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Regioselective Functionalization of 7-Azaindole by Controlled Annular Isomerism: The Directed Metalation-Group Dance
Michael E Dalziel1, Jignesh J Patel1, Meagan K Kaye1
1Department of Chemistry, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Abstract:
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 ClCONR2 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.
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