Copper(I)-Catalyzed Ketone, Amine, and Alkyne Coupling for the Synthesis of 2-Alkynylpyrrolidines and -piperidines

Wim E Van Beek; Joren Van Stappen; Philippe Franck; Kourosch Abbaspour Tehrani

doi:10.1021/acs.orglett.6b02127

Copper(I)-Catalyzed Ketone, Amine, and Alkyne Coupling for the Synthesis of 2-Alkynylpyrrolidines and -piperidines

Org Lett. 2016 Oct 7;18(19):4782-4785. doi: 10.1021/acs.orglett.6b02127. Epub 2016 Sep 13.

Authors

Wim E Van Beek¹, Joren Van Stappen¹, Philippe Franck¹, Kourosch Abbaspour Tehrani¹

Affiliation

¹ Organic Synthesis, Department of Chemistry, University of Antwerp , Groenenborgerlaan 171, B-2020 Antwerp, Belgium.

PMID: 27622964
DOI: 10.1021/acs.orglett.6b02127

Abstract

A Cu(I)-catalyzed coupling of a ω-chloro ketone, a primary amine, and an alkyne is described. This protocol allows for the synthesis of α-quaternary carbons in 2-alkynyl-substituted N-heterocycles. The key step is the in situ generation of a cyclic ketiminium species, which has enhanced reactivity for alkynylation compared to acyclic ketiminium species.

Publication types

Research Support, Non-U.S. Gov't