Copper-Catalyzed Alkynylation of Amides with Potassium Alkynyltrifluoroborates: A Room-Temperature, Base-Free Synthesis of Ynamides

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1 Supporting Information Copper-Catalyzed Alkynylation of Amides with Potassium Alkynyltrifluoroborates: A Room-Temperature, Base-Free Synthesis of Ynamides Kévin Jouvin, François Couty and Gwilherm Evano * Institut Lavoisier de Versailles, UMR CNRS 8180 Université de Versailles Saint-Quentin en Yvelines 45, avenue des Etats-Unis Versailles Cedex France General Information Experimental Procedures and Characterization Data for Unreported Compounds: Potassium Alkynyltrifluoroborates... 2 Experimental Procedures and Characterization Data for Unreported Compounds: Ynamides from Potassium Alkynyltrifluoroborate H and 13 C NMR spectra... 19

2 General Information. All solvents were reagent grade. Dichloromethane was freshly distilled from calcium hydride. THF was freshly distilled from sodium/benzophenone under argon prior to use. 4Å powdered molecular sieves was activated by heating (ca 200 C) under vacuum and stored in an oven at 100 C. All other reagents were used as supplied. Unless otherwise noted, reactions were magnetically stirred and monitored by thin layer chromatography using Merck-Kiesegel 60F 254 plates. Flash chromatography was performed with silica gel 60 (particle size m) supplied by SDS. Yields refer to chromatographically and spectroscopically pure compounds. Proton NMR spectra were recorded using an internal deuterium lock at ambient temperature on a Bruker 300 MHz spectrometer. Internal references of H 7.26 and H 2.50 were respectively used for CDCl 3 and DMSO-d 6. Data are presented as follows: chemical shift (in ppm on the scale relative to TMS = 0), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint. = quintuplet, sext. = sextuplet, sept. = septuplet, m = multiplet, br. = broad, app. = apparent), coupling constant (J/Hz) and integration. Resonances that are either partially or fully obscured are denoted obscured (obs.). Carbon-13 NMR spectra were recorded at 75 MHz. Internal references of C and C were respectively used for CDCl 3 and DMSO-d 6. Fluorine-19 and boron-11 spectra NMR were respectively recorded at 188 and 96 MHz. Optical rotations were recorded on a Perkin Elmer 341 polarimeter at 589 nm and 20 reported as follows: [ ] D, concentration (c in g/100 ml), and solvent. Melting points were recorded on a Buchi B-545. Infrared spectra were recorded on a Nicolet is 10 (SMART itr diamond ATR) spectrophotometer. Mass spectra were obtained on a Waters XevoQTof spectrometer. S1

3 Experimental Procedures and Characterization Data for Unreported Compounds: Potassium Alkynyltrifluoroborates General procedure for the synthesis of potassium alkynyltrifluoroborates: Potassium alkynyltrifluoroborates were synthesized according to literature procedure. S1 In the case of the preparation of potassium (1-hex-1-yn-3-ol)-trifluoroborate, two equivalents of n-buli were used instead of one. A solution of terminal alkyne (10.0 mmol, 1.0 equiv) in 20 ml of freshly distilled THF was cooled to -78 C under argon. n-buli (6.2 ml, 1.6 M in hexane, 10.0 mmol, 1.0 equiv) was added dropwise, and the solution was stirred for 1 h at this temperature. Trimethylborate (1.7 ml, 15.0 mmol, 1.5 equiv) was then added dropwise at -78 C. The solution was stirred at this temperature for 1 h after which it was allowed to warm to -20 C over 1 h. Potassium hydrogen difluoride (4.7 g, 60.0 mmol, 6.0 equiv) was then added as a saturated aqueous solution and the resulting mixture was vigourously stirred for 1 h at -20 C after which it was allowed to warm to room temperature for 1 h. Solvents were removed under reduced pressure, the resulting solid was dried under high vacuum to remove all water and extracted with boiling acetone. The hot acetone solution was filtered and concentrated under vacuum to afford a fluffy white solid. This solid was then dissolved in hot acetone and precipitated with diethyl ether, after which the solution was cooled overnight to -20 C to complete precipitation of the solid. The product was collected as a crystalline solid by filtration. Potassium (1-ethynyl-4-phenoxy-benzene)-trifluoroborate. Yield: 52%. White solid; Mp: 284 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): 7.40 (br. t, J = 7.4 Hz, 2H), 7.29 (br. d, J = 8.7 Hz, 2H), 7.15 (br. t, J = 7.4 Hz, 1H), 7.02 (br. d, J = 8.7 Hz, 2H), 6.89 (br. d, J = 8.7 Hz, 2H); 13 C S1 Katona, B. W.; Machrouhi, F.; Molander, G. A. J. Org. Chem. 2002, 67, S2

4 NMR (75 MHz, DMSO-d 6 ): 156.2, 155.5, 132.7, 130.1, 123.7, 120.6, 118.9, (sp carbons not observed); 11 B NMR (96 MHz, DMSO-d 6 ): (br. s); 19 F NMR (188 MHz, DMSO-d 6 ): (s); IR (ATR) max 2933, 2819, 1090, 951, 890, 579 cm -1 ; ESIMS (negative mode): 561.1, 261.1, 193.1; ESIHRMS m/z calcd for C 14 H 9 OBF 3 [M-K] , found Potassium (1-octyn-1-yl)-trifluoroborate. Yield: 85%. White solid; Mp: 275 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): 1.96 (br. s, 2H), (m, 8H), 0.86 (t, J = 6.9 Hz, 3H); 13 C NMR (75 MHz, DMSO-d 6 ): 89.5 (br.), 35.7, 33.7, 32.8, 26.8, 23.6, 18.7 (1 sp carbon not observed); 11 B NMR (96 MHz, DMSO-d 6 ): (br. s); 19 F NMR (188 MHz, DMSO-d 6 ): (s); IR (ATR) max 2933, 1086, 951, 898, 583 cm -1 ; ESIMS (negative mode): 393.2, 377.2, 177.2; ESIHRMS m/z calcd for C 8 H 13 BF 3 [M-K] , found Potassium [1-(3,3-dimethyl)-butyn-1-yl]-trifluoroborate. Yield: 81%. White solid; Mp: 290 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): 1.09 (s, 9H); 13 C NMR (75 MHz, DMSO-d 6 ): 97.2 (br.), 31.6, 26.9 (1 sp carbon not observed); 11 B NMR (96 MHz, DMSO-d 6 ): (br. s); 19 F NMR (188 MHz, DMSO-d 6 ): (d, J = 33.7 Hz); IR (ATR) max 2966, 1254, 1074, 947, 890, 747, 637 cm -1 ; ESIMS (negative mode): 337.1, 149.1; ESIHRMS m/z calcd for C 6 H 9 BF 3 [M-K] , found Potassium [1-(3-methoxy)-propyn-1-yl]-trifluoroborate. Yield: 41%. Brown solid; Mp: 228 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): 3.88 (br. s, 2H), 3.20 (br. s, 3H); 13 C NMR (75 MHz, DMSO-d 6 ): 60.0, 56.2 (sp carbons not observed); 11 B NMR (96 MHz, DMSO-d 6 ): S3

5 -2.05 (br. q, J = 35.2 Hz); 19 F NMR (188 MHz, DMSO-d 6 ): (m); IR (ATR) max 2929, 2814, 1601, 1376, 1086, 947, 898, 592 cm -1 ; ESIMS (negative mode): 137.0; ESIHRMS m/z calcd for C 4 H 5 OBF 3 [M-K] , found Potassium [1-(3-phenoxy)-propyn-1-yl]-trifluoroborate. Yield: 58%. White solid; Mp: 273 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): (m, 2H), (m, 3H), 4.57 (app. d, J = 1.4 Hz, 2H); 13 C NMR (75 MHz, DMSO-d 6 ): 157.8, 129.3, 120.6, 114.7, 56.4 (sp carbons not observed); 11 B NMR (96 MHz, DMSO-d 6 ): (br. d, J = 33.4 Hz); 19 F NMR (188 MHz, DMSO-d 6 ): (d, J = 39.5 Hz); IR (ATR) max 1585, 1486, 1376, 1229, 1102, 996, 947, 824, 747, 694, 600 cm -1 ; ESIMS (negative mode): 437.1, 199.0; ESIHRMS m/z calcd for C 9 H 7 OBF 3 [M-K] , found Potassium (2-cyclopropyl-ethyn-1-yl)-trifluoroborate. Yield: 41%. White solid; Mp: 294 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): (m, 1H), (m, 2H), (m, 2H); 13 C NMR (75 MHz, DMSO-d 6 ): 91.8 (br.), 7.4, 0.0 (1 sp carbon not observed); 11 B NMR (96 MHz, DMSO-d 6 ): (br. d, J = 34.0 Hz); 19 F NMR (188 MHz, DMSO-d 6 ): (d, J = 41.2 Hz); IR (ATR) max 2970, 1188, 1139, 1057, 923, 812 cm -1 ; ESIMS (negative mode): 133.0, 132.0, 107.1; ESIHRMS m/z calcd for C 5 H 5 BF 3 [M-K] , found Potassium (2-cyclohexyl-ethyn-1-yl)-trifluoroborate. Yield: 48%. White solid; Mp: 245 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): 2.13 (br. s, 1H), 1.64 (br. s, 4H), 1.46 (br. s, 1H), 1.21 (br. s, 5H); 13 C NMR (75 MHz, DMSO-d 6 ): 93.2 (br.), 33.0, 29.1, 25.5, 24.6 (1 sp carbon not S4

6 observed); 11 B NMR (96 MHz, DMSO-d 6 ): (br. s); 19 F NMR (188 MHz, DMSO-d 6 ): (s); IR (ATR) max 2929, 2843, 1115, 1004, 927, 567 cm -1 ; ESIMS (negative mode): 175.1; ESIHRMS m/z calcd for C 5 H 5 BF 3 [M-K] , found Potassium (1-hex-1-yn-3-ol)-trifluoroborate. Yield: 17%. White solid; Mp: 230 C (dec.); 1 H NMR (300 MHz, DMSO-d 6 ): 4.80 (d, J = 5.4 Hz, 1H), 3.99 (app. br. q, J = 6.1 Hz, 1H), (m, 4H), 0.85 (t, J = 7.0 Hz, 3H); 13 C NMR (75 MHz, DMSO-d 6 ): 60.7, 18.3, 13.8 (sp carbons not observed); 11 B NMR (96 MHz, DMSO-d 6 ): (br. s); 19 F NMR (188 MHz, DMSO-d 6 ): (s); IR (ATR) max 3538, 2962, 2864, 1123, 1000, 972, 841, 592 cm -1 ; ESIMS (negative mode): 369.1, 165.1; ESIHRMS m/z calcd for C 6 H 9 OBF 3 [M-K] , found S5

7 Experimental Procedures and Characterization Data for Unreported Compounds: Ynamides from Potassium Alkynyltrifluoroborate General procedure for the synthesis of ynamides from potassium alkynyltrifluoroborate In a 10 ml round bottom flask, the sulfonamide, amide, oxazolidinone or imidazolidinone (5.0 mmol, 5.0 eq) was dissolved in dry dichloromethane (5 ml). 1,2-Dimethylimidazole (38 mg, 0.4 mmol, 0.4 eq), CuCl 2 2H 2 O (27 mg, 0.15 mmol, 0.15 eq), 4Å molecular sieves (700 mg) and potassium alkynyltrifluoroborate (1.0 mmol, 1.0 eq) were successively added. The resulting blue-greenish heterogeneous mixture was vigorously stirred under an atmosphere of oxygen at room temperature for h, filtered over a plug of silica gel (washed with EtOAc), and concentrated. The crude residue was purified by flash chromatography over silica gel. 3-(Phenylethynyl)oxazolidin-2-one 3a. (This compound has been previously reported S2 ). Yield: 71%. 3-(Hex-1-yn-1-yl)oxazolidin-2-one 3b. (This compound has been previously reported S3 ). Yield: 57%. S2 Hamada, T.; Ye, X.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833. S3 Frederick, M. O.; Mulder, J. A.; Tracey, M. R.; Hsung, R. P.; Huang, J.; Kurtz, K. C. M.; Shen, L.; Douglas, C. J. J. Am. Chem. Soc. 2003, 125, S6

8 3-[(4-Phenoxyphenyl)ethynyl]oxazolidin-2-one 3c. Yield: 47%. White solid; Mp: 146 C; 1 H NMR (300 MHz, CDCl 3 ): (m, 4H), 7.13 (tt, J = 7.4 and 1.1 Hz, 1H), 7.01 (br. d, J = 8.5 Hz, 2H), 6.91 (br. d, J = 8.8 Hz, 2H), 4.45 (dd, J = 8.8 Hz and 7.0 Hz, 2H), 3.96 (dd, J = 8.9 Hz and 7.0 Hz, 2H); 13 C NMR (75 MHz, CDCl 3 ): 157.7, 156.3, 156.1, 133.5, 129.9, 123.9, 119.5, 118.3, 116.6, 78.4, 70.6, 63.2, 47.0; IR (ATR) max 2974, 2925, 1752, 1417, 1213, 1094, 1049,759 cm -1 ; ESIMS (positive mode): 581.2, 302.1, 280.1; ESIHRMS m/z calcd for C 17 H 13 NO 3 Na [M+Na] , found (Oct-1-yn-1-yl)oxazolidin-2-one 3d. (This compound has been previously reported S4 ). Yield: 52%. 3-(3,3-Dimethylbut-1-yn-1-yl)oxazolidin-2-one 3e. Yield: 85%. White solid; Mp: 69 C; 1 H NMR (300 MHz, CDCl 3 ): 4.37 (dd, J = 8.8 Hz and 7.2 Hz, 2H), 3.83 (dd, J = 8.8 and 7.2 Hz, 2H), 1.22 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ): 156.5, 79.0, 69.3, 62.8, 47.3, 31.2, 27.4; IR (ATR) max 2970, 1756, 1470, 1409, 1233, 1192, 1098, 1021, 751, 706 cm -1 ; ESIMS (positive mode): 357.1, 190.1, 168.1; ESIHRMS m/z calcd for C 9 H 13 NO 2 Na [M+Na] , found S4 Hamada, T.; Ye, X.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833. S7

9 3-(4-Phenylbut-1-yn-1-yl)oxazolidin-2-one 3f. (This compound has been previously reported S5 ). Yield: 49%. 3-(3-Methoxyprop-1-yn-1-yl)oxazolidin-2-one 3g. Yield: 61%. Yellow oil; 1 H NMR (300 MHz, CDCl 3 ): 4.43 (dd, J = 8.8 and 7.2 Hz, 2H), 4.22 (s, 2H), 3.90 (dd, J = 8.8 Hz and 7.2 Hz, 2H), 3.34 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ): 156.3, 76.4, 67.7, 63.2, 59.9, 57.5, 46.8; IR (ATR) max 2974, 2921, 1756, 1413, 1196, 1090, 1033, 894, 751 cm -1 ; ESIMS (positive mode): 178.0, 124.0; ESIHRMS m/z calcd for C 7 H 9 NO 3 Na [M+Na] , found (3-Phenoxyprop-1-yn-1-yl)oxazolidin-2-one 3h. Yield: quant. pale yellow solid; Mp: 50 C; 1 H NMR (300 MHz, CDCl 3 ): (m, 2H) (m, 3H), 4.75 (s, 2H), 4.28 (dd, J = 8.8 and 7.2 Hz, 2H), 3.76 (dd, J = 8.8 Hz and 7.2 Hz, 2H); 13 C NMR (75 MHz, CDCl 3 ): 157.5, 156.0, 129.5, 121.4, 114.8, 76.7, 67.0, 63.2, 56.0, 46.5; IR (ATR) max 2974, 2921, 1760, 1495, 1425, 1209, 1090, 1053, 882, 743 cm -1 ; ESIMS (positive mode): 240.0, 218.8, 174.0; ESIHRMS m/z calcd for C 7 H 9 NO 3 Na [M+Na] , found S5 Gourdet, B.; Lam, H. W. J. Am. Chem. Soc. 2009, 131, S8

10 3-(Cyclopropylethynyl)oxazolidin-2-one 3i. Yield: 64%. White solid; Mp: 41 C; 1 H NMR (300 MHz, CDCl 3 ): 4.37 (dd, J = 8.8 and 7.2 Hz, 2H), 3.83 (dd, J = 8.8 and 7.2 Hz, 2H), (m, 1H), (m, 2H), (m, 2H); 13 C NMR (75 MHz, CDCl 3 ): 156.9, 75.2, 65.7, 62.9, 47.1, 8.8, -0.8; IR (ATR) max 2974, 2921, 1740, 1429, 1290, 1131, 1086, 1033, 931, 743 cm -1 ; ESIMS (positive mode): 174.0; ESIHRMS m/z calcd for C 8 H 9 NO 2 Na [M+Na] , found (Cyclohexylethynyl)oxazolidin-2-one 3j. Yield: 72%. Colorless oil; 1 H NMR (300 MHz, CDCl 3 ): 4.35 (dd, J = 8.8 Hz and 8.0 Hz, 2H), 3.80 (dd, J = 8.8 Hz and 8.0 Hz, 2H), (m, 1H), (m, 2H), (m, 2H), (m, 6H); 13 C NMR (75 MHz, CDCl 3 ): 156.6, 74.8, 70.2, 62.9, 47.1, 32.7, 28.7, 25.7, 24.8; IR (ATR) max 2929, 2855, 1764, 1417, 1200, 1115, 1033, 751 cm -1 ; ESIMS (positive mode): 216.1, 194.1; ESIHRMS m/z calcd for C 11 H 15 NO 2 Na [M+Na] , found (5-Chloro-pent-1-ynyl)-oxazolidin-2-one 3k. Yield: 62%. Colorless oil; 1 H NMR (300 MHz, CDCl 3 ): 4.40 (dd, J = 8.8 and 7.2 Hz, 2H), 3.86 (dd, J = 8.8 and 7.2 Hz, 2H), 3.63 (t, J = 6.3 Hz, 2H), 2.49 (t, J = 6.9 Hz, 2H), 1.96 (app. quint., J = 6.5 Hz, 2H); 13 C NMR (75 MHz, CDCl 3 ): 156.7, 71.0, 69.3, 63.0, 47.0, 43.7, 31.4, 16.0; IR (ATR) max 2970, 2929, 1752, 1478, 1417, S9

11 1204, 1111, 1029, 751 cm -1 ; ESIMS (positive mode): 212.0, 210.0,188.0; ESIHRMS m/z calcd for C 8 H 10 NO 2 ClNa [M+Na] , found (3-Hydroxyhex-1-yn-1-yl)oxazolidin-2-one 3l. Yield: 43%. Colorless oil; 1 H NMR (300 MHz, CDCl 3 ): 4.52 (br. t, J = 6.0 Hz), 4.43 (dd, J = 8.9 and 7.3 Hz, 2H), 3.90 (dd, J = 8.9 and 7.3 Hz, 2H), 2.57 (br. s, 1H), (m, 2H), 1.46 (app. sext., J = 7.7 Hz, 2H), 0.93 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 156.5, 74.8, 72.7, 63.2, 62.3, 46.9, 39.8, 18.6, 13.8; IR (ATR) max 3411, 2974, 2929, 1752, 1478, 1421, 1196, 1127, 1102, 1033, 914, 722 cm -1 ; ESIMS (positive mode): 389.2, 349.2, 279.2, 206.1, 184.1; ESIHRMS m/z calcd for C 9 H 13 NO 3 Na [M+Na] , found (R)-4-Phenyl-3-(phenylethynyl)oxazolidin-2-one 5a. (This compound has been previously reported S6 ). Yield: 71%. S6 (a) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera, E. L. Org. Lett. 2004, 6, (b) Coste, A.; Karthikeyan, G.; Couty, F.; Evano, G. Angew. Chem. Int. Ed. 2009, 48, S10

12 (R)-3-(Hex-1-yn-1-yl)-4-phenyloxazolidin-2-one 5b. Yield: 66%. White solid; Mp: 52 C; 20 [ ] D -162 (c 1.4, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): (m, 3H), (m, 2H), 4.98 (dd, J = 8.8 and 7.2 Hz, 1H), 4.69 (app. t, J = 8.8 Hz, 1H), 4.20 (dd, J = 8.8 and 7.2 Hz, 1H), 2.2 (t, J = 6.8 Hz, 2H), (m, 4H), 0.76 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 156.4, 136.5, 129.4, 129.3, 127, 72.9, 70.7, 69.1, 62.2, 30.7, 21.6, 18, 13.6; IR (ATR) max 2978, 2925, 2872, 1768, 1397, 1102, 1049, 702 cm -1 ; ESIMS (positive mode): 266.1, 244.1; ESIHRMS m/z calcd for C 15 H 17 NO 2 Na [M+Na] , found (4R,5S)-4-Methyl-5-phenyl-3-phenylethynyl-oxazolidin-2-one 6a. Yield: 69%. Pale yellow 20 solid; Mp: 112 C; [ ] D +33 (c 0.3, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): (m, 5H), (m, 5H), 5.68 (d, J = 8.0 Hz, 1H), 4.37 (dq, J = 7.9 and 6.7 Hz, 1H), 0.92 (d, J = 6.6 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 155.4, 133.9, 131.6, 129.1, 128.9, 128.3, 128.2, 126.0, 122.3, 79.8, 78.1, 72.2, 58.3, 15.0; IR (ATR) max 3436, 2980, 2253, 2233, 1777, 1408, 1321, 1188,1101, 973, 768, 707, 661 cm -1 ; ESIMS (positive mode): 577.9, 300.4; ESIHRMS m/z calcd for C 18 H 15 NO 2 Na [M+Na] , found S11

13 (4R,5S)-3-(Hex-1-yn-1-yl)-4-methyl-5-phenyloxazolidin-2-one 6b. Yield: 57%. Colorless oil; 20 [ ] D 0 (c 0.55, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): (m, 3H), (m, 2H), 5.61 (d, J = 8.1 Hz, 1H), 4.23 (dq, J = 8.0 and 6.6 Hz, 1H), 2.26 (t, J = 6.9 Hz, 2H), (m, 2H), (m, 2H), 0.85 and 0.84 (d, J = 6.8 Hz, t, J = 6.8 Hz, 6H); 13 C NMR (75 MHz, CDCl 3 ): 156.2, 134.2, 129.0, 128.8, 126.1, 79.6, 72.3, 69.1, 58.2, 31.0, 22.1, 18.3, 14.9, 13.7; IR (ATR) max 2966, 2925, 2872, 1764, 1405, 1196, 1123, 706 cm -1 ; ESIMS (positive mode): 537.3, 280.1, 258.1; ESIHRMS m/z calcd for C 16 H 19 NO 2 Na [M+Na] , found (R)-4-Methyl-3-(phenylethynyl)oxazolidin-2-one 7a. (This compound has been previously reported S7 ). Yield: 41%. (R)-3-(Hex-1-yn-1-yl)-4-methyloxazolidin-2-one 7b. Yield: 66%. Colorless oil; [ ] 20 D +31 (c 0.3, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): 4.88 (app. t, J = 8.3 Hz, 1H), 4.04 (app. sext., J = 6.1 Hz, 1H), 3.93 (dd, J = 10.5 and 9 Hz, 1H), 2.32 (t, J = 6.9 Hz, 2H), (m, 7H), 0.91 (t, J = 4.5 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 156.4, 76.7, 72.6, 70.0, 53.9, 31.0, 22.0, 18.3, S7 Yao, B.; Liang, Z.; Niu, T.; Zhang, Y. J. Org. Chem. 2009, 74, S12

14 18.1, 13.7; IR (ATR) max 2974, 2921, 1764, 1409, 1204, 1041, 980, 882, 755 cm -1 ; ESIMS (positive mode): 385.2, 204.1, 182.1; ESIHRMS m/z calcd for C 10 H 15 NO 2 Na [M+Na] , found (S)-4-Isobutyl-3-(phenylethynyl)oxazolidin-2-one 8a. Yield: 79%. Colorless oil; [ ] 20 D +65 (c 1.0, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): (m, 2H), (m, 3H), 4.47 (t, J = 7.9 Hz, 1H), (m, 1H), 3.98 (dd, J = 8.1 and 6.8 Hz, 1H) (m, 1H), (m, 1H), (m, 1H), 0.96 and 0.89 (d, J = 6.5 Hz, d, J = 6.5 Hz, 6H); 13 C NMR (75 MHz, CDCl 3 ): 155.7, 131.5, 128.3, 128.2, 122.4, 78.4, 72.4, 69.4, 56.6, 42.1, 24.6, 23, 22.4; IR (ATR) max 2945, 2913, 1748, 1413, 1221, 1098, 1029, 751, 681 cm -1 ; ESIMS (positive mode): 266.1; ESIHRMS m/z calcd for C 15 H 17 NO 2 Na [M+Na] , found (S)-3-(Hex-1-yn-1-yl)-4-isobutyloxazolidin-2-one 8b. Yield: 79%. Colorless oil; [ ] 20 D +57 (c 1.0, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): (m, 1H), (m, 2H), 2.30 (t, J = 6.9 Hz, 2H), (m, 1H), (m, 1H), (m, 5H), 0.95, 0.92 and 0.89 (d, J = 6.6 Hz, d, J = 6.6 Hz, t, J = 7.2 Hz, 9H); 13 C NMR (75 MHz, CDCl 3 ): 156.5, 72.4, 69.3, 69.2, 56.4, 41.9, 30.9, 24.6, 23.1, 22.3, 21.9, 18.2, 13.6; IR (ATR) max 2958, 2933, 2868, 1764, 1409, S13

15 1192, 1107, 747 cm -1 ; ESIMS (positive mode): 469.3, 246.1; ESIHRMS m/z calcd for C 13 H 21 NO 2 Na [M+Na] , found (3aS,8aR)-3-(Phenylethynyl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one 9a. (ent- (9a) has been previously reported S8 ). Yield: 43%. (3aS,8aR)-3-(Hex-1-yn-1-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one 9b.Yield: 20 78%. Pale yellow solid; Mp: 68 C; [ ] D +143 (c 0.44, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): 7.35 (br. d, J = 6.9 Hz, 1H), (m, 3H), 5.14 (ddd, J = 7.4, 6.8 and 2.0 Hz, 1H), 5.03 (d, J = 7.5 Hz, 1H), 3.22 (dd, J = 18.1 and 6.9 Hz, 1H), 3.06 (br. d, J = 18.0 Hz, 1H), 2.16 (t, J = 6.9 Hz, 2H), (m, 2H), (m, 2H), 0.72 (t, J = 7.2 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 155.7, 140, 137.7, 130.3, 127.7, 125.6, 125.5, 78.5, 72.6, 69.3, 65.7, 38.8, 30.9, 22.0, 18.2, 13.6; IR (ATR) max 2978, 2933, 1760, 1401, 1180, 1123, 1037, 743 cm -1 ; ESIMS (positive mode): 511.3, 278.1; ESIHRMS m/z calcd for C 16 H 17 NO 2 Na [M+Na] , found S8 (a) Frederick, M. O.; Mulder, J. A.; Tracey, M. R.; Hsung, R. P.; Huang, J.; Kurtz, K. C. M.; Shen, L.; Douglas, C. J. J. Am. Chem. Soc. 2003, 125, (b) Coste, A.; Karthikeyan, G.; Couty, F.; Evano, G. Angew. Chem. Int. Ed. 2009, 48, S14

16 (4R,5S)-1,5-Dimethyl-4-phenyl-3-(phenylethynyl)imidazolidin-2-one 10a. (This compound has been previously reported S9 ). Yield: 43%. (4S,5R)-1-(Hex-1-yn-1-yl)-3,4-dimethyl-5-phenylimidazolidin-2-one 10b. Yield: 52%. White solid; Mp: 84 C ; [ ] 20 D -151 (c 0.67, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ): (m, 3H), (m, 2H), 4.86 (d, J = 8.7 Hz, 1H), 3.84 (dq, J = 8.7 and 6.6 Hz, 1H), 2.79 (s, 3H), 2.15 (t, J = 7.0 Hz, 2H), (m, 2H), 1.17 (app. sext., J = 7.0 Hz, 2H), 0.75 and 0.73 (d, J = 7.0 Hz, t, J = 7.0 Hz, 6H); 13 C NMR (75 MHz, CDCl 3 ): 158.7, 135.0, 128.5, 128.4, 127.9, 72.2, 71.0, 64.2, 55.7, 31.1, 29.0, 21.6, 18.3, 14.9, 13.6; IR (ATR) max 2970, 2933, 1705, 1425, 1392, 1090, 1049, 743, 698 cm -1 ; ESIMS (positive mode): 563.3, 541.4, 293.2, 271.2; ESIHRMS m/z calcd for C 17 H 22 N 2 ONa [M+Na] , found Phenylethynyl-pyrrolidin-2-one 11a. (This compound has been previously reported S10 ). Yield: 27%. S9 Dunetz, J. R.; Danheiser, R. L. Org. Lett. 2003, 5, S15

17 N-Benzyl-N-4-toluenesulfonyl-phenylethynylamine 12a. (This compound has been previously reported S11 ). Yield: 49%. N-Benzyl-N-4-toluenesulfonyl-hex-1-yn-1-ylamine 12b. Yield: 68%. White solid; Mp: 34 C; 1 H NMR (300 MHz, CDCl 3 ): 7.75 (t, J = 8.3, 2H), (m, 7H), 4.36 (s, 2H), 2.37 (s, 3H), 2.09 (t, J = 6.8 Hz, 2H), (m, 2H), 1.24 (app. sext., J = 6.7 Hz, 2H), 0.82 (t, J = 7.2 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 144.4, 135.0, 134.9, 129.7, 128.9, 128.5, 128.2, 127.8, 76.7, 73.4, 71.0, 55.7, 30.9, 21.8, 18.2, 13.7; IR (ATR) max 2953, 2921, 2868, 1454, 1356, 1182, 1086, 1021, 796, 681, 645 cm -1 ; ESIMS (positive mode): 705.3, 683.3, 364.2, 342.2; ESIHRMS m/z calcd for C 20 H 23 NO 2 SNa [M+Na] , found N-Allyl-N-4-toluenesulfonyl-phenylethynylamine 13a. (This compound has been previously reported S12 ). Yield: 68%. S10 (a) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera, E. L. Org. Lett. 2004, 6, (b) Hamada, T.; Ye, X.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833. (c) Coste, A.; Karthikeyan, G.; Couty, F.; Evano, G. Angew. Chem. Int. Ed. 2009, 48, S11 (a) Dunetz, J. R.; Danheiser, R. L. Org. Lett. 2003, 5, (b) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera, E. L. Org. Lett. 2004, 6, (c) Hamada, T.; Ye, X.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833. S12 (a) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera, E. L. Org. Lett. 2004, 6, (b) Coste, A.; Karthikeyan, G.; Couty, F.; Evano, G. Angew. Chem. Int. Ed. 2009, 48, S16

18 N-Allyl-N-4-toluenesulfonyl-hex-1-yn-1-ylamine 13b. Yield: 53%. Colorless oil; 1 H NMR (300 MHz, CDCl 3 ): 7.77 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.6 Hz, 2H), 5.71 (ddt, J = 17.0, 10.7 and 6.3 Hz, 1H), (m, 2H), 3.90 (dt, J = 6.3 and 1.3 Hz, 2H), 2.46 (s, 3H), 2.23 (t, J = 6.9 Hz, 2H), (m, 4H), 0.87 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 144.5, 134.8, 131.3, 129.7, 127.9, 119.7, 73.1, 70.5, 54.4, 31.1, 21.9, 21.7, 18.2, 13.7; IR (ATR) max 2970, 2925, 1356, 1165, 1086, 1045, 808, 669, 596 cm -1 ; ESIMS (positive mode): 605.2, ; ESIHRMS m/z calcd for C 16 H 21 NO 2 SNa [M+Na] , found N-Phenyl-N-4-toluenesulfonyl-phenylethynylamine 14a. (This compound has been previously reported S13 ). Yield: 65%. N-Phenyl-N-4-toluenesulfonyl-hex-1-yn-1-ylamine 14b. Yield: 72%. Orange solid; Mp: 45 C; 1 H NMR (300 MHz, CDCl 3 ): 7.4 (d, J = 8.4, 2H), (m, 7H), 2.32 (s, 3H), 2.19 (t, J = 6.8 Hz, 2H), (m, 2H), (m, 2H), 0.80 (t, J = 7.1 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 144.7, 139.4, 132.9, 129.4, 129.1, 128.9, 128.2, 127.9, 126.1, 122.9, 73.9, 70.4, 30.9, 21.9, 21.7, 18.2, 13.6 ; IR (ATR) max 2974, 2925, 1777, 1593, 1478, 1172, 1094, 1049, 882, 808, 763, 686, 649, 575 cm -1 ; ESIMS (positive mode): 677.3, 655.3, 350.1, 328.1; ESIHRMS m/z calcd for C 19 H 21 NO 2 SNa [M+Na] , found S13 Yao, B.; Liang, Z.; Niu, T.; Zhang, Y. J. Org. Chem. 2009, 74, S17

19 N-Benzyl-N-4-toluenesulfonyl-2-trimethylsilylethyn-1-yn-1-ylamine 15. (This compound has been previously reported S14 ). Yield: 65%.. S14 Hirano, S.; Tanaka, R.; Urabe, H.; Sato, F. Org. Lett. 2004, 6, 727. S18

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