The Journal of Organic Chemistry
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= 8.2 Hz, 2H), 7.35−7.27 (m, 4H), 5.80 (s, 1H), 4.16 (d, J = 12.5 Hz,
1H), 3.89 (dd, J = 11.6, 1.8 Hz, 1H), 3.47 (td, J = 11.1, 3.7 Hz, 1H),
2.93 (d, J = 12.5 Hz, 1H), 2.49−2.41 (m, 8H), 2.05−1.96 (s, 2H),
1.73−1.65 (m, 1H), 1.64−1.57 (m, 1H), 1.40−1.27 (m, 1H), 1.11−
1.00 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 200.3, 144.9, 143.7,
134.2, 133.1, 131.5, 129.7, 129.6, 128.5, 127.8, 126.1, 52.8, 49.3, 49.0,
38.1, 28.0, 25.2, 21.7, 21.5, 21.2; IR (CH2Cl2) 2925, 2360, 1673, 1348,
1161 cm−1; HRMS (ESI) calcd for C24H27NO3NaS [M + Na]+
432.1609, found 432.1600. Crystals suitable for X-ray diffraction
analysis were grown from CH2Cl2 and hexanes.
Data for m-Tolyl(2-tosyl-1,2,3,4,4a,5,6,7-octahydroisoquinolin-4-
yl)methanone (3c). In the typical procedure, to a solution of 1c (0.1 g,
0.19 mmol) in 1.9 mL of CH2Cl2 at room temperature under open
system was added TfOH (0.0017 mL, 0.019 mmol). The reaction
mixture was stirred for 3.5 h, and the crude mixture was purified by
flash column chromatography (silica gel, 1:10 ethyl acetate/hexanes)
to give 3c (0.067 g, 0.16 mmol, 88%) as colorless crystals: mp 144−
145 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.2 Hz, 2H), 7.62
(d, J = 8.2 Hz, 2H), 7.45−7.36 (m, 2H), 7.32 (d, J = 8.1 Hz, 2H), 5.80
(s, 1H), 4.17 (d, J = 12.5 Hz, 1H), 3.90 (d, J = 11.8 Hz, 1H), 3.49 (td,
J = 11.1, 3.7 Hz, 1H), 2.94 (d, J = 12.5 Hz, 1H), 2.48−2.41 (m, 8H),
2.05−1.97 (s, 2H), 1.73−1.66 (m, 1H), 1.65−1.58 (m, 1H), 1.41−
1.28 (m, 1H), 1.12−1.01 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
200.9, 143.7, 138.7, 136.7, 134.6, 133.0, 131.4, 129.7, 128.8, 127.8,
126.1, 125.6, 52.7, 49.2, 38.0, 27.9, 25.1, 21.5, 21.3, 21.1; IR (CH2Cl2)
2926, 2360, 1676, 1349, 1162 cm−1; HRMS (ESI) calcd for
C24H27NO3NaS [M + Na]+ 432.1609, found 432.1614.
Data for Naphthalen-1-yl(2-tosyl-1,2,3,4,4a,5,6,7-octahydroiso-
quinolin-4-yl)methanone (3d). In the typical procedure, to a solution
of 1d (0.1 g, 0.18 mmol) in 1.8 mL of CH2Cl2 at room temperature
under open system was added TfOH (0.0016 mL, 0.018 mmol). The
reaction mixture was stirred for 35 min, and the crude mixture was
purified by flash column chromatography (silica gel, 1:10 ethyl
acetate/hexanes) to give 3d (0.074 g, 0.17 mmol, 93%) as colorless
crystals: mp 187−188 °C; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J =
8.3 Hz, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.90
(d, J = 8.9 Hz, 1H), 7.63 (d, J = 8.2 Hz, 2H), 7.61−7.51 (m, 3H), 7.32
(d, J = 8 Hz, 2H), 5.79 (s, 1H), 4.18 (d, J = 12.6 Hz, 1H), 4.02 (dt, J =
11.8, 1.6 Hz, 1H), 3.48 (td, J = 11, 3.7 Hz, 1H), 2.99 (d, J = 12.5 Hz,
1H), 2.62 (t, J = 11.6 Hz, 1H), 2.56 (s, 1H), 2.44 (s, 3H), 2.02−1.95
(m, 2H), 1.83−1.75 (m, 1H), 1.62−1.55 (m, 1H), 1.42−1.30 (m, 1H),
1.16−1.03(m, 1H); 13C NMR (100 MHz, CDCl3) δ 204.1, 143.7,
135.5, 134.0, 133.7, 133.2, 131.3, 130.0, 129.7, 128.6, 128.3, 127.8,
126.6, 126.1, 125.5, 124.4, 53.0, 52.7, 49.3, 38.6, 28.0, 25.1, 21.5, 21.2;
IR (CH2Cl2) 2927, 2358, 1670, 1591, 1347, 1159 cm−1; HRMS (ESI)
calcd for C27H27NO3NaS [M + Na]+ 468.1609, found 468.1604.
Crystals suitable for X-ray diffraction analysis were grown from
CH2Cl2 and hexanes.
was added BF3·OEt2 (0.046 mL, 0.37 mmol). The reaction mixture
was stirred for 1 min and the crude mixture was purified by flash
column chromatography (silica gel, 1:5 ethyl acetate/hexanes) to give
1
5 (0.039 g, 0.093 mmol, 50%) as a pale-yellow oil: H NMR (400
MHz, CDCl3) δ 7.78 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.2 Hz, 2H),
7.25 (d, J = 8.2 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 5.84 (s, 1H), 5.53
(d, J = 17.1 Hz, 2H), 5.16 (t, J = 6.2 Hz, 1H), 3.88 (s, 3H), 3.58−3.44
(m, 2H), 3.28 (s, 1H), 2.38 (s, 3H), 2.08−1.99 (m, 1H), 1.95−1.84
(m, 1H), 1.53−1.45 (m, 3H), 1.42−1.35 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 197.5, 163.5, 149.3, 143.0, 137.6, 133.0, 132.2, 129.9,
129.4, 128.5, 127.2, 124.4, 113.6, 55.5, 47.6, 37.6, 27.8, 24.8, 21.4, 17.8;
IR (CH2Cl2) 3278, 2931, 1945, 1599, 1160 cm−1; HRMS (ESI) calcd
for C24H27NO4NaS [M + Na]+ 448.1559, found 448.1555.
Data for (Z)-4-(Fluoro(phenyl)methylene)-2-tosyl-2-azaspiro-
[4.5]dec-6-ene (11a). In the typical procedure, to a solution of 10a
(0.13 g, 0.25 mmol) in 101 mL of CH2Cl2 at room temperature under
an atmosphere of nitrogen was added BF3·OEt2 (0.062 mL, 0.51
mmol). The reaction mixture was stirred for 1 min and the crude
mixture was purified by flash column chromatography (silica gel, 1:30
ethyl acetate/hexanes) to give 11a (0.073 g, 0.18 mmol, 73%) as
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colorless crystals: mp 146−147 °C; H NMR (500 MHz, CDCl3) δ
7.74 (d, J = 8.2 Hz, 2H), 7.37−7.33 (m, 4H), 7.31 (d, J = 6.7 Hz, 1H),
7.28 (d, J = 7.6 Hz, 2H), 5.50−5.47 (m, 1H), 5.03 (d, J = 11.1 Hz,
1H), 4.28 (dd, J = 14.7, 3.4 Hz, 1H), 3.96 (dd, J = 14.7, 3.4 Hz, 1H),
3.40 (dd, J = 9.4, 2.5 Hz, 1H), 2.78 (d, J = 9.4 Hz, 1H), 2.46 (s, 3H),
1.99−1.91 (m, 1H), 1.83−1.75 (m, 1H), 1.70 (dd, J = 13.5, 2.9 Hz,
1H), 1.61 (dd, J = 12.0, 1.3 Hz, 1H), 1.53−1.43 (m, 1H); 13C NMR
(125 MHz, CDCl3) δ 151.9 (d, J = 242 Hz), 143.7, 132.3, 131.3 (d, J =
27 Hz), 129.7, 129.4, 129.3, 129.2, 128.8, 128.0, 127.5, 123.2 (d, J = 19
Hz), 59.4, 49.7 (d, J = 10 Hz), 44.6 (d, J = 5 Hz), 32.3 (d, J = 3 Hz),
24.4, 21.6, 20.0; 19F NMR (CDCl3, 376 MHz) δ −90.4; IR (CH2Cl2)
2935, 1713, 1598, 1446, 1351, 1163 cm−1; HRMS (ESI) calcd for
C23H24FNO2S [M − H]− 396.1434, found 396.1439. Crystals suitable
for X-ray diffraction analysis were grown from CH2Cl2 and hexanes.
Data for (Z)-4-(Fluoro(p-tolyl)methylene)-2-tosyl-2-azaspiro[4.5]-
dec-6-ene (11b). In the typical procedure, to a solution of 10b (0.13 g,
0.25 mmol) in 101 mL of CH2Cl2 at room temperature under an
atmosphere of nitrogen was added BF3·OEt2 (0.062 mL, 0.51 mmol).
The reaction mixture was stirred for 1 min and the crude mixture was
purified by flash column chromatography (silica gel, 1:30 ethyl
acetate/hexanes) to give 11b (0.08 g, 0.20 mmol, 77%) as colorless
crystals: mp 133−134 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J =
8.2 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.08
(d, J = 7.9 Hz, 2H), 5.52−5.49 (m, 1H), 5.05 (dd, J = 10.0, 1.0, Hz,
1H), 4.26 (dd, J = 14.6, 2.8 Hz, 1H), 3.95 (dd, J = 14.7, 3.3 Hz, 1H),
3.39 (dd, J = 9.3, 2.44 Hz, 1H), 2.78 (d, J = 9.3 Hz, 1H), 2.45 (s, 3H),
2.33 (s, 3H), 1.98−1.92 (m, 2H), 1.86−1.77 (m, 1H), 1.73−1.63 (m,
2H), 1.54−1.46 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 152.0 (d, J
= 242 Hz), 143.7, 139.3, 132.2, 129.7, 129.3, 128.6, 128.5, 128.2,
128.1, 128.0, 122.5 (d, J = 20 Hz), 59.4, 49.8 (d, J = 11 Hz), 44.5 (d, J
= 5 Hz), 32.1 (d, J = 2 Hz), 24.4, 21.4 (d, J = 22 Hz), 20.0; 19F NMR
(CDCl3, 376 MHz) δ −90.4; IR (CH2Cl2) 3027, 2935, 2865, 2361,
1712, 1598, 1451, 1350 cm−1; HRMS (ESI) calcd for C24H26FNO2S
[M − H]− 410.1590, found 410.1599.
Data for (Z)-N-(Phenyl(2-tosyl-2,3,4a,5,6,7-hexahydroisoquino-
lin-4(1H)ylid- ene)methyl)acetamide (4). In the typical procedure, to
a solution of 1a (0.1 g, 0.2 mmol) in 2.0 mL of CH3CN at room
temperature under open system was added BF3·OEt2 (0.048 mL, 0.39
mmol). The reaction mixture was stirred for 1 min, and the crude
mixture was purified by flash column chromatography (silica gel, 1:1
ethyl acetate/hexanes) to give 4 (0.068 g, 0.155 mmol, 79%) as
Data for (Z)-4-(Fluoro(naphthalen-1-yl)methylene)-2-tosyl-2-
azaspiro[4.5]dec-6-ene (11c). In the typical procedure, to a solution
of 10c (0.11 g, 0.25 mmol) in 101 mL of CH2Cl2 at room temperature
under an atmosphere of nitrogen was added BF3·OEt2 (0.062 mL, 0.51
mmol). The reaction mixture was stirred for 1 min and the crude
mixture was purified by flash column chromatography (silica gel, 1:30
ethyl acetate/hexanes) to give 11c (0.068 g, 0.15 mmol, 60%) as
1
colorless crystals: mp 204−205 °C; H NMR (400 MHz, CDCl3) δ
7.75 (d, J = 8.2 Hz, 2H), 7.33−7.30 (m, 5H), 7.10−7.08 (m, 2H), 6.75
(s, 1H), 5.59 (s, 1H), 4.21 (d, J = 13.9 Hz, 1H), 3.84 (d, J = 12.1 Hz,
1H), 3.75 (d, J = 12.1 Hz, 1H), 3.35 (d, J = 13.9 Hz, 1H), 2.98 (s, 1H),
2.42 (s, 3H), 2.09 (s, 3H), 1.90−1.88 (m, 2H), 1.56−1.48 (m, 2H),
1.26−1.13 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 168.3, 143.4,
137.1, 135.5, 131.6, 131.1, 131.0, 129.5, 128.7, 128.3, 128.2, 127.8,
127.5, 50.8, 43.7, 38.0, 28.3, 24.9, 23.5, 21.5; IR (CH2Cl2) 3247, 2929,
1669, 1507, 1158 cm−1; HRMS (ESI) calcd for C25H28N2O3NaS [M +
Na]+ 459.1718, found 459.1715. Crystals suitable for X-ray diffraction
analysis were grown from CH2Cl2 and hexanes.
1
colorless crystals: mp 193−194 °C; H NMR (400 MHz, CD2Cl2) δ
7.87−7.77 (m, 5H), 7.51−7.47 (m, 2H), 7.44−7.33 (m, 4H), 5.07 (dd,
J = 9.8, 5.6 Hz, 1H), 4.85 (d, J = 9.6 Hz, 1H), 4.44 (dd, J = 14.5, 2.9
Hz, 1H), 4.09 (dd, J = 14.5, 3.3 Hz, 1H), 3.39 (dd, J = 9.4, 2.6 Hz,
1H), 2.79 (d, J = 9.4 Hz, 1H), 2.49 (s, 3H), 1.90−1.87 (m, 1H), 1.67
(dd, J = 12.2, 4.3 Hz, 1H), 1.49−1.29 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 151.2 (d, J = 247 Hz), 143.7, 133.2, 132.7, 132.0, 130.4 (d, J
= 2 Hz), 129.8, 129.6, 129.5 (d, J = 4 Hz), 128.8, 128.6, 128.2, 128.0,
126.7, 126.1, 125.3 (d, J = 18 Hz), 125.3, 124.2, 59.1, 49.2 (d, J = 7
Data for N-((6-(3-(4-Methoxyphenyl)-3-oxoprop-1-en-2-yl)-
cyclohex-1-en-1-yl)methyl)-4-methylbenzenesulfonamide (5). In
the typical procedure, to a solution of 1i (0.1 g, 0.19 mmol) in 74.0
mL of CH2Cl2 at room temperature under an atmosphere of nitrogen
G
dx.doi.org/10.1021/jo400634c | J. Org. Chem. XXXX, XXX, XXX−XXX