Reactions of Copper Acetylides with Other Dipoles

Reactions of Copper Acetylides with Other Dipoles 

In the mechanism of the CuAAC reaction described above, the metal catalyst activates terminal alkyne for reaction with a Cu-coordinated azide. This mode of reactivity also operates with other dipolar reagents. In fact, the first example of a copper-catalzyed 1,3-dipolar cycloaddition reaction of alkynes was reported for nitriones by Kinugasa in 1972 [127]. An asymmetric version of the Kinugasa reaction was developed by Fu et al. in 2002 [128, 129]. 

In contrast, Cu(I) catalysis makes possible the efficient synthesis of 3,5-disubsti-tuted isoxazoles 57 from aromatic or aliphatic aldehydes and alkynes. Stable nitrile oxides can be isolated and subsequently submitted to the reaction [21] in isolated form and submitted to the reaction in one-pot, three-step process [131]. Here, nitrile oxide intermediates 56 are generated in situ via the corresponding aldoxime and halogenation/deprotonation by Chloramine-T [132]. Capture of the intermediate nitrile oxide by copper(I) acetylides occurs presumably before dimerization. In this case, the Cu catalyst was obtained from copper metal and copper(II) sulfate, and the products were isolated by simple filtration or aqueous work-up. Trace amounts of toluenesulfonamide and unreacted acetylene are easily removed by recrystallization or by passing the product through a short plug of silica gel. 

Copper catalyzed reactions of azomethine imines with alkynes yielding fused nitrogen heterocycles have also been reported [133]. 

1 Larock, R.C. (2005) Acetylene Chemistry Chemistry, Biolcgy, and Material Science (eds F. Diederich, P.J., Stang, and R.R. Tykwinsld), Wiley-VCH, Weinheim, pp. 51-100. 

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