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

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.

Automated summary

This method involves a halogen-lithium exchange reaction of (hetero)aromatic halides in the presence of various electrophiles, resulting in the formation of polyfunctional (hetero)arenes. The use of a flow set-up allows for the instant trapping of organolithiums with electrophiles, enabling the functionalization of (hetero)arenes containing highly sensitive functional groups such as esters that are not tolerated in batch conditions.