Gold(III) Salen Complex-Catalyzed Synthesis of Propargylamines via a Three-Component Coupling Reaction

Abstract

[reaction: see text] Propargylamines have been synthesized by a gold(III) salen complex-catalyzed three-component coupling reaction of aldehydes, amines, and alkynes in water in excellent yields at 40 degrees C. With chiral prolinol derivatives as the amine component, excellent diastereoselectivities (up to 99:1) have been attained. This coupling reaction has been applied to the synthesis of propargylamine-modified artemisinin derivatives with the delicate endoperoxide moieties remaining intact. Cytotoxicities with IC(50) values up to 1.1 microM against a human hepatocellular carcinoma cell line (HepG2) were exhibited by these artemisinin derivatives.

A general A³: coupling reaction based on functionalized alkynes

“…When the same reaction was performed at 50 or 100 mmol scales, adduct 4a was isolated in slightly better yields (75 or 80%, respectively, entry 12). Using more CuCl did not significantly improve the yield of adduct 4a (entries [17][18][19][20], but using less catalyst caused the yield to be significantly lower under the same reaction conditions (entries [13][14][15][16]. Other catalysts that have previously been used in A 3 -coupling reactions were also tested using our optimized conditions, but only CuBr (entry 21) performed comparatively well.…”

“…It is also applicable to various substrates. This transformation can be catalyzed by a large number of transition-metal salts, including copper, 4 iron, 5 cobalt, 6 nickel, 7 zinc, 8 ruthenium, 9 silver, 10 cadmium, 11 indium, 12 ytterbium, 13 iridium, 14 gold, 15 mercury, 16 bimetallic salt combinations, 17 supported metals, 18 and nanostructured materials. 19 It is interesting to note that, although the use of various amines and aldehydes in this method has been described, the number of alkynes used has been limited.…”

Selective chemical reactions in supercritical carbon dioxide, water, and ionic liquids

“…Later Che et al (188) reported that 1 mol% of gold(III)Ásalen complexes catalyzed the three-component coupling reaction of aldehydes (99), chiral amines (100), and alkynes (101) 3 and AuCl afforded the desired product at the same temperature (608C) with 86 and 20% yields, respectively. However, at room temperature a longer reaction time was required and lower product yields were observed using NaAuCl 4 .…”

Magnetically recoverable Fe3O4@Au-coated nanoscale catalysts for the A3-coupling reaction

“…4,5 Various homogeneous and heterogeneous metal catalysts have been reported for A 3 -coupling reactions, which include gold, silver, copper and iron salts as well as gold and iridium complexes that exhibit high catalytic activity and ease of optimisation. [6][7][8][9][10][11] However, these suffer from the difficulty in separating the catalysts from the reaction mixture which in turn results in multistep purification. 12 Colloidal nanocatalysts have emerged as a particularly desirable alternative as they operate at the intersection of homogeneous and heterogeneous catalysis.…”