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CuBr-Catalyzed Efficient Alkynylation of sp3 C-H Bonds Adjacent to a Nitrogen Atom

Zhiping Li and Chao-Jun Li*

*Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 2K6, Canada, Email: cj.limcgill.ca

Z. Li, C.-J. Li, J. Am. Chem. Soc., 2004, 126, 11810-11811.

DOI: 10.1021/ja0460763


Abstract

A simple and effective copper-catalyzed oxidative cross-coupling of dimethylanilines with alkynes in the presence of tert-BuOOH allows the construction of propargylamines via a combination of sp3 C-H bond and sp C-H bond activations followed by C-C bond formation.

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proposed mechanism



Details

The document discusses a study on the CuBr-catalyzed efficient alkynylation of sp3 C-H bonds adjacent to a nitrogen atom, conducted by Zhiping Li and Chao-Jun Li from McGill University. The research focuses on the direct oxidative functionalization of tertiary amines to form propargylic amines, which are valuable in pharmaceuticals and as synthetic intermediates. The study explores various copper salts as catalysts, with CuBr and CuCl showing the best results. The optimal reaction conditions involve a 2:1:1 ratio of N,N-dimethylaniline, alkynes, and tert-butyl hydroperoxide. The method effectively couples sp3 C-H bonds adjacent to nitrogen with terminal alkynes, yielding propargylic amines in good yields, especially with aromatic alkynes. The reaction tolerates functional groups like alcohol and ester. The proposed mechanism involves copper-catalyzed formation of an imine-type intermediate and activation of the terminal alkyne, leading to the desired product. This catalytic method offers a simple and efficient approach to synthesizing propargylic amines, with potential applications in natural product and pharmaceutical synthesis. The study is supported by various Canadian research foundations and McGill University.


Key Words

Propargylamines, tert-butyl hydroperoxide


ID: J48-Y2004-1720