S. Liao, H. Xu, L. Xu et al.
Tetrahedron 77 (2021) 131764
7.25e7.14 (m, 1H), 6.79 (s, 1H), 5.92 (s, 1H), 5.49 (s, 1H), 4.64 (dd,
J ¼ 7.6, 5.1 Hz, 1H), 1.92 (s, 1H), 1.84e1.77 (m, 1H), 1.76e1.70 (m, 1H),
1.59e1.49 (m, 1H), 1.48e1.39 (m, 1H), 0.97 (t, J ¼ 7.4 Hz, 3H). 13C
4.4. Diels-Alder reaction for the synthesis of (3aS,10cS,E)-5-
butylidene-2-phenyl-3a,4,5,10c-tetrahydro-1H-benzo[4,5]thieno
[3,2-e]isoindole-1,3(2H)-dione (4a)
NMR (176 MHz, CDCl3)
d 154.37, 154.24, 141.15, 128.69, 124.64,
122.80, 121.05, 112.35, 110.95, 103.31, 72.23, 38.89, 19.08, 13.89.
HRMS (ESI) m/z: [MþNa]þ Calcd for C14H16NaO2 239.1043; Found:
239.1041.
In a 4 mL vial, compound 3a (1.0 equiv., 0.13 mmol, 30 mg) and
N-phenylmaleimide (2.0 equiv., 0.26 mmol, 45 mg) was heated at
80 ꢀC in toluene for about 4 h. After completion, toluene was
removed, and the residue was dissolved in AcOEt and washed with
H2O. The organic layer was dried with MgSO4 and removed. The
crude product was purified with silica gel column chromatograph
to afford 4a as a white solid. M.p.: 123e126 ꢀC, yield: 65%. 1H NMR
4.3.22. 2-(5-Bromobenzofuran-2-yl)hex-1-en-3-ol (3v)
Following the general procedure, compound 3v was obtained as
a white solid. M.p.: 61e63 ꢀC. Yield: 48%. 1H NMR (700 MHz, CDCl3)
(700 MHz, CDCl3)
d
8.22 (d, J ¼ 8.0 Hz, 1H), 7.74 (d, J ¼ 8.0 Hz, 1H),
d
7.66 (d, J ¼ 1.9 Hz, 1H), 7.36 (dd, J ¼ 8.6, 1.9 Hz, 1H), 7.32 (d,
7.39 (dt, J ¼ 7.0, 4.2 Hz, 3H), 7.35e7.31 (m, 2H), 7.23 (dd, J ¼ 8.5,
1.1 Hz, 2H), 6.02 (t, J ¼ 7.4 Hz, 1H), 4.59 (d, J ¼ 8.2 Hz, 1H), 3.66 (dd,
J ¼ 8.1, 6.2, 4.6 Hz, 1H), 3.37 (dd, J ¼ 14.6, 4.5 Hz, 1H), 2.65 (dd,
J ¼ 14.6, 5.4 Hz,1H), 2.37e2.22 (m, 2H),1.51 (dt, J ¼ 21.3, 6.8 Hz, 3H),
J ¼ 8.6 Hz, 1H), 6.73 (s, 1H), 5.91 (s, 1H), 5.52 (s, 1H), 4.61 (dd, J ¼ 7.6,
5.1 Hz, 1H), 1.75 (d, J ¼ 5.4 Hz, 2H), 1.55e1.49 (m, 1H), 1.46e1.38 (m,
1H), 0.96 (t, J ¼ 7.4 Hz, 3H). 13C NMR (176 MHz, CDCl3)
d 155.49,
0.98 (t, J ¼ 7.4 Hz, 3H). 13C NMR (176 MHz, CDCl3)
d 177.08, 174.28,
153.13, 140.81, 130.73, 127.49, 123.65, 115.81, 113.40, 112.42, 102.76,
72.24, 38.85, 19.09, 13.90. HRMS (ESI) m/z: [MþNa]þ Calcd for
140.93, 138.94, 137.94, 131.70, 131.07, 128.98, 128.46, 126.25, 125.03,
124.51, 123.65, 122.22, 122.04, 41.65, 40.43, 30.14, 24.68, 22.64,
13.91. HRMS (ESI) m/z: [MþH]þ Calcd for C24H22NO2S 388.1366;
Found: 388.1368.
C
14H15BrNaO2 317.0148; Found: 317.0146, 319.0147.
4.3.23. 2-(Thiophen-2-yl)hex-1-en-3-ol (3w)
Following the general procedure, compound 3w was obtained
4.5. The synthesis of (3R,5R,8R,9S,10S,13R,14S,17R)-17-((2R)-6-
(benzo[b]thiophen-2-yl)-5-hydroxyhept-6-en-2-yl)-10,13-
dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol (4b)
as colorless oil. Yield: 17%. 1H NMR (700 MHz, CDCl3)
d 7.21 (d,
J ¼ 5.1 Hz, 1H), 7.13 (d, J ¼ 3.6 Hz, 1H), 6.99 (dd, J ¼ 5.1, 3.7 Hz, 1H),
5.45 (s, 1H), 5.27 (s, 1H), 4.58 (dd, J ¼ 7.7, 4.8 Hz, 1H), 1.80 (s, 1H),
1.74e1.68 (m, 1H), 1.65e1.59 (m, 1H), 1.53e1.45 (m, 1H), 1.44e1.35
Following the general procedure, two diastereoisomers 4b-1
and 4b-2 with equal amount were obtained, total yield 84%.
Compound 4b-1, M.p.: 80e82 ꢀC. 1H NMR (700 MHz, CDCl3)
(m, 1H), 0.93 (t, J ¼ 7.4 Hz, 3H). 13C NMR (176 MHz, CDCl3)
d 145.13,
142.21, 127.27, 124.52, 123.99, 111.25, 73.97, 38.43, 19.05, 13.89.
HRMS (ESI) m/z: [MþH]þ Calcd for C10H15OS 183.0838; Found:
183.0839.
d
7.77 (d, J ¼ 7.6 Hz, 1H), 7.72 (d, J ¼ 7.4 Hz, 1H), 7.36 (s, 1H),
7.34e7.29 (m, 2H), 5.58 (s, 1H), 5.41 (s, 1H), 4.63e4.57 (m, 1H),
3.64e3.57 (m, 1H), 1.92 (d, J ¼ 12.5 Hz, 1H), 1.89e1.80 (m, 2H), 1.77
(dd, J ¼ 14.4, 3.0 Hz, 2H), 1.75e1.70 (m, 1H), 1.65e1.59 (m, 2H),
1.59e1.53 (m, 1H), 1.53e1.47 (m, 2H), 1.41e1.33 (m, 6H), 1.29 (dd,
J ¼ 18.8, 7.6 Hz, 1H), 1.26e1.16 (m, 4H), 1.08 (tdd, J ¼ 19.6, 13.0,
6.7 Hz, 4H), 1.04e0.97 (m, 2H), 0.95 (td, J ¼ 14.2, 3.3 Hz, 1H), 0.90 (s,
3H), 0.87 (d, J ¼ 6.6 Hz, 3H), 0.61 (s, 3H). 13C NMR (176 MHz, CDCl3)
4.3.24. (Z)-2-(benzo[b]thiophen-2-yl)-1-bromohex-1-en-3-ol (3x)
Following the revised general procedure, compound 3x was
obtained as colorless oil. Yield: 38%. 1H NMR (700 MHz, CDCl3)
d
7.84 (d, J ¼ 7.7 Hz, 1H), 7.81 (d, J ¼ 7.1 Hz, 1H), 7.46 (s, 1H),
7.39e7.33 (m, 2H), 6.75 (d, J ¼ 0.8 Hz,1H), 4.56e4.52 (m,1H),1.91 (s,
1H), 1.65e1.54 (m, 3H), 1.51e1.42 (m, 1H), 1.41e1.33 (m, 1H), 0.90 (t,
d
145.30, 142.28, 140.14, 138.85, 124.60, 124.34, 123.61, 121.98,
120.82, 113.84, 74.66, 71.88, 56.41, 55.99, 42.65, 42.07, 40.39, 40.11,
36.42, 35.81, 35.60, 35.31, 34.53, 32.84, 31.97, 30.52, 28.20, 27.17,
26.38, 24.17, 23.35, 20.78, 18.66, 12.00. HRMS (ESI) m/z: [MþNa]þ
Calcd for C34H48NaO2S 543.3267; Found: 543.3254.
J ¼ 7.4 Hz, 3H). 13C NMR (176 MHz, CDCl3)
d 141.97, 140.05, 139.17,
137.01, 124.82, 124.67, 124.38, 123.79, 122.06, 108.16, 76.24, 37.88,
18.83, 13.76. HRMS (ESI) m/z: [MþNa]þ Calcd for C14H15BrNaOS
332.9919; Found: 332.9913, 334.9891.
Compound 4b-2, M.p.: 84e86 ꢀC. 1H NMR (700 MHz, CDCl3)
d
7.79e7.76 (m,1H), 7.73e7.70 (m, 1H), 7.34 (s, 1H), 7.31 (ddt, J ¼ 8.5,
7.2, 3.6 Hz, 2H), 5.58 (s,1H), 5.42 (s,1H), 4.62 (dd, J ¼ 7.6, 4.8 Hz,1H),
3.66e3.56 (m, 1H), 1.93 (dt, J ¼ 12.6, 3.1 Hz, 1H), 1.87e1.79 (m, 2H),
1.79e1.71 (m, 4H), 1.70e1.64 (m, 2H), 1.56e1.53 (m, 1H), 1.50 (ddt,
J ¼ 11.2, 5.4, 2.9 Hz, 2H), 1.42e1.33 (m, 6H), 1.31 (dd, J ¼ 11.8, 2.4 Hz,
1H), 1.29e1.17 (m, 5H),1.09 (dd, J ¼ 14.5,10.4, 6.3 Hz, 2H), 1.04e0.99
(m, 2H), 0.95 (td, J ¼ 14.2, 3.4 Hz,1H), 0.90 (s, 3H), 0.88 (d, J ¼ 6.6 Hz,
4.3.25. (Z)-2-(benzo[b]thiophen-2-yl)-1-iodohex-1-en-3-ol (3y)
Following the revised general procedure, compound 3y was
obtained as colorless oil. Yield: 44%. 1H NMR (700 MHz, CDCl3)
d
7.84 (d, J ¼ 7.9 Hz, 1H), 7.82 (dd, J ¼ 7.1, 1.2 Hz, 1H), 7.41e7.33 (m,
3H), 6.93 (d, J ¼ 0.7 Hz, 1H), 4.53 (dd, J ¼ 7.1, 5.5 Hz, 1H), 1.64e1.50
(m, 2H),1.49e1.41 (m, 1H),1.40e1.32 (m,1H), 0.90 (t, J ¼ 7.4 Hz, 3H).
3H), 0.62 (s, 3H). 13C NMR (176 MHz, CDCl3)
d 145.48, 142.38, 140.12,
13C NMR (176 MHz, CDCl3)
d 148.71, 140.08, 139.78, 139.26, 124.61,
138.84, 124.59, 124.33, 123.60, 121.98, 120.69, 113.58, 74.24, 71.88,
56.44, 56.05, 42.66, 42.07, 40.39, 40.12, 36.42, 35.81, 35.53, 35.31,
34.54, 32.98, 31.96, 30.52, 28.28, 27.17, 26.40, 24.19, 23.35, 20.78,
18.61, 12.02. HRMS (ESI) m/z: [MþNa]þ Calcd for C34H48NaO2S
543.3267; Found: 543.3258.
124.49, 124.39, 123.80, 122.16, 82.32, 77.05, 37.84, 18.75, 13.76.
HRMS (ESI) m/z: [MþNa]þ Calcd for C14H15INaOS 380.9781; Found:
380.9779.
4.3.26. Methyl (Z)-3-(benzo[b]thiophen-2-yl)-4-hydroxybut-2-
enoate (3z)
4.6. The synthesis of 4-(2-(benzo[b]thiophen-2-yl)-1-hydroxyallyl)
Following the general procedure, compound 3z was obtained as
phenyl 2-(4-isobutylphenyl)propanoate (4c)
colorless oil. Yield: 50%. 1H NMR (700 MHz, CDCl3)
d 7.82e7.79 (m,
1H), 7.78 (dd, J ¼ 6.6, 2.3 Hz, 1H), 7.45 (s, 1H), 7.37e7.32 (m, 2H),
Following the general procedure, compound 4c was obtained as
6.33 (s, 1H), 4.52 (d, J ¼ 1.7 Hz, 2H), 3.70 (s, 3H). 13C NMR (176 MHz,
colorless oil. Yield: 74%。1H NMR (700 MHz, CDCl3)
d 7.73e7.67 (m,
CDCl3)
d
166.33, 147.82, 140.19, 139.24, 136.67, 125.00, 124.77,
1H), 7.61e7.57 (m, 1H), 7.45 (d, J ¼ 8.6 Hz, 2H), 7.29e7.21 (m, 4H),
7.12 (d, J ¼ 8.0 Hz, 3H), 6.98 (d, J ¼ 8.6 Hz, 2H), 5.75 (s, 1H), 5.71 (s,
1H), 5.55 (s, 1H), 3.91 (q, J ¼ 7.1 Hz, 1H), 2.45 (d, J ¼ 7.2 Hz, 2H),
124.48,124.05,122.10,117.50, 66.62, 51.64. HRMS (ESI) m/z: [MþH]þ
Calcd for C13H13O3S 249.0580; Found: 249.0581.
8