R. Schobert, G. J. Gordon, A. Bieser, W. Milius
FULL PAPER
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4-Hydroxy-3-[syn-(1Ј-methyl-2Ј-phenyl-2Ј-propoxy)ethyl]-1-oxa-
spiro[4.5]dec-3-en-2-one (3b): This compound (497 mg, 1.44 mmol,
72%) was obtained from propanol (50 mL); mixture treated with
p-toluenesulfonic acid (170 mg, 1.00 mmol) and heated at 80 °C for
16 h; white, crystalline solid; m.p. 151 °C; Rf ϭ 0.32 (dichlorometh-
1H NMR (270 MHz, CDCl3): δ ϭ 0.99 (d, J ϭ 7.08 Hz, 3 H, 1Ј-
3
CH3), 1.18 (t, J ϭ 7.29 Hz, 3 H, NCCH3), 1.39Ϫ1.83 (m, 10 H,
3
6-H, 7-H, 8-H, 9-H, 10-H), 2.65 (dq, J ϭ 7.1 Hz, 2.1 Hz, 1 H, 1Ј-
3
H), 2.75Ϫ2.94 (q, J ϭ 7.29 Hz, 2 H, NCH2), 4.04 (m, 1 H, 2Ј-H),
7.19Ϫ7.38 (m, 5 H, Ph) ppm. 13CNMR (68 MHz, CDCl3): δ ϭ
ane). IR (KBr): ν˜ ϭ 3430 cmϪ1, 2937, 1701, 1657, 1604, 1451, 1322, 18.4 (1Ј-CH3), 20.0 (C-7, C-9), 28.4 (C-8), 28.5 (NCCH3), 31.1 (C-
1162. H NMR (270 MHz, CDCl3): δ ϭ 0.93 (t, 3J ϭ 7.48 Hz, 3 6, C-10), 39.3 (C-1Ј), 42.7 (NCH2), 71.0 (C-2Ј), 88.8 (C-5-spiro),
1
3
H, CH2CH3), 0.93 (d, J ϭ 7.39 Hz, 3 H, 1Ј-CH3), 1.15Ϫ1.92 (m, 105.5 (C-3), 133.1, 134.3, 135.3 (CH-ar), 144.2 (C-ipso), 181.5 (C-
12 H, 6-H, 7-H, 8-H, 9-H, 10 H, CH2CH3), 2.80 (dq, 3J ϭ 7.39 Hz, 2), 190.5 (C-4) ppm. MS (EI, 70 eV): m/z (%) ϭ 330 (5) [Mϩ ϩ 1],
2.11 Hz, 1 H, 1Ј-H), 3.37 (ddd, 2J ϭ 9.45, 3J ϭ 7.48, 5.74 Hz, 1 H, 329 (29) [Mϩ], 328 (3), 135 (64), 134 (100), 106 (88). C20H27NO3
2
3
OCHH), 3.51 (dt, J ϭ 9.45, J ϭ 7.48 Hz, 1 H, OCHH), 4.66 (d,
(329.43): calcd. C 72.92, H 8.26, N 4.25; found C 72.86, H 8.22,
3J ϭ 2.11 Hz, 1 H, 2Ј-H), 7.25Ϫ7.40 (m, 5 H, Ph), 10.29 (s, 1 H, N 4.33.
OH) ppm. 13CNMR (68 MHz, CDCl3): δ ϭ 10.3 (CH2CH3), 18.3
3-[syn-(2Ј-Benzylamino-1Ј-methyl)-2Ј-phenylethyl]-4-hydroxy-1-
(1Ј-CH3), 21.8 and 21.9 (C-7, C-9), 22.7 (OCCH2), 24.8 (C-8), 32.7,
33.2 (C-6, C-10), 35.8 (C-1Ј), 71.3 (OCH2), 81.9 (C-5-spiro), 85.6
(C-2Ј), 102.8 (C-3), 126.7, 127.8, 127.9, 128.3, 128.4 (CH-ar), 138.7
(C-ipso), 173.4 (C-2), 179.7 (C-4) ppm. MS (EI, 70 eV): m/z (%) ϭ
345 (1) [Mϩ ϩ 1], 344 (2) [Mϩ], 301 (3) [Mϩ Ϫ C3H7], 149 (100),
107 (66). C21H28O4 (344.44): calcd. C 73.23, H 8.19; found C 73.36,
H 8.12.
oxaspiro[4.5]dec-3-en-2-one (4c): This compound (630 mg,
1.62 mmol, 80%) was obtained from benzylamine (435 mg,
4.0 mmol); mixture in dry dichloromethane (25 mL) heated at re-
flux for 18 h; compound purified by filtration through a short plug
of neutral alumina; white crystalline solid; m.p. 63 °C. IR (KBr):
ν˜ ϭ 3422 cmϪ1, 3063, 2932, 2855, 1735, 1684, 1655, 1558, 1456,
1026, 962, 749. 1H NMR (300 MHz, CDCl3): δ ϭ 0.96 (d, 3J ϭ
4-Hydroxy-3-[syn-2Ј-methoxy-1Ј-methyl-2Ј-phenylethyl]-5-phenyl- 7.29 Hz, 3 H, 1Ј-CH3), 1.28Ϫ1.86 (m, 10 H, 6-H, 7-H, 8-H, 9-H,
3
2
(5H)furan-2-one (3c): White solid (417 mg, 1.12 mmol, 65%) from
2b and methanol (5 mL) heated at reflux in dry chloroform (15 mL)
10-H), 2.83 (dq, J ϭ 7.29 Hz, 2.19 Hz, 1 H, 1Ј-H), 3.58 (d, J ϭ
12.65 Hz, 1 H, NCHαPh), 3.83 (d, J ϭ 12.65 Hz, 1 H, NCHβPh),
2
3
for 12 h; 5(α)/3(β) mixture of diastereoisomers; m.p. 59 °C; Rf ϭ 4.07 (d, J ϭ 2.19 Hz, 1 H, 2Ј-H), 7.24Ϫ7.45 (m, 10 H, Ph), 15.98
0.21 (diethyl ether/hexane, 1:1, v/v). IR (KBr): ν˜ ϭ 3576 cmϪ1
,
(s, 1 H, OH) ppm. 13CNMR (75.4 MHz, CDCl3): δ ϭ 11.1 (1Ј-
1748, 1656, 1454, 1194. 1H NMR (300 MHz, CDCl3): δ ϭ 1.00 (d, CH3), 21.0, 21.1 (C-7, C-9), 23.7 (C-8), 31.7, 32.1 (C-6, C-10), 34.8
3J ϭ 7.27 Hz, 3 H, 1Ј-CH3α), 1.03 (d, 3J ϭ 5.91 Hz, 3 H, 1Ј-CH3β),
(C-1Ј), 49.1 (NCH2), 63.5 (C-2Ј), 81.5 (C-5-spiro), 96.8 (C-3), 125.9,
126.1, 127.1, 127.2, 127.9, 128.4, 133.2 (CH-ar), 136.3 (C-ipso),
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2.90 (dt, J ϭ 7.27, 1.66 Hz, 1 H, 1Ј-Hα), 2.97Ϫ3.02 (m, 1 H, 1Ј-
Hβ), 3.32 (s, 3 H, OCH3β), 3.40 (s, 3 H, OCH3α), 4.60 (d, 3J ϭ 174.7, 185.4 (C-2, C-4) ppm. MS (EI, 70 eV): m/z (%) ϭ 392 (2)
1.70 Hz, 1 H, 2Ј-Hβ), 4.66 (d, J ϭ 1.66 Hz, 1 H, 2Ј-Hα), 5.64 (s, 2
[Mϩ ϩ 1], 391 (4) [Mϩ], 372 (1) [Mϩ Ϫ H2O], 266 (8), 265 (16),
3
H, 5-Hα,β), 7.23Ϫ7.40 (m, 10 H, Phα,β), 10.62 (s, 1 H, OHβ), 10.68 197 (17), 196 (67), 130 (11), 118 (14), 107 (22), 106 (62), 91 (61),
(s, 1 H, OHα) ppm. 13CNMR (75.5 MHz, CDCl3): δ ϭ 11.6 (1Ј-
84 (16), 75 (16), 65 (18), 55 (77), 51 (82), 47 (58), 39 (54), 32 (72), 28
CH3α,β), 36.1, 36.2 (C-1Ј), 57.2, 58.3 (OCH3), 78.7, 78.8 (C-2Ј), (100). C25H29NO3: accurate mass: calcd. 391.2147; found 391.2133.
87.3, 89.3 (C-5), 104.3 (C-3), 126.7, 126.8, 128.2, 128.9, 129.2, 129.3
3-[syn-(2Ј-Butylamino-1Ј-methyl)-2Ј-phenylethyl]-4-hydroxy-1-
(CH-ar), 134.5, 134.9 (C-ipso), 137.6 (C-ipso), 173.9 and 174.8 (C-
oxaspiro[4.5]dec-3-en-2-one (4d): This compound (480 mg,
2, C-4) ppm. MS (EI, 70 eV): m/z (%) ϭ 325 (1) [Mϩ ϩ 1], 324 (3)
1.33 mmol, 67%) was obtained from butylamine (167 mg,
[Mϩ], 309 (1), 122 (10), 121 (100). C20H20O4 (324.38): calcd. C
2.33 mmol); mixture in dry chloroform (20 mL) stirred for 16 h at
74.06, H 6.21; found C 74.26, H 6.19.
room temp.; white crystalline solid; m.p. 124 °C; Rf ϭ 0.48 (ethyl
3-[syn-(2Ј-Diethylamino-1Ј-methyl)-2Ј-phenylethyl]-4-hydroxy-1-
oxaspiro[4.5]dec-3-en-2-one (4a): This compound (457 mg,
1.28 mmol, 64%) was obtained from diethylamine (150 mg,
acetate). IR (KBr): ν˜ ϭ 3448 cmϪ1, 2934, 1738, 1681, 1582, 1429,
1050, 963. 1H NMR (270 MHz, CDCl3): δ ϭ 0.89 (t, 3J ϭ 7.50 Hz,
3
3 H, CH2CH3), 0.95 (d, J ϭ 7.29 Hz, 3 H, 1Ј-CH3), 1.32 (mc, 2
2.0 mmol); mixture in dry chloroform (10 mL) stirred for 16 h at H, CH2CH3), 1.41Ϫ1.88 (m, 12 H, 6-H, 7-H, 8-H, 9-H, 10-H,
room temp.; white crystalline solid; m.p. 116 °C; Rf ϭ 0.46 (aceto-
NCCH2), 2.50Ϫ2.73 (m, 2 H, NCH2), 2.83 (dq, 3J ϭ 7.29 Hz,
nitrile). IR (KBr): ν˜ ϭ 3442 cmϪ1, 2980, 2938, 1709, 1605, 1403, 2.19 Hz, 1 H, 1Ј-H), 4.03 (m, 1 H, 2Ј-H), 7.17Ϫ7.37 (m, 5 H, Ph)
1030, 766. 1H NMR (270 MHz, CDCl3): δ ϭ 1.05 (d, 3J ϭ 6.86 Hz, ppm. 13C NMR (68 MHz, CDCl3): δ ϭ 12.0 (CH2CH3), 13.7 (1Ј-
3 H, 1Ј-CH3), 1.14Ϫ1.32 (m, 6 H, NCCH3), 1.51Ϫ1.89 (m, 10 H,
CH3), 20.2 (CH2CH3), 21.9 (C-7, C-9), 24.6 (C-8), 30.0 (NCCH2),
6-H, 7-H, 8-H, 9-H, 10-H), 2.45Ϫ2.63 (m, 1 H, NCH2), 2.81Ϫ3.02 32.7 (C-6, C-10), 36.1 (C-1Ј), 46.4 (NCH2), 65.3 (C-2Ј), 82.6 (C-5-
3
(m, 1 H, NCH2), 3.27 (dq, J ϭ 6.86 Hz, 2.19 Hz, 1Ј-H), 3.87 (d, spiro), 97.6 (C-3), 126.8, 127.9, 128.8 (CH-ar), 137.3 (C-ipso), 175.7
3J ϭ 2.19, 1 H, 2Ј-H), 7.25Ϫ7.42 (m, 5 H, Ph) ppm. 13CNMR (C-2), 186.2 (C-4) ppm. MS (EI, 70 eV): m/z (%) ϭ 358 (2) [Mϩ
(68 MHz, CDCl3): δ ϭ 16.7 (1Ј-CH3), 22.0, 22.2 (NCCH3), 24.8
ϩ
1], 357 (4) [Mϩ], 163 (47), 162 (100), 106 (90). C22H31NO3 (357.49):
(C-7, C-9), 31.6 (C-8), 33.0 (C-6, C-10), 33.2 (C-1Ј), 42.8 (NCH2), calcd. C 73.91, H 8.74, N 3.92; found C 74.06, H 8.72, N 4.03.
71.1 (C-2Ј), 82.0 (C-5-spiro), 91.5 (C-3), 128.8, 129.2, 130.1 (CH-
3-[syn-(2Ј-Ethylthio-1Ј-methyl)-2Ј-phenylethyl]-4-hydroxy-1-oxa-
spiro[4.5]dec-3-en-2-one (5a): This compound (362 mg, 1.06 mmol,
55%) was obtained from ethanethiol (1 mL); mixture in dry chloro-
form (10 mL) heated to 70 °C for 16 h in a sealed bomb tube; white
crystalline solid; m.p. 189 °C; Rf ϭ 0.32 (ethyl acetate/hexane, 1:1,
ar), 134.0 (C-ipso), 176.0 (C-2), 187.9 (C-4) ppm. MS (EI, 70 eV):
m/z (%) ϭ 358 (2) [Mϩ ϩ 1], 357 (3) [Mϩ], 356 (1) [Mϩ Ϫ 1], 284
(8), 266 (6), 163 (53), 162 (100), 134 (92). C22H31NO3 (357.49):
calcd. C 73.91, H 8.74, N 3.92; found C 74.02, H 8.70, N 3.98.
3-[syn-(2Ј-Ethylamino-1Ј-methyl)-2Ј-phenylethyl]-4-hydroxy-1- v/v). IR (KBr): ν˜ ϭ 3419 cmϪ1, 2937, 1701, 1661, 1635, 1455, 1264,
1
3
oxaspiro[4.5]dec-3-en-2-one (4b): This compound (497 mg,
1.54 mmol, 78%) was obtained from ethylamine (87 mg, 2.0 mmol);
mixture in dry chloroform (10 mL) stirred at room temp. for 16 h;
white crystalline solid; m.p. 112 °C; Rf ϭ 0.27 (ethyl acetate). IR
1156. H NMR (300 MHz, CDCl3): δ ϭ 1.19 (t, J ϭ 7.38 Hz, 3
H, SCCH3), 1.29 (d, 3J ϭ 7.08 Hz, 3 H, 1Ј-CH3), 1.30Ϫ1.80 (m,
10 H, 6-H, 7-H, 8-H, 9-H, 10-H), 2.42 (q, 3J ϭ 7.38 Hz, 2 H,
SCH2), 3.10 (dq, 3J ϭ 7.08, 4.92 Hz, 1 H, 1Ј-H), 4.19 (d, 3J ϭ
(KBr): ν˜ ϭ 3429 cmϪ1, 2934, 1730, 1682, 1563, 1453, 1024, 755. 4.92 Hz, 1 H, 2Ј-H), 7.20Ϫ7.43 (m, 5 H, Ph), 10.01 (s, 1 H, OH)
3642
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 3637Ϫ3647