The Journal of Organic Chemistry
Article
+
(
1,4-Dibutoxy-3-chlorobutan-2-yl)(trifluoromethyl)sulfane (5c).
−43.0. HRMS (ESI) m/z: [M + Na] calcd for C H ClF N O SNa:
21
38
3
6
8
The product (39.1 mg, 58% yield) was purified with silica gel
649.2005; found: 649.2008.
chromatography (petroleum ether/EtOAc = 10:1) as a colorless oil.
Bis((9H-fluoren-9-yl)methyl)(15-chloro-14-((trifluoromethyl)thio)-
1
3
,5,7,10,17,20,23,26-octaoxaoctacosane-1,28-diyl)dicarbamate
H NMR (500 MHz, CDCl ) δ = 4.58 (t, J = 6.8 Hz, 1H), 3.82−3.78
3
(
5j). The product (163.1 mg, 80% yield) was purified with silica gel
(
3
m, 2H), 3.74−3.72 (m, 2H), 3.68 (dd, J = 9.9 Hz, 5.8 Hz, 1H), 3.51−
1
chromatography (MeOH/CH Cl = 30:1) as a colorless oil. H NMR
2
2
.46 (m, 4H), 1.57−1.54 (m, 4H), 1.37 (ddd, J = 14.7 Hz, 7.4 Hz, 4.4
13
(500 MHz, CDCl ) δ = 7.76 (d, J = 7.5 Hz, 4H), 7.60 (d, J = 7.1 Hz,
3
Hz, 4H), 0.92 (td, J = 7.4 Hz, 3.3 Hz, 6H). C NMR (126 MHz,
4
H), 7.39 (t, J = 7.4 Hz, 4H), 7.31 (t, J = 7.3 Hz, 4H), 5.41 (s, 2H),
4.60 (d, J = 5.8 Hz, 1H), 4.40 (d, J = 6.2 Hz, 4H), 4.22 (d, J = 6.1 Hz,
CDCl ) δ = 130.9 (q, J = 307.4 Hz), 71.4, 71.3, 70.7, 57.4, 46.5, 31.80,
3
19
3
(
1.77, 19.4, 19.3, 14.0.+ F NMR (471 MHz, CDCl ) δ −43.1. HRMS
3
2H), 3.87−3.72 (m, 5H), 3.69−3.53 (m, 28H), 3.39 (d, J = 4.4 Hz,
ESI) m/z: [M + H] calcd for C H ClF O SH: 337.1210; found:
13 24 3 2
13
4
(
7
3
H). C NMR (126 MHz, CDCl3) δ 161.5, 156.7, 144.1, 141.4, 130.9
3
37.1223.
q, J = 307.4 Hz), 127.8, 127.2, 125.2, 120.1, 72.0, 71.2, 70.84, 70.75,
1
1-Chloro-10-((trifluoromethyl)thio)-2,4,6,13,16,19-hexaoxaico-
0.67, 70.60, 70.56, 70.5, 70.4, 70.3, 70.2, 69.8, 66.7, 57.3, 47.4, 41.1,
sane (5d). The product (57.5 mg, 67% yield) was purified with silica
1
9
7.9. F NMR (471 MHz, CDCl ) δ −43.0. HRMS (ESI) m/z: [M +
3
gel chromatography (petroleum ether/EtOAc = 5:1) as a colorless oil.
+
1
Na] calcd for C51H62ClF N O12SNa: 1041.3556; found: 1041.3554.
3 2
H NMR (500 MHz, CDCl ) δ = 4.64 (t, J = 7.0 Hz, 1H), 3.86 (dd, J
3
Di-tert-butyl 2,2′-((2-Chloro-3-((trifluoromethyl)thio)butane-1,4-
diyl)bis(oxy))diacetate (5k). The product (66.1 mg, 73% yield) was
=
(
12.3 Hz, 6.1 Hz, 2H), 3.83−3.75 (m, 3H), 3.72−3.60 (m, 12H), 3.55
dd, J = 6.9 Hz, 4.2 Hz, 4H), 3.39 (s, 6H). 13C NMR (126 MHz,
CDCl ) δ 130.85 (q, J = 307.4 Hz), 72.0, 71.2, 70.9, 70.8, 70.70, 70.68,
purified with silica gel chromatography (petroleum ether/EtOAc =
1
3
5
:1) as a colorless oil. H NMR (500 MHz, CDCl ) δ = 4.72 (t, J = 6.9
19
3
7
0.60, 70.57, 59.1, 57.2, 46.4.+ F NMR (471 MHz, CDCl ) δ −43.1.
13
3
Hz, 1H), 4.08−3.97 (m, 4H), 3.93−3.86 (m, 5H), 1.48 (s, 18H).
NMR (126 MHz, CDCl ) δ 169.2, 169.1, 130.8 (q, J = 307.4 Hz),
2.13, 82.05, 72.2, 71.4, 69.3, 69.2, 57.3, 46.5, 28.2. F NMR (471
MHz, CDCl ) δ −43.1. HRMS (ESI) m/z: [M + Na] calcd for
C H ClF O SNa: 475.1139; found: 475.1141.
C
HRMS (ESI) m/z: [M + Na] calcd for C H ClF O SNa: 451.1139;
15
28
3
6
3
found: 451.1145.
1-Chloro-1,20-diphenyl-10-((trifluoromethyl)thio)-
,4,6,13,16,19-hexaoxaicosane (5e). The product (81.4 mg, 70%
19
8
1
+
3
2
1
7
28
3
6
yield) was purified with silica gel chromatography (petroleum ether/
(1-Chloro-1-phenylpropan-2-yl)(trifluoromethyl)sulfane (5l). The
1
EtOAc = 5:1) as a colorless oil. H NMR (500 MHz, CDCl ) δ = 7.34
3
product (25.4 mg, 50% yield) was purified with silica gel
(
d, J = 4.3 Hz, 8H), 7.30−7.27 (m, 2H), 4.63 (t, J = 7.0 Hz, 1H), 4.56
chromatography (petroleum ether) as a mixture of diasteroisomers
(
s, 4H), 3.87−3.81 (m, 2H), 3.81−3.77 (m, 3H), 3.70−3.62 (m, 16H).
and regioisomers that cannot be isolated. 1H NMR (500 MHz,
1
3
C NMR (126 MHz, CDCl ) δ 138.4, 130.9 (q, J = 307.4 Hz), 128.5,
3
CDCl ) δ = 7.44−7.33 (m, 5H). 5.14 (d, J = 4.7 Hz, 1H), 3.80 (qd, J =
3
1
5
27.9, 127.8, 73.4, 72.1, 71.3, 71.0, 70.87, 70.86, 70.7, 70.64, 69.59,
13
7
.0 Hz, 4.8 Hz, 1H). 1.50 (d, J = 7.0 Hz, 3H). C NMR (126 MHz,
19
7.4, 46.4. F NMR (471 MHz, CDCl ) δ −43.0. HRMS (ESI) m/z:
3
CDCl ) δ 136.8, 130.9 (q, J = 307.4 Hz), 129.0, 128.9, 128.8, 128.4,
3
+
[
M + Na] calcd for C H ClF O SNa: 603.1765; found: 603.1753.
19
27
36
3
6
127.5, 65.6, 48.0 (q, J = 1.2 Hz), 18.9. F NMR (376 MHz, CDCl ) δ
3
1
,16-Diazido-9-chloro-8-((trifluoromethyl)thio)-2,4,11,14-tet-
−
42.8. HRMS (EI) m/z: [M] calcd for C H ClF S: 254.0144;
10 10 3
raoxahexadecane (5f). The product (61.3 mg, 68% yield) was
found: 254.0140.
purified with silica gel chromatography (petroleum ether/EtOAc =
(
6-Chlorodecan-5-yl)(trifluoromethyl)sulfane (5m). The product
(41.4 mg, 75% yield) was purified with silica gel chromatography
petroleum ether) as the mixture of diasteroisomers that cannot be
1
5
:1) as a colorless oil. H NMR (500 MHz, CDCl ) δ = 4.64 (t, J = 6.9
3
Hz, 1H), 3.90−3.86 (m, 2H), 3.84−3.75 (m, 3H), 3.73−3.66 (m,
(
1
2H), 3.39 (d, J = 4.2 Hz, 4H). 13C NMR (126 MHz, CDCl ) δ 130.9
1
3
isolated. H NMR (400 MHz, CDCl ) δ = 4.20−4.14 (m, 1H), 3.30−
3
(
5
q, J = 307.4 Hz), 72.1, 71.3, 70.9, 70.8, 70.7, 70.6, 70.24, 70.22, 57.2,
3
.24 (m, 1H), 1.88−1.75 (m, 3H), 1.60 (dddd, J = 16.9 Hz, 15.0 Hz,
0.8, 46.4. 19F NMR (471 MHz, CDCl ) δ −42.9. HRMS (ESI) m/z:
3
6.6 Hz, 3.2 Hz, 3H), 1.46−1.26 (m, 6H), 0.93 (td, J = 7.2 Hz, 2.0 Hz,
+
1
3
22
3
6
4
6H). 13C NMR (126 MHz, CDCl ) δ 131.2 (q, J = 306.2 Hz), 65.3,
[
M + Na] calcd for C H ClF N O SNa: 473.0956; found:
3
19
4
73.0965.
5
2.1, 34.5, 32.5, 29.3, 29.1, 22.3, 22.2, 14.03, 14.00. F NMR (376
1
5-Chloro-14-((trifluoromethyl)thio)-3,5,7,10,17,20,23,26-octaox-
MHz, CDCl ) δ −42.9. HRMS (EI) m/z: [M] calcd for C H ClF S:
3
11 20
3
aoctacosane-1,28-diol (5g). The product (61.9 mg, 58% yield) was
2
76.0926; found: 276.0930.
purified with silica gel chromatography (petroleum ether/EtOAc =
(
2-Azido-2-(naphthalen-1-yl)ethyl)(trifluoromethyl)sulfane (6). A
solution of 3p (0.1 mmol, 29.1 mg) and sodium azide (0.15 mmol,
0.0 mg) in 1 mL of DMF was heated to 80 °C, and the mixture was
1
1
:1) as a colorless oil. H NMR (500 MHz, CDCl ) δ = 4.63 (t, J = 6.7
3
Hz, 1H), 3.87−3.82 (m, 2H), 3.82−3.78 (m, 3H), 3.77−3.55 (m, 4H),
1
1
3
3
3
4
.72−3.62 (m, 28H). C NMR (126 MHz, CDCl ) δ 130.9 (q, J =
3
stirred for 8 h until 3p was completely transformed. The mixture was
cooled and concentrated in vacuo. The residue was directly subjected
07.4 Hz), 72.1, 71.5, 71.2, 70.9, 70.8, 70.7, 70.62, 70.59, 57.3, 46.4,
2.8. F NMR (471 MHz, CDCl ) δ −43.0. HRMS (ESI) m/z: [M +
K] calcd for C H ClF KO S: 615.1614; found: 615.1350.
19
3
to silica gel flash chromatography (petroleum ether) to afford the
+
1
21
40
3
10
desired product 6 (28.2 mg, 95%). H NMR (500 MHz, CDCl ) δ =
3
1
7-Chloro-1,32-diphenyl-16-((trifluoromethyl)thio)-
8
(
.03 (d, J = 8.4 Hz, 1H), 7.90 (dd, J = 20.3 Hz, 8.1 Hz, 2H), 7.57−7.50
2
,5,7,9,12,19,22,25,28,31-decaoxadotriacontane (5h). The product
m, 4H), 5.51 (dd, J = 9.5 Hz, 4.3 Hz, 1H), 3.41 (dd, J = 14.3 Hz, 4.4
(
(
109.1 mg, 72% yield) was purified with silica gel chromatography
petroleum ether/EtOAc = 1:1) as a colorless oil. H NMR (500
13
Hz, 1H), 3.26 (dd, J = 14.1 Hz, 9.7 Hz, 1H). C NMR (126 MHz,
1
CDCl ) δ 134.2, 133.09, 131.10 (q, J = 307.4 Hz), 130.4, 129.9, 129.5,
3
19
MHz, CDCl ) δ = 7.34 (d, J = 4.3 Hz, 8H), 7.28−7.26 (m, 2H), 4.62
3
127.3, 126.4, 125.5, 124.8, 122.3, 62.9, 35.8. F NMR (471 MHz,
(
(
1
7
t, J = 7.0 Hz, 1H), 4.56 (s, 4H), 3.84 (t, J = 8.9 Hz, 2H), 3.81−3.74
CDCl ) δ −44.0. HRMS (EI) m/z: [M] calcd for C H F N S:
3
13 10
3
3
13
m, 3H), 3.68−3.62 (m, 32H). C NMR (126 MHz, CDCl ) δ 138.3,
3
297.0548; found: 297.0551.
30.8 (q, J = 307.4 Hz), 128.4, 127.8, 127.6, 73.3, 72.0, 71.2, 70.8,
(2-(Naphthalen-1-yl)-2-thiocyanatoethyl)(trifluoromethyl)-
sulfane (7). A solution of 3p (0.1 mmol, 29.1 mg) and KSCN (0.15
mmol, 14.4 mg) in 1 mL of DMF was heated to 80 °C, and the
mixture was stirred for 8 h until 3p was completely transformed. The
mixture was cooled and concentrated in vacuo. The residue was
directly subjected to silica gel flash chromatography (petroleum ether/
0.71, 70.69, 70.53, 70.51, 69.5, 57.2, 46.4. 19F NMR (471 MHz,
+
CDCl ) δ −43.0. HRMS (ESI) m/z: [M + Na] calcd for
C H ClF O SNa: 779.2814; found: 779.2818.
3
3
5
52
3
10
1
,28-Diazido-15-chloro-14-((trifluoromethyl)thio)-
3
,5,7,10,17,20,23,26-octaoxaoctacosane (5i). The product (84.0 mg,
1
6
7% yield) was purified with silica gel chromatography (petroleum
AcOEt = 30:1) to afford the desired product 7 (28.2 mg, 90%). H
1
ether/EtOAc = 1:1) as a colorless oil. H NMR (500 MHz, CDCl ) δ
NMR (400 MHz, CDCl ) δ = 8.00 (d, J = 8.5 Hz, 1H), 7.96−7.92 (m,
3
3
=
4.63 (t, J = 6.6 Hz, 1H), 3.87−3.84 (m, 2H), 3.81−3.77 (m, 3H),
2H), 7.68−7.64 (m, 1H), 7.60 (dd, J = 11.1 Hz, 3.9 Hz, 1H), 7.56−
13
13
3
.67−3.64 (m, 28H), 3.40−3.38 (m, 4H). C NMR (126 MHz,
7.51 (m, 2H), 5.41 (t, J = 7.9 Hz, 1H), 3.91 (d, J = 7.8 Hz, 2H).
C
CDCl ) δ 130.9 (q, J = 307.4 Hz), 72.0, 71.2, 70.9, 70.80, 70.78, 70.75,
NMR (101 MHz, CDCl ) δ 134.3, 130.9, 130.5 (q, J = 140.39 Hz),
3
3
19
19
7
0.58, 70.55, 70.1, 57.3, 50.8, 46.4. F NMR (471 MHz, CDCl ) δ
129.7, 127.7, 126.8, 125.4, 121.9, 110.4, 34.7. F NMR (471 MHz,
3
H
J. Org. Chem. XXXX, XXX, XXX−XXX