Directing Group Repositioning Strategy Enabled Site- and Enantioselective Addition of Heteroaromatic C-H Bonds to Acyclic Internal Alkenes

Despite the notable advances achieved in the Murai-type hydroarylations, highly enantioselective catalytic addition of native (hetero)arenes to internal alkenes remains a prominent challenge. Herein, we report a directing group repositioning strategy, which enables the iridium-catalyzed enantioselective addition of heteroarenes including furan, benzofuran, and thiophene to internal enamides. The C-H bond at the C2 position of the heteroarene is site-selectively cleaved and added regioselectively to the beta- position of an enamide, affording a valuable beta-heteroaryl amide with high enantioselectivity. Mechanistic studies indicate that the rate and the enantioselectivity are determined by separate elementary steps.

Automated summary

Despite advances in the Murai-type hydroarylations, enantioselective addition of native (hetero)arenes to internal alkenes remains challenging. This study presents a directing group repositioning strategy for the enantioselective addition of heteroarenes to internal enamides. The C-H bond at the C2 position of heteroarenes is selectively cleaved and added to the beta-position of enamides, yielding beta-heteroaryl amides with high enantioselectivity. Mechanistic studies reveal separate elementary steps determining rate and enantioselectivity.