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

Heterocycles containing atropisomeric axes are becoming increasingly important throughout the drug discovery endeavor, and new methodologies that provide access to pharmaceutically relevant atropisomers are in demand. Herein, we report the Rhodium (II) catalyzed atropisomer selective ring expansion of 3-aryl indoles with alpha-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. Mechanistic studies suggest that the chemistry proceeds via a Dynamic Kinetic Resolution 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 chiral axis can epimerize. The isolated products were readily further functionalized to allow for a wide array of enantioenriched quinolines.