Hogan and O’Shea
(10 mL) and washed with water (10 mL). The organic layer was
dried over sodium sulfate and concentrated to dryness. Silica gel
chromatography (eluent: 3/1 diethyl ether/pentane) gave the purified
product as a pale yellow oil (31.9 mg, 22%). (Note: Compound
13C NMR (CDCl3, 100 MHz) δ: 171.6, 138.7, 135.9, 129.5, 128.9,
127.9, 127.6, 127.4, 126.1, 123.6, 115.8, 52.1, 51.0 (cis isomer),
46.0, 44.5 (cis isomer), 28.8, 20.9 (cis isomer), 11.9 (cis isomer),
11.6. IR (KBr disc): 1491, 1593, 1678, 2872, 2918, 2966, 3061,
3215 cm-1. ES-MS: m/z 252.1 [M + H]+. HRMS [M + H]+:
252.1396, C17H18NO requires 252.1388.
1
5a was also isolated in 51% yield.) H NMR (CDCl3, 500 MHz)
δ: 8.57 (bs, 1H), 7.26-7.10 (m, 6H), 7.09-7.07 (m, 1H), 7.00-
6.94 (m, 1H), 6.84-6.80 (m, 1H), 4.11 (s, 1H), 2.77 (s, 1H), 1.02
(s, 9H). 13C NMR (CDCl3, 75 MHz) δ: 172.6, 139.7, 136.9, 132.2,
128.7, 127.9, 127.1, 127.0, 122.7, 122.5, 115.6, 55.4, 48.2, 35.6,
27.8. IR (KBr disc): 1493, 1593, 1672, 2868, 2914, 2956, 3406
cm-1. ES-MS: m/z 280.2 [M + H]+. HRMS [M + H]+: 280.1688,
C19H22NO requires 280.1701.
4-tert-Butyl-2-hydroxy-3-phenyl-3,4-dihydro-2H-quinoline-1-
carboxylic Acid tert-Butyl Ester, 12a. A solution of 2a (409.1
mg, 1.38 mmol) in THF (18 mL) was cooled to -25 °C. t-BuLi
(2.75 mL, 3.47 mmol) was added dropwise over 15 min, during
which time a brown color developed. The reaction mixture was
stirred at -25 °C for 1 h and DMF (1.0 mL, 12.9 mmol) was added.
Stirring continued at -25 °C for 15 min. Hydrochloric acid (1M,
10 mL) was added, and the reaction mixture was warmed to room
temperature over 10 min. The THF was removed under reduced
pressure, and the aqueous layer was extracted with diethyl ether (2
× 10 mL). The combined organic layers were dried over sodium
sulfate and concentrated to dryness. Silica gel chromatography
(eluent: 95/5 cyclohexane/diethyl ether) gave the purified product
as two diastereoisomers. 2,3-cis-3,4-trans-12a was isolated as a
colorless solid (258.1 mg, 49%), mp 154-155 °C; 2,3-trans-3,4-
trans-12a was isolated as a colorless solid (141.0 mg, 27%), mp
71-72 °C. (Combined yield of both isomers 76%.) (Note: The
ratio of isomers obtained was dependent on the acidification
temperature, with lower temperatures giving higher yields of 2,3-
trans-3,4-trans-12a and increased temperatures resulting in im-
proved yields of 2,3-cis-3,4-trans-12a.) 2,3-cis-3,4-trans-12a: 1H
NMR (CDCl3, 300 MHz) δ: 7.43 (d, 1H, J ) 8.1 Hz), 7.28-7.16
(m, 6H), 7.12-7.07 (m, 2H), 6.00-5.97 (m, 1H), 3.79-3.76 (m,
1H), 2.83 (d, 1H, J ) 4.0 Hz), 2.36 (d, 1H, J ) 4.7 Hz), 1.52 (s,
9H), 0.88 (s, 9H). 13C NMR (CDCl3, 125 MHz) δ: 152.9, 142.0,
136.9, 132.0, 131.1, 129.2, 128.3, 126.7, 126.6, 125.9, 123.8, 81.3,
79.2, 53.8, 49.9, 36.3, 28.4, 27.8. IR (KBr disk): 3465, 2963, 1671
cm-1. ES-MS m/z 380.2 [M - H]-. HRMS [M - H]-: 380.2212,
C24H30NO3 requires 380.2226. Analysis calcd for C24H31NO3: C,
75.56; H, 8.19; N, 3.67. Found: C, 75.27; H, 7.94; N, 3.65. 2,3-
trans-3,4-trans-12a: 1H NMR (CDCl3, 300 MHz) δ: 7.34-7.12
(m, 9H), 6.38 (d, 1H, J ) 9.2 Hz), 4.72 (t, 1H, J ) 8.9 Hz), 3.50
(dd, 1H, J ) 8.9/4.0 Hz), 2.88 (d, 1H, J ) 4.0 Hz), 1.48 (s, 9H),
0.89 (s, 9H). 13C NMR (CDCl3, 75 MHz) δ: 154.9, 144.7, 140.7,
132.4, 131.3, 128.5, 128.3, 126.5, 126.5, 125.8, 124.7, 88.9, 82.0,
trans/cis-4-Butyl-3-phenyl-3,4-dihydro-1H-quinolin-2-one, 11b.
Method A: Compound 10f (56.9 mg, 0.14 mmol) was dissolved
in ethyl acetate (4 mL), and hydrochloric acid (12 M, 2 mL) was
added. The mixture was stirred at room temperature for 24 h.
Sodium hydrogen carbonate (1 M, 20 mL) was added slowly
(caution: CO2 eVolVed), and the aqueous layer was extracted with
ethyl acetate (2 × 10 mL). The combined organic layers were dried
over sodium sulfate, and the solvent was removed under reduced
pressure to give the pure product as a pale yellow solid (26.4 mg,
68%). Method B: A solution of 2a (100.9 mg, 0.34 mmol) in THF
(5 mL) was cooled to -25 °C. n-BuLi (0.51 mL, 1.02 mmol) was
added dropwise over 15 min, during which time a red color
developed. The mixture was allowed to warm to 0 °C and stirred
for 1 h by which time the color had faded to pale yellow, and treated
with methanol (1 mL). The THF was removed under reduced
pressure. The residue was dissolved in dichloromethane (10 mL)
and washed with water (10 mL). The organic layer was dried over
sodium sulfate and concentrated to dryness. Silica gel chromatog-
raphy (eluent: diethyl ether) gave the purified product as a pale
yellow solid (86.1 mg, 90%), mp 78-82 °C. [The product was
1
analyzed as a 90:10 mixture of trans/cis-11b.] H NMR (CDCl3,
500 MHz) δ: 8.32 (bs, 1H, trans isomer), 8.13 (bs, 1H, cis isomer),
7.19-7.14 (m, 6H, trans isomer), 7.10-7.07 (m, 1H, trans isomer),
7.05-7.02 (m, 1H, cis isomer), 7.00-6.97 (m, 1H, trans isomer),
6.83-6.81 (m, 1H, cis isomer), 6.78-6.77 (m, 1H, trans isomer),
4.03 (d, 1H, J ) 5.3 Hz, cis isomer), 3.84 (d, 1H, J ) 1.2 Hz,
trans isomer), 3.10-3.06 (m, 2H, both isomers), 1.76-1.68 (m,
1H, trans isomer), 1.68-1.60 (m, 1H, trans isomer), 1.45-1.38
(m, 1H, trans isomer), 1.35-1.28 (m, 3H, trans isomer), 0.88 (t,
3H, J ) 7.1 Hz, trans isomer), 0.79 (t, 3H, J ) 7.1 Hz, cis isomer).
13C NMR (CDCl3, 150 MHz) of trans isomer δ: 171.3, 138.4,
135.7, 129.2, 128.7, 127.6, 127.3, 127.2, 126.4, 123.4, 115.5, 52.1,
44.3, 35.5, 29.0, 22.6, 13.9. IR (KBr disc): 1489, 1597, 1676, 2856,
2920, 2947, 3246 cm-1. ES-MS: m/z 280.2 [M + H]+. HRMS [M
+ H]+: 280.1702, C19H22NO requires 280.1701.
57.6, 51.9, 36.8, 28.4, 27.8. IR (KBr disk): 3446, 2963, 1675 cm-1
.
ES-MS m/z 382.2 [M + H]+. HRMS [M + H]+: 382.2364, C24H32-
NO3 requires 382.2382. Analysis calcd for C24H31NO3: C, 75.56;
H, 8.19; N, 3.67. Found: C, 75.26; H, 7.99; N, 3.69.
4-Butyl-2-hydroxy-3-phenyl-3,4-dihydro-2H-quinoline-1-car-
boxylic Acid tert-Butyl Ester, 12b. A solution of 2a (398.6 mg,
1.35 mmol) in THF (15 mL) was cooled to -25 °C. PMDTA (0.85
mL, 4.06 mmol) was added followed by n-BuLi (2.40 mL, 4.10
mmol), added dropwise over 15 min. The reaction mixture was
stirred at -25 °C for 1 h and DMF (1.05 mL, 13.55 mmol) was
added. Stirring continued at -25 °C for 15 min. Hydrochloric acid
(1 M, 10 mL) was added, and the reaction mixture warmed to room
temperature over 10 min. The THF was removed under reduced
pressure, and the aqueous layer was extracted with diethyl ether (2
× 10 mL). The combined organic layers were dried over sodium
sulfate and concentrated to dryness. Silica gel chromatography
(eluent: 9/1 cyclohexane/diethyl ether) gave the purified product
as a colorless solid (326.9 mg, 63%), mp 95-103 °C. (The product
was isolated and characterized as a 1:1 mixture of two diastereoi-
somers 2,3-cis-3,4-trans-12b and 2,3-trans-3,4-trans-12b.) 1H NMR
(CDCl3, 500 MHz) δ: 7.63 (d, 1H, J ) 8.0 Hz, 2,3-trans-3,4-
trans isomer), 7.45-7.44 (m, 1H, 2,3-cis-3,4-trans isomer), 7.36-
7.17 (m, 7H 2,3-cis-3,4-trans isomer, 7H 2,3-trans-3,4-trans
isomer), 7.14-7.11 (m, 1H, 2,3-cis-3,4-trans isomer), 7.07-7.04
(m, 1H, 2,3-trans-3,4-trans isomer), 5.98-5.97 (m, 1H, 2,3-trans-
3,4-trans isomer), 5.77 (dd, 1H, J ) 7.6/3.6 Hz, 2,3-cis-3,4-trans
isomer), 3.42 (bs, 1H, 2,3-cis-3,4-trans isomer), 3.37-3.34 (m, 1H,
2,3-trans-3,4-trans isomer), 3.23 (dd, 1H, J ) 9.4/3.6 Hz, 2,3-trans-
trans/cis-4-Ethyl-3-phenyl-3,4-dihydro-1H-quinolin-2-one, 11c.
A solution of 2a (148.7 mg, 0.50 mmol) in THF (6 mL) was cooled
to -25 °C. EtLi (0.94 mL, 1.50 mmol) was added dropwise over
15 min, during which time a red color developed. The reaction
mixture was warmed to 0 °C and stirred for 2 h, by which time the
color had faded to pale orange, and treated with methanol (1 mL).
The THF was removed under reduced pressure. The residue was
dissolved in diethyl ether (10 mL) and washed with hydrochloric
acid (1 M, 10 mL). The organic layer was dried over sodium sulfate
and concentrated to dryness. Silica gel chromatography (eluent:
diethyl ether) gave the product as a pale yellow oil (106.1 mg,
84%). (The product was analyzed as an 80:20 mixture of trans:
cis-11c; 13C NMR signals quoted refer to the trans isomer unless
1
otherwise stated.) H NMR (CDCl3, 400 MHz) δ: 8.51 (bs, 1H,
trans isomer), 8.28 (bs, 1H, cis isomer), 7.33-7.25 (m, 1H, trans
isomer), 7.22-7.15 (m, 5H, trans isomer), 7.11-7.09 (m, 1H, trans
isomer), 7.06-7.02 (m, 1H, cis isomer), 7.00-6.97 (m, 1H, trans
isomer), 6.84-6.82 (m, 1H, cis isomer), 6.80-6.78 (m, 1H, trans
isomer), 4.06 (d, 1H, J ) 5.4 Hz, cis isomer), 3.85 (d, 1H, J ) 1.8
Hz, trans isomer), 3.03-2.95 (m, 2H, both isomers), 1.84-1.72
(m, 1H, trans isomer), 1.71-1.60 (m, 1H, trans isomer), 0.98 (t,
3H, J ) 7.4 Hz, trans isomer), 0.84 (t, 3H, J ) 7.4 Hz, cis isomer).
9568 J. Org. Chem., Vol. 72, No. 25, 2007