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

Niels Weidmann; Rodolfo H. V. Nishimura; Johannes H. Harenberg; Paul Knochel

doi:10.1055/s-0040-1707259

Synthesis, Table of Contents

Synthesis 2021; 53(03): 557-568
DOI: 10.1055/s-0040-1707259

paper

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

Niels Weidmann‡

^aLudwig-Maximilians-Universität München, Department Chemie, Butenandtstraße 5–13, 81377 München, Germany Email: Paul.knochel@cup.uni-muenchen.de

,

Rodolfo H. V. Nishimura‡

^bColegiado de Ciências Farmacêuticas, Universidade Federal do Vale do São Francisco, Avenue José de Sá Maniçoba, Petrolina, 56304-205 Petrolina, Brazil

,

Johannes H. Harenberg

^aLudwig-Maximilians-Universität München, Department Chemie, Butenandtstraße 5–13, 81377 München, Germany Email: Paul.knochel@cup.uni-muenchen.de

,

Paul Knochel ∗

^aLudwig-Maximilians-Universität München, Department Chemie, Butenandtstraße 5–13, 81377 München, Germany Email: Paul.knochel@cup.uni-muenchen.de

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Abstract

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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

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References

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