Copper(II)-Catalyzed Amidations of Alkynyl Bromides as a General Synthesis of Ynamides and Z-Enamides. An Intramolecular Amidation for the Synthesis of Macrocyclic Ynamides
Xuejun Zhang, Yanshi Zhang, Jian Huang, Richard P. Hsung,* Kimberly C. M. Kurtz, Jossian Oppenheimer, Matthew E. Petersen, Irina K. Sagamanova, Lichun Shen, and Michael R. Tracey
*Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53705, Email: rphsungpharmacy.wisc.edu
X. Zhang, Y. Zhang, J. Huang, R. P. Hsung, K. C. M. Kurtz, J. Oppenheimer, M. E. Petersen, I. K. Sagamanova, L. Shen, M. R. Tracey, J. Org. Chem., 2006, 71, 4170-4177.
DOI: 10.1021/jo060230h (free Supporting Information)
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A general and efficient method for the coupling of a wide range of amides with alkynyl bromides using copper(II) sulfate-pentahydrate and 1,10-phenanthroline as catalyst leads to a structurally diverse array of ynamides including macrocyclic ynamides via an intramolecular amidation.
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M. O. Frederick, J. A. Mulder, M. R. Tracey, R. P. Hsung, J. Huang, K. C. M. Kurtz, L. Shen, C. J. Douglas, J. Am. Chem. Soc., 2003, 125, 2368-2369.
Skrydstrup's finding in his paper (J. Org. Chem., 2008, 73, 9447-9450. Abstract) is interesting and could very well be a factor responsible for some of consistencies one finds in these couplings. What we have found is that the basicity for the base employed in these couplings overall appears to be a key issue, which is also true in other types of amidative cross-couplings. Thus, the varying amount of water content in the phosphate base, or varying degrees of its purity, based on sources of supply, could play a role or impact the coupling from the basicity perspective.
That said, the quality or the source of any bases we have used has not been the most handicapping factor in our overall experiences.
Richard P. Hsung, March 25, 2010