Synlett 2018; 29(13): 1700-1706
DOI: 10.1055/s-0037-1610200
letter
© Georg Thieme Verlag Stuttgart · New York

Manganese-Catalyzed Kumada Cross-Coupling Reactions of Aliphatic Grignard Reagents with N-Heterocyclic Chlorides

Brittney E. Petel
Department of Chemistry, University of Rochester, Rochester, New York 14627, USA   Email: [email protected]
,
Merjema Purak
Department of Chemistry, University of Rochester, Rochester, New York 14627, USA   Email: [email protected]
,
Ellen M. Matson*
Department of Chemistry, University of Rochester, Rochester, New York 14627, USA   Email: [email protected]
› Author Affiliations
The authors thank the University of Rochester for providing the funding for this research.
Further Information

Publication History

Received: 08 May 2018

Accepted after revision: 11 June 2018

Publication Date:
29 June 2018 (online)


Abstract

Herein we report the use of manganese(II) chloride for the catalytic generation of C(sp2)–C(sp3) bonds via Kumada cross-coupling. Rapid and selective formation of 2-alkylated N-heterocyclic complexes were observed in high yields with use of 3 mol% MnCl2THF1.6 and under ambient reaction conditions (21 °C, 15 min to 20 h). Manganese-catalyzed cross-coupling is tolerant toward both electron-donating and electron-withdrawing functional groups in the 5-position of the pyridine ring, with the latter resulting in an increased reaction rate and a decrease in the amount of nucleophile required. The use of this biologically and environmentally benign metal salt as a catalyst for C–C bond formation highlights its potential as a catalyst for the late-stage functionalization of pharmaceutically active N-heterocyclic molecules (e.g., pyridine, pyrazine).

Supporting Information

 
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