Rhodium(III)-Catalyzed\nAtroposelective Indolization\nto Access Planar-Chiral Macrocycles

Macrocycles incorporating conformationally defined indoles\nare\nwidely found in bioactive natural products. However, the catalytic\nenantioselective synthesis of planar-chiral indoles via indolization\ninvolving macrocyclization remains elusive. Herein, we present the\nfirst rhodium(III)-catalyzed atroposelective macrocyclization, which\ninvolves the C–H activation of aniline, and a subsequent oxidation\n[3 + 2] annulation reaction with an intramolecular alkyne. This protocol\nachieves the construction of indoles, macrocyclization, and planar\nchirality control in a single step. Importantly, this strategy produces\nmacrocyclic atropisomers bearing full-carbon ansa chains, which represent\nchallenging targets in organic synthesis. Thermodynamic experiments\nrevealed that the rotational barrier of the full-carbon ansa chain-linked\nmacrocyclic atropisomer was lower than that of the atropisomer bearing\nan oxa-ansa chain. The reaction mechanism was elucidated by computational\nstudies, which revealed that the C–H activation and intramolecular\nalkyne insertion steps collectively determined the enantioselectivity.