Acknowledgments.-This work was supported by the U. S. Atomic Energy Commission under Contract.No. AT(ll-l)-958. We are grateful to Professors É. LeGoff, W. Reusch, and D. Farnum of this department for helpful discussions of the procedures. We also thank Dr .

Thin-layer chromatography was performed on Merck 60F2m (0.25 mm) sheets, which were visualized with molybdophosphoric acid in ethanol. Merck 70-230 silica gel 60 was employed for column chromatography. A Perkin-Elmer 397 spectrophotometer was used to record the IR spectra (as Nujol films). A Bruker AM 300 spectrometer was employed for the 1H and 13C NMR spectra (CDC13 solutions). Mass spectra were obtained on an AEI MS-30 or VG 30F mass spectrometer (90 eV, direct insert probe). Optical rotations were measured on a Perkin-Elmer 241 polarimeter. Melting points were obtained with a Büchi-Tottoli apparatus and are not corrected. Microanalyses were performed by the Central Service of the CNRS.

A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amides with KHMDS followed by reaction with CuI and an alkynyl bromide.We report herein a convenient and general method for the synthesis of ynamides via the copperpromoted coupling of amides with alkynyl bromides. Interest in the application of ynamides in organic synthesis has increased enormously in recent years.1 Considerably more robust than simple ynamines, ynamides are more easily stored and handled and tolerate a variety of conditions destructive to typical ynamines. Ynamides have thus emerged as versatile building blocks in a wide range of useful synthetic transformations including Pauson-Khand reactions, 2 ring-closing metatheses, 3 cycloadditions (and other ring-forming processes), 4 and a variety of hydrometalation and hydrohalogenation reactions. 5 , 6In connection with our studies on [4 + 2] cycloadditions of conjugated enynes7 and heteroenynes,8 we required an efficient method for the preparation of a wide range of ynamides, preferably via the direct alkynylation of carbamates, sulfonamides, and other simple amide derivatives. Initially we focused our attention on the reaction of metalated amides with alkynyl (phenyl)iodonium salts (eq 1). 9 Stang 10 and Feldman 11 have shown that this process provides an excellent route to "push-pull"-type ynamides (4, Z = COR, CO 2 R, SO 2 Ar, etc.), and more recently Witulski and Rainier have extended this chemistry to the preparation of ynamides where Z = hydrogen, TMS, and phenyl.2a-d ,4b Unfortunately, this approach is not applicable to the synthesis of ynamides in which Z is a simple alkyl group. The addition of soft nucleophiles to alkynyl(phenyl)iodonium salts is believed to proceed via the rearrangement of alkylidenecarbene intermediates of type 3, and the requisite 1,2-shift only is a facile process when Z is a hydrogen atom or trialkylsilyl or aryl group. 12 In addition, whereas sulfonamide derivatives (e.g., 1, EWG = Ts) participate smoothly in the desired transformation, reactions of lactams, 1a oxazolidinones, 1a and acyclic carbamates 13 proceed at best in low yield. NIH Public Access Author ManuscriptOrg Lett. Author manuscript; available in PMC 2010 July 6. The aforementioned limitations of alkynyl(phenyl)iodonium methodology prompted us to consider alternative and potentially more general approaches to the synthesis of the ynamides required for our studies. Recent developments in the laboratories of Buchwald and Hartwig have revolutionized methodology for carbon-nitrogen bond formation. 14 Encouraged, in particular, by Buchwald's recent success in achieving copper-catalyzed amidation of aryl halides,15 , 16 we turned our attention to the coupling of amide derivatives with readily available alkynyl halides. 17 Initial results were disappointing. Application of Buchwald's catalyst system 15 to the coupling of acyclic carbamates w...

Ynamides react with ketenes in [2+2] cycloadditions leading to a variety of substituted 3-aminocyclobut-2-en-1-ones. The ynamides employed in these reactions are readily available via the copper-promoted N-alkynylation of carbamates and sulfonamides with alkynyl bromides and iodides. The scope of the [2+2] cycloaddition with regard to both the ketene and ynamide component is described.

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