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

C(sp2)–C(sp3) axially chiral scaffolds represent an unusual class of atropisomeric systems. Given their low configurational stability, the asymmetric synthesis of C(sp2)–C(sp3) atropisomers remains dauntingly challenging. Reported herein is the enantioselective synthesis of isoquinolones bearing both a C(sp2)–C(sp3) 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.