Synthesis of (+)-discodermolide by catalytic stereoselective borylation reactions

Abstract

The marine natural product (+)-discodermolide was first isolated in 1990 and, to this day, remains a compelling synthesis target. Not only does the compound possess fascinating biological activity, but it also presents an opportunity to test current methods for chemical synthesis and provides an inspiration for new reaction development. A new synthesis of discodermolide employs a previously undisclosed stereoselective catalytic diene hydroboration and also establishes a strategy for the alkylation of chiral enolates. Furthermore, this synthesis of discodermolide provides the first examples of the asymmetric 1,4-diboration of dienes and borylative diene-aldehyde couplings in complex-molecule synthesis. Borylation-based synthesis: The development of a strategy for stereocontrol in catalytic diene hydroboration enables the synthesis of a critical building block for the assembly of (+)-discodermolide. Combined with asymmetric catalytic diboration, hydroformylation, and borylative aldehyde-diene coupling reactions, (+)-discodermolide could then be prepared from simple hydrocarbon-based building blocks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.