F.-D. Wang, J.-M. Yue
FULL PAPER
The spectroscopic data of 8b were identical to those of 8a, except
for the opposite optical rotation value: [α]2D0 = +5 (c = 1.73, ace-
tone).
with dichloromethane/PE (1:1), to afford (R)-diester 10c (221.5 mg,
88%) as colorless crystals (from EtOAc and PE). M.p. 114–115 °C.
[α]2D0 = –6 (c = 1.15, acetone). IR (KBr): ν = 1731.8, 1716.4, 1525.4,
˜
1348.0, 1288.2 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.05–2.30
(m, 2 H, CH2), 2.77–2.86 (m, 2 H, PhCH2), 4.54 (dd, J = 12.1,
6.9 Hz, 1 H, one of CH2O), 4.68 (dd, J = 12.1, 3.2 Hz, 1 H, one
of CH2O), 5.58 (m, 1 H, CH), 7.19–7.20 (m, 3 H, H, arom.), 7.26–
7.31 (m. 2 H, H, arom.), 8.14–8.17 (m, 4 H, H-C6H4-NO2-p), 8.26–
8.30 (m, 4 H, H-C6H4-NO2-p) ppm. 13C NMR (100 MHz, CDCl3):
δ = 31.6 (CH2), 32.3 (CH2), 66.2 (CH2O), 72.7 (CH), 123.6 (4C,
arom.), 126.4 (C, arom.), 128.3 (2C, arom.), 128.6 (2C, arom.),
130.7 (4C, arom.), 134.8(C, arom.), 135.0(C, arom.), 140.3 (C,
arom.), 150.6 (2C, arom.), 164.2 (C=O), 164.3 (C=O) ppm.
C24H20N2O8 (464.44): calcd. C 62.07, H 4.31, N 6.03; found C
62.29, H 4.33, N 5.93.
(S)-6-Phenethyldihydropyran-2,4-dione (9a) and its Isomer 9b: p-Tol-
uenesulfonic acid (12 mg, 0.063 mmol) was added at room tempera-
ture to a stirred solution of 8a (168 mg, 0.67 mmol) in CH2Cl2
(10 mL), and the reaction was stirred for 2 h. The resultant mixture
was then diluted with CH2Cl2 (10 mL). After filtration, the organic
phase was washed with saturated NaHCO3 and brine, in that order,
and then dried with anhydrous Na2SO4. The crude product ob-
tained after removal of the solvent was crystallized from a mixture
of PE and diethyl ether to give compound 9a (123.7 mg, 84%) as
colorless crystals. M.p. 126–127 °C (ref.[5] 124 °C). [α]2D0 = +47 (c =
1.25, CH2Cl2), [ref.[5] [α]2D0 = +28.9 (c = 3.99, CH2Cl2)]. IR (KBr):
ν
˜
=
2956.4, 1685.5, 1581.4, 1388.5, 1284.4 cm–1. 1H NMR
(R)-4-Phenyl-1,2-butanediol (5b): Sodium (2.0 mg, 0.087 mmol) was
added at room temperature to a solution of MeOH (10 mL) con-
taining diester 10c (221.5 mg, 0.48 mmol) and the mixture stirred
for 1 h. Solid NH4Cl (50 mg) was then added to the mixture. After
removal of MeOH in vacuo, the residue was dissolved in EtOAc
(25 mL), washed with brine, and dried with anhydrous Na2SO4.
After evaporation of EtOAc on a rotary evaporator, the crude pro-
duct was purified by flash chromatography on a column of silica
gel, eluting with PE/EtOAc (1:1), to afford the desired diol 5b
(72.1 mg, 91%) as a colorless oil. Its spectroscopic data were iden-
tical to those of 5a, except that the optical rotation value is oppo-
site: [α]2D0 = +33 (c = 1.88, EtOH).
(400 MHz, CDCl3): δ = 1.96–2.12 (m, 1 H, one of CH2), 2.13–2.21
(m, 1 H, one of CH2), 2.50 (dd, J = 11.4, 18.2 Hz, 1 H, one of
CH2CO), 2.69 (dd, J = 2.7, 18.2 Hz, 1 H, one of CH2CO), 2.83–
2.96 (m, 2 H, PhCH2), 3.43 (d, J = 18.7 Hz, 1 H, one of
COCH2CO), 3.55 (d, J = 18.7 Hz, 1 H, one of COCH2CO), 4.55–
4.62 (m, 1 H, CH), 7.20–2.26 (m, 3 H, H, arom.), 7.30–7.34 (m, 2
H, H, arom.) ppm. Enantiomer 9b was synthesized in a similar
manner from 8b. The spectroscopic data of 9b were identical to
those of 9a, except for the optical rotation value: [α]2D0 = –38 (c =
1.04, CH2Cl2).
(S)-Dihydrokavain (1a) and its Isomer (R)-Dihydrokavain (1b): Di-
methyl sulfate (40 μL, 0.48 mmol) was added to a dry acetone
(5 mL) solution containing 9a (55 mg, 0.25 mmol) and potassium
carbonate (60 mg, 0.48 mmol), according to a previous report,[5]
and stirred for 20 h. Water (5 mL) was then added to the resultant
mixture and the acetone was removed in vacuo. The aqueous solu-
tion was extracted with ethyl acetate, and the extract was dried
with anhydrous Na2SO4. After removal of the solvent in vacuo, the
residue was purified by flash chromatography on a column of silica
gel, eluting with PE/EtOAc (10:3), to afford the target molecule 1a
(50.5 mg, 86%) as colorless crystals (from a mixture of diethyl ether
and PE). M.p. 54–55 °C, [ref.[20] 56–58 °C]. [α]2D0 = +29 (c = 1.21,
Acknowledgments
Financial support from the National Scientific Foundation
(30025044) of P. R. China and the Ministry of Science and Technol-
ogy (2002CB512807) of P. R. China are gratefully acknowledged.
[1] A. Yoshinori, O. Yukiko, Y. Masashi, S. Yukie, S. Hirohito, U.
Katsuyuki, M. Natsuko, Patent JP 316260; Chem. Abstr. 2001,
135, 352792r.
EtOH), [ref.[20] [α]1D0 = +30 (c = 1, EtOH)]. IR (KBr): ν = 2923.6,
˜
[2] V. R. Hänsel, D. Weiß, B. Schmidt, Planta Med. 1966, 14, 1–
1708.6, 1623.8, 1396.2 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.94
(m, 1 H, one of CH2), 2.13–2.17 (m, 1 H, one of CH2), 2.30 (dd, J
= 17.2, 3.9 Hz, 1 H, one of CH2C=C), 2.53 (dd, J = 17.2, 1.7 Hz,
1 H, one of CH2C=C), 2.78–2.89 (m, 2 H, PhCH2), 4.36 (m, 1 H,
CH), 5.14 (d, J = 1.6 Hz, 1 H, C=CH–), 7.20–2.26 (m, 3 H, H,
arom.), 7.30–7.34 (m, 2 H, H, arom.) ppm. 13C NMR (100 MHz,
CDCl3): δ = 30.9 (PhCH2), 33.0 (CH2C=C), 36.2 (PhCH2CH2),
56.0 (OCH3), 74.8 (CH2CHOCH2), 90.3 (= CHCOO), 126.1 (C,
arom.), 128.4 (2C, arom.), 128.5 (2C, arom.), 140.8 (C, arom.),
167.3 (C=O), 172.7 (= COMe) ppm. EIMS: m/z (%) = 232 (18)
[M+]. HREIMS calcd. for C14H16O3: 232.1099; found 232.1098.
Enantiomer 1b was synthesized in a similar manner from 9b as
colorless crystals (m.p. 55.5–56.5 °C). The spectroscopic data of 1b
were identical to those of natural S-(+)-dihydrokavain except for
the opposite optical rotation value: [α]2D0 = –28 (c = 1.92, EtOH).
9.
[3] For a total synthesis of dihydrokavain-5-ol, see: a) R. P. Singh,
V. K. Singh, J. Org. Chem. 2004, 69, 3425–3430; b) Y. Arai, T.
Masuda, S. Yoneda, Y. Masaki, M. Shiro, J. Org. Chem. 2000,
65, 258–262.
[4] a) S. Sotheeswaran, Chem. Aust. 1987, 377–378; b) M. W.
Klohs, F. Keller, R. E. Williams, M. I. Tockes, G. E. Cronheim,
J. Med. Pharm. Chem. 1959, 1, 95–103.
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6503–6506.
[6] W. R. Huck, T. Mallat, A. Baiker, New J. Chem. 2002, 26, 6–
8.
[7] T. E. Smith, M. Djang, A. J. Velander, C. W. Downey, K. A.
Carroll, S. V. Alphen, Org. Lett. 2004, 6, 2317–2320.
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4074; b) C. Pierres, P. George, L. V. Hijfte, J.-B. Ducep, M.
Hibert, A. Mann, Tetrahedron Lett. 2003, 44, 3645–3647.
[9] C. R. Schmid, J. D. Bryant, M. Dowlatzedah, J. L. Phillips,
D. E. Prather, R. D. Schantz, N. L. Sear, C. S. Vianco, J. Org.
Chem. 1991, 56, 4056–4058.
[10] E. E. Blaise, C. R. Hebd. Séances Acad. Sci. 1901, 132, 478.
[11] J. Syed, S. Förster, F. Effenberger, Tetrahedron: Asymmetry
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[12] S. M. Hannick, Y. Kishi, J. Org. Chem. 1983, 48, 3833–3835.
[13] a) K. Narkunan, B. J. Uang, Synthesis 1998, 1713–1714; b)
A. S.-Y. Lee, R.-Y. Cheng, O.-G. Pan, Tetrahedron Lett. 1997,
38, 443–446.
(R)-Diester 10c: DIAD (94%; 0.23 mL, 1.08 mmol) was added
dropwise, under nitrogen, to a solution of dry THF (5 mL) contain-
ing PPh3 (284.1 mg, 1.08 mmol), diol 5a (90.0 mg, 0.54 mmol) and
p-nitrobenzoic acid (181.1 mg, 1.08 mmol), at 0 °C. The reaction
mixture was stirred for 2 h at room temperature. After work-up,
the residue was dissolved in EtOAc (25 mL), washed with saturated
NaHCO3 solution and brine, and dried with anhydrous Na2SO4.
Evaporation of the solvent gave a crude product, which was puri-
fied by flash chromatography on a column of silica gel, eluting
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Eur. J. Org. Chem. 2005, 2575–2579