Stereoselective access to furan-fused [5.5.0] bicyclic heterocycles enabled by gold-catalyzed asymmetric [8 + 4] cycloaddition

Abstract

The construction of fused [5.5.0] bicyclic heterocycles with precise regio-, stereo-, and enantioselective control remains a significant challenge in asymmetric catalysis. In this work, we introduce a novel gold-catalyzed asymmetric [8 + 4] cycloaddition reaction of 1-(1-alkynyl)cyclopropyl ketones with simple tropones, yielding highly functionalized cyclohepta[b]furo[3,4-d]oxepine derivatives with excellent diastereo- and enantioselectivity (38 examples, all >20 : 1 dr, up to 95% ee). Additionally, an efficient kinetic resolution (KR) process is achieved (s factor up to 104). The gram-scale synthesis and subsequent synthetic transformations of the cycloadducts further demonstrate the synthetic potential of this method. Furthermore, the cycloadduct can undergo a [1,5]-H shift under acid catalysis, adding another dimension to the structural diversity.