Ligand-Controlled Chemo- and Enantiodivergent Rh(III)-Catalyzed Redox-Neutral Annulation of Aryl Hydroxamates with Cyclopropenes via C–H and C–C Activation

Asymmetric C–H bond functionalization employing rhodium catalysts has gained significant attention in the recent past, given the possibility of introducing chirality at the late stage in organic scaffolds. This strategy has been generally restricted to enantioselective approaches, but achieving enantiodivergence and chemodivergence from the same starting point is limited and requires possibly different catalytic systems. Herein, we disclose that a general and efficient ligand-controlled chemo- and enantiodivergent synthesis of isoquinolones and isoindolinones has been achieved from aryl hydroxamates and cyclopropenes through chiral cyclopentadienylrhodium(III)-catalyzed [4 + 2] and [4 + 1] annulations, respectively. The reaction involves both C–H/C–C bond activation and C–C/C–N bond formation and explores the reactivity of cyclopropenes as both C2 and C1 synthons. These redox-neutral transformations exhibit mild reaction conditions and broad substrate scope as well as require catalytic amounts of additives for the synthesis of both isoquinolones and isoindolinones in high yields (up to 97%) and chemo- and enantioselectivity (up to 99:1 er). These selectivities were controlled by the substituents present at the 3,3′-position of the binaphthyl and cyclopentadienyl moieties of the ligand. The size of both substituents differentiates the orientation of C–H-activated species to offer high enantiodivergence, but the substituent at the 3,3′-position of binaphthyl alone contributes to the observed chemodivergence. The synthetic applicability of the methods has been demonstrated through the synthetic modification of the isoquinolones and isoindolinones and late-stage functionalization.