Talytic ynamide addition for the activated quinoline ring showed quantitative conversion to 1,2-dihydro-2-aminoethynylquinoline, 16, inside 20 min, whereas no product was isolated when the reaction was carried out inside the absence of CuI for 2.five h. In conclusion, we have created the initial catalytic addition of a readily offered ynesulfonamide to aliphatic and aromatic acyl chlorides. A slightly modified process has been successfully applied for regioselective 1,2-addition of ynamides to pyridines and quinolines. Each reactions occur beneath mild conditions and provide unprecedented access to a variety of 3aminoynones and 1,2-dihydro-N-heterocycles in great to highdx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167-The Journal of Organic ChemistryNoteFigure three. (Left) Proposed mechanism on the CuI-catalyzed formation of aminoynone, 2, and 1,2-dihydro-2-aminoethynylquinoline, 16, and (right) conversion from the ynamide to two and 16 vs time.yields. The handy access to these synthetically versatile ynamide derivatives is anticipated to prove invaluable to medicinal chemistry and natural solution synthesismercially out there reagents and solvents were employed with out additional purification. Anhydrous solvents have been applied as bought and not dried any additional. NMR spectra had been obtained at 400 MHz (1H NMR) and 100 MHz (13C NMR) in deuterated chloroform. Chemical shifts are reported in ppm relative to TMS. Common Procedure for the Copper-Catalyzed Ynamide Addition to Acyl Chlorides. Copper iodide (two.3 mg, 12 mol), N-ethynyl-ATP Citrate Lyase MedChemExpress N-phenyl-4-tolylsulfonamide (32.five mg, 0.12 mmol), and N,N-diisopropylethylamine (31.0 mg, 0.24 mmol) have been dissolved in chloroform (0.15 mL) beneath nitrogen. Immediately after 30 min an acyl chloride (0.18 mmol) was added, and the mixture was stirred till completion as determined by TLC. Solvents were evaporated under a stream of nitrogen, plus the crude residue was purified by flash Na+/K+ ATPase Compound chromatography on silica gel (particle size 40-63 m) as described under. General Process for the Copper-Catalyzed Ynamide Addition to Pyridines and Quinolines. The ynamide (54.two mg, 0.20 mmol), CuI (3.8 mg, 0.02 mmol), and N,N-diisopropylethylamine (70 L, 0.40 mmol) have been dissolved in 1 mL of anhydrous dichloromethane. Then, a option on the N-heterocycle (0.24 mmol) and ethyl chloroformate (38 L, 0.40 mmol) in 1 mL of anhydrous dichloromethane was added. The mixture was stirred below nitrogen till the reaction was completed according to NMR and TLC evaluation. Solvents have been then removed, as well as the crude residue was straight loaded onto a silica gel column (particle size 32-63 m) and purified by flash chromatography as described beneath unless stated otherwise. N-(3-Phenyl-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfonamide, two. The reaction with benzoyl chloride (25.1 mg, 0.18 mmol) and the ynamide (32.five mg, 0.12 mmol) was performed at 30 for 22 h. The concentrated crude residue was purified by column chromatography (two:1 dichloromethane/hexanes) to offer 40.5 mg (0.108 mmol, 90 ) of a white solid. 1H NMR (400 MHz): 8.19 (d, J = six.9 Hz, 2H), 7.67-7.57 (m, 3H), 7.52 (dd, J = 8.4 Hz, 6.9 Hz, 2H), 7.41-7.34 (m, 3H), 7.30-7.22 (m, 4H), two.42 (s, 3H). 13C NMR (one hundred MHz): 176.eight, 145.9, 137.2, 136.9, 133.6, 132.9, 129.9, 129.five, 129.17, 129.15, 128.six, 128.1, 126.five, 90.1, 74.9, 21.6. Anal. Calcd For C22H17NO3S: C, 70.38; H, four.56; N, three.73. Discovered: C, 70.51; H, four.73; N, three.86. Mp 139-140 . N-(3-(2-Chlorophenyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfonamide, 3. The reaction with 2-chloro.
