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Updated: Sep 3, 2025

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Copper(I)-Catalyzed Cross-Coupling of 1-Bromoalkynes with N-Heterocyclic Organozinc Reagents
Christian Frabitore1, Jérome Lépeule1, Tom Livinghouse1
1Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA.
Abstract:
Nitrogen-containing heterocycles represent the majority of FDA-approved small-molecule pharmaceuticals. Herein, we describe a synthetic method to produce saturated N-heterocyclic drug scaffolds with an internal alkyne for elaboration. The treatment of N,N-dimethylhydrazinoalkenes with Et2Zn, followed by a Cu(I)-catalyzed cross-coupling with 1-bromoalkynes, results in piperidines and pyrrolidines with a good yield. Five examples are reported and a proposed mechanism for the Cu(I)-catalyzed cross-coupling is presented.
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