Enantioselective Synthesis of 3-Methylcarbapentofuranose Derivatives
FULL PAPER
stirred under reflux for 4 d. After the mixture had been cooled in
an ice bath, Celite (2.5 g) and Na2SO4·10H2O (2.5 g) were added.
After 20 min, the reaction mixture was filtered through a pad of
MgSO4 and concentrated. MeOH (5 mL) and 5 mol% Pd/C (1 mg)
J ϭ 6.4 Hz, 1 H), 2.73 (dd, J ϭ 10.5, 9.1 Hz, 1 H), 2.29 (dt, J ϭ
14.4, 8.2 Hz, 1 H), 1.84 (ddd, J ϭ 14.4, 10.6, 5.2 Hz, 1 H), 1.21 (t,
J ϭ 7.2 Hz, 3 H), 1.08 (s, 3 H) ppm. 13C NMR (50 MHz, D2O):
δ ϭ 175.7 (C), 80.9 (C), 79.8 (CH), 68.4 (CH), 62.7 (CH2), 50.9
was added to the crude material and the suspension was flushed (CH), 32.3 (CH2), 18.0 (CH3), 14.2 (CH3).
with H2. After stirring for 1 d at room temp., the mixture was
(1R,2R,3R,4R)-3,4-Diacetoxy-2-hydroxy-2-methylcyclopentyl-
filtered, washed with MeOH (5 mL) and concentrated. Column
chromatography afforded (؉)-5 as a colourless oil in 93% overall
yield (42 mg, 0.29 mmol). [α]2D5 ϭ ϩ18.5 (c ϭ 1.0, MeOH). IR
methyl Acetate [(؉)-7]: A solution of (؉)-16 (100 mg, 0.49 mmol)
in dry THF (5 mL) was slowly added at 0 °C to a stirred slurry of
LiAlH4 (38 mg, 1.00 mmol) in dry THF (2 mL). The solution was
allowed to warm to room temp. After 1 h, H2O (1 mL) was added
and the mixture was concentrated. Pyridine (8 mL) and Ac2O
(2.0 mL, 20 mmol) were added to the crude material, and the mix-
ture was stirred at room temp. After 2 d, solvents were removed
and purification of the residue by column chromatography afforded
(؉)-7 as a colourless oil in 86% overall yield (121 mg, 0.42 mmol).
[α]2D5 ϭ ϩ7.2 (c ϭ 1.0, MeOH). IR (neat): ν˜ ϭ 3489, 1733, 1237,
(neat): ν˜ ϭ 3358, 1205, 1109, 1068 cmϪ1 1H NMR (300 MHz,
.
D2O): δ ϭ 4.39 (quint, 1 H, J ϭ 7.1 Hz), 3.77 and 3.53 (ABX, J ϭ
11.0, 8.5, 5.7 Hz, 2 H), 2.39 (dt, J ϭ 13.4, 7.5 Hz, 1 H), 2.13 (dd,
J ϭ 14.0, 7.6 Hz, 1 H), 2.09 (dq, J ϭ 8.1, 5.6 Hz, 1 H), 1.65 (dd,
J ϭ 14.2, 6.3 Hz, 1 H), 1.34 (ddd, J ϭ 13.4, 6.5, 2.7 Hz, 1 H), 1.26
(s, 3 H) ppm. 13C NMR (75 MHz, D2O): δ ϭ 79.6 (C), 70.2 (CH),
63.1 (CH2), 51.0 (CH), 49.8 (CH2), 37.9 (CH2), 24.0 (CH3).
1049 cmϪ1 1H NMR (400 MHz, CDCl3): δ ϭ 5.32 (dt, J ϭ 8.5,
.
Ethyl (1S,2S,4R,5R)-4-Hydroxy-1-methyl-6-oxabicyclo[3.1.0]hex-
ane-2-carboxylate [(؊)-15]: A mixture of allylic alcohol (؊)-1
(50 mg, 0.29 mmol) and VO(acac)2 (0.16 mg) in benzene (5 mL)
was heated at reflux under argon for 10 min. tBuOOH (1.6 mL, 0.5
in benzene, 0.80 mmol) was added, and the mixture was stirred
under reflux for 20 h. After cooling, the solution was diluted with
5.7 Hz, 1 H, 1-H), 4.92 (d, J ϭ 6.2 Hz, 1 H, 2-H), 4.17 and 4.07
(ABX, J ϭ 11.0, 7.8, 6.7 Hz, 2 H, 5-H), 2.43 (dt, J ϭ 14.4, 8.6 Hz,
1 H, 6-Ha), 2.22 (dq, J ϭ 9.6, 7.7 Hz, 1 H, 4-H), 2.06 (s, 3 H, CH3),
2.03 (s, 3 H, CH3), 1.99 (s, 3 H, CH3), 1.46 (ddd, J ϭ 15.2, 9.9,
5.5 Hz, 1 H, 6-Hb), 1.21 (s, 3 H, CH3) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 170.9 (C), 170.6 (C), 170.0 (C), 80.2 (CH), 78.8 (C),
69.6 (CH), 64.6 (CH2), 43.7 (CH), 31.8 (CH2), 20.9 (CH3), 20.8
(CH3), 20.6 (CH3), 18.2 (CH3) ppm. C13H20O7 (288.3): calcd. C
54.16, H 6.99; found C 54.43, H 7.02.
CH2Cl2 and washed with
a saturated aqueous solution of
NaHCO3, water and brine. The organic layer was dried and con-
centrated, and the residue was purified by column chromatography
to afford (؊)-15 as a white solid in 98% yield (53 mg, 0.285 mmol).
M.p. 86Ϫ87 °C. [α]2D5 ϭ Ϫ13.6 (c ϭ 1.0, CHCl3). IR (KBr): ν˜ ϭ
3451, 1735, 1247, 1127 cmϪ1 1H NMR (200 MHz, CDCl3): δ ϭ
.
Acknowledgments
The authors acknowledge Dr. M. Giorgi for performing X-ray dif-
fraction experiments and Dr. R. Faure for running NOESY experi-
ments.
4.32Ϫ4.19 (m, 1 H), 4.17 (q, J ϭ 7.2 Hz, 2 H), 3.27 (d, J ϭ 1.3 Hz,
1 H), 2.70 (dd, J ϭ 10.2, 8.2 Hz, 1 H), 2.17 (dt, J ϭ 13.2, 8.0 Hz,
1 H), 1.65 (ddd, J ϭ 13.2, 10.2, 8.3 Hz, 1 H), 1.52 (s, 3 H), 1.26 (t,
J ϭ 7.2 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 171.2
(C), 71.4 (CH), 64.8 (CH), 63.2 (C), 60.8 (CH2), 46.6 (CH), 32.0
(CH2), 16.9 (CH3), 14.2 (CH3) ppm. C9H14O4 (186.2): calcd. C
58.05, H 7.58; found C 57.80, H 7.68.
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1 H), 2.04 (dd, J ϭ 14.3, 7.3 Hz, 1 H), 1.90Ϫ1.72 (m, 1 H), 1.65
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Ethyl
(1S,2R,3R,4R)-2,3,4-Trihydroxy-2-methylcyclopentane-1-
carboxylate [(؉)-16]: Perchloric acid (70% in water, 0.1 mL) was
added at room temp. to epoxide (؊)-15 (100 mg, 0.54 mmol), sus-
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Amberlyst A-21 resin (1.5 g) was added. After 20 min, the reac-
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.
D2O): δ ϭ 4.15 (q, J ϭ 7.0 Hz, 2 H), 4.15Ϫ4.05 (m, 1 H), 3.71 (d,
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97