Synthesis of Simple Diynals, Diynones, Their Hydrazones, and Diazo Compounds: Precursors to a Family of Dialkynyl Carbenes (R 1 C C C C C R 2 )

Supporting Information Synthesis of Simple Diynals, Diynones, Their Hydrazones, and Diazo Compounds: Precursors to a Family of Dialkynyl Carbenes (R 1 C C C C C R 2 ) Nathan P. Bowling, Nicola J. Burrmann, Robert J. Halter, Jonathan A. Hodges, and Robert J. McMahon* Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706 mcmahon@chem.wisc.edu General Experimental Methods...2 Precursors of t-buc 5 -t-bu (5)... 2-3 Precursors of MeSi 3 C 5 H (6)... 4-6 Precursors of MeSi 3 C 5 SiMe 3 (7)... 6-7 Precursors of PhC 5 H (8)... 7-9 Precursors of PhC 5 Ph (9)... 9-13 Notes and References...13 1 H and 13 C NMR Spectra... 14-55 1

General Experimental Methods. THF was distilled from CaH 2 and then freshly distilled from Na/benzophenone. CH 2 Cl 2 was freshly distilled from CaH 2. Air-sensitive reactions were run under an atmosphere of N 2 and glassware was oven-dried overnight or flame-dried. Flash column chromatography was conducted on silica gel unless specified otherwise. 1 H NMR spectra (300 MHz) and 13 C NMR spectra (75.4 MHz) were obtained in CDCl 3 ; chemical shifts (δ) are reported as ppm downfield from internal SiMe 4. The tosylhydrazones described in the current study are thermally unstable at elevated temperature. Upon heating above ca. 100 C, a white tosylhydrazone will typically turn red (presumably reflecting formation of the diazo compound), then turn black with the evolution of gas (N 2 ). We are unable to determine whether the solid melts, followed by decomposition to the diazo compound in the melt, or whether the diazo compound is formed in the solid state, prior to melting. It is unlikely that the onset temperature for thermal decomposition (color change, gas evolution) corresponds to a true melting point (temperature of a first-order phase transition). Synthetic details for the precursors of t-buc 5 -t-bu (5). 2,2,8,8-Tetramethyl-nona-3,6-diyn-5-ol (14f). A flask was charged with 60 ml dry THF and 1.85 ml (15.0 mmol) 3,3-dimethylbutyne (18c) and was cooled to 0 C. After the addition of 6.0 ml (15.0 mmol, 2.5 M in hexane) n-buli, the mixture was stirred for 15 min at 0 C. Methyl formate (0.37 ml, 6.0 mmol) was added via syringe, the mixture was allowed to warm to room temperature for 30 min. The mixture was then heated with a heat gun for 2-3 min. An aqueous NH 4 Cl solution was added to quench the reaction mixture. The contents of the flask were washed into a separatory funnel with water and ether. The aqueous layer was extracted with ether (3 30 ml). The combined organic layers were washed with water, dried with 2

MgSO 4, filtered and concentrated under reduced pressure to give crude white solid. This solid was recrystallized from hexane to afford alcohol 14f as white needles (1.08 g, 5.63 mmol, 94% yield). 1 H NMR (CDCl 3 ) δ 5.09 (d, J = 6.3 Hz, 1H), 2.21 (d, J = 6.3 Hz, 1H), 1.23 (s, 18H). 2,2,8,8-Tetramethyl-nona-3,6-diyn-5-one (15f). A flask was charged with 300 mg (1.56 mmol) alcohol 14f, 30 ml dry CH 2 Cl 2, and 3.0 g (34.5 mmol) MnO 2. The mixture was stirred for 2 h at room temperature, at which point the reaction was complete by TLC. The reaction mixture was filtered through Celite and washed through with CH 2 Cl 2 (5 25 ml). The organic phase was dried with MgSO 4, filtered, and concentrated under reduced pressure to yield 237 mg crude white solid. With crystallization from hexane, ketone 15f was isolated as white needles (185 mg, 0.97 mmol, 62% yield). 1 H NMR (CDCl 3 ) δ 1.30 (s, 18H). 2,2,8,8-Tetramethyl-nona-3,6-diyn-5-one Tosylhydrazone (16f). A flask equipped with a condenser was charged with 360 mg (1.89 mmol) ketone 15f, 352 mg (1.89 mmol) p- toluenesulfonhydrazide, and 6.5 ml AcOH. The mixture was heated at 90-95 C for 45 min. After cooling to room temperature, ice water (~10 ml) was added to the mixture. The aqueous phase was extracted with 15 ml chloroform. The organic phase was then washed with cold water (3 10 ml), dried with MgSO 4, filtered, and concentrated under reduced pressure to give an orange oil. Several drops of hexane were added. With scratching, a white solid precipitated. The white solid was isolated via suction filtration revealing tosylhydrazone 16f (236 mg, 0.66 mmol, 35% yield). 1 H NMR (CDCl 3 ) δ 8.39 (s, 1H), 7.84 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 2.44 (s, 3H), 1.31 (s, 9H), 1.25 (s, 9H). 3

Synthetic details for the precursors of Me 3 SiC 5 H (6). 5-Trimethylsilylpenta-2,4-diyn-1-ol (10g). To an oven-dried round-bottom flask was added 50 ml dry THF and 0.9875 g (5.08 mmol) 1,4-bis(trimethylsilyl)butadiyne. The solution was cooled to 10 ºC and allowed to stir for 10 min, after which 4.29 ml MeLi LiBr (1.5 M in ether, 6.44 mmol, 1.26 equiv.) was added dropwise. The solution turned golden in color, and was allowed to stir at 10 ºC for an additional 15 min. The cold bath was then removed, and the solution was allowed to warm to room temperature and stir for 2 h. The golden solution was then cooled to 0 ºC, and a suspension of 0.2620 g (8.72 mmol, 1.72 equiv.) paraformaldehyde in 10 ml dry THF was added slowly, which caused the mixture to become cloudy. The mixture was then warmed to room temperature and was allowed to stir for an additional 5 h. The resultant mixture was washed sequentially with saturated NH 4 Cl solution, saturated NaHCO 3 solution, and brine. The aqueous washings were combined and extracted with ether. The combined organics were dried over anhydrous MgSO 4, filtered, and concentrated under reduced pressure. The resultant golden oil was purified using flash column chromatography (CHCl 3 ) and concentration of the appropriate fractions yielded 10g as a pale golden oil (0.6589 g, 4.33 mmol, 85%). 1 H NMR (CDCl 3 ) δ 4.31 (s, 2H), 2.50 (s, 1H), 0.19 (s, 9H). 13 C NMR (CDCl 3 ) δ 87.8, 87.4, 76.1, 70.7, 51.4, 0.4. EIMS (70 ev), m/z: M + 152 (12), 137 (100), 118 (43), 107 (30), 77 (16), 75 (43), 63 (4). 5-Trimethylsilylpenta-2,4-diynal (11g). Dess-Martin periodinane (0.6388g, 1.51 mmol, 1.51 equiv.) was added to a solution of 5-trimethylsilylpenta-2,4-diyn-1-ol (10g) (0.1519 g, 1.00 mmol) in 10 ml dry CH 2 Cl 2. The suspension was allowed to stir under nitrogen for 1 h, after which the reaction was shown to be complete by TLC. Ether was added to precipitate the oxidant, which was removed using filtration through a Celite plug. The organics were 4

concentrated under reduced pressure, revealing 11g as a yellow oil (0.1457 g, 0.97 mmol, 97%), which did not require purification. 1 H NMR (CDCl 3 ) δ 9.19 (s, 1H), 0.24 (s, 9H). 13 C NMR (CDCl 3 ) δ 175.9, 99.9, 85.5, 79.3, 73.3, 0.7. EIMS (70 ev), m/z: M + 150 (3), 136 (12), 135 (100), 121 (65), 107 (31), 97 (3), 86 (18), 73 (31). 5-Trimethylsilylpenta-2,4-diynal Tosylhydrazone (12g). 5-Trimethylsilylpenta-2,4- diynal (11g, 0.0806 g, 0.54 mmol) was dissolved in 10 ml dry CH 2 Cl 2, and p- toluenesulfonhydrazide (0.1530 g, 0.82 mmol, 1.52 equiv.) was added. The solution was stirred under nitrogen overnight, after which the mixture was filtered to remove the precipitate that formed. The filtrate was poured into a separatory funnel containing CH 2 Cl 2 and saturated NaHCO 3 solution. The organic portion was washed first with saturated NH 4 Cl, then with brine. The aqueous portions were combined and extracted with CH 2 Cl 2. The organic portions were combined, dried over anhydrous MgSO 4, filtered, and concentrated under reduced pressure. The resultant golden oil was purified using flash column chromatography (CHCl 3 ) and concentration of the appropriate fractions yielded 12g as an off-white solid (0.1158 g, 0.36 mmol, 68%). 1 H NMR (CDCl 3 ) δ 8.75 (s, 1H, br), 7.83 (d, J = 7.8 Hz, 2H), 7.37 (d, J = 7.8 Hz, 2H), 6.61 (s, 1H), 2.44 (s, 3H), 0.26 (s, 9H). 13 C NMR (CDCl 3 ) δ144.9, 135.3, 130.0, 128.1, 123.3, 99.3, 87.4, 85.6, 64.1, 21.8, 0.6. HRMS (ESI) calcd. [MH + ] 319.0932, found 319.0920. 1,1-Dibromo-4-trimethylsilyl-but-1-ene-3-yne (22d). 1,2 A slurry of Zn dust (0.3982 g, 6.56 mmol, 3.9 equiv.), PPh 3 (1.4295 g, 5.45 mmol, 3.2 equiv.), and CBr 4 (1.8149 g, 5.47 mmol, 3.26 equiv.) was prepared in an oven-dried round-bottom flask in 10 ml CH 2 Cl 2. The bright yellow solution was stirred under nitrogen and cooled to 0 ºC. Upon dropwise addition of a solution of trimethylsilylpropynal (21d) (0.25 ml, 1.68 mmol) in 10 ml CH 2 Cl 2, the yellow color disappeared. The mixture was allowed to stir at 0 ºC for 5 minutes and then was allowed to 5

warm to room temperature and stirred for 1 h, after which the starting material was gone by TLC. Pentane was added to precipitate PPh 3, which was then removed using filtration. The solid was rinsed with additional pentanes, the washings were combined with the filtrate, and the solvent was removed using rotary evaporation. Enyne 22d was obtained as golden oil (0.4647 g, 1.65 mmol, 97%) and used without further purification. 1 H NMR (CDCl 3 ) δ 6.57 (s, 1H), 0.22 (s, 9H). 13 C NMR (CDCl 3 ) δ 119.9, 104.1, 103.4, 101.0, 0.1. EIMS (70 ev), m/z: M + 282 (29), 267 (100), 202 (51), 185 (6), 161 (13), 139 (17), 107 (14), 77 (19), 71 (21), 57 (27). Synthetic details for the precursors of Me 3 SiC 5 SiMe 3 (7). 1,5-Bis(trimethylsilyl)-1,4-pentadiyn-3-ol (14h). Using the procedure of Rubin, 3 21.2 mmol n-buli in hexane was added to a solution of trimethylsilylacetylene (18d) (21.2 mmol) in 60 ml THF at 0 C. The colorless mixture was stirred for 15 min at 0 C. Methyl formate (10.6 mmol) was then added dropwise, and the bright yellow mixture was heated to near reflux using a heat gun (ca. 5 min). After cooling to room temperature, the red mixture was poured into a separatory funnel containing 50 ml ethyl acetate and 50 ml sat. aq. NH 4 Cl solution. The contents were mixed. The layers were separated and the organic layer was washed with 50 ml water and then 50 ml brine. The organic phase was dried with MgSO 4, filtered, and concentrated to reveal a deep red oil. This oil was purified via flash chromatography (CHCl 3, silica) yielding 2.15 g (9.58 mmol, 90% yield) alcohol 14h as a yellow oil. 1 H NMR δ 5.13 (d, J = 6.9 Hz, 1H), 2.58 (d, J = 6.9 Hz, 1H) 0.22 (s, 18H). 13 C NMR δ 102.0, 89.7, 53.1, 0.2. EIMS (70 ev) m/z: M + 224 (17), 209 (19), 193 (30), 181 (62), 169 (75), 155 (25), 141 (75), 134 (94), 110 (49), 97 (82), 73 (100). 6

1,5-Bis(trimethylsilyl)-1,4-pentadiyn-3-one (15h). Using the oxidation procedure of Rubin, 3 5.0 mmol BaMnO 4 was added to a solution of 1,5-bis(trimethylsilyl)-1,4-pentadiyn-3-ol (14h) (2.96 mmol) in 10 ml CH 2 Cl 2. Thin layer chromatography indicated that this reaction was complete after 2 h. The mixture was filtered through a short plug of silica gel. The filtrate was dried with MgSO 4, filtered, and concentrated to yield ketone 15h (0.586 g, 2.63 mmol, 89% yield) as colorless needles. When necessary, flash chromatography (CHCl 3, silica) can be used for further purification. 1 H NMR δ 0.26 (s, 18 H). 13 C NMR δ 160.5, 102.8, 99.5, 0.9. EIMS (70 ev) m/z: M + 222 (11), 207 (93), 179 (100), 155 (64), 97 (51), 73 (76). 1,5-Bis(trimethylsilyl)-1,4-pentadiyn-3-one Tosylhydrazone (16h). A flask was charged with 0.540 g (2.43 mmol) ketone 15h, 0.453 g (2.43 mmol) tosylhydrazide, and 5 ml AcOH. The mixture was stirred overnight at room temperature then poured into a separatory funnel containing 25 ml CH 2 Cl 2 and 10 ml H 2 O. The layers were separated and the organic layer was washed twice more with water. The organic layer was dried with MgSO 4, filtered, and concentrated to reveal tosylhydrazone 16h as a white solid (0.808 g, 2.07 mmol, 85% yield). 1 H NMR (CDCl 3 ) δ 8.67 (s, 1H), 7.84 (d, J = 7.8 Hz, 2H), 7.34 (d, J = 7.8 Hz, 2H), 2.44 (s, 3H), 0.28 (s, 9H), 0.21 (s, 9H). HRMS (ESI) calcd. C 18 H 26 N 2 O 2 SSi 2 Na + 413.1151, found 413.1164. Synthetic details for the precursors of PhC 5 H (8). 5-Phenyl-penta-2,4-diyn-1-ol (10i). To a flask was added 21.8 mg (0.22 mmol) CuCl and 6.0 ml of a 30% n-bunh 2 /H 2 O solution. Upon the addition of phenylacetylene (18e, 1.22 ml, 11.1 mmol), the solution turned bright yellow in color and a fine precipitate was observed. The flask was covered in foil and the mixture was cooled to 0 C. 3-Bromopropargyl alcohol (19a, 0.99 g, 7.34 mmol) was added dropwise and the solution turned red-orange in color and an 7

oil was visible. The solution was allowed to stir at 0 C for 15 min, after which the ice bath was removed and the color of the solution darkened slightly. NH 2 OH HCl crystals were added in small increments, until the solution remained a yellow-orange color. After 15 min, the mixture was poured into a separatory funnel containing water and ether. The aqueous portion was then extracted (3 20 ml) with ether. The combined organic extracts were dried with MgSO 4, filtered, and concentrated to reveal a dark gold oil. Purification via flash chromatography (CHCl 3 ) yielded 0.99 g (6.34 mmol, 87% yield) of alcohol 10i as a pale yellow oil. 1 H NMR (CDCl 3 ) δ 7.47 (dd, J = 8.1 Hz, 1.7 Hz, 2H), 7.29 (multiplet, 3H), 4.42 (s, 2H), 2.97 (s, br, 1H). 13 C NMR (CDCl 3 ) δ 132.7, 129.4, 128.5, 121.4, 80.7, 78.7, 73.4, 70.4, 51.6. EIMS (70 ev) m/z: M + 156 (100), 139 (80), 128 (98), 113 (20), 102 (97), 87 (43), 77 (79), 63 (57), 55 (7). 5-Phenyl-penta-2,4-diynal Tosylhydrazone (12i). Dry CH 2 Cl 2 (10 ml) and Dess- Martin periodinane (1.5197 g, 3.58 mmol) were added to alcohol 10i (0.3706 g, 2.37 mmol) and allowed to stir under nitrogen at room temperature. The reaction was shown to be complete by TLC after 1 h. Diethyl ether was added and the resulting suspension was flash-filtered through a fritted funnel into a round-bottom flask containing p-toluenesulfonhydrazide (0.7175 g, 3.85 mmol). (Attempts to isolate the resulting aldehyde were unsuccessful, due to its reactivity.) The mixture was allowed to stir under nitrogen at room temperature overnight. The solution was washed with saturated sodium bicarbonate solution, then the organic layer was washed with brine, followed by water. The combined aqueous layers were extracted with CH 2 Cl 2, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and purified using flash column chromatography (CHCl 3 ). Concentration of the appropriate fractions revealed tosylhydrazone 12i as an off-white solid (0.3336 g, 1.03 mmol, 44 % yield). 1 H NMR (CDCl 3 ) δ 8.81 (s, 1H), 7.85 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.3 Hz, 2H), 7.45 (tt, J = 7.7 Hz, 1.4 Hz, 1H), 8

7.38 (d, J = 7.7 Hz, 2H), 7.34 (t, J = 7.7 Hz, 2H), 6.70 (s, 1H), 2.43 (s, 3H). 13 C NMR (CDCl 3 ) δ 144.8, 135.3, 133.0, 130.7, 128.9, 128.1, 123.8, 120.4, 111.0, 88.4, 87.5, 72.1, 69.1, 21.8. HRMS (ESI) calcd. [MH + ] 323.0849, found 323.0851. Synthetic details for the precursors of PhC 5 Ph (9). A. Route via unsymmetrical ketone 1,5-diphenyl-penta-2,4-diyn-1-one (11j). 3-Bromo-1-phenyl-prop-2-yn-1-ol (19e). To a flask were added 4.71 g (84.0 mmol) KOH pellets and 40 ml deionized water. After the pellets had dissolved, 1.19 ml Br 2 was added via syringe. The flask was covered with foil and cooled to 0 C. 1-Phenyl-2-propyn-1-ol (2.43 ml, 20.0 mmol) was added dropwise via syringe, and the solution changed from clear and yellow to milky and pale yellow in appearance. The mixture was allowed to stir for 4 h at 0 C, then at room temperature without the foil for 30 min. The mixture was extracted three times with ether. The combined organic layers were dried over MgSO 4, filtered, and concentrated under reduced pressure, revealing the bromoalcohol 19e (3.60 g, 17.0 mmol, 85% yield) as a redorange oil. No purification was needed. 1 H NMR (CDCl 3 ) δ 7.46 (dd, J = 7.4 Hz, 1.6 Hz, 2H), 7.33 (m, 3H), 5.39 (d, J = 6.0 Hz, 1H), 2.81 (d, J = 6.0 Hz, 1H). 13 C NMR (CDCl 3 ) δ 139.9, 128.7, 128.5, 126.6, 79.8, 65.3, 47.3. EIMS (70 ev) m/z: M + 212 (31), 195 (17), 172 (7), 147 (2), 131 (100), 103 (71), 77 (66), 62 (7). 1,5-Diphenyl-penta-2,4-diyn-1-ol (10j). To a flask was added 11.6 mg (0.12 mmol) CuCl and 6.0 ml of a 30% n-bunh 2 /H 2 O solution. Upon the addition of phenylacetylene (18e, 0.65 ml, 5.92 mmol), the solution turned bright yellow in color. The flask was covered in foil and the mixture was cooled to 0 C. 3-Bromo-1-phenyl-prop-2-yn-1-ol (19e, 0.83 g, 3.94 mmol) was added and the solution turned pea green in color and more precipitate was visible. The ice 9

bath was removed and NH 2 OH HCl crystals were added in small increments. As the NH 2 OH HCl was added, an oil formed and then disappeared as more precipitate formed and the solution lightened in color. After 30 min, the mixture was poured into a separatory funnel containing water and ether. The aqueous portion was then extracted (3 20 ml) with ether. The combined organic extracts were dried with MgSO 4, filtered, and concentrated to reveal a dark golden oil. Purification via flash chromatography (CHCl 3 ) yielded 0.698 g (3.00 mmol, 74% yield) of alcohol 10j as a pale yellow solid. 1 H NMR (CDCl 3 ) δ 7.54 (dd, J = 7.4 Hz, 1.6 Hz, 2H), 7.48 (dd, J = 7.4 Hz, 1.6 Hz, 2H), 7.34 (m, 6H), 5.57 (d, J = 6.1 Hz, 1H), 2.47 (d, J = 6.1 Hz, 1H). 13 C NMR (CDCl 3 ) δ 139.7, 132.6, 129.4, 128.8, 128.7, 128.4, 126.7, 121.3, 81.7, 79.4, 73.2, 71.3, 65.2. EIMS (70 ev) m/z: M + 232 (63), 203 (63), 153 (16), 131 (100), 102 (68), 77 (76), 63 (13). 1,5-Diphenyl-penta-2,4-diyn-1-one (11j). To a flask containing alcohol 10j (1.27 g, 5.45 mmol) were added 20 ml dry CH 2 Cl 2 and BaMnO 4 (1.54 g, 11.1 mmol). After stirring under nitrogen at room temperature for 45 min, the reaction was shown to be complete by TLC. The contents of the flask were flash-filtered through a fritted funnel. The filtrate was dried with anhydrous MgSO 4, filtered, and concentrated under reduced pressure, revealing ketone 11j (1.00 g, 4.33 mmol, 80% yield) as a pale orange solid. No purification was necessary. 1 H NMR (CDCl 3 ) δ 8.14 (d, J = 7.4 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.57 (d, J = 7.4 Hz, 2H), 7.49 (d, J = 7.4 Hz, 2H), 7.38 (m, 3H). 13 C NMR (CDCl 3 ) δ 177.0, 136.7, 134.6, 133.2, 130.7, 129.5, 128.84, 128.81, 120.3, 86.6, 78.0, 77.6, 72.7. EIMS (70 ev), m/z: M + 230 (100), 202 (71), 175 (8), 153 (67), 125 (28), 98 (18), 77 (20). 1,5-Diphenyl-penta-2,4-diyn-1-one Tosylhydrazone (12j). To a flask containing ketone 11j (0.616 g, 2.68 mmol) were added glacial acetic acid (7.0 ml) and p- 10

toluenesulfonhydrazide (1.25 g, 6.71 mmol). The mixture was stirred overnight under nitrogen, then poured into a beaker containing saturated NaHCO 3 solution. More NaHCO 3 was added incrementally, with stirring, until bubbling in the solution ceased, at which point CH 2 Cl 2 was added and the mixture was allowed to stir for an additional 15 min. The mixture was then poured into a separatory funnel and the layers were separated. The organic phase was washed with brine, followed by water. The aqueous layers were combined and extracted twice with CH 2 Cl 2. The organic portions were then combined, dried over MgSO 4, filtered, concentrated under reduced pressure, and purified using flash chromatography (CHCl 3 ). Concentration of the appropriate fractions revealed 0.803 g (2.01 mmol, 75% yield) of tosylhydrazone 12j as a pale yellow solid. 1 H NMR (CDCl 3 ) δ 8.752 (s, 1H), 7.91 (d, J = 8.4 Hz, 2H), 7.82 (dd, J = 6.9 Hz, 2.3 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.37 (m, 6H), 7.31 (d, J = 8.4 Hz, 2H), 2.39 (s, 3H). 13 C NMR (CDCl 3 ) δ 144.7, 134.63, 134.56, 133.7, 133.7, 130.4, 130.01, 129.96, 128.9, 128.7, 128.1, 126.7, 120.4, 88.8, 88.4, 72.2, 69.0, 21.8. HRMS (ESI) calcd. C 24 H 18 N 2 O 2 SNa + 421.0987, found 421.0995. Synthetic details for the precursors of PhC 5 Ph (9). B. Route via symmetrical ketone 1,5-diphenyl-penta-1,4-diyn-3-one (15j). 1,5-Diphenyl-penta-1,4-diyn-3-ol (14j). A flame-dried 100 ml round-bottom flask was charged with 30 ml dry THF, covered in foil, and cooled to 0 C. Phenylacetylene (18e, 1.12 ml, 10.2 mmol) and n-buli (8.6 ml, 11.2 mmol, 1.31 M solution in hexane) were added via syringe and the solution turned yellow in color. The mixture was allowed to stir for 15 min at 0 C. Methyl formate (0.28 ml, 4.52 mmol) was added via syringe. The mixture was allowed to stir at 0 C for an additional 5 min, then the cold bath was removed. After warming to room 11

temperature, the mixture was heated to near-reflux with a heat gun in order to ensure reaction completion, and the solution turned deep red in color. The mixture was allowed to cool to room temperature, and then was poured into a separatory funnel containing ethyl acetate and aqueous saturated NH 4 Cl solution. The organic phase was washed with a brine solution, followed by deionized water. The combined aqueous portions were extracted with ethyl acetate. The combined organic phases were dried over MgSO 4, filtered, and concentrated under reduced pressure, revealing a brown oil. Purification using flash column chromatography (70% CHCl 3 / 30% EtOAc) and concentration of the appropriate fractions revealed alcohol 14j as a golden crystalline solid (0.849 g, 3.64 mmol, 80% yield). 1 H NMR (CDCl 3 ) δ 7.51 (dd, J = 7.2 Hz, 1.6 Hz, 4H), 7.33 (m, 6H), 5.66 (d, J = 6.7 Hz, 1H), 3.28 (d, J = 6.7 Hz, 1H). 13 C NMR (CDCl 3 ) δ 132.2, 129.1, 128.6, 122.3, 86.5, 84.8, 53.4. EIMS (70 ev) m/z: M + 231 (69), 203 (79), 174 (10), 159 (8), 145 (12), 131 (64), 102 (100), 84 (26), 66 (39). 1,5-Diphenyl-penta-1,4-diyn-3-one (15j). To the flask containing alcohol 14j (0.327 g, 1.40 mmol) were added 10 ml dry CH 2 Cl 2 and BaMnO 4 (0.769 g, 3.00 mmol). After stirring under nitrogen at room temperature for 45 min, the reaction was shown to be complete by TLC. The contents of the flask were flash-filtered through a fritted funnel. The filtrate was dried with MgSO 4, filtered, and concentrated under reduced pressure, revealing a golden oil. Purification using flash column chromatography (CHCl 3 ) and concentration of the appropriate fractions revealed ketone 15j (0.270 g, 1.17 mmol, 83% yield) as a pale yellow powder. 1 H NMR (CDCl 3 ) δ 7.63 (dd, J = 7.6 Hz, 1.4 Hz, 4H), 7.48 (tt, J = 7.6 Hz, 1.4 Hz, 2H), 7.39 (t, J = 7.6 Hz, 4H). 13 C NMR (CDCl 3 ) δ 160.8, 133.3, 131.2, 128.7, 119.5, 91.6, 89.4. EIMS (70 ev), m/z: M + 230 (54), 202 (100), 175 (17), 150 (26), 129 (34), 101 (26), 75 (55). 12

1,5-Diphenyl-penta-1,4-diyn-3-one Tosylhydrazone (16j). To the flask containing ketone 15j (0.270 g, 1.17 mmol) were added glacial acetic acid (5.0 ml) and p- toluenesulfonhydrazide (0.41 g, 2.2 mmol). The mixture was stirred overnight under nitrogen, then poured into a separatory funnel containing 2:1 water and CH 2 Cl 2. The organic phase was dried over MgSO 4, filtered, concentrated under reduced pressure, and purified using flash chromatography (70% CHCl 3 / 30% EtOAc). Concentration of the appropriate fractions revealed 0.289 g (0.73 mmol, 62% yield) of a 5:1 ratio of tosylhydrazone 16j to pyrazole. Attempts to separate the tosylhydrazone and pyrazole were unsuccessful. Partial spectral data attributable to tosylhydrazone 16j: 1 H NMR (CDCl 3 ) δ 8.83 (s, 1H), 7.89 (d, J = 8.4 Hz, 2H), 2.42 (s, 3H). Partial spectral data attributable to pyrazole: 1 H NMR (CDCl 3 ) δ 7.21, (d, J = 8.4 Hz, 2H), 6.42 (1H, s), 2.39 (3H, s). Notes and References (1) Uenishi, J.; Kawahama, R.; Yonemitsu, O.; Tsuji, J. J. Org. Chem. 1996, 61, 5716-5717. (2) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13, 3769-3772. (3) An, Y.-Z.; Rubin, Y.; Schaller, C.; McElvany, S. W. J. Org. Chem. 1994, 59, 2927-2929. 13

14

15

O N S NH O H 12b 16

17

18

19

20

O N S NH O 12d 21

O N S NH O 12d 22

23

24

O N S NH O N O N S O 16d 3.0 2.5 2.0 1.5 PPM 10 8 6 4 2 PPM 25

O N S NH O 20d 26

O N S NH O 20d 27

28

10 8 6 4 2 0 PPM 29

Br Br H 22c 10 8 6 4 2 0 PPM 30

10 8 6 4 2 PPM 31

10 8 6 4 2 0PPM 32

160 140 120 100 80 60 40 20 PPM 33

OH 14f 34

O 15f 35

36

Br Br H Si 22d 37

38

O N S NH O H Si 12g 39

O N S NH O H Si 12g 40

41

OH Si Si 14h 42

O Si Si 15h 43

O N S NH O Si Si 16h 44

45

O N S NH O H 12i 46

O N S NH O H 12i 47

48

49

O 11j 50

51

52

53

54

O N S NH O N O N S O 16j 55