Synthesis 2020; 52(20): 3036-3046
DOI: 10.1055/s-0040-1707167
paper
© Georg Thieme Verlag Stuttgart · New York

Preparation of Diorganomagnesium Reagents by Halogen–Lithium Exchange of Functionalized Heteroaryl Halides and Subsequent in situ Trapping with MgCl2·LiCl in Continuous Flow

Rodolfo Hideki Vicente Nishimura
a  Colegiado de Ciências Farmacêuticas, Universidade Federal do Vale do São Francisco, Avenue José de Sá Maniçoba, Petrolina, 56304-205 Petrolina, Brazil
,
Niels Weidmann
b  Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstraße 5–13, 81377 München, Germany   Email: Paul.knochel@cup.uni-muenchen.de
,
b  Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstraße 5–13, 81377 München, Germany   Email: Paul.knochel@cup.uni-muenchen.de
› Author Affiliations
Funding Information: Studienstiftung des Deutschen Volkes, (Grant / Award Number: ) Fundação de Amparo à Pesquisa do Estado de São Paulo, (Grant / Award Number: '2018/08856-5')
R. H. V. Nishimura thanks Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grant number: 2018/08856-5) for financial support. N. Weidmann thanks the German Academic Scholarship Foundation for a fellowship. We thank the DFG and LMU for financial support. We further thank BASF (Ludwigshafen) and Albemarle (Frankfurt) for the generous gift of chemicals, and Vapourtec and Uniqsis for technical support.
Further Information

Publication History

Received: 28 May 2020

Accepted after revision: 30 May 2020

Publication Date:
29 June 2020 (online)


These authors contributed equally.

In memory of Prof. Dr. Rolf Huisgen

Abstract

A halogen–lithium exchange in the presence of MgCl2·LiCl on a broad range of heterocyclic scaffolds using a commercial flow set-up with nBuLi as exchange reagent is reported. The resulting diheteroarylmagnesium species were subsequently trapped with various electrophiles, such as ketones, aldehydes, allylic bromides, or disulfides affording functionalized heterocycles. A scale-up was performed by simply increasing the run-time without further optimizations.

Supporting Information

 
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