The Journal of Organic Chemistry
Article
(2-(4′-(tert-Butyl)-[1,1′-biphenyl]-2-yl)-1,1-difluoroethyl)(octyl)-
sulfane (5s). Following general procedure A, compound 1s (0.136 g,
0.500 mmol) was reacted with 1-octanethiol (0.130 mL, 0.750 mmol)
in the presence of pyridine (0.01 mL, 0.10 mmol), LiOTf (0.008 g,
0.050 mmol), and 2-methoxyethanol (0.080 mL, 1.00 mmol) in 1.5 mL
of o-xylene using a heating mantle at 110 °C for 24 h. The material was
worked up according to the general procedure and purified by normal-
phase flash chromatography using EtOAc and hexanes (1:10) to furnish
0.144 g (69% yield) of desired product 5s as a colorless oil. 1H NMR
(500 MHz, chloroform-d): δ 7.58−7.51 (m, 4H), 7.48 (d, J = 8.3 Hz,
2H), 7.40 (t, J = 7.6 Hz, 1H), 7.26 (d, J = 9.0 Hz, 1H), 3.46 (t, J = 14.5
Hz, 2H), 2.81 (t, J = 7.5 Hz, 2H), 1.62 (p, J = 7.4 Hz, 2H), 1.37 (s, 9H),
1.36 (s, 2H), 1.31−1.23 (m, 9H), 0.88 (t, J = 6.9 Hz, 3H). 13C{1H}
EtOAc and hexanes (1:10) to furnish 0.033 g (22% yield) of desired
product 5v as a colorless oil. 1H NMR (500 MHz, chloroform-d): δ 7.16
(d, J = 8.3 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 4.89 (s, 1H), 3.32 (t, J =
14.5 Hz, 2H), 2.83−2.74 (t, J = 7.5 Hz, 2H), 1.61 (p, J = 7.4 Hz, 2H),
1.42−1.18 (m, 10H), 0.88 (t, J = 6.9 Hz, 3H). 13C{1H} NMR (126
MHz, chloroform-d): δ 155.1, 131.8, 130.3 (t, 1JC−F = 277.7 Hz), 124.5
2
(t, 3JC−F = 4.0 Hz), 115.3, 44.7 (t, 2JC−F = 24.8 Hz), 31.8, 29.8, 29.1,
2
2
29.0, 28.8, 27.9 (t, 3JC−F = 3.6 Hz), 22.6, 14.1. 19F NMR (471 MHz,
2
chloroform-d): δ −72.83 (t, J = 14.6 Hz). IR (film): 3381, 2953, 2920,
2875, 2851, 1516, 1453, 1257, 1153, 998, 785, 766, 749, 707 cm−1.
HRMS (ESI)− m/z: calcd C16H23F2OS [M − H]−, 301.1432; found,
301.1436.
NMR (126 MHz, chloroform-d): δ 150.3, 141.1, 132.5, 130.0 (t, 1JC−F
(1,1-Difluoro-2-(4-(methoxymethoxy)phenyl)ethyl)(octyl)sulfane
(5w). Following general procedure A, compound 1w (0.100 g, 0.500
mmol) was reacted with 1-octanethiol (0.130 mL, 0.750 mmol) in the
presence of pyridine (0.01 mL, 0.10 mmol), LiOTf (0.008 g, 0.050
mmol), and 2-methoxyethanol (0.080 mL, 1.00 mmol) in 1.5 mL of o-
xylene using a heating mantle at 110 °C for 24 h. The material was
worked up according to the general procedure and purified by normal-
phase flash chromatography using EtOAc and hexanes (1:10) to furnish
0.086 g (50% yield) of desired product 6w as a colorless oil. 1H NMR
(500 MHz, chloroform-d): δ 7.24 (d, J = 8.5 Hz, 2H), 7.03 (d, J = 8.6
Hz, 2H), 5.20 (s, 2H), 3.51 (s, 3H), 3.36 (t, J = 14.6 Hz, 3H), 2.83 (t, J =
7.5 Hz, 3H), 1.65 (p, J = 14.8, 7.3 Hz, 2H), 1.45−1.18 (m, 11H), 0.91
(t, J = 6.9 Hz, 3H). 13C{1H} NMR (126 MHz, chloroform-d): δ 156.9,
2
2
= 277.4 Hz), 129.2, 129.0, 126.8, 126.3, 125.6, 45.7 (t, JC−F = 24.5
2
Hz), 31.7, 31.3, 29.7, 29.0, 28.9, 28.7, 27.9, 22.5, 14.0. 19F NMR (471
MHz, chloroform-d): δ −73.85 (t, J = 14.5 Hz). IR (film): 2957, 2926,
2855, 1728, 1483, 1267, 1191, 1152, 1008, 835, 766, 750, 703 cm−1
.
HRMS (APCI)+ m/z: calcd C26H36F2S [M + H]+, 419.2586; found,
419.2586.
Ethyl (E)-3-(3-(2,2-Difluoro-2-(octylthio)ethyl)phenyl)acrylate
(5t). Following general procedure A, compound 1t (0.119 g, 0.500
mmol) was reacted with 1-octanethiol (0.130 mL, 0.750 mmol) in the
presence of pyridine (0.01 mL, 0.10 mmol), LiOTf (0.008 g, 0.050
mmol), and 2-methoxyethanol (0.080 mL, 1.00 mmol) in 1.5 mL of o-
xylene using a heating mantle at 110 °C for 24 h. The material was
worked up according to the general procedure and purified by normal-
phase flash chromatography using EtOAc and hexanes (1:10) to furnish
0.146 g (76% yield) of desired product 5t as a colorless oil. 1H NMR
(500 MHz, chloroform-d): δ 7.68 (d, J = 16.0 Hz, 1H), 7.48 (d, J = 7.6
Hz, 1H), 7.45 (s, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H),
6.45 (d, J = 16.0 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.40 (t, J = 14.4 Hz,
2H), 2.80 (t, J = 7.5 Hz, 2H), 1.61 (p, J = 14.0, 6.9 Hz, 2H), 1.35 (m,
2H), 1.34 (t, J = 7.1 Hz, 3H), 1.27 (m, 8H), 0.87 (t, J = 6.9 Hz, 3H).
13C{1H} NMR (126 MHz, chloroform-d): δ 166.9, 144.2, 134.7, 133.0,
1
3
131.6, 130.2 (t, JC−F = 278.5 Hz), 125.5 (t, JC−F = 4.3 Hz), 116.1,
2
2
94.4, 56.0, 44.8 (t, 2JC−F = 24.8 Hz), 31.8, 29.8, 29.1, 29.1, 28.9, 27.9 (t,
3JC−F = 3.6 Hz), 22.7, 14.1. 19F NMR (471 MHz, chloroform-d)
2
2
−72.80 (t, J = 14.6 Hz). IR (film): 2961, 2926, 2855, 151, 1236, 1151,
1079, 1003, 779, 722, 652 cm−1. HRMS (APCI)+ m/z: calcd
C18H29F2O2S [M + H]+, 346.1773; found, 346.1780.
(2-(4-(Benzyloxy)phenyl)-1,1-difluoroethyl)(octyl)sulfane (5x).
Following general procedure A, compound 1x (0.123 g, 0.500 mmol)
was reacted with 1-octanethiol (0.130 mL, 0.750 mmol) in the presence
of pyridine (0.01 mL, 0.10 mmol), LiOTf (0.008 g, 0.050 mmol), and 2-
methoxyethanol (0.080 mL, 1.00 mmol) in 1.5 mL of o-xylene using a
heating mantle at 110 °C for 24 h. The material was worked up
according to the general procedure and purified by normal-phase flash
chromatography using EtOAc and hexanes (1:10) to furnish 0.171 g
132.3, 130.2, 129.9 (t, 1JC−F = 276.8 Hz), 128.9, 127.3, 118.7, 60.5, 46.4
2
2
3
(t, JC−F = 24.9 Hz), 31.8, 29.8, 29.1, 29.0, 28.8, 28.0 (t, JC−F = 3.5
2
2
Hz), 22.6, 14.3, 14.1. 19F NMR (471 MHz, chloroform-d): δ −73.03 (t,
J = 14.4 Hz). IR (film): 2925, 2854, 1712, 1639, 1309, 1177, 1161,
1129, 992, 864 cm−1. HRMS (APCI)+ m/z: calcd C21H30F2O2S [M +
H]+, 385.2007; found, 385.1962.
1
(87% yield) of desired product 5x as a colorless oil. H NMR (500
4-(2,2-Difluoro-2-(octylthio)ethyl)-N,N-diethylbenzamide (5u).
Following general procedure A, compound 1t (0.120 g, 0.500 mmol)
was reacted with 1-octanethiol (0.130 mL, 0.750 mmol) in the presence
of pyridine (0.01 mL, 0.10 mmol), LiOTf (0.008 g, 0.050 mmol), and 2-
methoxyethanol (0.080 mL, 1.00 mmol) in 1.5 mL of o-xylene using a
heating mantle at 110 °C for 24 h. The material was worked up
according to the general procedure and purified by normal-phase flash
chromatography using EtOAc and hexanes (1:5) to furnish 0.121 g
(63% yield) of desired product 5t as a colorless oil. 1H NMR (500 MHz,
chloroform-d): δ 7.27 (d, J = 15.0 Hz, 2H), 7.25 (d, J = 15.0 Hz, 2H),
3.48 (s, 2H), 3.33 (t, J = 14.5 Hz, 2H), 3.20 (s, 2H), 2.74 (t, J = 7.5 Hz,
2H), 1.55 (p, J = 7.5 Hz, 2H), 1.31−1.25 (m, 2H), 1.19 (s, 8H), 1.05 (s,
6H), 0.80 (t, J = 6.8 Hz, 3H). 13C{1H} NMR(126 MHz, chloroform-d):
δ 170.9, 136.5, 133.2 (t, 3JC−F = 3.6 Hz), 130.5, 129.8 (t, 1JC−F = 277.3
MHz, chloroform-d): δ 7.43 (d, J = 7.3 Hz, 2H), 7.39 (t, J = 7.5 Hz, 2H),
7.33 (t, J = 7.2 Hz, 1H), 7.21 (d, J = 8.5 Hz, 2H), 6.95 (d, J = 8.5 Hz,
2H), 5.06 (s, 2H), 3.33 (t, J = 14.5 Hz, 2H), 2.80 (t, J = 7.5 Hz, 2H),
1.62 (p, J = 7.4 Hz, 2H), 1.39−1.32 (m, 2H), 1.32−1.22 (m, 8H), 0.88
(t, J = 6.9 Hz, 3H). 13C{1H} NMR (126 MHz, chloroform-d): δ 158.4,
136.9, 131.5, 130.3 (t, 1JC−F = 277.1 Hz), 128.6, 127.9, 127.5, 124.5 (t,
2
3JC−F = 4.0 Hz), 114.7, 70.0, 45.7 (t, 2JC−F = 24.7 Hz), 31.7, 29.8, 29.1,
2
2
29.0, 28.8, 27.9 (t, 3JC−F = 3.6 Hz), 22.6, 14.0. 19F NMR (471 MHz,
2
chloroform-d): δ −73.31 (t, J = 14.5 Hz). IR (film): 2925, 2854, 1512,
1245, 1220, 1008, 988, 869, 764, 739, 696 cm−1. HRMS (APCI)+ m/z:
calcd C23H31F2OS [M + H]+, 393.2064; found, 393.2059.
4-(2,2-Difluoro-2-(octylthio)ethyl)dibenzo[b,d]thiophene (5y).
Following general procedure A, compound 1y (0.123 g, 0.500 mmol)
was reacted with 1-octanethiol (0.130 mL, 0.750 mmol) in the presence
of pyridine (0.01 mL, 0.10 mmol), LiOTf (0.008 g, 0.050 mmol), and 2-
methoxyethanol (0.080 mL, 1.00 mmol) in 1.5 mL of o-xylene using a
heating mantle at 110 °C for 24 h. The material was worked up
according to the general procedure and purified by normal-phase flash
chromatography using EtOAc and hexanes (1:10) to furnish 0.143 g
2
2
Hz), 126.4, 45.4 (t, 2JC−F = 25.0 Hz), 43.3, 39.2, 31.7, 29.7, 29.1, 29.0,
2
3
28.8, 27.9 (t, JC−F = 3.5 Hz), 22.6, 14.1. 19F NMR (471 MHz,
2
chloroform-d): δ −73.11 (t, J = 14.5 Hz). IR (film): 2925, 2854, 1630,
1457, 1425, 1285, 1219, 1094, 1011, 990, 784, 744 cm−1. HRMS
(APCI)+ m/z: calcd C21H33F2NOSNa [M + Na]+, 408.2149; found,
408.2137.
4-(2,2-Difluoro-2-(octylthio)ethyl)phenol (5v). Following general
procedure A, compound 1v (0.078 g, 0.500 mmol) was reacted with 1-
octanethiol (0.130 mL, 0.750 mmol) in the presence of pyridine (0.01
mL, 0.10 mmol), LiOTf (0.008 g, 0.050 mmol), and 2-methoxyethanol
(0.080 mL, 1.00 mmol) in 1.5 mL of o-xylene using a heating mantle at
110 °C for 24 h. The material was worked up according to the general
procedure and purified by normal-phase flash chromatography using
1
(72% yield) of desired product 5y as a colorless oil. H NMR (500
MHz, chloroform-d): δ 8.18−8.09 (m, 2H), 7.91−7.83 (m, 1H), 7.51−
7.43 (m, 4H), 3.71 (t, J = 14.4 Hz, 2H), 2.84 (t, J = 7.5 Hz, 2H), 1.63 (p,
J = 7.4 Hz, 2H), 1.39−1.32 (m, 2H), 1.32−1.22 (m, 8H), 0.89 (t, J = 7.0
Hz, 3H). 13C{1H} NMR (126 MHz, chloroform-d): δ 141.0, 139.0,
136.1, 135.9, 131.4 (t, 1JC−F = 278.6 Hz), 129.0, 126.9, 126.8, 124.7,
2
124.5, 122.7, 121.7, 121.1, 45.8 (t, 2JC−F = 25.8 Hz), 31.7, 29.7, 29.1,
2
2307
J. Org. Chem. 2021, 86, 2297−2311