Enantioselective Synthesis of 2,2-Disubstituted Tetrahydrofurans: Palladium-Catalyzed [3+2] Cycloadditions of Trimethylenemethane with Ketones

摘要

Found throughout nature and in synthetic products, tetrahydrofurans are a ubiquitous structural motif with wide-reaching biological activity. Among the many approaches towards their synthesis, cycloaddition represents a powerful and attractive strategy, but catalytic enantioselective variants remain rare.We recently disclosed one such approach involving the palladium-catalyzed cycloaddition of trimethylenemethane (TMM) with aldehydes. Herein, we describe the surprising success of this method in reactions with aromatic ketones, a substrate class which was previously unknown in Pd/TMM reactions using achiral ligands.