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S.-H. Xiang et al. / Tetrahedron: Asymmetry 20 (2009) 2021–2026
(400 MHz, CDCl3) d 1.20 (d, J = 6.6 Hz, 3H, CH3), 2.60 (d, J = 6.7 Hz,
2H, H-3), 3.65 (dq, J = 6.5, 6.6 Hz, 1H, H-5), 3.96 (d, J = 15.1 Hz, 1H,
NCH2), 4.10 (dt, J = 6.5, 6.7 Hz, 1H, H-4), 4.44 (d, J = 11.9 Hz, 1H,
OCH2), 4.53 (d, J = 11.9 Hz, 1H, OCH2), 5.01 (d, J = 15.1 Hz, 1H,
NCH2), 7.21–7.36 (m, 10H, ArH) ppm; 13C NMR (100 MHz, CDCl3)
d 12.5, 36.5, 43.8, 56.0, 71.4, 73.5, 127.4, 127.5, 127.8, 127.9,
128.4, 128.6, 136.6, 137.7, 172.0 ppm; MS (ESI): 318 m/z
(M+Na+); Anal. Calcd for C19H21NO2: C, 77.26; H, 7.17; N, 4.74.
Found: C, 77.71; H, 6.75; N, 4.75.
4.10. (4S,5S)-1-Benzyl-4-(benzyloxy)-5-isobutyl-2-
pyrrolidinone 1be
Following the general procedure, the hydrogenation of enamide
9be8a (130 mg, 0.39 mmol) for 12 h gave compound 1be (89 mg,
69%) as a colorless oil. ½a D20
ꢀ
¼ þ7:3 (c 1.0, CHCl3); IR (film) mmax
:
3034, 2957, 2937, 2867, 1692, 1451, 1412 cmꢁ1
;
1H NMR (400
MHz, CDCl3) d 0.75 (d, J = 6.6 Hz, 3H, CH3), 0.88 (d, J = 6.6 Hz, 3H,
CH3), 1.29–1.39 (m, 1H, C2H6CH), 1.54–1.68 (m, 1H, NCHCH2),
1.78–1.88 (m, 1H, NCHCH02), 2.54 (dd, J = 6.0, 16.8 Hz, 1H, H-3),
2.64 (dd, J = 3.8, 16.8 Hz, 1H, H-30), 3.54 (ddd, J = 3.8, 5.5, 6.0 Hz,
1H, H-5), 3.93 (d, J = 15.1 Hz, 1H, NCH2), 4.08 (ddd, J = 4.2, 5.5,
9.5 Hz, 1H, H-4), 4.38 (d, J = 11.6 Hz, 1H, OCH2), 4.56 (d, J = 11.6 Hz,
1H, OCH2), 5.06 (d, J = 15.1 Hz, 1H, NCH2), 7.18–7.38 (m, 10H, ArH)
ppm; 13C NMR (100 MHz, CDCl3) d 21.9, 23.7, 24.7, 35.4, 36.8, 44.0,
58.9, 71.2, 73.1, 127.4, 127.5, 127.8, 127.8, 128.4, 128.6, 136.6,
137.6, 172.8 ppm; MS (ESI): 360 m/z (M+Na+); Anal. Calcd for
C22H27NO2: C, 78.30; H, 8.06; N, 4.15. Found: C, 77.92; H, 8.19; N,
4.04.
4.7. (4S,5S)-1-Benzyl-4-(benzyloxy)-5-ethyl-2-pyrrolidinone 1bb
Following the general procedure, the hydrogenation of enamide
9bb8a (100 mg, 0.33 mmol) for 2 h gave compound 1bb (80 mg,
80%) as white crystals in CHCl3. Mp 80–82 °C; ½a D20
¼ ꢁ2:7 (c 1.0,
ꢀ
CHCl3); IR (film) mmax: 3030, 2969, 2930, 2871, 1688, 1455, 1424,
1065 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.88 (t, J = 7.4 Hz, 3H,
;
CH3), 1.68–1.80 (m, 2H, CH2), 2.56 (dd, J = 6.1, 16.8 Hz, 1H, H-3),
2.63 (dd, J = 4.8, 16.8 Hz, 1H, H-30), 3.48 (ddd, J = 3.9, 6.1, 8.8 Hz,
1H, H-5), 3.97 (d, J = 15.1 Hz, 1H, OCH2), 4.13 (ddd, J = 4.8, 6.1,
6.1 Hz, 1H, H-4), 4.41 (d, J = 11.7 Hz, 1H, NCH2), 4.57 (d, J =
11.7 Hz, 1H, NCH2), 5.02 (d, J = 15.1 Hz, 1H, OCH2), 7.18–7.38 (m,
10H, ArH) ppm; 13C NMR (100 MHz, CDCl3) d 9.7, 19.9, 37.1, 44.0,
61.6, 71.3, 72.8, 127.4, 127.5, 127.8, 127.8, 128.4, 128.6, 136.7,
137.8, 172.8 ppm; MS (ESI): 332 m/z (M+Na+); Anal. Calcd for
C20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C, 77.20; H, 7.36;
N, 4.44.
4.11. (4S,5S)-1,5-Dibenzyl-4-(benzyloxy)-2-pyrrolidinone 1bf
Following the general procedure, the hydrogenation of enamide
9bf8a (136 mg, 0.37 mmol) for 4 h gave compound 1bf (130 mg,
94%) as a white solid. Mp 82–84 °C (EtOAc/PE); ½a D20
¼ ꢁ4:2 (c
ꢀ
1.0, CHCl3); IR (film) mmax: 3062, 3030, 2918, 2856, 1696, 1500,
1450, 1100 cmꢁ1 1H NMR (400 MHz, CDCl3) d 2.50 (dd, J = 6.4,
;
16.8 Hz, 1H, H-3), 2.56 (dd, J = 5.5, 16.8 Hz, 1H, H-30), 2.90 (dd,
J = 5.9, 13.5 Hz, 1H, NCHCH2), 3.09 (dd, J = 7.9, 13.5 Hz, 1H,
NCHCH2), 3.71 (d, J = 15.1 Hz, 1H, NCH2), 3.78 (ddd, J = 5.9, 5.9,
7.9 Hz, 1H, NCH), 3.97 (ddd, J = 5.5, 5.9, 6.4 Hz, 1H, OCH), 4.30 (d,
J = 11.5 Hz, 1H, OCH2), 4.46 (d, J = 11.5 Hz, 1H, OCH2), 5.07 (d,
J = 15.1 Hz, 1H, NCH2), 7.05–7.11 (m, 4H, ArH), 7.18–7.36 (m,
11H, ArH) ppm; 13C NMR (100 MHz, CDCl3) d 33.4, 36.5, 44.4,
61.8, 71.4, 73.4, 126.5, 127.5, 127.7, 127.8, 127.9, 128.4(2C),
128.6, 129.4, 136.4, 135.5, 137.8, 172.5 ppm; MS (ESI): 394 m/z
(M+Na+); Anal. Calcd for C25H25NO2: C, 80.83; H, 6.78; N, 3.77.
Found: C, 80.78; H, 7.11; N, 3.62.
4.8. (4S,5S)-1-Benzyl-4-(benzyloxy)-5-butyl-2-pyrrolidinone 1bc
Following the general procedure, the hydrogenation of ena-
mide 9bc8a (100 mg, 0.30 mmol) for 2 h gave compound 1bc
(83 mg, yield: 83%) as a colorless oil. ½a D20
¼ þ7:8 (c 1.0, CHCl3);
ꢀ
IR (film) mmax
: 3025, 2952, 2935, 2863, 1688, 1456, 1423,
1092 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.84 (t, J = 6.9 Hz, 3H,
;
CH3), 1.12–1.38 (m, 4H, CH3C2H4), 1.55–1.66 (m, 1H, NCHCH2),
1.71–1.81 (m, 1H, NCHCH02), 2.55 (dd, J = 6.3, 16.8 Hz, 1H, H-3),
2.62 (dd, J = 4.6, 16.8 Hz, 1H, H-30), 3.46–3.54 (ddd, J = 4.0, 5.9,
9.5 Hz, 1H, H-5), 3.97 (d, J = 15.1 Hz, 1H, NCH2), 4.09 (ddd,
J = 4.6, 5.9, 6.3 Hz, 1H, H-4), 4.39 (d, J = 11.7 Hz, 1H, OCH2), 4.56
(d, J = 11.7 Hz, 1H, OCH2), 5.02 (d, J = 15.1 Hz, 1H, NCH2), 7.18–
7.37 (m, 10H, ArH) ppm; 13C NMR (100 MHz, CDCl3) d 13.8,
22.8, 26.5, 27.3, 37.0, 44.0, 60.6, 71.2, 72.9, 127.4, 127.5, 127.7,
127.8, 128.3, 128.6, 136.6, 137.6, 172.7 ppm; MS (ESI): 360 m/z
(M+Na+); HRESIMS calcd for [C22H27NO2+H+]: 338.2120; found:
338.2122.
4.12. (S,E)-1-Benzyl-4-(benzyloxy)-5-octylidene-2-
pyrrolidinone 9bg
To a solution of hemiaminal 8bg (500 mg, 1.22 mmol) in dry
CH2Cl2 (12 mL) was added 25 mg of TsOH at 0 °C. The mixture
was stirred for 20 min. The reaction was quenched with saturated
NaHCO3 (5 mL), and the resultant mixture was extracted with
CH2Cl2 (3 ꢂ 10 mL). The combined organic phases were washed
with brine (5 mL), dried over anhydrous Na2SO4, and filtered. After
concentration under reduced pressure, the residue was purified by
flash chromatography on silica gel (EtOAc/PE = 1: 5) to give ena-
mide 9bg (260 mg, yield 55%; 92% based on recovered starting
4.9. (4S,5S)-1-Benzyl-4-(benzyloxy)-5-pentyl-2-pyrrolidinone 1bd
Following the general procedure, the hydrogenation of enamide
9bd8a (100 mg, 0.29 mmol) for 2 h gave compound 1bd (72 mg,
72%) as a colorless oil. ½a D20
ꢀ
¼ þ7:9 (c 1.0, CHCl3); IR (film) mmax
:
material (40%)) as a colourless oil. ½a D20
¼ þ80:0 (c 1.0, CHCl3); IR
ꢀ
3027, 2957, 2933, 2853, 1695, 1450, 1415, 1099 cmꢁ1
;
1H NMR
(film) mmax: 3027, 2925, 2848, 1727, 1664, 1454, 1408, 1337,
(400 MHz, CDCl3) d 0.84 (t, J = 6.8 Hz, 3H, CH3), 1.13–1.38 (m, 6H,
CH3C3H6), 1.52–1.68 (m, 1H, NCHCH2), 1.71–1.83 (m, 1H, NCHCH2),
2.55 (dd, J = 6.0, 16.8 Hz, 1H, H-3), 2.62 (dd, J = 4.6, 16.8 Hz, 1H, H-
30), 3.50 (ddd, J = 3.9, 6.0, 9.4 Hz, 1H, H-5), 3.97 (d, J = 15.1 Hz, 1H,
NCH2), 4.10 (ddd, J = 4.6, 6.0, 6.4 Hz, 1H, H-4), 4.40 (d, J = 11.7 Hz,
1H, OCH2), 4.57 (d, J = 11.7 Hz, 1H, OCH2), 5.02 (d, J = 15.1 Hz, 1H,
NCH2), 7.18–7.34 (m, 10H, ArH) ppm; 13C NMR (100 MHz, CDCl3)
d 13.9, 22.5, 24.9, 26.9, 32.0, 37.1, 44.1, 60.6, 71.3, 73.0, 127.4,
127.6, 127.8, 127.9, 128.4, 128.6, 136.7, 137.7, 172.8 ppm; MS
(ESI): 374 m/z (M+Na+); Anal. Calcd for C23H29NO2: C, 78.59; H,
8.32; N, 3.99. Found: C, 78.28; H, 8.25; N, 3.81.
1205 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.90 (t, J = 7.0 Hz, 3H,
;
CH3), 1.13–1.39 (m, 10H, CH3C5H10), 1.98–2.16 (m, 2H, C6H13CH2),
2.71 (dd, J = 2.1, 17.8 Hz, 1H, H-3), 2.80 (dd, J = 6.9, 17.8 Hz, 1H,
H-30), 4.47 (d, J = 11.2 Hz, 1H, OCH2), 4.56 (d, J = 11.2 Hz, 1H,
OCH2), 4.72 (s, 2H, NCH2), 4.78 (ddd, J = 1.1, 2.1, 6.9 Hz, 1H, H-4),
4.86 (dt, J = 1.1, 7.7 Hz, 1H, C@CH), 7.21–7.40 (m, 10H, ArH) ppm;
13C NMR (100 MHz, CDCl3) d 14.0, 22.6, 26.7, 29.1(2C), 30.2, 31.7,
36.6, 43.4, 69.9, 70.2, 108.2, 127.0, 127.2, 127.9, 128.1, 128.4,
128.5, 135.9, 137.3, 138.7, 173.0 ppm; MS (ESI): 414 m/z
(M+Na+); Anal. Calcd for C26H33NO2: C, 79.76; H, 8.50; N, 3.58.
Found: C, 79.98; H, 8.19; N, 3.41.