Propargylamines, asymmetric synthesis

This method has been used for a general asymmetric synthesis of amines by a similar mono- or dialkylalion of propargylamine using the same ehiral adjunct... 

SCHEME 3.50 Asymmetric synthesis of propargylamines by Cu-catalyzed A -couplings. 

A Mannich-type reaction of j0-keto ester with C-alkynyl imines generated in situ delivers asymmetric synthesis of propargylamines with two adjacent stereocentres organocatalytically. " ... 

The author expected that a reaction with a chiral ligand which coordinates to a copper atom could produce optically active 2-(aminomethyl)indoles. Knochel recently developed a novel asymmetric synthesis of chiral propargylamines with excellent ee values through a copper-catalyzed asymmetric Mannich-type reaction of alkynes with an aldehyde and a secondary amine using QUINAP as a chiral ligand (up to 98% ee) [1-3]. Carreira reported the similar synthesis of propargylic amine in up to 99% ee with PINAP [4, 5]. The author initially examined the... 

Chen XY, Qiu XL, Qing FL. Asymmetric synthesis of tri-fluoromethylated propargylamines via 1,2-additions of tri-fluoromethylacetyUde to IV-tm-butanesuUinyl imines. Tetrahedron 2008 64 2301-2306. 

Copper complexes of chiral Pybox (pyridine-2,6-bis(oxazoline))-type ligands have been found to catalyze the enantioselective alkynylation of imines [26]. Moreover, the resultant optically active propargylamines are important intermediates for the synthesis of a variety of nitrogen compounds [27], as well as being a common structural feature of many biologically active compounds and natural products. Portnoy prepared PS-supported chiral Pybox-copper complex 35 via a five-step solid-phase synthetic sequence [28]. Cu(l) complexes of the polymeric Pybox ligands were then used as catalysts for the asymmetric addition of phenylacetylene to imine 36, as shown in Scheme 3.11. tBu-Pybox gave the best enantioselectivity of 83% ee in the synthesis of 37. 

N. Gommermann, P. Knochel, Chem. Commun. 2005,4175-4177. 2-PhenaUyl as a versatile protecting group for the asymmetric one-pot three-component synthesis of propargylamines. 

Colombo, R, Benaglia, M., Orlandi, S., Usuelli, R (2006). Asymmetric multicomponent copper catalyzed synthesis of chiral propargylamines. Journal of Molecular Catalysis A Chemical, 260,128-134. 

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