Rhodium-Catalyzed Atroposelective Synthesis of Conformationally Stable C(sp ² )–C(sp ³ ) Atropisomers via C–H Activation and Annulation with 9-Fluorenylacetylene

C(sp 2 )–C(sp 3 ) axially chiral scaffolds represent an unusual class of atropisomeric systems. Given their low configurational stability, the asymmetric synthesis of C(sp 2 )–C(sp 3 ) atropisomers remains dauntingly challenging. Reported herein is the enantioselective synthesis of isoquinolones bearing both a C(sp 2 )–C(sp 3 ) axis and a proximal stereogenic center with a 5,6-ring linkage. This is realized via Rh(III)-catalyzed C–H activation of benzamides and [4 + 2] annulation with rationally designed 9-fluorenylacetylenes. The coupling system features mild, redox-neutral conditions and excellent enantioselectivity and diastereoselectivity. Migratory insertion into the alkyne has been established as both an enantio- and diastereodetermining step in the catalytic cycle.