Copper-free catalysis

The protected propargylamines 224 (R = H, CH2C02Me or CH2CH2C02Me) react with aqueous formaldehyde under copper bromide catalysis to yield the allene derivatives 225. Deprotection with ethereal hydrogen chloride affords the free amines218. 

The original Sonogashira protocol involves palladium-copper co-catalysis. Attempts have been made over the last few years to overcome some of the limitations in this method, specifically to eliminate the undesired dimerization of terminal alkynes. Various copper-free conditions have been developed in order to reduce the amount of diacetylene formation. The focus seems to have been on changing the ligand. 

C. J. Pierce, C. H. Larsen, Green Chem. 2012,14, 2672-2676. Copper(II) catalysis provides cyclohexanone-derived propar-gylamines free of solvent or excess starting materials sole by-product is water. 

Stable nanometric copper clusters are efficient ligand-free catalysts, probably due to their great surface area [55]. In the reaction between benzyl azide and prop-2-yn-l-ol, copper nanocluster catalysis affords 100% conversion after 18 h [9]. 

Free radicals derived from thiourea have been proposed as intermediates in several oxidations of thiourea. However, the reactions have not yielded much information regarding the identity or thermochemistry of the species implicated. For example, oxidation by IrCl62- occurs with a second-order dependence on [thiourea], a complex pH dependence, and hints of copper catalysis (244). Oxidation by Cu-(me2-phen)2+ is suggested to be an inner-sphere mechanism (92). At this time it is difficult even to guess at the redox potential of the thiourea radical. 

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