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

doi:10.1002/ange.201901724

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

Authors

Victor Snieckus

Jignesh Patel

Dr Matthew Kitching matthew.o.kitching@durham.ac.uk
Royal Society University Research Fellow

Michael Dalziel

Jennifer Cosman

Meagan Kaye

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

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Copyright Statement
This is the accepted version of the following article: Snieckus, Victor, Patel, Jignesh, Kitching, Matthew, Dalziel, Michael, Cosman, Jennifer & Kaye, Meagan (2019). Regioselective Functionalization of 7‐Azaindole by Controlled Annular Isomerism: The Directed Metalation‐Group Dance. Angewandte Chemie 131(22): 7391-7395 which has been published in final form at https://doi.org/10.1002/ange.201901724. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.