Copper(I)-Catalyzed Synthesis of Azoles. DFT Study Predicts Unprecedented Reactivity and Intermediates
Fahmi Himo, Timothy Lovell, Robert Hilgraf, Vsevolod V. Rostovtsev, Louis Noodleman,* K. Barry Sharpless* and Valery V. Fokin*
*Department of Molecular Biology, and Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, Email: fokinscripps.edu, sharplessscripps.edu, louscripps.edu
F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless, V. V. Fokin, J. Am. Chem. Soc., 2005, 127, 210-216.
DOI: 10.1021/ja0471525 (free Supporting Information)
Cycloadditions of copper(I) acetylides to azides and nitrile oxides provide ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted isoxazoles, respectively. The process is highly reliable and exhibits an unusually wide scope with respect to both components. Computational studies revealed a nonconcerted mechanism involving unprecedented metallacycle intermediates.
see article for more examples
proposed mechanism (newer mechanistic proposal see click chemistry)