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Regioselective oxidative arylation of indoles bearing N-alkyl protecting groups: dual C-H functionalization via a concerted metalation-deprotonation mechanism.

ABSTRACT: 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.

SUBMITTER: Potavathri S

PROVIDER: S-EPMC2954267 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Regioselective oxidative arylation of indoles bearing N-alkyl protecting groups: dual C-H functionalization via a concerted metalation-deprotonation mechanism.

Potavathri Shathaverdhan S Pereira Kyle C KC Gorelsky Serge I SI Pike Andrew A LeBris Alexis P AP DeBoef Brenton B

Journal of the American Chemical Society 20101001 41

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 exper ...[more]

PMID: 20863119

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