A Copper-Catalyzed C-N Bond Formation Involving sp-Hybridized Carbons. A Direct Entry to Chiral Ynamides via N-Alkynylation of Amides
Michael O. Frederick, Jason A. Mulder, Michael R. Tracey, Richard P. Hsung,* Jian Huang, Kimberly C. M. Kurtz, Lichun Shen and Christopher J. Douglas
*Division of Pharmaceutical Sciences and Department of
Chemistry, University of Wisconsin, Madison, Wisconsin 53705, Email: rphsung
pharmacy.wisc.edu
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.
DOI: 10.1021/ja021304j
Abstract
A copper-catalyzed direct N-alkynylation of amides has been developed leading to a facile entry for syntheses of chiral ynamides.
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Details
The document discusses a copper-catalyzed method for forming C-N bonds involving sp-hybridized carbons, providing a direct route to chiral ynamides via N-alkynylation of amides. Despite the known stability and utility of ynamides, their synthetic accessibility has been limited. Inspired by palladium-catalyzed N-arylation methods, the authors initially attempted palladium-catalyzed coupling but faced issues with homocoupling of alkynes. They then explored copper-catalyzed N-arylation, which showed promise. The study found that using alkynyl bromides instead of iodides led to consistent results, with CuCN providing more reliable outcomes than CuI. The method tolerated various substitutions and worked well with oxazolidinone-based amides and lactams, though urea-based auxiliaries were less effective. The authors successfully synthesized a parent ynamide and demonstrated its further functionalization. This new method is expected to enhance the synthetic utility of ynamides significantly. The research was supported by NSF and other fellowships, with detailed experimental procedures and data available online.
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.
Key Words
ID: J48-Y2003-1320
