Open AccessModular Synthesis of Highly Substituted 3-Azapyrroles by Rh(II)-Catalyzed N–H Bond Insertion and Cyclodehydration
Author(s) -
Matthew B. Williams,
Alistair Boyer
Publication year - 2022
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.2c00434
Subject(s) - catalysis , chemistry , modular design , combinatorial chemistry , medicinal chemistry , stereochemistry , organic chemistry , computer science , operating system
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 BF 3 ·OEt 2 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.