Modular synthesis of highly substituted 3-Azapyrroles by Rh(II)-catalyzed N–H bond insertion and cyclodehydration

Williams, M. B. and Boyer, A. (2022) Modular synthesis of highly substituted 3-Azapyrroles by Rh(II)-catalyzed N–H bond insertion and cyclodehydration. Journal of Organic Chemistry, 87(24), pp. 16139-16156. (doi: 10.1021/acs.joc.2c00434) (PMID:35503987)

Abstract

A modular synthesis of highly substituted 3-azapyrroles has been developed using a three-step sequence comprising copper-catalyzed alkyne–azide cycloaddition (CuAAC), N–H bond insertion, and cyclodehydration. 1-Sulfonyl-1,2,3-triazoles (1-STs) can be accessed from common alkyne and sulfonyl azide building blocks by CuAAC using CuTC. Rhodium(II)-acetate-promoted 1-ST denitrogenation results in highly electrophilic rhodium azavinyl carbenes that, here, underwent insertion into the N–H bond of secondary α-aminoketones to form 1,2-aminoalkenes. These products were cyclized and dehydrated using BF3·OEt2 into highly substituted 3-azapyrroles. The three steps (CuAAC, N–H bond insertion, and cyclodehydration) could be telescoped into a one-pot process. The method proved to be highly efficient and tolerated a wide range of substituents.

• Item Type: Articles
• Additional Information: A.B. thanks the Royal Society and TATA for a University Research Fellowship. M.B.W. thanks the Royal Society for a PhD studentship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Boyer, Dr Alistair and Williams, Matthew
• Authors: Williams, M. B., and Boyer, A.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Journal of Organic Chemistry
• Publisher: American Chemical Society
• ISSN: 0022-3263
• ISSN (Online): 1520-6904
• Published Online: 03 May 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Journal of Organic Chemistry 87(24): 16139-16156
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
301911		Extending the 1-ST Toolbox for the Synthesis of Functional Materials	Alistair Boyer	The Royal Society (ROYSOC)	RGF\R1\180060	Chemistry
173484		Sulfonyl Triazoles: A Next-Generation Building Block for Molecular Complexity	Alistair Boyer	The Royal Society (ROYSOC)	UF150316	Chemistry