reagent. While use of 9-BBN provides E-allylic alcohols as thermodynamic products, the reaction with HB(Sia)₂ gives Z-allylic alcohols as kinetic products. The developed method was successfully applied to the unified total synthesis of madangamine alkaloids.