Halogen–Lithium Exchange of Sensitive (Hetero)aromatic Halides under Barbier Conditions in a Continuous Flow Set-Up

In memory of Prof. Dr. Kilian Muñiz

Abstract

A halogen–lithium exchange reaction of (hetero)aromatic halides performed in the presence of various electrophiles such as aldehydes, ketones, Weinreb amides, and imines using BuLi as exchange reagent and a commercially available flow set-up is reported. The organolithiums generated in situ were instantaneously trapped with various electrophiles (Barbier conditions) resulting in the formation of polyfunctional (hetero)arenes. This method enables the functionalization of (hetero)arenes containing highly sensitive functional groups such as esters­, which are not tolerated in batch conditions.

Key words

heterocycles - flow chemistry - organolithiums - Barbier reaction - halogen–lithium exchange

Publication History

Received: 21 July 2020

Accepted after revision: 29 July 2020

Article published online:
02 September 2020

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