Concise, Enantioselective, and Versatile Synthesis of (-)-Englerin A Based on a Platinum-Catalyzed [4C+3C] Cycloaddition of Allenedienes

摘要

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.