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

Herein, we describe the development of a deconstructive strategy for the first asymmetric synthesis of (−)‐thebainone A, capitalizing on an enantioselective C−C bond activation and a C−O bond cleavage reaction. The rhodium‐catalyzed asymmetric “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 optimized conditions show broad substrate scope and excellent enantioselectivity (up to 99.5:0.5 er). Taking advantage of boron‐mediated ether bond cleavage, we completed the synthesis of the morphine alkaloid (−)‐thebainone A by two complementary routes.