Organic & Biomolecular Chemistry
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1H NMR (500 MHz, CDCl3): δ 7.92 (s, 1H, Ar-H), 7.63 (d, 2H, Ar-H, J = 7.8 Hz), 7.41 (t, 2H, Ar-H, J = 7.6 Hz), 7.31 (t, 1H,
Ar-H, J = 9.3 Hz), 7.36–7.32 (m, 4H, Ar-H), 7.28–7.25 (m, 1H, Ar-H, J = 7.4 Hz), 7.04 (d, 2H, Ar-H, J = 9.2 Hz), 3.87 (s, 3H,
Ar-H), 7.02 (d, 2H, Ar-H, J = 8.3 Hz), 3.87 (s, 3H, CH3), 3.57 (s, CH3), 2.57 (d, 3H, CH3, J = 3.7 Hz). 13C NMR (125 MHz,
2H, CH2), 3.00 (t, 2H, CH2, J = 4.9 Hz), 2.59–2.54 (m, 6H, CDCl3): δ 160.2, four resonances at 145.8, 143.9, 143.7, 143.4
3CH2). 13C NMR (125 MHz, CDCl3): δ 160.2, four resonances at (two doublets for 2C), 138.6, 130.3, 128.5 (d, 2C, JCF = 4.1 Hz),
143.4, 143.2, 142.9, 141.6 (two doublets for 2C), 138.4, 130.4, 128.4 (2C), 127.5, 122.4 (2C), 120.5, 118.0 (d, JCF = 12.4 Hz),
129.4 (2C), 128.4 (2C), 127.3, 122.4 (2C), 119.9, 118.9 (d, JCF
=
115.1 (2C), 55.9, 17.5 (d, JCF = 3.7 Hz). 19F NMR (282 MHz,
15.1 Hz), 115.0 (2C), 63.1, 55.8, 54.3, 53.8, 27.0 (d, JCF = 4.6 CDCl3): δ −116.57 (s). Minor isomer: Rf (20% EtOAc in hexanes)
1
Hz), 26.2 (d, JCF = 7.3 Hz). 19F NMR (282 MHz, CDCl3): = 0.22. H NMR (500 MHz, CDCl3): δ 7.40–7.32 (m, 5H, Ar-H),
δ −121.99 (s). HRMS (ESI) calcd for C22H24FN4O [M + H]+ 7.27–7.25 (m, 2H, Ar-H), 6.94 (d, 2H, Ar-H, J = 9.2 Hz), 6.91 (s,
379.1929, found 379.1924.
1-Benzyl-4-{fluoro[1-(3-phenylpropyl)-1H-1,2,3-triazol-4-yl]-
methylene}piperidine (27).
1H, Ar-H), 3.83 (s, 3H, CH3), 2.21 (d, 3H, CH3, J = 3.7 Hz).
13C NMR (125 MHz, CDCl3): δ 160.1, 145.9 (d, JCF = 240.8 Hz),
141.5 (d, JCF = 35.0 Hz), 139.4 (d, JCF = 7.3 Hz), 130.2, 129.2
(2C), 128.8 (d, 2C, JCF = 2.7 Hz), 128.1, 122.3 (2C), 120.6 (d,
JCF = 5.1 Hz), 119.7 (d, JCF = 19.2 Hz), 114.9 (2C), 55.8, 17.8 (d,
JCF = 6.0 Hz). 19F NMR (282 MHz, CDCl3): δ −116.46 (s). HRMS
(ESI) calcd for C18H17FN3O [M + H]+ 310.1350, found 310.1353.
(E/Z)-4-(1-Fluoro-2-phenylprop-1-en-1-yl)-1-(3-phenylpropyl)-
1H-1,2,3-triazole (29).
Prepared from 1-benzylpiperidin-4-one (20.0 mg, 0.11 mmol),
sulfone 9 (52.8 mg, 0.13 mmol, 1.2 molar equiv.), and LHMDS
(0.264 mL, 0.264 mmol, 2.4 molar equiv.), in THF (1.3 mL), in
a reaction time of 2 h. Chromatography was performed using
20% EtOAc in hexanes to obtain compound 27 as an off-white
semi-solid (25.0 mg, 58%). Rf (20% EtOAc in hexanes) = 0.23.
1H NMR (500 MHz, CDCl3): δ 7.53 (s, 1H, Ar-H), 7.36–7.25 (m,
7H, Ar-H), 7.22 (t, 1H, Ar-H, J = 7.4 Hz), 7.18 (d, 2H, Ar-H, J =
7.8 Hz), 4.36 (t, 2H, CH2, J = 6.9 Hz), 3.55 (s, 2H, CH2), 2.94 (t,
2H, CH2, J = 4.8 Hz), 2.66 (t, 2H, CH2, J = 7.6 Hz), 2.56–2.52 (m,
6H), 2.26 (quint, 2H, CH2, J = 7.2 Hz). 13C NMR (125 MHz,
CDCl3): δ 142.8 (d, JCF = 227.9 Hz), 142.7 (d, JCF = 40.3 Hz),
140.3, 138.8, 129.4 (2C), 128.9 (2C), 128.7 (2C), 128.4 (2C),
127.2, 126.7, 121.6, 118.5 (d, JCF = 14.8 Hz), 63.2, 54.4, 53.9,
Prepared from acetophenone (20.0 mg, 0.17 mmol), sulfone 9
(83.2 mg, 0.20 mmol, 1.2 molar equiv.), and LHMDS
(0.410 mL, 0.410 mmol, 2.4 molar equiv.), in THF (2.0 mL), in
a reaction time of 30 min. The major/minor isomer ratio was
determined to be 80 : 20. Chromatography was performed
using 20% EtOAc in hexanes to obtain the major isomer Z-29
as a white solid (33.0 mg, 60%), and the minor isomer E-29 as
a white solid (9.2 mg, 17%). Analysis of the major isomer by
X-ray diffraction showed Z stereochemistry of the alkene (crys-
tals were obtained by slow evaporation from a solution in
methylene chloride).
49.7, 32.8, 31.7, 27.2 (d, JCF = 4.6 Hz), 26.3 (d, JCF = 7.8 Hz). 19
F
NMR (282 MHz, CDCl3): δ −121.52 (s). HRMS (ESI) calcd for
C24H28FN4 [M + H]+ 391.2293, found 391.2298.
(E/Z)-4-(1-Fluoro-2-phenylprop-1-en-1-yl)-1-(4-methoxyphenyl)-
1H-1,2,3-triazole (28).
Major isomer Z-29.
1
Rf (20% EtOAc in hexanes) = 0.20. H NMR (500 MHz, CDCl3):
Prepared from acetophenone (20.0 mg, 0.17 mmol), sulfone 4 δ 7.65 (s, 1H, Ar-H), 7.48 (d, 2H, Ar-H, J = 7.4 Hz), 7.39 (t, 2H,
(80.9 mg, 0.20 mmol, 1.2 molar equiv.), and LHMDS Ar-H, J = 7.6 Hz), 7.33–7.28 (m, 3H, Ar-H), 7.24–7.19 (m, 3H,
(0.410 mL, 0.410 mmol, 2.4 molar equiv.), in THF (2.0 mL), in Ar-H), 4.40 (t, 2H, CH2, J = 7.1 Hz), 2.69 (t, 2H, CH2, J = 7.4 Hz),
a reaction time of 15 min. The major/minor isomer ratio was 2.52 (d, 3H, CH3, J = 3.2 Hz), 2.30 (quint, 2H, CH2, J = 7.2 Hz).
determined to be 72 : 28. Chromatography was performed 13C NMR (125 MHz, CDCl3): δ 145.1 (d, JCF = 233.9 Hz), 143.0
using 20% EtOAc in hexanes and compound E/Z-28 was (d, JCF = 39.4 Hz), 140.2, 138.6, 128.9 (2C), 128.6 (2C), 128.4 (d,
obtained as a white solid (33.0 mg, 64%). Major isomer: Rf 2C, JCF = 4.1 Hz), 128.3 (2C), 127.5, 126.6, 122.3 (d, JCF = 2.3
(20% EtOAc in hexanes) = 0.27. 1H NMR (500 MHz, CDCl3): Hz), 117.4 (d, JCF = 13.3 Hz), 49.7, 32.6, 31.8, 17.4 (d, JCF = 4.1
δ 8.04 (s, 1H, Ar-H), 7.67 (d, 2H, Ar-H, J = 8.8 Hz), 7.50 (d, 2H, Hz). 19F NMR (282 MHz, CDCl3): δ −116.33 (s).
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem., 2015, 13, 1536–1549 | 1547