P.-Q. Huang et al.
IR (KBr): n=3390, 2969, 2930, 2864, 1657, 1631, 1505, 1459, 1366, 1333,
2955, 2929, 1651, 1630, 1514, 1462, 1348, 1250, 1179, 1037 cmÀ1; MS
(ESI): m/z (%): 370 (100) [M+Na+]; HRMS calcd for [C20H29NO4+Na+]:
370.1989; found: 370.2000.
˜
1248, 1122, 1027 cmÀ1; MS (ESI): m/z (%): 320 (100) [M+H+], 342 (92)
[M+Na+]; HRMS: m/z: calcd for [C18H25NO4+Na+]: 342.1676; found:
342.1653.
(R)-5-Hexyl-1-[(R)-1-(3-hexyl-4-methoxyphenyl)-2-hydroxyethyl]-4-me-
thoxy-1H-pyrrol-2(5H)-one (14d): Dialkylated product 14d: white solid;
m.p. 148–1508C (EtOAc/PE); [a]2D0 =À11.3 (c=1.0 in CHCl3); 1H NMR
(400 MHz, CDCl3): d=0.88 (t, J=6.9 Hz, 6H), 0.93–1.07 (m, 1H), 1.15–
1.40 (m, 13H), 1.49–1.57 (m, 2H), 1.64–1.70 (m, 2H), 2.56 (t, J=7.7 Hz,
2H), 3.77 (s, 3H), 3.79 (s, 3H), 3.81 (t, J=4.0 Hz, 1H), 3.93 (ddd, J=3.2,
7.2, 12.2 Hz, 1H), 4.24 (ddd, J=7.2, 8.0, 12.2 Hz, 1H), 4.35 (dd, J=3.2,
8.0 Hz, 1H), 5.06 (s, 1H), 5.07 (t, J=7.2 Hz), 6.78 (d, J=8.3 Hz, 1H),
6.94 (d, J=2.3 Hz, 1H), 6.99 ppm (dd, J=2.3, 8.3 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=14.0, 14.1, 21.6, 22.6, 22.7, 27.5, 29.1, 29.2, 29.7,
30.2, 31.6, 31.7, 55.3, 58.1, 60.5, 61.7, 65.0, 94.5, 110.3, 125.4, 128.5, 129.9,
131.7, 157.0, 173.5, 175.9 ppm; IR (KBr): n˜ =3360, 2954, 2927, 2914, 2856,
1658, 1630, 1501, 1352, 1249, 1033 cmÀ1; MS (ESI): m/z (%): 454.2 (100)
[M+Na+]; HRMS: m/z: calcd for [C26H41NO4+H+]: 432.3108; found:
432.3090.
5-Butyl-1-[(R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]-4-methoxy-1H-
pyrrol-2(5H)-one (12c): Diastereomeric ratio: 33:1 (combined yield:
78%), dialkylated product 14c (2.8%), and recovered (R)-9 (7%).
(5R,1’R)-12c (major diastereomer): Colorless oil; [a]2D0 =À27.0 (c=1.1 in
CHCl3); 1H NMR (400 MHz, CDCl3): d=0.87 (t, J=7.2 Hz, 3H), 0.93–
1.04 (m, 1H), 1.13–1.33 (m, 3H), 1.63–1.73 (m, 2H), 3.77 (s, 3H), 3.78 (s,
3H), 3.82 (t, J=4.0 Hz, 1H), 3.98 (ddd, J=3.3, 7.2, 12.2 Hz, 1H), 4.22
(ddd, J=7.2, 7.7, 12.2 Hz, 1H), 4.39 (dd, J=3.3, 7.7 Hz, 1H), 5.07 (s,
1H), 5.16 (t, J=7.2 Hz, 1H), 6.84–6.88 (m, 2H), 7.12–7.16 ppm (m, 2H);
13C NMR (100 MHz, CDCl3): d=13.8, 22.4, 23.7, 27.2, 55.2, 58.1, 60.4,
61.2, 64.8, 94.4, 114.1, 114.1, 128.2, 128.2, 130.3, 159.0, 173.5, 175.9 ppm;
˜
IR (KBr): n=3294, 2961, 2930, 2857, 1657, 1629, 1514, 1352, 1237, 1171,
1035 cmÀ1; MS (ESI): m/z (%): 342 (100) [M+Na+]; elemental analysis
calcd (%) for C18H25NO4: C 67.69, H 7.89, N 4.39; found: C 67.90, H
8.11, N 4.45.
5-Allyl-1-[(R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]-4-methoxy-1H-
pyrrol-2(5H)-one (12e): Diastereomeric ratio: 9.2:1 (combined yield:
49%), recovered (R)-9 (10%).
ACHTUNGTRENNUNG
(5S,1’R)-13c (minor diastereomer): Colorless oil; [a]2D0 =+51.6 (c=1.1 in
CHCl3); 1H NMR (400 MHz, CDCl3): d=0.68 (t, J=6.9 Hz, 3H), 0.80–
1.08 (m, 4H), 1.45–1.54 (m, 1H), 1.58–1.67 (m, 1H), 3.76 (s, 3H), 3.79 (s,
3H), 3.77–3.84 (m, 1H), 3.93 (t, J=4.1 Hz, 1H), 4.06 (dd, J=4.3,
11.4 Hz, 1H), 4.14–4.24 (m, 1H), 4.71 (dd, J=4.3, 7.8 Hz, 1H), 5.06 (s,
1H), 6.83–6.88 (m, 2H), 7.25–7.29 ppm (m, 2H); 13C NMR (100 MHz,
CDCl3): d=13.7, 22.3, 23.9, 28.9, 55.3, 58.0, 60.8, 62.8, 65.0, 94.2, 113.9,
A
CHCl3); 1H NMR (400 MHz, CDCl3, two rotamers, M/m=3.6:1): d=
2.38–2.48 (m, 1H), 2.48–2.58 (m, 1H), 3.78 (s, 3H; rotamer M), 3.79 (s,
3H; rotamer M), 3.83 (dd, J=3.7, 4.6 Hz, 1H), 3.86 (s, 3H; rotamer m),
3.98 (ddd, J=3.1, 6.6, 12.3 Hz, 1H), 4.12–4.25 (m, 1H), 4.37 (dd, J=3.0,
7.1 Hz, 1H; rotamer m), 4.44 (dd, J=3.1, 7.5 Hz, 1H; rotamer M), 5.02–
5.16 (m, overlapped, 3H), 5.08 (s, overlapped, 1H), 5.48–5.60 (m, 1H),
6.76–6.79 (m, 2H; rotamer m), 6.86–6.89 (m, 2H; rotamer M), 7.12–7.15
(m, 2H; rotamer M), 7.17–7.20 ppm (m, 2H; rotamer m); 13C NMR
(100 MHz, CDCl3, two rotamers): d=32.2, 55.3, 56.4, 58.2, 58.2, 60.2,
60.8, 61.7, 64.6, 64.8, 94.8, 100.0, 111.0, 114.2, 114.2, 119.3, 119.5, 128.3,
128.3, 128.5, 130.1, 130.3, 130.3, 132.4, 132.4, 138.0, 159.2, 173.4,
175.3 ppm; IR (KBr): n˜ =3368, 3117, 3070, 2969, 2938, 2844, 1657, 1632,
1514, 1365, 1249, 1179, 1034 cmÀ1; MS (ESI): m/z (%): 326.1 (100)
[M+Na+]; HRMS: m/z: calcd for [C17H21NO4+H+]: 304.1543; found:
304.1531.
˜
113.9, 129.1, 129.1, 130.2, 159.1, 173.7, 175.7 ppm; IR (KBr): n=3291,
2965, 2931, 2860, 1655, 1630, 1514, 1350, 1237, 1171, 1032 cmÀ1; MS
(ESI): m/z (%): 342 (100) [M+Na+]; HRMS: m/z: calcd for
[C18H25NO4+Na+]: 342.1676; found: 342.1665.
(R)-5-Butyl-1-[(R)-1-(3-butyl-4-methoxyphenyl)-2-hydroxyethyl]-4-me-
thoxy-1H-pyrrol-2(5H)-one (14c): Dialkyl product 14c: white solid; m.p.
135–1368C (EtOAc/PE); [a]2D0 =À23.5 (c=0.96 in CHCl3); 1H NMR
(400 MHz, CDCl3): d=0.88 (t, J=7.3 Hz, 3H), 0.92 (t, J=7.3 Hz, 3H),
0.95–1.06 (m, 1H), 1.14–1.38 (m, 5H), 1.48–1.60 (m, 2H), 1.62–1.74 (m,
2H), 2.57 (t, J=7.7 Hz, 2H), 3.77 (s, 3H), 3.79 (s, 3H), 3.81 (t, J=4.0 Hz,
1H), 3.94 (ddd, J=3.2, 7.3, 12.1 Hz, 1H), 4.25 (ddd, J=7.3, 8.0, 12.1 Hz,
1H), 4.35 (dd, J=3.2, 8.0 Hz, 1H), 5.07 (s, 1H), 5.09 (t, J=7.3 Hz, 1H),
6.78 (d, J=8.3 Hz, 1H), 6.94 (d, J=2.3 Hz, 1H), 6.99 ppm (dd, J=2.3,
8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=13.9, 14.0, 22.5, 22.6, 23.8,
27.2, 29.9, 31.9, 55.3, 58.1, 60.5, 61.7, 65.0, 94.5, 110.3, 125.4, 128.5, 129.9,
AHCTUNGTRENNUNG
(5S,1’R)-13e (minor diastereomer): Colorless oil; [a]2D0 =+28.4 (c=1.0 in
CHCl3); 1H NMR (400 MHz, CDCl3): d=2.33–2.43 (m, 2H), 3.43–3.52
(brm, 1H), 3.75 (s, 3H), 3.77 (s, 3H), 3.80 (s, 3H; rotamer M), 3.87 (s,
3H; rotamer m), 3.90 (t, J=4.2 Hz, 1H), 3.94 (t, J=4.2 Hz, 1H), 4.00–
4.10 (m, 1H), 4.13–4.25 (m, 1H), 4.74 (dd, J=4.2, 7.8 Hz, 1H), 4.82–4.91
(overlapped m, 1H), 4.94–4.99 (m, 1H), 5.07 (s, 1H), 5.09 (s, 1H), 5.34–
5.46 (m, 1H), 6.78–6.87 (m, 2H), 7.25–7.33 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3): d=33.9, 55.3, 56.4, 58.1, 58.2, 59.8, 59.9, 61.8, 62.3,
64.6, 64.7, 94.4, 101.1, 114.0, 114.0, 119.0, 119.2, 129.2, 129.2, 129.8, 130.9,
132.1, 159.1, 173.6, 173.8, 174.9, 175.4 ppm; IR (KBr): n˜ =3365, 3120,
3070, 2969, 2940, 2846, 1655, 1630, 1514, 1366, 1249, 1175, 1034 cmÀ1; MS
(ESI): m/z (%): 326 (100) [M+Na+]; HRMS: m/z: calcd for
[C17H21NO4+H+]: 304.1543; found: 304.1535.
˜
131.7, 157.0, 173.5, 175.9 ppm; IR (KBr): n=3349, 2955, 2931, 2872, 2859,
1659, 1631, 1503, 1357, 1249, 1034 cmÀ1; MS (ESI): m/z (%) 398 (100)
[M+Na+]; HRMS: m/z: calcd for [C22H33NO4+Na+]: 398.2302; found:
398.2310.
5-Hexyl-1-[(R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]-4-methoxy-1H-
pyrrol-2(5H)-one (12d): Diastereomeric ratio: 48.2:1 (combined yield:
63%), dialkylated product 14d (3.8%), and recovered (R)-9 (19%).
A
CHCl3); 1H NMR (400 MHz, CDCl3): d=0.88 (t, J=6.9 Hz, 3H), 0.93–
1.09 (m, 1H), 1.15–1.35 (m, 7H), 1.63–1.72 (m, 2H), 3.77 (s, 3H), 3.79 (s,
3H), 3.81 (t, J=4.1 Hz, 1H), 3.97 (ddd, J=3.2, 6.6, 12.3 Hz, 1H), 4.23
(ddd, J=7.7, 7.8, 12.3 Hz, 1H), 4.36 (dd, J=3.2, 7.7 Hz, 1H), 5.07 (s,
1H), 5.11 (dd, J=6.6, 7.8 Hz, 1H), 6.84–6.88 (m, 2H), 7.10–7.16 ppm (m,
2H); 13C NMR (100 MHz, CDCl3): d=14.0, 21.6, 22.6, 27.5, 29.1, 31.6,
55.3, 58.1, 60.6, 61.4, 64.9, 94.5, 114.2, 114.2, 128.3, 128.3, 130.4, 159.2,
Ethyl-2-{2,5-dihydro-1-[(R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]-3-me-
thoxy-5-oxo-1H-pyrrol-2-yl}acetate (12f): Diastereomeric ratio: 5.5:1
(combined yield: 72%) and recovered (R)-9 (11%).
A
CHCl3); 1H NMR (400 MHz, CDCl3): d=1.24 (t, J=7.1 Hz, 3H), 2.64
(dd, J=3.6, 14.1 Hz, 1H), 2.69 (dd, J=4.2, 14.1 Hz, 1H), 3.78 (s, 3H),
3.80 (s, 3H), 4.00 (ddd, J=3.4, 7.1, 12.2 Hz, 1H), 4.08–4.17 (m, 3H), 4.26
(ddd, J=7.1, 7.6, 12.2 Hz, 1H), 4.50 (dd, J=3.4, 7.6 Hz, 1H), 4.62 (t, J=
7.1 Hz, 1H), 5.09 (s, 1H), 6.85–6.89 (m, 2H), 7.23–7.25 ppm (m, 2H);
13C NMR (100 MHz, CDCl3): d=14.1, 35.0, 55.3, 57.8, 58.4, 61.1, 61.3,
64.6, 94.5, 114.2, 114.2, 128.4, 128.4, 130.0, 159.2, 169.4, 173.2, 175.2 ppm;
IR (KBr): n˜ =3397, 3117, 2980, 2939, 2832, 1732, 1661, 1634, 1514, 1360,
1247, 1179, 1031 cmÀ1; MS (ESI): m/z (%): 350 (73) [M+H+], 372 (100)
[M+Na+]; HRMS: m/z: calcd for [C18H23NO2+H+]: 350.1598; found:
350.1594.
˜
173.5, 175.9 ppm; IR (KBr): n=3390, 2955, 2854, 1660, 1632, 1503, 1463,
1378, 1249, 1035 cmÀ1; MS (ESI): m/z (%): 370 (100) [M+Na+]; elemen-
tal analysis calcd (%) for C20H29NO4: C 69.14, H 8.41, N 4.03; found: C
69.33, H 8.59, N 3.91.
ACHTUNGTRENNUNG
(5S,1’R)-13d (minor diastereomer): Colorless oil; [a]2D0 =+58.6 (c=1.1 in
CHCl3); 1H NMR (400 MHz, CDCl3): d=0.80 (t, J=7.2 Hz, 3H), 0.99
(m, 2H), 1.05–1.34 (m, 5H), 1.51 (m, 1H), 1.82 (m, 2H), 3.76 (s, 3H),
3.79 (s, 3H), 3.85 (dd, J=5.0, 7.7 Hz, 1H), 3.93 (t, J=4.2 Hz, 1H), 4.06
(m, 1H), 4.17 (m, 1H), 4.68 (dd, J=4.2, 7.7 Hz, 1H), 5.06 (s, 1H, H-3),
6.83–6.88 (m, 2H), 7.10–7.16 ppm (m, 2H); 13C NMR (100 MHz, CDCl3):
d=14.0, 21.4, 22.3, 27.5, 29.6, 31.6, 55.2, 58.0, 60.5, 61.3, 64.9, 94.5, 114.1,
AHCTUNGTRENNUNG
(5S,1’R)-13 f (minor diastereomer): Colorless oil; [a]2D0 =+15.7 (c=1.0 in
CHCl3); 1H NMR (400 MHz, CDCl3): d=1.14 (t, J=7.1 Hz, 3H), 2.49
(dd, J=5.7, 16.0 Hz, 1H), 2.58 (dd, J=5.3, 16.0 Hz, 1H), 3.78 (s, 6H),
˜
114.1, 128.1, 128.1, 130.4, 159.4, 173.5, 175.7 ppm; IR (KBr): n=3368,
964
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 958 – 968