Page 7 of 12
The Journal of Organic Chemistry
(0.34 g, 1.00 mmol) and (thienꢀ3ꢀylmethyl)zinc(II) chloride
77%). TLC, Rf 0.45 (3:2 EtOAc: pentane); m.p. 128ꢀ129
°C; IR (diamondꢀATR): νmax/cmꢀ1 3386, 3328, 3099, 2949,
2916, 2853, 1731, 1601, 1493, 1481, 1452, 1431, 1327,
1127, 1057, 1028, 1011, 992, 942, 855, 828, 786, 757, 729,
(11) (2.30 mL, 0.64 M THF solution 1.50 mmol) to yield
(12d) as colorless plates (0.28 g, 0.92 mmol, 92%) after
column chromatography (3:2 EtOAc:pentane). Rf (3:2
EtOAc: pentane) 0.46; m.p. 109ꢀ111 °C; IR (diamondꢀ
ATR): νmax/cmꢀ1 3387, 3324, 3100, 2928, 2834, 1609, 1580,
1508, 1481, 1461, 1432, 1327, 1301, 1247, 1174, 1127,
1062, 1033, 1010, 990, 942, 879, 829, 783, 763, 722, 691,
1
2
3
1
4
5
6
7
8
9
700, 632, 583, 493, 434; H NMR (500.1 MHz, CDCl3) δ
7.32 – 7.27 (m, 3H), 7.24 – 7.19 (m, 3H), 6.98 – 6.95 (m,
2H), 4.28 (d, J = 5.3 Hz, 2H), 4.22 (d, J = 5.3 Hz, 2H), 3.71
(s, 2H), 3.70 (s, 2H), 1.25 (t, J = 5.3 Hz, 1H), 1.20 (t, J =
5.3 Hz, 1H); 13C{1H}NMR (125.6 MHz, CDCl3) δ 140.5,
139.9, 136.7, 128.9 (2C), 128.7 (2C), 128.3, 126.5, 126.2,
121.2, 62.2, 61.9, 35.8, 30.8; HRMS (ESIꢀTOF) m/z: [M +
Na]+ Calcd for C16H18NaO2S 297.0920, Found 297.0918.
1
625, 513; H NMR (500.1 MHz, CDCl3) δ 7.30 – 7.24 (m,
1H), 7.11 (d, J = 8.6 Hz, 2H), 6.94 (m, 2H), 6.84 (d, J = 8.6
Hz, 2H), 4.27 (s, 2H), 4.19 (s, 2H), 3.78 (s, 3H), 3.68 (s,
2H), 3.63 (s, 2H), overlapped by 1.76 (m, 2H);
13C{1H}NMR (125.8 MHz CDCl3) δ 158.3, 140.4, 137.1,
136.3, 131.6, 129.6 (2 C), 128.3, 126.2, 121.2, 114.3 (2 C),
62.1, 61.8, 55.4, 35.0, 30.9; HRMS (ESIꢀTOF) m/z: [M +
Na]+ Calcd for C17H20NaO3S 327.1025; Found 327.1024.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(E)ꢀ2ꢀ(4ꢀmethylbenzyl)ꢀ3ꢀ(thienꢀ3ꢀylmethyl)butꢀ2ꢀeneꢀ1,4ꢀ
diol (12b): Prepared by a method analogous to (12a) using
(Z)ꢀ2ꢀiodoꢀ3ꢀ(4ꢀmethylbenzyl)butꢀ2ꢀeneꢀ1,4ꢀdiol
(1.00 g, 3.71 mmol) and (thienꢀ3ꢀylmethyl)zinc(II) chloride
(11) (7.71 mL, 0.64 M THF solution, 4.71 mmol) to yield
(12b) as a colorless powder (0.75 g, 2.60 mmol, 83%) after
column chromatography (3:2 EtOAc:pentane). TLC: Rf
(ethyl acetate) 0.66. Colorless thin needles from hot aceꢀ
(10a)
Homocoupling of (E)ꢀ2,3ꢀdiiodobutꢀ2ꢀeneꢀ1,4ꢀdiol (20) to
the symmetrical diol (E)ꢀ2,3ꢀbis(thienꢀ3ꢀylmethyl)butꢀ2ꢀ
eneꢀ1,4ꢀdiol (21): In dry Schlenk tube LiCl (0.12 g, 2.94
mmol, 2.4 equiv) was heated using heat gun for (5 min.)
under high vacuum at >200 °C until free flowing, and then
cooled under a argon atmosphere to 25 °C. The diol (20)
(0.50 g, 1.47 mmol) was added followed by tricyclohexꢀ
ylphosphine (12.3 mg, 44 ꢁmol, 3 mol%) and the solid
mixture held under high vacuum for 30 min. Under an atꢀ
mosphere of argon THF (5.6 mL) was added and the colorꢀ
less solution was heated to 50 °C. Solid Pd(OAc)2 (11.6
mg, 55 ꢁmol, 3.5 mol%) was added to the heated mixture
to form a dark chocolate colored mixture. Promptly (thienꢀ
2ꢀylmethyl)zinc(II) chloride (11) (0.42 M in THF, 8.8 mL,
3.7 mmol, 2.5 equiv) was added in one portion forming a
clear yellow mixture. After 25 min the reaction became
dark black and TLC analysis (3:2 EtOAc:pentane) showed
the starting material was >90% consumed and new spots
appeared due to (21) and HOCH2C≡CCH2OH. The mixture
cooled to room temperature, quenched with saturated amꢀ
monium chloride solution (4 mL) and extracted with
EtOAc (3 × 10 ml). The organic layer was washed with
immediately with saturated NaHCO3 (3 × 4 mL), dried
(Na2SO4), filtered and concentrated giving a crude yellow
solid. Purification by column chromatography (3:2 EtOAc:
pentane) gave (21) as a colorless solid (0.13 g, 0.46 mmol,
31%). [Important note: in our experience (21) is rather acid
sensitive. Concentration of EtOAc its solutions containing
even traces of residual NH4OAc (pKa 4.8) led to decompoꢀ
sition; washing with hydrogen carbonate avoids this]. TLC
(3:2 EtOAc: pentane) Rf 0.35; m.p. 117ꢀ118 °C; IR (diaꢀ
mondꢀATR): νmax/cmꢀ1 3373, 3312, 3099, 2943, 2901,
2850, 1533, 1481, 1433, 1411, 1383, 1337, 1246, 1202,
1127, 1069, 992, 945, 878, 856, 829, 777, 709, 686, 636,
572; 1H NMR (500.1 MHz, CDCl3) δ 7.28 (dd, J = 4.8, 3.0
Hz, 2H), 7.01 – 6.92 (m, 4H), 4.26 (d, J = 5.5 Hz, 4H), 3.68
(s, 4H), 1.24 (t, J = 5.5 Hz, 2H); 13C{1H}NMR (125.6 MHz
CDCl3) δ 140.4, 136.5, 128.3, 126.3, 121.2, 62.1, 30.8.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd. for C14H16O2S2
303.0484; Found 303.0476.
o
tonitrile on cooling to ambient, then 4 C with m.p. 127ꢀ
129 °C; IR (diamondꢀATR): νmax/cmꢀ1 3381, 3310, 3101,
2950, 2917, 1509, 1482, 1433, 1383, 1331, 1298, 1205,
1128, 1065, 1011, 992, 942, 926, 880, 855, 829, 806, 783,
1
760, 722, 699, 627, 523, 491; H NMR (500.1 MHz,
CDCl3) δ 7.28 – 7.26 (m, 1H), δ 7.12 – 7.08 (m, 4H), 7.97
– 6.94 (m, 2H), 4.27 (s, 2H), 4.21 (s, 2H), 3.68 (s, 2H),
3.66 (s, 2H), 2.32 (s, 3H), 1.43 (broad, 2H); 13C{1H}NMR
(125.8 MHz CDCl3) δ 140.5, 136.9, 136.6, 136.4, 136.0,
129.5, 128.5, 128.3, 126.2, 121.2, 62.2, 61.9, 35.4, 30.8,
21.1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C17H19NaO2S 311.1076, Found 311.1075. Anal: calcd for
C17H20O2S C, 70.80; H, 6.99; Found C, 70.61; H, 6.94%.
(E)ꢀ2ꢀ(4ꢀisopropylbenzyl)ꢀ3ꢀ(thienꢀ3ꢀylmethyl)butꢀ2ꢀeneꢀ
1,4ꢀdiol (12c): Prepared by a method analogous to (12a)
using (Z)ꢀ2ꢀiodoꢀ3ꢀ(4ꢀisopropylbenzyl)butꢀ2ꢀeneꢀ1,4ꢀdiol
(10c) (1.50 g, 4.33 mmol) and (thienꢀ3ꢀylmethyl)zinc(II)
chloride (10.0 mL 6.70 mmol, 0.67 M THF solution). To
yield (12c) as a colorless powder (1.10 g, 4.48 mmol, 80%)
after column chromatography (3:2 EtOAc:pentane). TLC;
Rf (3:2 EtOAc:pentane) 0.41; IR (diamondꢀATR): νmax/cmꢀ
1
3389, 3334, 3103, 2956, 2889, 2869, 1511, 1481, 1467,
1432, 1415, 1382, 1333, 1296, 1128, 1064, 1009, 990, 942,
928, 880, 856, 837, 784, 719, 700, 623, 550; H NMR
1
(500.1 MHz, CDCl3) δ 7.28 (dd, J = 4.8, 3.0 Hz, 1H), 7.17
(d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.97 (m, 2H),
4.27 (d, J = 5.4 Hz, 2H), 4.22 (d, J = 5.4 Hz, 2H), 3.69 (s,
2H), 3.67 (s, 2H), 2.88 (hept, J = 7.0 Hz, 1H), 1.32 (t, J =
5.4 Hz, 1H), 1.29 (t, J = 5.4 Hz, 1H), 1.24 (d, J = 7.0 Hz,
6H); 13C{1H}NMR (125.8 MHz CDCl3) δ 147.1, 140.5,
137.0, 136.8, 136.5, 128.5 (2C), 128.4, 126.9 (2C), 126.1,
121.2, 62.2, 62.0, 35.4, 33.8, 30.8, 24.2 (2C); HRMS (ESIꢀ
TOF) m/z: [M + Na]+ Calcd for C19H24NaO2S 339.1389,
Found 339.1384.
(E)ꢀ2ꢀ(4ꢀmethoxybenzyl)ꢀ3ꢀ(thienꢀ3ꢀylmethyl)butꢀ2ꢀeneꢀ1,4ꢀ
diol (12d): Prepared by a method analogous to (12a) using
(Z)ꢀ2ꢀiodoꢀ3ꢀ(4ꢀmethoxybenzyl)butꢀ2ꢀeneꢀ1,4ꢀdiol (10d)
G
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