Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance

Snieckus, Victor; Patel, Jignesh; Kitching, Matthew; Dalziel, Michael; Cosman, Jennifer; Kaye, Meagan

Abstract

The regioselective functionalization of 7‐azaindole by controlled annular directed metalation group isomerism is reported. The N‐7 carbamoyl azaindoles 2a–b undergo regioselective metalation and electrophile quench to furnish C‐6 substituted derivatives 3 which, in the presence of catalytic amount of ClCONR2 afford products 4 by an N‐7 to N‐1 carbamoyl group dance. A second directed metalation‐electrophile quench sequence leads to 2,6‐substituted azaindoles 5. Optimization of metalation conditions for C‐2 and C‐6, 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 annular isomerism of a carbamoyl directing group allows multiple functionalization events of the bioactive azaindole scaffold.

Citation

Snieckus, V., Patel, J., Kitching, M., Dalziel, M., Cosman, J., & Kaye, M. (2019). Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance. Angewandte Chemie, 131(22), 7391-7395. https://doi.org/10.1002/ange.201901724

• Journal Article Type: Article
• Acceptance Date: Mar 14, 2019
• Online Publication Date: Mar 15, 2019
• Publication Date: May 27, 2019
• Deposit Date: Mar 27, 2019
• Publicly Available Date: Mar 15, 2020
• Journal: Angewandte Chemie
• Print ISSN: 0044-8249
• Electronic ISSN: 1521-3757
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 131
• Issue: 22
• Pages: 7391-7395
• DOI: https://doi.org/10.1002/ange.201901724
• Public URL: https://durham-repository.worktribe.com/output/1305285