Concise, enantioselective, and versatile synthesis of (−)-Englerin A Based on a platinum-catalyzed [4C+3C] cycloaddition of allenedienes

Abstract

A practical synthesis of (−)-englerin A was accomplished in 17 steps and 11 % global yield from commercially available achiral precursors. The key step consists of a platinum-catalyzed [4C+3C] allenediene cycloaddition that directly delivers the trans-fused guaiane skeleton with complete diastereoselectivity. The high enantioselectivity (99 % ee) stems from an asymmetric ruthenium-catalyzed transfer hydrogenation of a readily assembled diene–ynone. The synthesis also features a highly stereoselective oxygenation, and a late-stage cuprate alkylation that enables the preparation of previously inaccessible structural analogues