A Rh(II)-Catalyzed Atropisomer Selective Ring Expansion of 3-Aryl Indoles to 4-Aryl Quinolines

Heterocycles containing stereogenic axes are becoming increasingly important throughout the drug discovery endeavor, and methodologies that provide access to pharmaceutically relevant atropisomers are in high demand. Herein, we report the rhodium(II)-catalyzed atropisomer selective ring expansion of 3-aryl indoles with α-halodiazoacetates to furnish 4-aryl quinolines in good yields and enantioselectivity, with strong correlations between enantioselectivity and steric bulk observed at different positions of the substrate. Computational studies suggest that the chemistry proceeds via a Dynamic Kinetic Resolution (DKR) process wherein the catalyst reacts preferentially with the Ra conformation of the rapidly racemizing 3-aryl indole starting material to give a cyclopropanated indoline intermediate that undergoes a Ciamician–Dennstedt-type ring expansion before the intermediate’s prospective stereogenic axis can epimerize. The utility of this skeletal transformation is further demonstrated by the derivatization of enantioenriched products, granting access to a structurally diverse array of enantioenriched quinolines.