Copper-Catalyzed Coupling of Imines, Acid Chlorides, and Alkynes: A Multicomponent Route to Propargylamides
Daniel A. Black and Bruce A. Arndtsen*
*Department of Chemistry, McGill University, 801 Sherbrooke Street West,
Montreal, Quebec H3A 2K6, Canada, Email: bruce.arndtsenmcgill.ca
D. A. Black, B. A. Arndtsen, Org. Lett., 2004, 6, 1107-1110.
DOI: 10.1021/ol036462+
Abstract
A copper-catalyzed coupling of imines with alkynes and acid chlorides provides an efficient and general three-component coupling method to prepare propargylamides. The coupling can also be diversified to allow the formation of N-carbamate-protected propargylamines with the use of chloroformates.
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Details
The document describes a copper-catalyzed multicomponent coupling reaction involving imines, acid chlorides, and alkynes to efficiently synthesize propargylamides. This method, using CuI as the catalyst, offers a rapid and general approach to create these compounds, which are significant in various biological and chemical applications. Traditional methods for synthesizing propargylamides have limitations, but this new approach overcomes them by using mild conditions and allowing for structural diversification. The reaction proceeds efficiently with CuI alone, without the need for Pd(0), and is tolerant of various functional groups and substrates, including electron-rich and electron-poor imines, alkynes, and acid chlorides. Additionally, the methodology can be extended to synthesize N-carbamate-protected propargylamines using chloroformates. The proposed mechanism involves the formation of a copper acetylide and an N-acyliminium salt, which then couple to form the desired product. This method also allows for the functionalization of nitrogen heterocycles, such as pyridine, demonstrating its versatility. The study highlights the potential for further exploration in enantioselective control and the use of other transmetalating agents or CdN substrates. The research is supported by NSERC and FCAR, with additional synthesis and spectral data available online.
Key Words
Multicomponent Reactions, Copper, Propargylamines
ID: J54-Y2004-310