Dual Role of the Arylating Agent in a Highly C(2)-Selective Pd-Catalysed Functionalisation of Pyrrole Derivatives

Abstract

Pyrrole derivatives with C(2)-aryl substituents are an important and widespread class of heterocyclic compounds. Their synthesis can be accomplished using several strategic variants which usually entail either protection of the N–H functionality followed by the arylation, or a direct arylation. Although direct arylation is a preferable process due to a reduced number of synthetic steps, it often requires vigorous conditions or challenging reagents. To this synthetic repertoire, we add a novel method that is based on the dual role of the arylating agent. It serves as the nitrogen protecting group while also being involved in the arylation step. Deprotection as a final stage is carried out simultaneously utilising amines as reacting components. This approach ensures relatively mild conditions and exclusive C(2) selectivity yielding 2-arylpyrroles with the amide functionality. While aromatic amines are not suitable partners under studied conditions, most likely due to lower nucleophilicity, aliphatic amines, either primary or secondary, afford products in good yields.

Key words

pyrroles - palladium - catalysis - arylation - regioselectivity

Publication History

Received: 28 December 2021

Accepted after revision: 02 February 2022

Accepted Manuscript online:
02 February 2022

Article published online:
29 March 2022

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