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Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance
Author(s) -
Dalziel Michael E.,
Patel Jignesh J.,
Kaye Meagan K.,
Cosman Jennifer L.,
Kitching Matthew O.,
Snieckus Victor
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201901724
Subject(s) - metalation , regioselectivity , electrophile , chemistry , surface modification , combinatorial chemistry , quenching (fluorescence) , stereochemistry , catalysis , organic chemistry , physics , quantum mechanics , fluorescence
The regioselective functionalization of 7‐azaindole by controlled annular isomerism employing a directed metalation‐group migration is reported. The N7 carbamoyl azaindoles undergo regioselective metalation and quenching with an electrophile to furnish C6‐substituted derivatives which, in the presence of a catalytic amount of ClCONR 2 promotes a carbamoyl group shift or dance from N7 to N1. A second directed metalation/electrophile quench sequence leads to 2,6‐substituted azaindoles. Optimization of the metalation conditions for C2 and C6, separately and iteratively, is presented. Using the directed metalation group dance strategy, a late‐stage deuteration of an antipsychotic drug is described. Overall, the controlled migration of the carbamoyl directing group allows multiple functionalization events of the bioactive azaindole scaffold.