Enantioselective Synthesis of Propargylamines by Copper-Catalyzed Addition of Alkynes to Enamines
Christopher Koradin, Kurt Polborn und Paul Knochel*
*Department Chemie, Ludwig Maximilians-Universität, Butenandstrasse 5-13,
Haus F, 81377 München (Deutschland), Email: paul.knochelcup.uni-muenchen.de
C. Koradin, K. Polborn, P. Knochel, Angew. Chem. Int. Ed., 2002, 41, 2535-2538.
DOI: 10.1002/1521-3773(20020715)41:14<2535::AID-ANIE2535>3.0.CO;2-M
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Abstract
A mild, copper(I)/Quinap-catalyzed addition of functionalized alkynes to enamines in high yields and with up to 90% ee is reported. Some selective transformations of the propargylamine products show the potential synthetic utility of this method.
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proposed mechanism
Details
Koradin, Polborn, and Knochel report a novel copper(I)-catalyzed enantioselective addition of alkynes to enamines to synthesize propargylamines, which are valuable as synthetic intermediates and biologically active compounds. They tested various metal salts and found that copper(I) and copper(II) bromide provided the fastest conversions. The reaction was performed using copper(I) bromide (5 mol%) in toluene at room temperature or 60°C, yielding propargylamines with 66-98% efficiency. The study also explored the enantioselective synthesis using Quinap as a chiral ligand, achieving up to 90% enantiomeric excess. The authors isolated the complex [BrCu(Quinap)]2 and characterized it via X-ray crystallography. They demonstrated the synthetic utility of the method through selective deprotection and further transformations of the propargylamines. Preliminary mechanistic studies suggested a zwitterionic intermediate formation. This work represents the first copper-catalyzed asymmetric reaction using Quinap, highlighting its potential for broad synthetic applications.
Key Words
alkynes, asymmetric synthesis, CH activation, heterogeneous catalysis, propargylamines
ID: J06-Y2002-370