5830
J. A. Seijas et al. / Tetrahedron Letters 46 (2005) 5827–5830
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38. Seijas, J. A.; Vazquez-Tato, M. P.; Martınez, M. M.;
Santiso, V. Tetrahedron Lett. 2004, 45, 1937–1939.
39. Experimental procedure for compound 5. Freshly
prepared Grignard reagent 4b—by refluxing a-bromo-
styrene (6.26 g, 34.2 mmol), Mg (1.56 g, 64.2 mmol) and
1,2-dibromoethane (462 mg, 2.46 mmol) in THF for
2 h—was added to a solution of 2-methoxy-2-phenyl-
4,4-dimethyl-2-oxazoline 3 (3.36 g, 16.4 mmol) in dry
THF (30 ml) at room temperature. After being stirred
for 16 h, the mixture was partitioned between satd. aq.
NH4Cl and ether. The ether extract was dried, concen-
trated and purified by column chromatography (SiO2,
AcOEt/hexane, 3:7), giving 5 (4.07 g, 90%) as a pale
yellow oil.
0.24 mmol) in abs. EtOH (10 ml) and heated at 50 °C for
12 h. The solvent was evaporated and the residue purified
by column chromatography (SiO2, AcOEt/hexane, 3:7),
giving compound 8 (34 mg, 80% yield) as a white solid.
44. Experimental procedure for 2-methyl-4-phenyltetrahydro-
isoquinoline (1a). A solution of compound 8 (66 mg,
0.28 mmol) in THF (10 ml) was added to a suspension of
LiAlH4 (22 mg, 0.59 mmol) in THF (5 ml) at room
temperature, and then was refluxed for 2 h. The reaction
was worked up by sequential addition of water (0.5 ml), aq
10% NaOH (1 ml) and water (0.5 ml). The organic layer
was dried, evaporated and purified by column chroma-
tography, (SiO2, AcOEt/hexane, 4:6), giving 2-methyl-4-
phenyltetrahydroisoquinoline (1a) (57 mg, 92%) as a
viscous oil.
40. Experimental procedure for compound 6. 2-Oxazoline 5
(306 mg, 1.11 mmol) in dry THF (15 ml) was added
dropwise to a solution of lithium amide, prepared by the
addition of n-BuLi (1.97 ml, 3.15 mmol, 1.6 M in hexanes)
to a solution of N-methylbenzylamine (381 mg, 3.15
mmol), in dry THF at 0 °C for 30 min. The reaction was
allowed to warm to room temperature and left for 24 h.
The reaction mixture was quenched with MeOH, and
partitioned between 10% aq NaOH and ether. The ether
extract was dried, evaporated and purified by column
chromatography (SiO2, AcOEt/hexane, 3:7), giving com-
pound 5 (279 mg, 63%) as a colorless oil.
41. In fact, the LUMO energy of the compound without
phenyl substituent is lower than that of LUMO+1 for
compound with the phenyl group. The addition must take
place at LUMO+1, in order to have the appropriate
orbital coefficients with lobes on the vinyl group. Orbitals
were modeled by Fujitsu, CAChe Pro, version 6.1, based
on PM3 Hamiltonian.
42. Experimental procedure for compound 7. 20% aq H2SO4
(20 ml) in absolute EtOH was added to a solution of
compound 6 (162 mg, 0.41 mmol) at room temperature.
After refluxing for 24 h, the solvent was evaporated and
the resulting residue was partitioned between ether and
satd aq NaHCO3. The aqueous layer was extracted with
ether, and the combined ether extracts were dried,
concentrated and purified by column chromatography
(SiO2, AcOEt/hexane, 3:7) giving 7 (91 mg, 60%) as a
yellow oil.
43. Experimental procedure for compound 8. A solution of
compound 7 (67 mg, 0.18 mmol) in AcOH/EtOH (1:9,
10 ml) in presence of Pd–C (15 mg) was hydrogenated at
50 psi for 12 h. The reaction mixture was filtrated through
Celite, and concentrated. The resulting residue was
45. All the new compounds exhibit satisfactory spectral data.
Selected spectral data. Compound 6: IR (KBr film): 1650
1
(C@N) cmÀ1. H NMR (CDCl3, 300 MHz): 1.35 (s, 3H,
Me), 1.40 (s, 3H, Me), 2.30 (s, 3H, NMe), 2.90–3.02 (m,
2H, CH2CHPh), 3.55 (d, 1H, PhCH2NMe, J = 13.2 Hz),
3.61 (d, 1H, PhCH2NMe, J = 13.3 Hz), 4.09 (s, 2H,
CH2O), 5.60 (t, 1H, J = 7.8 Hz, CH2CHPh), 7.17–7.36
(m, 13H, ArH), 7.74 (d, 1H, J = 6.7 Hz, ArH). 13C NMR
(CDCl3, 75 MHz): 28.5 (NMe), 42.4, 43.3 (C(CH3)2), 62.1
(PhCH2NMe), 62.6 (CH2CHPh), 67.9 (C(CH3)2), 78.6
(CH2O), 125.8, 126.0, 126.8, 127.9, 128.1, 128.7, 128.8,
129.1, 130.0, 130.4, 139.3, 143.6 and 143.7 (Ar), 162.6
(C@N). MS m/z (EI): 398 (M+, 1), 134 (100), 91 (62).
C27H30N2O calcd. (%): C, 81.37; H, 7.59; N, 7.03, found
C, 81.41; H, 8.08; N, 7.04. Compound 8: mp 95.6–97.3 °C
(hexane) (lit.48 79–80 °C). IR (KBr): 1642 (CON) cmÀ1. 1H
NMR (CDCl3, 300 MHz): 3.10 (s, 3H, NMe), 3.71 (dd,
1H, J = 8.0, 12.4 Hz, CH2CHPh), 3.81 (dd, 1H, J = 5.2,
12.4 Hz, CH2CHPh), 4.33 (dd, 1H, J = 5.2, 8.0 Hz,
CH2CHPh), 6.90 (m, 1H, ArH), 7.18 (m, 2H, ArH),
7.30–7.39 (m, 5H, ArH), 8.19 (m, 1H, ArH). 13C NMR
(CDCl3, 75 MHz): 35.3 (NMe), 43.9 (CH2CHPh), 55.0
(CH2CHPh), 121.1, 127.3, 127.4, 128.2, 128.4, 128.8,
129.4, 131.8, 140.6 and 140.7 (Ar), 164.6 (C@O). MS
(EI): 238 (M++1, 7), 237 (M+, 34), 194 (100). C16H15NO
calcd. (%): C, 80.98; H, 6.37; N, 5.90, found C, 80.53; H,
6.60; N: 5.93.
46. Miller, R. B.; Svoboda, J. J. Synth. Commun. 1994, 24,
1187–1193.
´
´
47. Martınez, M. M.; Onega, M. G.; Tellado, M. F.; Seijas,
´
J. A.; Vazquez-Tato, M. P. Tetrahedron 1997, 53, 14127–
14130.
48. Narasimhan, N. S.; Patil, P. A. J. Chem. Soc., Chem.
Commun. 1987, 191–192.
dissolved in
a solution of sodium acetate (20 mg,