The Journal of Organic Chemistry
Note
765, 729, 694, 671, 610. HRMS (ESI/Q-TOF) m/z: [M + H]+ calcd
for C17H15FN3O2, 312.1143; found, 312.1147.
fluoro-3,3-dimethyl-1-(4-phenyl-1H-1,2,3-triazol-1-yl)butan-2-one 6h
was isolated as a crystalline colorless solid (19.5 mg, 75%; mp = 105−
107 °C). Rf = 0.40 (5:1, hexane/ethyl acetate). 1H NMR (400 MHz,
CDCl3): δ 8.07 (1H, s), 7.87−7.85 (2H, m), 7.47−7.43 (2H, m),
7.40−7.35 (1H, m), 7.23 (1H, d, J = 48.0 Hz), 1.27 (9H, app. bd, J =
0.5 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 203.0 (d, J = 23.0 Hz),
149.1, 129.7, 129.1, 129.0, 126.1, 118.9 (d, J = 1.5 Hz), 89.6 (d, J =
218.0 Hz), 44.2, 25.8. 19F NMR (377 MHz, CDCl3): δ −145.2 (1F, d,
J = 48.0 Hz). IR: ν (neat, ATR)/cm−1 3140, 2974, 2876, 1732, 1480,
1459, 1433, 1369, 1241, 1191, 1139, 1111, 1074, 1045, 1034, 1020,
982, 918, 874, 837, 797, 765, 712, 694, 634. HRMS (ESI/Q-TOF)
m/z: [M + H]+ calcd for C14H17FN3O, 262.1350; found, 262.1356.
1-((1R,3R,5R,7R)-Adamantan-2-yl)-2-fluoro-2-(4-phenyl-1H-
1,2,3-triazol-1-yl)ethan-1-one 6i. Following general procedure B,
from 1-((1R,3R,5R,7R)-adamantan-2-yl)-2-(dimethyl(oxo)-λ6-
sulfaneylidene)ethan-1-one 4i (25.4 mg, 0.1 mmol), sodium azide
(9.8 mg, 0.15 mmol), Selectfluor (53 mg, 0.15 mmol), acetonitrile
(0.5 mL), then t-BuOH/H2O (10:1, 0.5 mL), phenylacetylene (12
μL, 0.11 mmol), CuSO4·5H2O (7.5 mg, 30 mol %), and sodium
ascorbate (6 mg, 30 mol %), the desired product 1-((1R,3R,5R,7R)-
adamantan-2-yl)-2-fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethan-1-
one 6i was isolated as a colorless oil (13 mg, 38%). Rf = 0.45 (5:1,
hexane/ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 8.04 (1H, s),
7.87−7.84 (2H, m), 7.47−7.43 (2H, m), 7.40−7.35 (1H, m), 7.25
(1H, d, J = 48.0 Hz), 2.08 (3H, bs), 1.87 (6H, d, J = 3.0 Hz), 1.79−
1.68 (6H, m). 13C{1H} NMR (151 MHz, CDCl3): δ 201.1 (d, J =
22.0 Hz), 149.1, 129.7, 129.1, 128.9, 126.1, 118.9 (d, J = 1.5 Hz), 88.8
(d, J = 218.0 Hz), 46.5, 38.8, 37.3, 36.6, 36.2, 28.0, 27.5. 19F NMR
(377 MHz, CDCl3): δ −146.6 (1F, d, J = 48.0 Hz). IR: ν (neat,
ATR)/cm−1 3139, 2907, 2853, 1726, 1612, 1559, 1485, 1455, 1433,
1367, 1265, 1242, 1197, 1184, 1161, 1104, 1075, 1033, 1021, 999,
970, 933, 881, 846, 792, 763, 712, 694, 670, 628. HRMS (ESI/Q-
TOF) m/z: [M + H]+ calcd for C20H23FN3O, 340.1820; found,
340.1820.
2-Fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-1-(p-tolyl)ethan-
1-one 6c. Following general procedure B, from 2-(dimethyl(oxo)-λ6-
sulfanylidene)-1-(p-tolyl) ethan-1-one 4c (21 mg, 0.1 mmol), sodium
azide (9.8 mg, 0.15 mmol), Selectfluor (53 mg, 0.15 mmol),
acetonitrile (0.5 mL), then t-BuOH/H2O (10:1, 0.5 mL), phenyl-
acetylene (12 μL, 0.11 mmol), CuSO4·5H2O (7.5 mg, 30 mol %), and
sodium ascorbate (6 mg, 30 mol %), the desired product 2-fluoro-2-
(4-phenyl-1H-1,2,3-triazol-1-yl)-1-(p-tolyl)ethan-1-one 6c was iso-
lated as a white solid (6.5 mg, 22%; mp = 116−118 °C). Rf = 0.17
1
(5:1, hexane/ethyl acetate). H NMR (600 MHz, CDCl3): δ 8.03
(1H, s), 7.92 (2H, d, J = 8.3 Hz), 7.84−7.83 (2H, m), 7.70 (1H, d, J =
48.0 Hz), 7.44−7.43 (2H, m), 7.37−7.34 (1H, m), 7.32 (2H, d, J =
8.4 Hz), 2.43 (3H, s). 13C{1H} NMR (151 MHz, CDCl3): δ 186.3 (d,
J = 26.0 Hz), 149.3, 147.1, 130.2, 129.9, 129.6, 129.4 (d, J = 1.5 Hz),
129.1, 129.0, 126.1, 119.0 (d, J = 1.8 Hz), 91.4 (d, J = 218.0 Hz),
22.1. 19F NMR (376 MHz, CDCl3): δ −147.2 (1F, d, J = 47.2 Hz).
IR: ν (neat, ATR)/cm−1 3140, 2950, 2921, 2852, 1704, 1605, 1459,
1370, 1252, 1182, 1093, 1022, 967, 871, 799, 765, 691, 621. HRMS
(ESI/Q-TOF) m/z: [M + H]+ calcd for C17H15FN3O, 296.1194;
found, 296.1200.
1-(4-Chlorophenyl)-2-fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-
yl)ethan-1-one 6d. Following general procedure B, from 1-(4-
chlorophenyl)-2-(dimethyl(oxo)-λ6-sulfanylidene)ethan-1-one 4d (23
mg, 0.1 mmol), sodium azide (9.8 mg, 0.15 mmol), Selectfluor (53
mg, 0.15 mmol), acetonitrile (0.5 mL), then t-BuOH/H2O (10:1, 0.5
mL), phenylacetylene (12 μL, 0.11 mmol), CuSO4·5H2O (7.5 mg, 30
mol %), and sodium ascorbate (6 mg, 30 mol %), the desired product
1-(4-chlorophenyl)-2-fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethan-
1-one 6d was isolated as a colorless oil (14 mg, 44%). Rf = 0.38 (5:1,
hexane/ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 8.03 (1H, s),
8.00−7.97 (2H, m), 7.85−7.83 (2H, m), 7.64 (1H, d, J = 48.0 Hz),
7.52−7.49 (2H, m), 7.45−7.43 (2H, m), 7.39−7.36 (1H, m).
13C{1H} NMR (151 MHz, CDCl3): δ 185.8 (d, J = 27.0 Hz), 149.4,
2-Fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-1-(quinoxalin-2-
yl)ethan-1-one 6j. Following general procedure B, from 2-
(dimethyl(oxo)-λ6-sulfaneylidene)-1-(quinoxalin-2-yl)ethan-1-one 4j
(24.8 mg, 0.1 mmol), sodium azide (9.8 mg, 0.15 mmol), Selectfluor
(53 mg, 0.15 mmol), acetonitrile (0.5 mL), then t-BuOH/H2O (10:1,
0.5 mL), phenylacetylene (12 μL, 0.11 mmol), CuSO4·5H2O (7.5 mg,
30 mol %), and sodium ascorbate (6 mg, 30 mol %), the desired
product 2-fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-1-(quinoxalin-2-
yl)ethan-1-one 6j was isolated as a crystalline yellow solid (14.5
mg, 44%; mp = 132−134 °C). Rf = 0.2 (dichloromethane). 1H NMR
(500 MHz, CDCl3): δ 9.61 (1H, s), 8.34 (1H, d, J = 50.0 Hz), 8.21
(1H, s), 8.20 (1H, dd, J = 8.5, 1.0 Hz), 8.12 (1H, dd, J = 8.5, 1.0 Hz),
7.97−7.93 (1H, m), 7.89−7.85 (1H, m), 7.85−7.83 (2H, m), 7.45−
7.41 (2H, m), 7.38−7.34 (1H, m). 13C{1H} NMR (125 MHz,
CDCl3): δ 186.9 (1C, d, J = 26.0 Hz), 149.1, 144.8, 143.6, 143.5,
140.8, 133.9, 131.8, 130.8, 129.8, 129.6, 129.1, 129.0, 126.1, 119.5
(1C, d, J = 2.0 Hz) 89.8 (1C, d, J = 216.0 Hz). 19F NMR (377 MHz,
CDCl3): δ −152.2 (1F, d, J = 52 Hz). IR: ν (neat, ATR)/cm−1 3138,
2955, 2925, 2851, 1731, 1568, 1486, 1460, 1435, 1367, 1300, 1141,
1075, 989, 945, 807, 763, 695. HRMS (ESI/Q-TOF) m/z: [M + H]+
calcd for C18H13FN5O, 334.1104; found, 334.1103.
142.4, 130.72, 130.71, 129.9, 129.10, 129.06, 126.1, 119.1 (d, J = 2.0
Hz), 117.3, 91.7 (d, J = 218.0 Hz). 19F NMR (377 MHz, CDCl3): δ
−146.7 (1F, d, J = 48.0 Hz). IR: ν (neat, ATR)/cm−1 3139, 2923,
2851, 1711, 1589, 1570, 1487, 1460, 1433, 1403, 1365, 1279, 1243,
1207, 1180, 1139, 1093, 1015, 968, 916, 873, 764, 669. HRMS (ESI/
Q-TOF) m/z: [M + H]+ calcd for C16H12ClFN3O, 316.0647; found,
316.0655.
2-Fluoro-1-(4-fluorophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-
yl)ethan-1-one 6e. Following general procedure B, from 2-
(dimethyl(oxo)-λ6-sulfanylidene)-1-(4-fluorophenyl)ethan-1-one 4e
(21.4 mg, 0.1 mmol), sodium azide (9.8 mg, 0.15 mmol), Selectfluor
(53 mg, 0.15 mmol), acetonitrile (0.5 mL), then t-BuOH/H2O (10:1,
0.5 mL), phenylacetylene (12 μL, 0.11 mmol), CuSO4·5H2O (7.5 mg,
30 mol %), and sodium ascorbate (6 mg, 30 mol %), the desired
product 2-fluoro-1-(4-fluorophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-
yl)ethan-1-one 6e was isolated as a white solid (9 mg, 30%; mp =
1
121−123 °C). Rf = 0.29 (5:1, hexane/ethyl acetate). H NMR (600
MHz, CDCl3): δ 8.14−8.06 (2H, m), 8.04 (1H, s), 7.86−7.80 (2H,
m), 7.72−7.59 (1H, m), 7.47−7.40 (2H, m), 7.40−7.34 (1H, m),
7.23−7.18 (2H, m). 13C{1H} NMR (151 MHz, CDCl3): δ 185.3 (d, J
= 26.0 Hz), 167.1 (d, J = 259.8 Hz), 149.5, 132.4 (d, J = 9.9 Hz),
129.5, 129.12, 129.06, 128.9 (d, J = 3.2 Hz), 126.1, 119.0, 116.9 (d, J
= 22.2 Hz), 91.68 (d, J = 218.3 Hz). 19F NMR (377 MHz, CDCl3): δ
−146.5 (1F, d, J = 47.3 Hz), −99.8 (1F). IR: ν (neat, ATR)/cm−1
2957, 2923, 2852, 1708, 1598, 1459, 1432, 1365, 1238, 1177, 1093,
1073, 1019, 967, 874, 846, 802, 762, 692, 669, 617. HRMS (ESI/Q-
TOF) m/z: [M + H]+ calcd for C16H12F2N3O, 300.0943; found,
300.0952.
1-Fluoro-3,3-dimethyl-1-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)-
butan-2-one 6k. Following general procedure B, from 1-(dimethyl-
(oxo)-λ6-sulfanylidene)-3,3-dimethylbutan-2-one 4h (17.6 mg, 0.1
mmol), sodium azide (9.8 mg, 0.15 mmol), Selectfluor (53 mg, 0.15
mmol), acetonitrile (0.5 mL), then t-BuOH/H2O (10:1, 0.5 mL), 4-
ethynyltoluene (14 μL, 0.11 mmol), CuSO4·5H2O (7.5 mg, 30 mol
%), and sodium ascorbate (6 mg, 30 mol %), the desired product 1-
fluoro-3,3-dimethyl-1-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)butan-2-one
6k was isolated as a cream solid (15 mg, 55%; mp = 108−110 °C). Rf
1-Fluoro-3,3-dimethyl-1-(4-phenyl-1H-1,2,3-triazol-1-yl)-
butan-2-one 6h. Following general procedure B, from 1-(dimethyl-
(oxo)-λ6-sulfanylidene)-3,3-dimethylbutan-2-one 4h (17.6 mg, 0.1
mmol), sodium azide (9.8 mg, 0.15 mmol), Selectfluor (53 mg, 0.15
mmol), acetonitrile (0.5 mL), then t-BuOH/H2O (10:1, 0.5 mL),
phenylacetylene (12 μL, 0.11 mmol), CuSO4·5H2O (7.5 mg, 30 mol
%), and sodium ascorbate (6 mg, 30 mol %), the desired product 1-
1
= 0.36 (5:1, hexane/ethyl acetate). H NMR (400 MHz, CDCl3): δ
8.02 (1H, s), 7.76−7.73 (2H, m), 7.27−7.25 (2H, m), 7.22 (1H, d, J
= 48.0 Hz), 2.39 (3H, s), 1.26 (9H, d, J = 0.5 Hz). 13C{1H} NMR
(151 MHz, CDCl3): δ 203.0 (d, J = 23.0 Hz), 149.2, 138.9, 129.8,
126.9, 126.0, 118.5 (d, J = 2.0 Hz), 89.6 (d, J = 218.0 Hz), 44.2, 25.8,
21.5. 19F NMR (377 MHz, CDCl3): δ −145.3 (1F, d, J = 48.0 Hz).
F
J. Org. Chem. XXXX, XXX, XXX−XXX