Deconstructive Asymmetric Total Synthesis of Morphine‐Family Alkaloid (−)‐Thebainone A

Abstract

Herein, we describe the development of ad econstructive strategy for the first asymmetric synthesis of (À)thebainone A, capitalizing on an enantioselective CÀCb ond activation and aC ÀOb ond cleavage reaction. The rhodiumcatalyzeda symmetric "cut-and-sew" transformation between sterically hindered trisubstituted alkenes and benzocyclobutenones allowed efficient construction of the fused A/B/C rings and the quaternary center of the natural product. The newly optimizedconditions show broad substrate scope and excellent enantioselectivity (up to 99.5:0.5 er). Taking advantage of boron-mediated ether bond cleavage,w ec ompleted the synthesis of the morphine alkaloid (À)-thebainone Ab yt wo complementary routes. Figure 1. Morphine and related alkaloids.