The Journal of Organic Chemistry
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129.8, 128.8, 127.4, 127.3, 126.4, 125.9, 115.4, 58.1, 41.8, 40.4, 30.5,
30.3, 26.0, 20.3; HRMS (ESI+) calcd for [C20H23NO + H]+ requires
m/z 294.1853, found m/z 294.1853.
(m, 2H), 7.06 (d, J = 6.7 Hz, 1H), 6.97 (d, J = 9.0 Hz, 2H), 6.78 (d, J
= 8.1 Hz, 2H), 4.75 (dd, J = 9.4, 4.3 Hz, 1H), 3.57 (m, 2H), 3.09 (m,
2H), 2.96 (m, 1H), 2.69 (dt, J = 16.5, 5.3 Hz, 1H), 2.35 (m, 1H), 2.24
(m, 1H), 2.20 (s, 3H); 1 3C NMR (125 MHz, CDCl3) 200.1, 147.9,
138.5, 137.1, 134.9, 132.8, 129.7, 128.8, 128.5, 128.0, 127.4, 126.4,
125.9, 115.6, 58.4, 42.0, 35.5, 31.0, 26.1, 20.3; HRMS (ESI+) calcd for
[C25H25NO + H]+ requires m/z 356.2009, found m/z 356.2012.
3-(2-(p-Tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)propanal (Table
3, entry 4): white solid; experiment 1, 117 mg (0.42 mmol, 94% yield);
experiment 2, 121 mg (0.43 mmol, 97% yield); IR (thin film) 3063,
2920, 2246, 1719, 1616, 1517, 909 cm−1; 1H NMR (500 MHz,
CDCl3) δ 9.70 (t, J = 1.4 Hz, 1H), 7.14 (m, 3H), 7.06 (d, J = 6.9 Hz,
1H), 7.02 (d, J = 8.2 Hz, 2H), 6.79 (d, J = 8.5 Hz, 2H), 4.61 (dd, J =
10.1, 5.3 Hz, 1H), 3.52 (m, 2H), 2.92 (m, 1H), 2.65 (dt, J = 16.0, 4.5
Hz, 1H), 2.52 (m, 2H), 2.28 (m, 1H), 2.23 (s, 3H), 2.11 (m, 1H); 13C
NMR (125 MHz, CDCl3) 201.7, 147.7, 137.9, 135.0, 129.8, 128.9,
128.2, 127.2, 126.5, 126.0, 116.3, 58.4, 42.5, 41.1, 29.8, 25.9, 20.3;
HRMS (ESI+) calcd for [C19H21NO + H]+ requires m/z 280.1696,
found m/z 3280.1706; mp = 66 °C.
2-Methyl-3-(2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)-
propanal (Table 3, entry 5): inseparable 1:1.5 mixture of
diastereomers, colorless oil; experiment 1, 120 mg (0.41 mmol, 91%
yield); experiment 2, 124 mg (0.43 mmol, 94% yield); IR (thin film)
2965, 2922, 2247, 1719, 1615, 1513, 1038 cm−1; 1H NMR (500 MHz,
CDCl3) major diastereoisomer δ 9.58 (d, J = 1.1 Hz, 1H), 6.99−7.18
(m, 6H), 6.76 (dt, J = 8.7, 2.9 Hz, 2H), 4.69 (dd, J = 9.8, 4.7 Hz, 1H),
3.49 (m, 2H), 2.86 (m, 1H), 2.43- 2.66 (m, 3H), 2.22 (s, 3H), 2.15
(m, 1H), 1.14 (d, J = 6.9 Hz, 3H); minor diastereomer d 9.57 (d, J =
2.5 Hz, 1H), 6.99- 7.18 (m, 6H), 6.80 (dt, J = 8.7, 2.7 Hz, 2H), 4.61
(dd, J = 10.8, 4.6 Hz, 1H), 3.49 (m, 2H), 2.86 (m, 1H), 2.43- 2.66 (m,
2H), 2.22 (s, 3H), 2.21 (m, 1H), 1.74 (dt, J = 1.45, 4.9 Hz, 1H), 1.11
(d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) 203.8, 203.4, 147.7,
138.0, 137.8, 135.0, 134.9, 129.8, 129.7, 129.1, 129.0, 128.8, 128.8,
127.2, 126.5, 126.4, 126.0, 126.0, 117.3, 117.3, 57.5, 55.5, 44.8, 43.5,
43.0, 42.4, 39.9, 38.6, 25.4, 25.0, 20.4, 14.6, 13.5; HRMS (ESI+) calcd
for [C20H23NO + H]+ requires m/z 294.1853, found m/z 294.1864.
1-Phenyl-5-(2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)pentan-
3-one (11). The yields represented here are 1H NMR yields, calculated
from the crude against an internal standard. A clean sample of the
product was obtained by using a 1:1 mixture of starting material and
acceptor. The data for that sample is shown below: white solid;
experiment 1, 94% yield; experiment 2, 97% yield; IR (thin film) 3030,
2927, 2360, 1713, 1601, 1501, 1398 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.27−7.07 (m, 11H), 6.86 (d, J = 7.9 Hz, 2H), 6.73 (t, J =
6.7 Hz, 1H), 4.71 (dd, J = 9.6, 5.7 Hz, 1H), 3.56 (m, 2H), 2.98 (m,
1H), 2.85 (t, J = 8.3 Hz, 2H), 2.73 (dt, J = 16.6, 4.7 Hz, 1H), 2.65 (m,
2H), 2.51 (t, J = 6.7 Hz, 2H), 2.24 (m, 1H), 2.05 (m, 1H); 13C NMR
(125 MHz, CDCl3) 209.6, 149.8, 141.1, 138.3, 134.9, 129.4, 128.8,
128.5, 128.3, 127.3, 126.5, 126.1, 125.9, 117.8, 114.6, 58.0, 44.6, 41.4,
39.7, 30.4, 29.7, 26.3; HRMS (ESI+) calcd for [C26H27NO + H]+
requires m/z 370.2166, found m/z 370.2177; mp = 114 °C.
4-(2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)-
butan-2-one (Table 2, entry 3): white solid; experiment 1, 120 mg
(0.39 mmol, 93% yield); experiment 2, 124 mg (0.40 mmol, 96%
1
yield); IR (thin film) 2997, 2950, 1711, 1509, 1037 cm−1; H NMR
(500 MHz, CDCl3) δ 7.16 (m, 2H), 7.13 (m, 1H), 7.06 (d, J = 7.0 Hz,
1H), 6.84 (dt, J = 8.6, 2.5 Hz, 2H), 6.78 (dt, J = 9.2, 2.3 Hz, 2H), 4.51
(dd, J = 10.2, 4.4 Hz, 1H), 3.73 (s, 3H), 3.48 (dd, J = 7.6, 4.4 Hz, 2H),
2.89 (m, 1H), 2.63 (dt, J = 16.3, 4.2 Hz, 1H), 2.55 (td, J = 7.3, 2.1 Hz,
2H), 2.17 (m, 1H), 2.08 (s, 3H), 2.03 (m, 1H); 13C NMR (125 MHz,
CDCl3) 208.8, 152.9, 144.6, 138.4, 134.9, 128.9, 127.2, 126.3, 125.9,
118.2, 114.6, 58.7, 55.6, 43.0, 40.4, 30.6, 30.3, 25.8; HRMS (ESI+)
calcd for [C20H23NO2 + H]+ requires m/z 310.1802, found m/z
310.1817.
4-(2-(4-Chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)butan-
2-one (Table 2, entry 4): white solid. Experiment 1: 133 mg (0.42
mmol, 99% yield). Experiment 2: 133 mg (0.42 mmol, 99% yield). IR
(thin film): 2923, 2847, 1712, 1594, 1496, 1159 cm−1; 1H NMR (500
MHz, CDCl3) δ 7.15 (m, 5H), 7.10 (m, 1H), 6.79 (dt, J = 9.5, 3.2 Hz,
2H), 4.66 (dd, J = 9.4, 4.9 Hz, 1H), 3.54 (dd, J = 7.2, 4.9 Hz, 2H), 2.96
(m, 1H), 2.77 (dt, J = 16.2, 4.7 Hz, 1H), 2.53 (t, J = 7.1 Hz, 2H), 2.20
(m, 1H), 2.09 (s, 3H), 2.02 (m, 1H); 13C NMR (125 MHz, CDCl3)
208.4, 137.9, 134.7, 129.1, 128.8, 127.2, 126.7, 126.0, 122.4, 115.6,
58.0, 41.8, 40.2, 30.2, 30.2, 26.3; HRMS (ESI+) calcd for
[C19H20ClNO + H]+ requires m/z 314.1307, found m/z 314.1322.
4-(6,7-Dimethoxy-2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)-
butan-2-one (Table 2, entry 6): colorless oil; experiment 1, 120 mg
(0.35 mmol, 95% yield); experiment 2, 123 mg (0.36 mmol, 98%
1
yield); IR (thin film) 2999, 2935, 2252, 1710, 1597, 1249 cm−1; H
NMR (500 MHz, CDCl3) δ 7.21 (td, J = 7.7, 1.8 Hz, 2H), 6.87 (d, J =
8.0 Hz, 2H), 6.73 (t, J = 7.4 Hz, 1H), 6.67 (s, 1H), 6.56 (s, 1H), 4.65
(dd, J = 9.8, 4.9 Hz, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.65 (dt, J = 13.1,
4.6 Hz, 1H), 3.50 (m, 1H), 2.91 (m, 1H), 2.58 (m, 3H), 2.16 (m, 1H),
2.09 (s, 3H), 2.04 (m, 1H); 13C NMR (125 MHz, CDCl3) 208.8,
150.1, 147.6, 147.3, 130.3, 129.3, 126.7, 118.0, 115.1, 111.5, 110.2,
57.6, 56.0, 55.8, 41.3, 40.3, 30.3, 30.3, 25.5; HRMS (ESI+) calcd for
[C21H25NO3 + H]+ requires m/z 340.1908, found m/z 340.1920.
4-(7-Chloro-2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)butan-2-
one (Table 2, entry 7): colorless oil; experiment 1, 123 mg (0.39
mmol, 96% yield); experiment 2, 122 mg (0.38 mmol, 95% yield); IR
1
(thin film) 2924, 1711, 1599, 1507, 749, 693 cm−1; H NMR (500
MHz, CDCl3) δ 7.21 (m, 3H), 7.10 (dd, J = 8.2, 1.8 Hz, 1H), 7.00 (d,
J = 8.2 Hz, 1H), 6.85 (d, J = 8.0 Hz, 2H), 6.75 (t, J = 7.2 Hz, 1H), 4.68
(dd, J = 9.2, 5.4 Hz, 1H), 3.64 (dt, J = 13.3, 4.2 Hz, 1H), 3.49 (tt, J =
10.4, 4.6 Hz, 1H), 2.92 (m, 1H), 2.64 (dt, J = 16.3, 3.7 Hz, 1H), 2.57
(t, J = 6.7 Hz, 2H), 2.18 (m, 1H), 2.09 (s, 3H), 2.05 (m, 1H); 13C
NMR (125 MHz, CDCl3) 208.3, 149.7, 140.2, 133.2, 131.4, 130.2,
129.4, 127.1, 126.6, 118.3, 115.1, 57.7, 41.1, 40.2, 30.3, 25.4; HRMS
(ESI+) calcd for [C19H20ClNO + H]+ requires m/z 314.1307, found
m/z 314.1303.
ASSOCIATED CONTENT
* Supporting Information
1-(2-(p-Tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)pentan-3-one
(Table 3, entry 1): colorless oil; experiment 1, 135 mg (0.44 mmol,
98% yield); experiment 2, 137 mg (0.45 mmol, 99% yield); IR (thin
■
S
Experimental details for kinetic and NMR titration studies and
spectral data for all new compounds. This material is available
1
film): 3023, 2975, 2249, 1710, 1615, 1517, 909 cm−1; H NMR (500
MHz, CDCl3) δ 7.14 (m, 2H), 7.11 (m, 1H), 7.05 (d, J = 7.0 Hz, 1H),
7.01 (d, J = 8.4 Hz, 2H), 6.78 (dt, J = 8.7, 3.1 Hz, 2H), 4.64 (dd, J =
9.8, 5.4 Hz, 1H), 3.55 (m, 1H), 3.51 (m, 1H), 2.94 (m, 1H), 2.66 (dt, J
= 16.8, 4.3 Hz, 1H), 2.52 (t, J = 6.7 Hz, 2H), 2.35 (m, 2H), 2.22 (s,
3H), 2.18 (m, 1H), 2.06 (m, 1H), 1.01 (t, 3H); 13C NMR (125 MHz,
CDCl3) 211.4, 147.8, 138.5, 134.9, 129.8, 128.8, 127.3, 126.4, 125.8,
115.4, 58.2, 41.7, 39.1, 36.1, 30.5, 26.0, 20.3, 7.8; HRMS (ESI+) calcd
for [C21H25NO + H]+ requires m/z 308.2009, found m/z 308.2004.
1-Phenyl-3-(2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)-
propan-1-one (Table 3, entry 2): white solid; experiment 1, 143 mg
(0.40 mmol, 90% yield); experiment 2, 146 mg (0.41 mmol, 92%
yield); IR (thin film) 3061, 3025, 2247, 1682, 1615, 1517, 999 cm−1;
1H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 7.6 Hz, 2H), 7.50 (t, J =
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Prof. Bob Bergman and Prof. Clark Landis for helpful
discussions concerning the mechanism of this process. We are
grateful for funding from the NIH (GM095666) and the Sloan
7.6 Hz, 1H), 7.39 (t, J = 8.1 Hz, 2H), 7.21 (d, J = 6.7 Hz, 1H), 7.14
4113
dx.doi.org/10.1021/jo400428m | J. Org. Chem. 2013, 78, 4107−4114