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Enantioselective, Copper(I)-Catalyzed Three-Component Reaction for the Preparation of Propargylamines

Nina Gommermann, Christopher Koradin, Kurt Polborn, Paul Knochel*

*Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377 München, Germany, Email: paul.knochelcup.uni-muenchen.de

N. Gommermann, C. Koradin, K. Polborn, P. Knochel, Angew. Chem. Int. Ed., 2003, 42, 5763-5766.

DOI: 10.1002/anie.200352578


Abstract

A wide range of chiral propargylamines can be prepared in a one-pot three-component reaction between an alkyne, an aldehyde and a secondary amine at room temperature in the presence of CuBr and (R)-quinap in good yield and good enantioselectivity. Remarkably, the copper-catalyzed reaction is highly diastereoselective if a chiral amine or aldehyde is used.

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Details

The document discusses an enantioselective, copper(I)-catalyzed three-component reaction for synthesizing propargylamines. This reaction involves an alkyne, an aldehyde, and a secondary amine, yielding propargylamines with high enantioselectivity (up to 96% ee) and excellent yields (up to 99%). The process avoids the generation of sensitive enamines and extends the scope to nonenolizable aldehydes. The reaction is typically complete within 12 to 48 hours for racemic reactions and one to six days for enantioselective reactions. Various alkynes and aldehydes, including aromatic and branched aliphatic aldehydes, can be used, with yields and enantioselectivities varying based on the substituents. The reaction mechanism involves a dimeric chiral copper complex that facilitates the formation of the propargylamine. The study also highlights the reaction's high diastereoselectivity when using chiral amines or aldehydes. Preliminary mechanistic investigations suggest that a dimeric Cu/quinap complex is the active catalyst. The research demonstrates the potential for synthesizing a wide range of chiral propargylamines in a one-pot procedure, with ongoing studies aimed at further applications and mechanistic understanding.


Key Words

alkynes, asymmetric catalysis, C-H activation, multicomponent reactions, propargylamines


ID: J06-Y2003-1120