Gao et al.
MS (EI) m/z 188 (M+, 1%), 143 (47), 91 (100). Anal. Calcd. for
C12H12O2: C, 76.57; H, 6.43. Found: C, 76.56; H, 6.46.
stirred at 0 °C for another 80 min, an aqueous solution of Na2CO3
(10%) was added, and the resulting mixture was extracted with
dichloromethane (3 × 10 mL). The combined organic phase was
washed with brine (20 mL) and dried over with anhydrous MgSO4.
The solvent was removed, and the residue was subjected to silica
gel column chromatography using a mixture of petroleum ether
and ethyl acetate (11:4 - 2:1) to give pure (3S,5R)-3-benzyl-5-(4-
methoxybenzoyl)-1-(4-methoxyphenyl)pyrrolidin-2-one 14 (36.1
mg, 58%) and (3S,5S)-3-benzyl-5-(4-methoxybenzoyl)-1-(4-meth-
oxyphenyl)pyrrolidin-2-one 15 (21.3 mg, 34%). 14: mp 148-150
Synthesis of (3S,5E)-3-Benzyl-5-(iodomethylene)dihydrofu-
ran-2(3H)-one 10 from Iodolactonization of (R)-(-)-2-Benzyl-
pent-4-ynamide (R)-(-)-2b. To a mixture of (R)-(-)-2b (120 mg,
0.642 mmol) in acetonitrile (6.48 mL) and water (108 µL), which
was cooled in an ice-bath, was added iodine (326.1 mg, 2 equiv).
After the mixture was stirred for 2 h, water (9 mL) was added, and
the mixture was kept stirring for another 10 min. The saturated
aqueous Na2SO3 solution was added until the purple color of the
mixture vanished. Extraction with ethyl acetate (3 × 50 mL), drying
over with anhydrous MgSO4, and concentration under vacuum gave
a residue. Chromatography on a silica gel column using a mixture
of petroleum ether and ethyl acetate (35:1) as an eluant afforded
1
25
°C; [RD ] ) +15.0 (c 2.0, C6H6); H NMR (CDCl3/300 MHz) δ
7.87 (d, 2H, J ) 8.8 Hz), 7.35-7.20 (m, 7H), 6.93 (d, 2H, J ) 8.8
Hz), 6.83 (d, 2H, J ) 8.9 Hz), 5.34 (dd, 1H, J ) 9.6, 1.8 Hz),
3.86(s, 3H), 3.75 (s, 3H), 3.34 (dd, 1H, J ) 13.9, 4.2 Hz), 3.07-
2.96 (m, 1H), 2.80 (dd, 1H, J ) 13.7, 9.2 Hz), 2.34-2.23 (m, 1H),
2.17-2.07 (m, 1H); 13C NMR (75 MHz/CDCl3) δ 194.6, 175.4,
164.2, 157.2, 139.0, 131.6, 130.7, 129.1, 128.5, 126.9, 126.5, 124.1,
114.2, 62.1, 55.6, 55.4, 42.6, 36.9, 29.9; IR (KBr) 1688 cm-1; MS
(EI) m/z 416 (M+ + 1, 2), 415 (M+, 6%), 280 (100). Anal. Calcd.
for C26H25NO4: C, 75.16; H, 6.06; N, 3.37. Found: C, 74.96; H,
25
pure 10 (107 mg, 53%): oil; [RD ] ) -32.7 (c 3.0, CHCl3); ee
1
>99.5% (HPLC analysis); H NMR (CDCl3/300 MHz) δ 7.29-
7.11 (m, 5H), 5.67 (t, 1H, J ) 2.3 Hz), 3.19-3.07 (m, 2H), 2.89-
2.74 (m, 2H), 2.52-2.49 (m, 1H); 13C NMR (75 MHz/CDCl3) δ
176.1, 153.2, 137.1, 128.92, 128.89, 127.2, 53.5, 41.7, 36.5, 32.9;
IR (KBr) 1802, 1656 cm-1; MS (EI) m/z 315 (M+ + 1, 8), 314
(M+, 100%), 187 (94), 145 (66), 117 (88), 91 (64). Anal. Calcd.
for C12H11IO2: C, 45.88; H, 3.53. Found: C, 45.52; H, 3.73.
Synthesis of (3S,5R)-3-Benzyl-5-(4-methoxybenzoyl)-1-(4-
methoxyphenyl)pyrrolidin-2-one 14 and (3S,5S)-3-Benzyl-5-(4-
methoxybenzoyl)-1-(4-methoxyphenyl)pyrrolidin-2-one 15. A
solution of DCC (0.525 mmol) and HOBT (0.525 mmol) in CH2-
Cl2 (1 mL) was added to the solution of 2-benzylpent-4-ynoic acid
(S)-(-)-3b (94 mg, 0.5 mmol) in CH2Cl2 (1 mL) while cooling in
an ice bath. p-Anisidine (92.3 mg, 0.75 mmol) solution in CH2Cl2
(1 mL) was then added, and the resulting mixture was stirred at
room temperature for 24 h. A saturated ammonium chloride solution
(10 mL) was then added, and the organic phase was separated. The
aqueous phase was extracted with CH2Cl2 (3 × 20 mL), and the
organic phase was combined and dried over with anhydrous MgSO4.
After removal of the solvent, the residue was subjected to silica
gel column chromatography with a mixture of petroleum ether and
ethyl acetate (4:1) as the eluant to give 12 (131.9 mg, 90%): mp
6.13; N, 3.68. 15: oil; [RD ] ) -30.4 (c 2.0, C6H6); 1H NMR
25
(CDCl3/300 MHz) δ 7.88 (d, 2H, J ) 8.9 Hz), 7.35 (d, 2H, J )
9.0 Hz), 7.23-7.14 (m, 5H), 6.92 (d, 2H, J ) 8.9 Hz), 6.84 (d,
2H, J ) 9.0 Hz), 5.58 (dd, 1H, J ) 8.7, 6.7 Hz), 3.87(s, 3H), 3.75
(s, 3H), 3.44 (dd, 1H, J ) 14.0, 3.9 Hz), 3.07-2.96 (m, 1H), 2.72
(dd, 1H, J ) 13.8, 11.3 Hz), 2.62-2.52 (m, 1H), 1.87-1.78 (m,
1H); 13C NMR (75 MHz/CDCl3) δ 195.3, 175.3, 164.2, 157.3,
139.3, 131.4, 130.7, 128.9, 128.6, 127.3, 126.4, 124.3, 114.2, 62.3,
55.6, 55.4, 44.3, 37.6, 29.4; IR (KBr) 1690 cm-1; MS (EI) m/z
416 (M+ + 1, 2), 415 (M+, 7%), 280 (100). HRMS for C26H25-
NO4: 415.1784. Found: 415.1786.
Synthesis of (R)-3-Allyl-1-phenyl-3,4-dihydro-1H-quinolin-2-
one 19. Under argon protection, a mixture of (R)-2-(2-bromoben-
zyl)pent-4-enamide 18 (ee > 99.5%) (80 mg, 0.3 mmol), CuI (22.9
mg, 0.12 mmol), DMGC (33.5 mg, 0.24 mmol), Cs2CO3 (97.7 mg,
0.3 mmol), and iodobenzene (50.4 µL, 0.45 mmol) in dry
1,4-dioxane (12 mL) was gently refluxed for 19 h. After filtration
through a short silica gel (100-200 mesh) pad, the filtrate was
concentrated under vacuum. The residue was chromatographed on
a silica gel column eluted with a mixture of petroleum ether and
ethyl acetate (12:1) to give pure 19 (72 mg, 91%) as white solids:
1
25
123-124 °C; [RD ] ) +54.7 (c 1.5, CHCl3); H NMR (CDCl3/300
MHz) δ 7.32-7.20 (m, 7H), 6.97 (br s, 1H, CONH), 6.80 (d, 2H,
J ) 8.9 Hz), 3.76 (s, 3H), 3.06-2.96 (m, 2H), 2.70-2.46 (m, 3H),
2.10-2.09 (m, 1H); 13C NMR (75 MHz/CDCl3) δ 171.3, 156.6,
139.0, 130.4, 129.0, 128.7, 126.7, 122.2, 114.1, 81.9, 70.7, 55.5,
49.5, 38.2, 21.5; IR (KBr) 3430, 3297, 1652 cm-1; MS (EI) m/z
295 (M+ + 2, 2), 294 (M+ + 1, 13), 293 (M+, 76%), 254 (63),
123 (100). Anal. Calcd. for C19H19NO2: C, 77.79; H, 6.53; N, 4.77.
Found: C, 77.43; H, 6.65; N, 4.82.
25
mp 77-78 °C; [RD ] ) +20.0 (c 1.5, CHCl3); ee >99.5% (HPLC
analysis); 1H NMR (CDCl3/300 MHz) δ 7.53-7.41 (m, 3H), 7.23-
7.19 (m, 3H), 7.05-6.98 (m, 2H), 6.34 (d, 1H, J ) 8.0 Hz), 5.95-
5.81 (m, 1H), 5.14-5.08 (m, 2H), 3.13-3.07 (m, 1H), 2.93-2.70
(m, 3H), 2.31-2.26 (m, 1H); 13C NMR (75 MHz/CDCl3) δ 171.8,
141.3, 138.7, 135.5, 129.8, 129.0, 128.10, 128.06, 127.1, 124.8,
122.9, 117.4, 116.8, 40.6, 34.0, 30.4; IR (KBr) 1676 cm-1; MS
(EI) m/z 265 (M++2, 2), 264 (M++1, 16), 263 (M+, 100%), 180
(50). Anal. Calcd. for C18H17NO: C, 82.10; H, 6.51; N, 5.32.
Found: C, 82.45; H, 6.57; N, 5.52.
Under argon protection, a mixture of 12 (59 mg, 0.2 mmol),
p-iodoanisole (71 mg, 0.3 mmol), Pd(PPh3)4 (11.6 mg, 5 mol %),
CuI (15.4 mg, 0.08 mmol), and Et3N (67.1 µL, 0.5 mmol) in dry
THF (1 mL) was stirred at room temperature for 1 h. After filtration
through a short silica gel (100-200 mesh) pad, the filtrate was
concentrated under vacuum and subjected to a silica gel column
chromatography using a mixture of petroleum ether and ethyl
acetate (3:1) as the mobile phase. Compound 13 (79.3 mg, 99%)
25
was obtained as brown solids: mp 135-136 °C; [RD ] ) -29.0 (c
1
2.0, CHCl3); H NMR (CDCl3/300 MHz) δ 7.32-7.20 (m, 9H),
7.09 (br s, 1H, CONH), 6.80 (dd, 4H, J ) 8.8, 2.0 Hz), 3.80 (s,
3H), 3.77 (s, 3H), 3.13-3.00 (m, 2H), 2.81-2.67 (m, 3H); 13C
NMR (75 MHz/CDCl3) δ 171.6, 159.4, 156.6, 139.2, 133.0, 130.6,
129.0, 128.7, 126.6, 122.1, 115.4, 114.09, 113.95, 85.7, 82.9, 55.5,
55.3, 49.9, 38.2, 22.5; IR (KBr) 3318, 1653 cm-1; MS (EI) m/z
401 (M+ + 2, 1), 400 (M+ + 1, 6), 399 (M+, 20%), 308 (100).
HRMS for C26H25NO3: 399.1834. Found: 399.1830.
To a solution of 13 (60 mg, 0.15 mmol) in CF3CH2OH (1.4 mL),
which was cooled in an ice-bath, was added dropwise a solution
of PIFA (95 mg, 0.22 mmol) in CF3CH2OH (1.6 mL). After being
Acknowledgment. We thank the Ministry of Science and
Technology (2003CB716005, 2006CB806106), the National
Natural Science Foundation of China, and the Chinese Academy
of Sciences for financial support.
Supporting Information Available: Preparation of all starting
nitriles, spectroscopic data of all products, 1H and 13C NMR spectra
of 2, 3, 5, 6, 8, 9, 10-15, and 17-19, HPLC analysis of all chiral
products. This material is available free of charge via the Internet
(21) Kotake, T.; Hayashi, Y.; Rajesh, S.; Mukai, Y.; Takiguchi, Y.;
Kimura, T.; Kiso, Y. Tetrahedron 2005, 61, 3819.
JO070581B
6066 J. Org. Chem., Vol. 72, No. 16, 2007