Supplementary Figures

Supplementary Figures Supplementary Figure 1. 1 H NMR (400 MHz, CDCl3) spectrum of 3a Supplementary Figure 2. 13 C NMR (75 MHz, CDCl3) spectrum of 3a 1

Supplementary Figure 3. 1 H NMR (400 MHz, CDCl3) spectrum of 2j Supplementary Figure 4. 13 C NMR (75 MHz, CDCl3) spectrum of 2j 2

Supplementary Figure 5. 1 H NMR (400 MHz, CDCl3) spectrum of 3o Supplementary Figure 6. 13 C NMR (75 MHz, CDCl3) spectrum of 3o 3

Supplementary Figure 7. 1 H NMR (400 MHz, CDCl3) spectrum of 3n Supplementary Figure 8. 13 C NMR (75 MHz, CDCl3) spectrum of 3n 4

Supplementary Figure 9. 1 H NMR (400 MHz, CDCl3) spectrum of 3w Supplementary Figure 10. 13 C NMR (75 MHz, CDCl3) spectrum of 3w 5

Supplementary Figure 11. 1 H NMR (400 MHz, CDCl3) spectrum of 2f Supplementary Figure 12. 13 C NMR (75 MHz, CDCl3) spectrum of 2f 6

Supplementary Figure 13. 1 H NMR (400 MHz, CDCl3) spectrum of 3s Supplementary Figure 14. 13 C NMR (75 MHz, CDCl3) spectrum of 3s 7

Supplementary Figure 15. 1 H NMR (400 MHz, CDCl3) spectrum of 3q Supplementary Figure 16. 13 C NMR (75 MHz, CDCl3) spectrum of 3q 8

Supplementary Figure 17. 1 H NMR (400 MHz, CDCl3) spectrum of 3c Supplementary Figure 18. 13 C NMR (75 MHz, CDCl3) spectrum of 3c 9

Supplementary Figure 19. 1 H NMR (400 MHz, CDCl3) spectrum of 3b Supplementary Figure 20. 13 C NMR (75 MHz, CDCl3) spectrum of 3b 10

Supplementary Figure 21. 1 H NMR (400 MHz, CDCl3) spectrum of 2e Supplementary Figure 22. 13 C NMR (75 MHz, CDCl3) spectrum of 2e 11

Supplementary Figure 23. 1 H NMR (400 MHz, CDCl3) spectrum of 3p Supplementary Figure 24. 13 C NMR (75 MHz, CDCl3) spectrum of 3p 12

Supplementary Figure 25. 1 H NMR (400 MHz, CDCl3) spectrum of 3v Supplementary Figure 26. 13 C NMR (75 MHz, CDCl3) spectrum of 3v 13

Supplementary Figure 27. 1 H NMR (400 MHz, CDCl3) spectrum of 3x Supplementary Figure 28. 13 C NMR (75 MHz, CDCl3) spectrum of 3x 14

Supplementary Figure 29. 1 H NMR (400 MHz, CDCl3) spectrum of 3j Supplementary Figure 30. 13 C NMR (75 MHz, CDCl3) spectrum of 3j 15

Supplementary Figure 31. 1 H NMR (400 MHz, CDCl3) spectrum of 3f Supplementary Figure 32. 13 C NMR (75 MHz, CDCl3) spectrum of 3f 16

Supplementary Figure 33. 1 H NMR (400 MHz, CDCl3) spectrum of 3g Supplementary Figure 34. 13 C NMR (75 MHz, CDCl3) spectrum of 3g 17

Supplementary Figure 35. 1 H NMR (400 MHz, CDCl3) spectrum of 2b Supplementary Figure 36. 13 C NMR (75 MHz, CDCl3) spectrum of 2b 18

Supplementary Figure 37. 1 H NMR (400 MHz, CDCl3) spectrum of 2i Supplementary Figure 38. 13 C NMR (75 MHz, CDCl3) spectrum of 2i 19

Supplementary Figure 39. 1 H NMR (400 MHz, CDCl3) spectrum of 2h Supplementary Figure 40. 13 C NMR (75 MHz, CDCl3) spectrum of 2h 20

Supplementary Figure 41. 1 H NMR (400 MHz, CDCl3) spectrum of 2a Supplementary Figure 42. 13 C NMR (75 MHz, CDCl3) spectrum of 2a 21

Supplementary Figure 43. 1 H NMR (400 MHz, CDCl3) spectrum of 2d Supplementary Figure 44. 13 C NMR (75 MHz, CDCl3) spectrum of 2d 22

Supplementary Figure 45. 1 H NMR (400 MHz, CDCl3) spectrum of 2l Supplementary Figure 46. 13 C NMR (75 MHz, CDCl3) spectrum of 2l 23

Supplementary Figure 47. 1 H NMR (400 MHz, CDCl3) spectrum of 2k Supplementary Figure 48. 13 C NMR (75 MHz, CDCl3) spectrum of 2k 24

Supplementary Figure 49. 19 F NMR (400 MHz, CDCl3) spectrum of 2k 25

Supplementary Figure 50. 1 H NMR (400 MHz, CDCl3) spectrum of 3r Supplementary Figure 51. 13 C NMR (75 MHz, CDCl3) spectrum of 3r 26

Supplementary Figure 52. 1 H NMR (400 MHz, CDCl3) spectrum of 3y Supplementary Figure 53. 13 C NMR (75 MHz, CDCl3) spectrum of 3y 27

Supplementary Figure 54. 1 H NMR (300 MHz, CDCl3) spectrum of 3k Supplementary Figure 55. 13 C NMR (75 MHz, CDCl3) spectrum of 3k 28

Supplementary Figure 56. 1 H NMR (400 MHz, CDCl3) spectrum of 3l (cis + trans) Supplementary Figure 57. 13 C NMR (75 MHz, CDCl3) spectrum of 3l (cis + trans) 29

Supplementary Figure 58. 1 H NMR (400 MHz, CDCl3) spectrum of 3i Supplementary Figure 59. 13 C NMR (75 MHz, CDCl3) spectrum of 3i 30

Supplementary Figure 60. 1 H NMR (400 MHz, CDCl3) spectrum of 3x Supplementary Figure 61. 13 C NMR (75 MHz, CDCl3) spectrum of 3x 31

Supplementary Figure 62. 1 H NMR (400 MHz, CDCl3) spectrum of 2c Supplementary Figure 63. 13 C NMR (75 MHz, CDCl3) spectrum of 2c 32

Supplementary Figure 64. 1 H NMR (400 MHz, CDCl3) spectrum of 3h Supplementary Figure 65. 13 C NMR (75 MHz, CDCl3) spectrum of 3h 33

34

Supplementary Discussions Supplementary Figure 66. GC trace of iodo-bromo exchange reaction We attempted to synthesize the cyclopropyl-ethyl iodide (a secondary iodide) to investigate the mechanism. However, we were not able to obtain the compound by using the traditional S N 2 reaction. Instead of the desired product, we only isolated the ring opening product. Eventually, we chose the cyclopropyl methyl iodide as the substrate to investigate the mechanism. Curran and co-workers have carried out extensive research on the addition of radical intermediates to alkynes (Please see Tetrahedron 1991, 47, 6171). However, in their work, a radical initiator such as Bu 3 SnSnBu 3 was required; and (as shown below) in the absence of a radical initiator, no addition product could be produced at all. Note that our system does not require this radical initiator, which could differentiate these two systems. 35

In order to further check whether our reaction undergoes a radical addition-elimination mechanism, we attempted to detect the addition intermediate by removing the base of our system. As shown below, no addition product was detected. Note that a regular radical reaction is less solvent dependent. However, as shown in Table 1 of the manuscript, our reaction is highly solvent dependent, which suggests that the mechanism of our reaction system should be more than radical chemistry. One of the referees suggested experiments to investigate whether the alkyne bearing the iodide could undergo the cyclization; such studies were already carried out by Curran and co-workers (Please see J. Am. Chem. Soc. 1989, 111, 6265-6276). Without the radical initiator (Bu 3 SnSnBu 3 ), the cyclization would not occur. As suggested by the referee, -iodo styrene derivative was synthesized to investigate the elimination rate under our conditions. (For the synthesis procedure, please see Curran et.al. Tetrahedron 1991, 47, 6171). Under our standard conditions, the mixture of the E/Z iodo- isopropylstyrene can undergo the elimination very fast. When 4-bromophenylacetylene was tested under the standard conditions, besides the desired product, the iodine-bromo exchange product was also detected. The GC trace was shown in Supplementary Figure 66. 36

Br I Chemical Formula: C 14 H 15 Br Exact Mass: 262.04 Chemical Formula: C 14 H 15 I Exact Mass: 310.02 Supplementary Methods General comments and materials. Solvents and reagents were purchased from Sigma-Aldrich chemical company and were used without further purification unless otherwise specified. 1 H NMR and 13 C NMR spectra were recorded on Varian 300 MHz, 400 MHz, or 500 MHz spectrometers and 19 F NMR spectra were recorded on Bruker 400 MHz spectrometer. All signals are reported in ppm with the internal reference of 7.26 ppm or 77.0 ppm for chloroform as standard. Data are reported as follows: multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublet), coupling constant (J/Hz) and integration. All NMR spectra were recorded at room temperature (23 C) unless otherwise indicated. High-resolution mass spectrometry was conducted through using atmospheric pressure chemical ionization (APCI) or electro-spraying ionization (ESI), and was performed at McGill University on a Thermo-Scientific Exactive Orbitrap. Protonated molecular ions [M+H] + or sodium adducts [M+Na] +, were used for empirical formula confirmation. All preparative chromatography separations were performed by using gradient eluents (hexanes and ethyl acetate) on a Biotage Isolera One automated chromatography system with SNAP ultra silica gel cartridges and sample cartridges. Infra-red spectra were recorded on a Nicolet Nexus 670 FT-IR with ATR spectrophotometer. Absorptions are given in wavenumbers (cm -1 ). The UV lamp employed in this investigation was purchased from Atlas Specialty Lighting. General protocol for the preparation of secondary and primary iodides. 1 Iodine chips (1.2 equiv) were added to a solution of Ph 3 P (1.2 equiv) and imidazole (1.2 equiv) in dry CH 2 Cl 2 (0.2 M) at 0 C. The alcohol (neat or a solution in CH 2 Cl 2 ) was added dropwise to the reaction mixture at 0 C. The mixture was allowed to warm to r.t. and stirred overnight. Next, the solvent was removed on a rotary evaporator. The residue was diluted with hexanes/et 2 O (4:1), filtered, concentrated, and purified by flash column chromatography with hexanes. General protocol for the preparation of tertiary iodides. 1 MeSO 3 H (2.0 equiv) was added dropwise to a solution of NaI (2.0 equiv) and the tertiary alcohol in MeCN (0.2 M in the tertiary alcohol) at 0 o C. The reaction mixture was allowed to warm up to room temperature and it was stirred for an additional 30 mins. Next, the reaction mixture was diluted with Et 2 O, washed with H 2 O, NaHCO 3, Na 2 S 2 O 3, and brine, dried over anhydrous Na 2 SO 4, and concentrated with rotatory evaporation. Further purification of the tertiary iodide would be done by distillation or column chromatography. General protocol for the coupling reaction. To a 5 ml quartz tube with a rubber septum and a stir bar was added the NaO t Bu (80 mg, 0.83 mmol). Following this, 1.5 ml distilled water was added into the tube. After the salt was dissolved and a clear solution was obtained, the solution was degassed and refilled with pre-purified Argon for three times by using the thaw-frozen technique. Then 100 L (0.77 mmol) iodocyclohexane and 10 L 4-methoxyphenylacetylene (0.077 mmol) were added successively, which resulted in a two-phase mixture. The rubber septum was replaced by a screw cap quickly and 37

settled in a pre-heated 50 o C water bath. Thereafter, the UV lamp, 10 cm away from the tube, was turned on. Two hours later, the reaction was stopped and EtOAc (3 ml x 3) was added to extract the organic products. After dried over Na 2 SO 4 and evaporated on rota-vapor, the residue was subjected to a flash column chromatography (Still protocol) by using pure hexane as the eluent to isolate the desired product (12.5 mg, 76%, colorless oil). Analytical Data. O 1-(cyclohexylethynyl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 12.2 mg colorless oil was obtained (74%). Rf value (Hexane): 0.12 IR (cm -1 ): 2928, 2853, 2250, 1605, 1508, 1287, 1031, 830 1 H NMR (300 MHz): d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H), 2.59-2.52 (m, 1H), 1.89-1.73 (m, 4H), 1.57-1.33 (m, 3H), 1.33-1.26 (m, 3H); 13 C NMR (75 MHz): 158.9, 132.8, 116.3, 113.7, 92.8, 80.1, 55.2, 32.8, 29.7, 25.9, 24.9. HRMS-APCI: C15H19O [M+H] +, calculated: 215.14304, found: 215.14301. O 1-(cyclopentylethynyl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 12.3 mg colorless oil was obtained (80%). Rf value (Hexane): 0.12 IR (cm -1 ): 2955, 2869, 2252, 1606, 1508, 1287, 1245, 1031, 830 1 H NMR (300 MHz): d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H), 2.85-2.75 (m, 1H), 2.05-1.95 (m, 2H), 1.84-1.56 (m, 6H); 38

13 C NMR (75 MHz): 158.9, 132.8, 116.3, 113.7, 92.9, 79.7, 55.2, 33.9, 30.8, 25.0. HRMS-APCI: C14H17O [M+H] +, calculated: 201.12739, found: 201.12748. O 1-methoxy-4-(3-methylbut-1-yn-1-yl)benzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 10.2 mg colorless oil was obtained (76%). : Rf value (Hexane): 0.17 IR (cm -1 ): 2968, 2932, 2853, 1607, 1508, 1287, 1245, 1031, 830 1 H NMR (300 MHz): d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H), 2.81-2.71 (m, 1H), 1.25 (d, J = 6.9 Hz, 6H); 13 C NMR (75 MHz): 158.9, 132.8, 116.1, 113.7, 94.1, 55.2, 23.1, 21.1. HRMS-APCI: C12H15O [M+H] +, calculated: 175.11174, found: 175.11169. O 1-(hex-1-yn-1-yl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 7 mg colorless oil was obtained (47%). Rf value (Hexane): 0.12 IR (cm -1 ): 2956, 2928, 2860, 2250, 1605, 1508, 1287, 1172, 1031, 830 1 H NMR (400 MHz): d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 3.79 (s, 3H), 2.39 (t, J = 7.2 Hz, 2H), 1.60-1.55 (m, 2H), 1.50-1.46 (m, 2H), 0.94 (t, J = 14.4 Hz, 3H); 13 C NMR (75 MHz): 158.9, 132.8, 116.2, 113.8, 88.7, 80.2, 55.2, 30.9, 22.0, 19.1, 13.6. HRMS-APCI: C13H17O [M+H] +, calculated: 189.12739, found: 189.12727. 39

O 1-(3,3-dimethylbut-1-yn-1-yl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 5.2 mg colorless oil was obtained (35%). Rf value (Hexane): 0.15 IR (cm -1 ): 2966, 2928, 2853, 1607, 1508, 1287, 1247, 1041, 830 1 H NMR (400 MHz): d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 1.30 (s, 9H); 13 C NMR (75 MHz): 158.9, 132.8, 116.2, 113.7, 96.9, 78.6, 55.2, 31.1, 27.9. HRMS-APCI: C13H17O [M+H] +, calculated: 189.12739, found: 189.12751. O 1-(3,3-dimethylpent-1-yn-1-yl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 6.1 mg colorless oil was obtained (39%). Rf value (Hexane: EtOAc=10:1): 0.65 IR (cm -1 ): 2966, 2924, 1607, 1509, 1287, 1246, 1036, 830 1 H NMR (400 MHz): d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 1.50 (q, J = 7.6 Hz, 2H), 1.25 (s, 6H), 1.04 (t, J = 7.6 Hz, 3H); 13 C NMR (75 MHz): 158.9, 132.8, 116.3, 113.7, 95.6, 80.0, 55.2, 36.1,32.0, 28.8, 9.75. HRMS-APCI: C14H19O [M+H] +, calculated: 203.1430, found: 203.1431 O 1-methoxy-4-(prop-1-yn-1-yl)benzene 40

By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used; however the starting material cannot be separated from the product and the yield was determined by HNMR with benzyl alcohol as an internal standard. Appearance: colorless oil Rf value (hexane): 0.13 IR (cm -1 ): 3300, 2918, 2852, 2250, 1605, 1508, 1291, 1245, 1031, 830 1 H NMR and 13 C NMR: This compound can not be separated from 4-methoxyphenylacetylene. HRMS-APCI: C10H11O [M+H] +, calculated: 147.08044, found: 147.08041. O 1-(hepta-1,6-diyn-1-yl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 5.5 mg colorless oil was obtained (36%) and 4 mg 4-methoxyphenylacetylene was recovered. Rf value (Hex: EtOAc=10:1): 0.56 IR (cm -1 ): 3295, 2927, 2850, 2250, 1607, 1508, 1287, 1244, 1031, 830 1 H NMR (300 MHz): d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H), 2.52 (t, J = 7.2 Hz, 2H), 2.37 (dt, J1 = 2.7 Hz, J2 = 6.9 Hz, 2H), 1.98 (t, J = 2.7 Hz, 1H), 1.83 (m, 2H); 13 C NMR (75 MHz): 159.1, 132.9, 115.9, 113.8, 87.3, 83.7, 80.9, 68.8, 55.2, 29.7, 27.7, 17.6. HRMS-APCI: C14H15O [M+H] +, calculated: 199.1117, found: 199.1120 O O 2-(3-(4-methoxyphenyl)prop-2-yn-1-yl)tetrahydrofuran By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 7.8 mg colorless oil was obtained (47%). 41

Rf value (Hexane: EtOAc=10:1): 0.24 IR (cm -1 ): 2925, 2855, 2250, 1607, 1509, 1287, 1067, 830 1 H NMR (300 MHz): d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 4.10 (m, 1H), 3.95 (m, 1H), 3.80 (s, 3H), 3.79 (m, 1H), 2.62 (m, 2H), 2.20-1.70 (m, 4H); 13 C NMR (75 MHz): 159.1, 132.9, 115.9, 113.8, 85.1, 81.4, 77.2, 68.5, 55.2, 30.8, 26.3, 25.8. HRMS-ESI: C14H16NaO2 [M+Na] +, calculated: 239.1043, found: 239.1046 O Cl 1-(5-chloropent-1-yn-1-yl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 8.3 mg colorless oil was obtained (52%). Rf value (Pure Hexane): 0.05 IR(cm -1 ): 2928, 2838, 2150, 1607, 1509, 1288, 1245, 1034, 832 1 H NMR (300 MHz): d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H), 3.71 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.9 Hz, 2H), 2.05 (m, 2H); 13 C NMR (75 MHz): 159.1, 132.9, 115.9, 113.8, 86.4, 81.2, 55.2, 43.8, 31.6, 16.9. HRMS-APCI: C12H14ClO [M+H] +, calculated: 209.0728, found: 209.0726 (cyclohexylethynyl)benzene By employing the general protocol, 9 L (0.077 mmol) phenylacetylene was used and 12.2 mg colorless oil was obtained (86%). : Rf value (pure hexane): 0.48 42

IR (cm -1 ): 2928, 2853, 2300, 1599, 1491, 1448, 755, 691 1 H NMR (400 MHz): m, 2H), 7.27-7.25 (m, 3H), 2.61-2.56 (m, 1H), 1.90-1.86 (m, 2H), 1.77-1.73 (m, 2H), 1.58-1.49 (m, 3H), 1.37-1.32 (m, 3H); 13 C NMR (75 MHz): 131.5, 128.1, 127.4, 124.1, 94.4, 80.5, 32.7, 29.6, 25.9, 24.9. HRMS-APCI: C14H17 [M+H] +, calculated: 185.13248, found: 185.13244. (cyclopentylethynyl)benzene By employing the general protocol, 9 L (0.077 mmol) phenylacetylene was used and 10.9 mg colorless oil was obtained (83%). : Rf value (pure hexane): 0.48 IR (cm -1 ): 2957, 2869, 2300, 1605, 1508, 1490, 755, 691 1 H NMR (300 MHz): m, 2H), 7.29-7.25 (m, 3H), 2.87-2.77 (m, 1H), 2.03-1.96 (m, 2H), 1.80-1.56 (m, 6H); 13 C NMR (75 MHz): 131.5, 128.1, 127.3, 124.1, 94.6, 80.0, 33.9, 30.8, 25.0. HRMS-APCI: C13H15 [M+H] +, calculated: 171.11683, found: 171.11676. hex-1-yn-1-ylbenzene By employing the general protocol, 9 L (0.077 mmol) phenylacetylene was used and 6.0 mg colorless oil was obtained (49%). Rf value (pure hexane): 0.48 IR (cm -1 ): 2957, 2928, 2859, 2250, 1733, 1490, 1287, 1031, 755, 691 43

1 H NMR (400 MHz): m, 2H), 7.29-7.25 (m, 3H), 2.41 (t, J = 14.0, 2H), 1.61-1.58 (m, 2H), 1.51-1.45(m, 2H), 0.95(t, J = 7.6, 3H); 13 C NMR (75 MHz): 131.5, 128.1, 127.4, 124.0, 90.4, 80.5, 30.8, 21.99, 19.1, 13.6. HRMS-APCI: C12H15 [M+H] +, calculated: 159.11683, found: 159.11687. (3-methylbut-1-yn-1-yl)benzene By employing the general protocol, 9 L (0.077 mmol) phenylacetylene was used and 5.0 mg colorless oil was obtained (45%). Rf value (pure hexane): 0.42 IR (cm -1 ): 2957, 2869, 2300, 1605, 1508, 1490, 755, 691 1 H NMR (400 MHz): m, 2H), 7.29-7.25 (m, 3H), 2.81-2.74 (m, 1H), 1.26 (d, J = 6.8 Hz, 6H); 13 C NMR (75 MHz): 131.5, 128.1, 127.4, 123.9, 95.7, 79.7, 23.0, 21.1. HRMS-APCI: C11H12 [M+H] +, calculated: 145.10118, found: 145.10124. 1-(cyclohexylethynyl)-4-methylbenzene By employing the general protocol, 9 mg (0.077 mmol) 4-methylphenylacetylene was used and 11.6 mg colorless oil was obtained (76%). Rf value (pure hexane): 0.42 IR(cm -1 ): 2928, 2853, 2250, 1510, 1448, 815, 536. 1 H NMR (300 MHz): d, J = 8.1 Hz, 2H), 7.07 (d, J = 7.8 Hz, 2H), 2.60-2.54 (m, 1H), 2.32 (s, 3H), 1.89-1.84 (m, 2H), 1.78-1.73 (m, 2H), 1.58-1.47 (m, 3H), 1.37-1.30 (m, 3H); 13 C NMR (75 MHz): 137.3, 131.4, 128.9, 121.0, 93.6, 80.5, 32. 8, 29.7, 25.9, 24.9, 21.4. HRMS-APCI: C15H19 [M+H] +, calculated: 199.14813, found: 199.14826. 44

1-(cyclopentylethynyl)-4-methylbenzene By employing the general protocol, 9 mg (0.077 mmol) 4-methylphenylacetylene was used and 11.5 mg colorless oil was obtained (81%). Rf value (pure hexane): 0.40 IR (cm -1 ): 2958, 2870, 2250, 1509, 1450, 816, 533. 1 H NMR (300 MHz): d, J = 8.1 Hz, 2H), 7.07 (d, J = 7.8 Hz, 2H), 2.85-2.76 (m, 1H), 2.32 (s, 3H), 2.32-1.97 (m, 2H), 1.97-1.54 (m, 6H); 13 C NMR (75 MHz): 137.3, 131.3, 128.9, 121.0, 93.7, 80.0, 33.9, 30.8, 25.0, 21.4. HRMS-APCI: C14H17 [M+H] +, calculated: 185.13248, found: 185.13256. 1-methyl-4-(3-methylbut-1-yn-1-yl)benzene By employing the general protocol, 9 mg (0.077 mmol) 4-methylphenylacetylene was used and 6.7 mg colorless oil was obtained (55%). Rf value (pure hexane): 0.37 IR (cm -1 ): 2928, 2853, 2250, 1605, 1508, 1287, 1031, 830 1 H NMR (400 MHz): d, J = 8.0 Hz, 2H), 7.07 (d, J = 8 Hz, 2H), 2.80-2.73 (m, 1H), 2.32 (s, 3H), 1.25 (d, J = 6.8 Hz, 6H); 13 C NMR (75 MHz): 137.4, 131.4, 128.9, 120.9, 95.0, 79.7, 23.1, 21.4, 21.1 HRMS-APCI: C12H15 [M+H] +, calculated: 159.11683, found: 159.11687. 45

1-(hex-1-yn-1-yl)-4-methylbenzene By employing the general protocol, 9 mg (0.077 mmol) 4-methylphenylacetylene was used and 8.6 mg colorless oil was obtained (65%). Rf value (pure hexane): 0.46 IR (cm -1 ): 2957, 2928, 2860, 2250, 1509, 1465, 1105, 815, 525. 1 H NMR (400 MHz): d, J = 8.0 Hz, 2H), 7.07 (d, J = 8 Hz, 2H), 2.80-2.73 (m, 1H), 2.40 (t, J = 12.8 Hz, 2H), 2.32 (s, 3H), 1.60-1.57 (m, 2H), 1.50-1.45 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H); 13 C NMR (75 MHz): 137.4, 131.4, 128.9, 120.9, 89.5, 80.5, 30.9, 22.0, 21.4, 19.1, 13.6. HRMS-APCI: C13H17 [M+H] +, calculated: 173.13248, found: 173.13246. Br 1-bromo-4-(cyclohexylethynyl)benzene By using the general protocol, 10 L 4-bromophenylacetylene was used. However, the product cannot be separated from the I-Br exchange product and the yield was determined by HNMR using benzyl alcohol as an internal standard. Rf value (pure hexane): 0.54 IR (cm -1 ): 2928, 2853, 2250, 1485, 1448, 1070, 1010, 830. 1 H NMR and 13 C NMR: This compound cannot be separated from the iodo-bromo exchange product. HRMS-APCI: C14H16Br [M+H] +, calculated: 263.04299, found: 263.04295. 46

Br 1-bromo-4-(cyclopentylethynyl)benzene By using the general protocol, 10 L 4-bromophenylacetylene was used. However, the product cannot be separated from the I-Br exchange product and the yield was determined by HNMR using benzyl alcohol as an internal standard. Rf value (pure hexane): 0.50 IR (cm -1 ): 2959, 2870, 2250,1487, 1393, 1070, 1010, 822 1 H NMR and 13 C NMR: This compound cannot be separated from the iodo-bromo exchange product HRMS-APCI: C13H14Br [M+H] +, calculated: 249.02734, found: 249.02722. Br 1-bromo-4-(3-methylbut-1-yn-1-yl)benzene By using the general protocol, 10 L 4-bromophenylacetylene was used. However, the product cannot be separated from the I-Br exchange product and the yield was determined by HNMR using benzyl alcohol as an internal standard. Rf value (pure hexane): 0.56 IR (cm -1 ): 2969, 2927, 2870, 2250, 1485, 1322, 1071, 1010, 821. 1 H NMR and 13 C NMR: This compound cannot be separated from the iodo-bromo exchange product HRMS-APCI: C11H12Br [M+H] +, calculated: 223.01169, found: 223.01159. Br 1-bromo-4-(hex-1-yn-1-yl)benzene 47

By using the general protocol, 10 L 4-bromophenylacetylene was used. However, the product cannot be separated from the I-Br exchange product and the yield was determined by HNMR using benzyl alcohol as an internal standard. Rf value (pure hexane): 0.50 IR (cm -1 ): 2928, 2853, 2250, 1484, 1070, 1007, 821, 520. 1 H NMR and 13 C NMR: This compound cannot be separated from the iodo-bromo exchange product HRMS-APCI: C12H14Br [M+H] +, calculated: 237.02734, found: 237.02739. N 3-(cyclohexylethynyl)pyridine According to the general protocol, 8.2 mg (0.077 mmol) 3-ethynylpyridine (97%) was used and 10.3 mg colorless oil was obtained (72%) Rf value (hexane: EtOAc=10:1): 0.25 IR (cm -1 ): 3029, 2928, 2853, 2231, 1560, 1475, 1448, 1405, 1287, 803, 705 1 H NMR (400 MHz): br, 2H), 7.70 (d, J = 8 Hz, 1H), 7.27-7.22 (m, 1H), 2.70-2.60 (m, 1H), 1.90-1.85 (m, 2H), 1.80-1.70 (m, 2H), 1.60-1.50 (m, 3H), 1.40-1.30 (m, 3H); 13 C NMR (75 MHz): 152.1, 147.5, 146.0, 138.7, 123.1, 98.3, 77.3, 46.8, 32.5, 31.4, 29.7, 25.6, 25.5, 24.9. HRMS-ESI: C13H16N [M+H] +, calculated: 186.1277, found: 186.1280. O 1-((4-(tert-butyl)cyclohexyl)ethynyl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 14.1 mg colorless oil was obtained (68%) as a mixture of cis/trans isomers, the ratio of which was determined by HNMR analysis. Rf value (hexane: EtOAc=10:1): 0.58(cis), 0.77(trans) 48

IR (cm -1 ): 2936, 2857, 1606, 1508, 1244, 1170, 1031, 830 1 H NMR (400 MHz) cis + trans isomer: m, 2H), 7.07 (m, 2H), 3.80 (s, 2H), 2.40-2.10 (m, 1H), 1.90-1.70 (m, 4H), 1.20-1.10 (m, 4H), 0.90-0.80 (m, 9H); 13 C NMR (75 MHz): 158.9, 132.8, 129.9, 127.0, 116.5, 116.2, 113.9, 113.7, 93.0, 91.9, 81.7, 79.6, 55.2, 48.0, 47.3, 33.7, 32.6, 31.7, 30.4, 27.4, 26.9, 22.9. HRMS-APCI: C19H27O [M+H] +, calculated: 271.2056, found: 271.2063 O N O O tert-butyl 4-(4-(4-methoxyphenyl)but-3-yn-1-yl)piperidine-1-carboxylate By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 13.7 mg colorless oil was obtained (52%) Rf value (hexane: EtOAc=10:1): 0.25 IR (cm -1 ): 2974, 2928, 2849, 1687, 1605, 1508, 1367, 1243, 1161, 831 1 H NMR (400 MHz): d, J = 8.0 Hz, 2H), 6.80 (d, J = 8.0 Hz, 2H), 4.10-4.0 (m, 2H), 3.80 (s, 3H), 2.70-2.60 (m, 2H), 2.42 (t, J = 9.6 Hz, 2H), 1.70-1.57 (m, 5H), 1.45 (s, 9H), 1.20 (m, 3H); 13 C NMR (75 MHz): 159.0, 154.9, 132.8, 116.0, 113.8, 88.2, 80.5, 79.2, 55.2, 35.3, 35.1, 31.8, 28.5, 16.7. HRMS-ESI: C21H29NO3Na [M+Na] +, calculated: 366.2040, found: 173.2047 N 2-(cyclohexylethynyl)pyridine By employing the general protocol, 8 L (0.077 mmol) 2-ethynylpyridine was used and 7.6 mg colorless oil was obtained (53%) Rf value (hexane: EtOAc=10:1): 0.18 IR (cm -1 ): 2929, 2854, 2232, 1582, 1463, 1427, 778z 49

1 H NMR (400 MHz): m m, 1H), 7.37 (d, J = 4 Hz, 1H), 7.20-7.10 (m, 1H), 2.60 (m, 1H), 1.90 (m, 2H), 1.77 (m, 2H), 1.60-1.57 (m, 3H), 1.35 (m, 3H). 13 C NMR (75 MHz): 149.5, 143.8, 136.2, 126.9, 122.2, 95.4, 80.1, 32.3, 29.6, 25.8, 24.9. HRMS-ESI: C13H15NNa [M+Na] +, calculated: 208.1097, found: 208.1101 1-butyl-4-(cyclohexylethynyl)benzene By employing the general protocol, 14 L (0.077 mmol) 4-butylphenylacetylene was used and 15.6 mg colorless oil was obtained (84%) Rf value (hexane: EtOAc=10:1): 0.87 IR (cm -1 ): 2928, 2853, 2250, 1605, 1509, 1448, 832. 1 H NMR (400 MHz): d, J = 5.4 Hz, 2H), 7.07(d, J = 5.4 Hz, 2H), 2.58 (t, J = 10.4 Hz, 3H), 1.95-1.65 (m, 4H), 1.62-1.45 (m, 6H), 1.45-1.25 (m, 5H); 13 C NMR (75 MHz): 142.3, 131.4, 128.2, 121.2, 93.6, 80.5, 35.5, 33.4, 32.7, 29.7, 25.9, 24.9, 22.3, 13.9. HRMS-APCI: C18H25 [M+H] +, calculated: 241.1951, found: 241.1962 O 1-(4,4-dimethylpent-1-yn-1-yl)-4-methoxybenzene By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 9.5 mg colorless oil was obtained (61%) Rf value (hexane: EtOAc=10:1): 0.58 IR (cm -1 ): 2956, 2902, 2836, 1608, 1509, 1246, 1036, 831 1 H NMR (400 MHz): d, J = 4.4 Hz, 2H), 6.811 (d, J = 4.4 Hz, 2H), 3.80 (s, 3H), 2.30 (s, 2H), 1.04 (s, 9H). 13 C NMR (75 MHz): 158.9, 132.8, 116.3, 113.7, 87.1, 81.7, 55.2, 34.4, 31.4, 29.1. HRMS-APCI: C14H19O [M+H] +, calculated: 203.1430, found: 203.1421 50

O (3r,5r,7r)-1-((4-methoxyphenyl)ethynyl)adamantane When the standard protocol was used, no desired coupling product could be obtained. Therefore, water was replaced by acetonitrile. Using 10 L (0.077 mmol) 4-methoxyphenylacetylene, 6.6 mg of a white powder product was obtained (32%). Appearance: white powder Rf value (hexane: EtOAc=10:1): 0.58 IR (cm -1 ): 2904, 2850, 1607, 1509, 1246, 1034, 830, 539. 1 H NMR (400 MHz): d, J = 6.0 Hz, 2H), 6.791 (d, J = 6 Hz, 2H), 2.89 (s, 3H), 1.95 (s, 6H), 1.71 (s, 6H), 1.25 (s, 3H); 13 C NMR (75 MHz): 158.9, 132.9, 116.2, 113.7, 96.8, 78.9, 55.2, 43.0, 36.4, 28.0. HRMS-APCI: C19H23O [M+H] +, calculated: 267.1743, found: 267.1752 F 3 C 1-(cyclohexylethynyl)-4-(trifluoromethyl)benzene By employing the general protocol, 13 L (0.077 mmol) 4-trifluoromethylphenylacetylene was used and 13.4 mg colorless oil was obtained (69%) Rf value (hexane: EtOAc=10:1): 0.87 IR (cm -1 ): 2935, 2250, 1738, 1448, 1372, 1234, 1044, 844, 634. 1 H NMR (400 MHz): m, 4H), 2.60 (m, 1H), 1.90-1.86 (m, 2H), 2.32 (s, 3H), 1.78-1.73 (m, 4H), 1.52-1.51 (m, 3H), 1.39-1.35 (m, 3H); 13 C NMR (75 MHz): 131.7, 129.3, 128.9, 128.0, 127.9, 125.8, 125.1, 125.0, 124.9, 122.2, 97.2, 79.4, 32.5, 29.6, 25.8, 24.8. HRMS-APCI: C15H16F3 [M+H] +, calculated: 253.1199, found: 253.1203 F 1-((4-(tert-butyl)cyclohexyl)ethynyl)-4-fluorobenzene By employing the general protocol, 9 L (0.077 mmol) 4-F-phenylacetylene was used and 12.7 mg colorless oil was obtained (64%) as a mixture of cis/trans isomers, the ratio of which was determined through HNMR analysis with benzyl alcohol as an internal standard. 51

Rf value (pure hexane): 0.46 (cis), 0.57 (trans) IR (cm -1 ): 2938, 2858, 2250, 1601, 1507, 1366, 1231, 1155, 834. 1 H NMR (400 MHz): cis + trans isomer: m, 2H), 6.96 (m, 2H), 2.40-2.10 (m, 1H), 1.90-1.70 (m, 4H), 1.20-1.10 (m, 4H), 0.90-0.80 (m, 9H); 13 C NMR (75 MHz): 163.6, 160.3, 133.3, 133.2, 130.6, 130.5, 120.3, 120.1, 115.5, 115.2, 93.2, 80.9, 48.0, 47.3, 33.6, 32.6, 31.6, 30.3, 27.4, 26.9, 22.9. HRMS-APCI: C18H24F [M+H] +, calculated: 259.1857, found: 259.1865 1,4-bis(cyclohexylethynyl)benzene By employing the general protocol, 9.7 mg (0.077 mmol) 4-ethynylphenylacetylene was used and 15.4 mg yellowish oil was obtained (69%) Appearance: yellowish oil Rf value (pure hexane): 0.36 IR (cm -1 ): 2929, 2854, 2229, 1703, 1508, 1448, 836. 1 H NMR (400 MHz): s, 4H), 2.52 (m, 2H), 1.78-1.73 (m, 8H), 1.52-1.51 (m, 6H), 1.39-1.35 (m, 6H); 13 C NMR (75 MHz): 131.3, 123.1, 95.8, 80.3, 32.6, 29.7, 25.9, 24.9. HRMS-APCI: C22H27 [M+H] +, calculated: 291.2107, found: 291.2115 N 4-(cyclohexylethynyl)-N,N-dimethylaniline By employing the general protocol, 11.2 mg (0.077 mmol) 4-N,N ' -dimethylphenylacetylene was used and 9.9 mg colorless oil was obtained (57%) Rf value (hexane: EtOAc=10:1): 0.55 IR (cm -1 ): 2927, 2852, 1610, 1520, 1446, 1355, 1189, 1031, 816. 1 H NMR (400 MHz): m, 2H), 6.65 (m, 2H), 2.97 (s, 6H), 2.57 (m, 1H), 1.90-1.86 (m, 2H), 1.78-1.73 (m, 2H), 1.52-1.51 (m, 3H), 1.39-1.35 (m, 3H); 13 C NMR (75 MHz): 149.6, 132.5, 111.9, 111.3, 91.8, 80.9, 40.3, 33.0, 29.8, 26.0, 25.0. 52

HRMS-ESI: C16H22N [M+H] +, calculated: 228.1747, found: 228.1756 F 1-(cyclohexylethynyl)-4-fluorobenzene By employing the general protocol, 9 L (0.077 mmol) 4-F-phenylacetylene was used and 11.0 mg colorless oil was obtained (71%) Rf value (pure hexane): 0.54 IR (cm -1 ): 2929, 2854, 2250, 1601, 1506, 1231, 1155, 834. 1 H NMR(400 MHz): m, 2H), 6.99 (m, 2H), 2.60 (m, 1H), 1.95-1.85 (m, 2H), 1.80-1.70 (m, 2H), 1.60-1.50 (m, 3H), 1.40-1.30 (m, 3H); 13 C NMR (75 MHz): 163.2, 160.8, 133.4, 133.3, 120.2, 115.3, 94.1, 79.4, 32.7, 29.6, 25.9, 24.9. 19 F NMR (400 MHz): -112.6 HRMS-APCI: C14H16F [M+H] +, calculated: 203.1231, found: 203.1221 4-(cyclohexylethynyl)-1,1'-biphenyl By employing the general protocol, 14 mg (0.077 mmol) 4-phenylphenylacetylene was used and 17.4 mg colorless oil was obtained (87%) Rf value (pure hexane): 0.36 IR (cm -1 ): 3031, 2927, 2853, 2250, 1486, 839, 762, 697. 1 H NMR (400 MHz): m, 9H), 2.60 (m, 1H), 1.95-1.85 (m, 2H), 1.80-1.70 (m, 2H), 1.60-1.50 (m, 3H), 1.40-1.30 (m, 3H); 13 C NMR (75 MHz): 140.5, 140.1, 131.9, 128.8, 127.4, 126.9, 126.8, 123.1, 95.2, 80.3, 32.7, 29.7, 25.9, 24.9. HRMS-APCI: C20H21 [M+H] +, calculated: 261.1638, found: 261.1646 O O Si tert-butyl((7-(4-methoxyphenyl)hept-6-yn-1-yl)oxy)dimethylsilane 53

By employing the general protocol, 10 L (0.077 mmol) 4-methoxyphenylacetylene was used and 13.0 mg colorless oil was obtained (51%) Rf value (hexane: EtOAc=10:1): 0.55 IR (cm -1 ): 2929, 2856, 1607, 1509, 1245, 1097, 830, 774. 1 H NMR (400 MHz): d, J = 4.4 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H), 3.63 (t, J = 6.4 Hz, 2H), 2.39 (t, J = 6.4 Hz, 2H), 1.60-1.45 (m, 6H), 0.89 (s, 9H), 0.05 (s, 6H). 13 C NMR (75 MHz): 158.9, 132.9, 116.3, 113.8, 88.6, 80.3, 63.1, 55.3, 32.4, 28.7, 26.0, 25.2, 19.4, 18.4, -5.2. HRMS-ESI: C13H17 [M+Na] +, calculated: 355.2064, found: 355.2069 Supplementary References 1. Zultanski, S. L. & Fu, G. C. Nickel-catalyzed carbon carbon bond-forming reactions of unactivated tertiary alkyl halides: Suzuki arylations. J. Am. Chem. Soc. 135, 624-627 (2012). 54