Regioselective oxidative arylation of indoles bearing N-alkyl protecting groups: Dual c-h functionalization via a concerted metalation-deprotonation mechanism

Shathaverdhan Potavathri, University of Rhode Island
Kyle C. Pereira, University of Rhode Island
Serge I. Gorelsky, Centre de Recherche et d’Innovation en Catalyse
Andrew Pike, University of Rhode Island
Alexis P. Lebris, University of Rhode Island
Brenton Deboef, University of Rhode Island


The most direct method for synthesizing 2-arylindoles is oxidative coupling of an arene with an indole. We have shown that both the activity and regioselectivity of this cross-coupling reaction are correlated with the acidity of the medium. This insight has been applied to predict the best conditions for the oxidative cross-coupling of N-alkylindoles, an important class of substrates that has heretofore been incompatible with the harsh conditions required for oxidative cross-coupling. Both experimental and computational data indicate that the mechanism for C-H palladation of both the indoles and simple arenes is best described as concerted metalation-deprotonation, regardless of the substitution on the arene. © 2010 American Chemical Society.