8
Tetrahedron
ACCEPTED MANUSCRIPT
m), 7.34-7.21 (7H, m), 7.01 (1H, s), 4.08 (2H, s), 3.03 (3H, s),
References and notes
2.47 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 158.25, 151.80,
149.17, 148.51, 148.24, 143.14, 140.13, 137.60, 136.84, 135.28,
131.89, 130.11, 129.93, 128.95, 128.89, 127.93, 127.62, 119.12,
44.56, 36.24, 24.57; m/z HRMS (DART) found [M+H]+
481.0792, C25H22ClN2O2S2+ requires 481.0806.
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4.2.2.20. ethyl-4-(4-benzylthio)-8-chloro-5,6-
dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridine-
11-ylidene)piperidine-1-carboxylate (2t)
Prepared according to general procedure using sodium hydride
(60% dispersion in mineral oil, 22 mg, 0.55 mmol), benzyl thiol
(65 µL, 0.55 mmol), (8-chloro-11-(1-(ethoxycarbonyl)piperidin-
4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-
4-yl)triphenylphosphonium trifluoromethanesulfonate (1t, 397
mg, 0.50 mmol) and THF (2.0 mL). Flash column
chromatography (basic alumina, dry load, gradient elution: 20%
EtOAc in hexanes to 30% EtOAc in hexanes) afforded the title
compound (2t) as a white solid (129 mg, 0.36 mmol, 51% yield).
mp 200-203 ºC; IR νmax/cm-1 (film): 2989,2901, 1694, 1548,
1
1431, 1216, 1108, 1001, 764, 712, 697; H NMR (400 MHz,
CDCl3) δ: 8.23 (1H, d, J = 5.3 Hz), 7.40-7.24 (5H, m), 7.16-7.05
(3H, m), 6.99 (1H, d, J = 5.3 Hz), 4.18-4.08 (4H, m), 3.88-3.68
(2H, m), 3.42-3.31 (1H, m), 3.18-3.04 (3H, m), 2.92-2.71 (2H,
m), 2.52-2.39 (1H, m), 2.38-2.23 (3H, m), 1.24 (3H, t, J = 7.1
Hz); 13C NMR (100 MHz, CDCl3) δ: 156.28, 155.61, 149.07,
146.31, 139.75, 137.95, 137.67. 135.37, 134.25, 133.07, 130.35,
129.87, 128.95, 128.94, 128.88, 127.91, 126.33, 117.96, 61.45,
44.88, 36.28, 30.97, 30.75, 28.79, 14.83; m/z HRMS (DART)
found [M+H]+ 505.1705, C29H30ClN2O2S+ requires 505.1711.
4.2.2.21. (1S,2S4S,5R)-2-((R)-benzyloxy)(2-
(benzylthio)quinoline-4-yl)methyl)-5-
vinylquinuclidine (2u)
Prepared according to general procedure using sodium hydride
(60% dispersion in mineral oil, 22 mg, 0.55 mmol), benzyl thiol
(65 µL, 0.55 mmol), (4-((R)-(benzyloxy)((1S,2S,4S,5R)-5-
vinylquinuclidin-2-yl)methyl)quinolin-2-
yl)triphenylphosphonium trifluoromethanesulfonate (1u, 397 mg,
0.50 mmol) and THF (2.0 mL). Flash column chromatography
(basic alumina: 30% EtOAc in hexanes) afforded the title
compound (2u) as a yellow amorphous solid (157 mg, 0.31
mmol, 62% yield). IR νmax/cm-1 (film): 3063, 3029, 2928, 2863,
1591, 1549, 1452, 1290, 1094, 907, 758, 729, 697; 1H NMR (400
MHz, CDCl3) δ: 8.09-7.95 (2H, m), 7.66 (1H, dd, J = 8.2, 7.1
Hz), 7.55-7.42 (3H, m), 7.39-7.18 (9H, m), 5.80-5.66 (1H, m),
5.19 (1H, br s), 4.99-4.85 (2H, m), 4.61 (2H, s), 4.45 (1H, d, J =
11.4 Hz), 4.37 (1H, d, J = 11.4 Hz), 3.44-3.28 (1H, m), 3.17-3.00
(2H, m), 2.72-2.54 (2H, m), 2.30-2.18 (1H, m), 1.86-1.39 (4H,
m); 13C NMR (100 MHz, CDCl3) δ: 158.90, 148.85, 145.88,
142.07, 138.48, 137.89, 129.48, 129.32, 129.13, 128.59, 128.55,
127.88, 127.17, 125.47, 124.57, 123.39 (br), 118.05 (br), 114.31,
81.17 (br), 71.51, 60.67, 57.22, 43.28, 40.18, 34.03, 28.06, 27.85,
22.40 (br); m/z HRMS (DART) found [M+H]+ 507.2484,
C33H35N2OS+ requires 507.2465.
6. (a) Razuvaev, G. A.; Osanova, N. A. J. Organomet. Chem. 1972,
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900.
8. 1H NMR yields of phosphonium ion displacement with double
thiolate addition shown in parentheses: 2j – 92% (1%); 2k – 93%
(2%), 2l – 84% (8%). 1,3,5-trimethoxybenzene was used as an
internal standard.
9. Cernak, T.; Dykstra, K. D.; Tyagarajan, S.; Vachal, P.; Krska, S.
W. Chem. Soc. Rev. 2016, 45, 546.
Supplementary Material
Acknowledgments
Supplementary data related to this article can be found at
We acknowledge Colorado State University for startup funds
and the ACS Petroleum Research Fund (ACS PRF56878-DNI1)
for supporting this project.