W.-D. Fessner, J.-L. Reymond et al.
FULL PAPER
1H NMR (300 MHz, CDCl3): d 7.82 (d, J 8.3, 2H), 7.34 (d, J 8.3, 2H),
4.97 (m, 2H), 4.65(m, 2H), 4.18 (s, 4H), 3.87 (m, 3H), 3.38 (s, 3H), 3.35(s,
3H), 2.45(s, 3H), 1.27 (s, 3H), 1.43 (s, 3H) ppm; 13C NMR (75MHz,
CD3OD): d 144.8, 132.7, 129.8, 128.1, 101.9, 98.6, 96.4, 89.9, 83.2, 81.5,
79.1, 69.3, 63.8, 55.9, 55.6, 27.7, 21.6, 19.7 ppm; IR (CHCl3): nÄ 2952, 2253,
1373, 1170, 990, 915, 746 cmÀ1; HRMS: calcd for C20H30O10S: 463.1629;
found: 463.1623 [MH] .
1,3-O-Isopropylidene-2,4-di-O-(methoxymethyl)-6-O-(2-oxo-2H-chro-
men-7-yl)-d-fructofuranose (6): Tosylate 5 (45mg, 0.098 mmol) was added
mixture of methyltriphenylphosphonium bromide sodium amide (™instant
ylide∫, 3.7 g, 8.85mmol) in THF (100 mL) was stirred for 30 minutes under
N2 at RT. A solution of 11 (1.8 g, 5.91 mmol) in THF (3 mL) was added, and
the mixture became white and was stirred for a further 6 h. The reaction
mixture was quenched with water and extracted with EtOAc (3 Â 100 mL),
and the combined organic extracts were washed with brine (3 Â 50 mL),
dried (Na2SO4), and evaporated under reduced pressure. The crude
product was purified by flash chromatography (hexane/ether/CH2Cl2
7:2:1) yielding compound 12 as a colorless oil (1.3 g, 74%). Spectral data
1
were in agreement with the published data: H NMR (300 MHz, CDCl3):
to
a solution of the sodium salt of umbelliferone, prepared from
d 6.09 5.98 (m, 1H), 5.39 (dt, J 15.8, 1.7 Hz, 1H), 5.26 (dt, J 11.8,
1.7 Hz, 1H), 4.69 (t, J 6.6 Hz, 1H), 4.08 4.03 (m, 1H), 3.83 3.80 (m,
1H), 3.70 3.65(m, 2H), 1.47 (s, 3H), 1.36 (s, 3H), 0.91 (s, 9H), 0.09 (s,
6H) ppm; 13C NMR (75MHz, CDCl 3): d 134.8, 118.2, 109.4, 79.5, 78.0,
70.2, 64.9, 28.5, 26.5, 26.1, 18.9, À4.68, À4.77 ppm.
umbelliferone (24 mg, 0.15mmol) and sodium hydride (6.5mg, 0.16 mmol)
in DMF (1.5mL). After 24 h at 80 8C, the reaction mixture was diluted with
ethyl acetate and washed with aq. NaOH (1n). Evaporation of the organic
phase and flash chromatography (AcOEt/hexane 1:1, Rf 0.35) gave 6
(36 mg, 70%) as a yellow oil. 1H NMR (300 MHz, CDCl3): d 7.64 (d, J
9.6 Hz, 1H), 7.38 (d, J 8.5Hz, 1H), 6.91 (dd, J 8.5, 2.4 Hz, 1H), 6.86 (d,
J 2.4 Hz, 1H), 6.26 (d, J 9.6 Hz, 1H), 4.97 (m, 2H), 4.65(m, 2H), 4.18
(s, 4H), 3.87 (m, 3H), 3.38 (s, 3H), 3.35(s, 3H), 2.45(s, 3H), 1.49 (s, 3H),
1.38 (s, 3H) ppm; 13C NMR (75MHz, CDCl 3): d 161.8, 163.7, 155.8, 143.3,
129.7, 113.4, 112.9, 113.5, 102.4, 101.9, 98.6, 89.9, 80.6, 77.4, 77.1, 73.0, 68.8,
63.9, 55.9, 55.6, 27.7, 19.8 ppm.
5-O-Acetyl-6-O-tert-butyldimethylsilyl-1,2-dideoxy-3,4-O-isopropylidene-
d-ribo-hex-1-enitol (13): Acetic anhydride (15mL) was slowly added at
08C to a solution of 12 (1.3 g, 4.30 mmol) in dry pyridine (15mL). The
mixture was stirred for 1 h at 08C and at 258C overnight, then quenched
with water and extracted with EtOAc (3 Â 50 mL). The combined organic
extracts were dried (Na2SO4) and evaporated under reduced pressure to
give 13 as a colorless oil (1.4 g, 95%). [a]2D0 À3.3 (CH3OH, c 0.24);
1H NMR (300 MHz, CDCl3): d 5.81 5.75 (m, 1H), 5.33 (dt, J 16.9,
1.09 Hz, 1H), 5.22 (dt, J 11.7, 1.09 Hz, 1H), 4.84 4.80 (m, 1H), 4.65 4.61
(m, 1H), 4.43 4.38 (m, 1H), 3.89 3.82 (m, 2H), 2.01 (s, 3H), 1.48 (s, 3H),
1.38 (s, 3H), 0.89 (s, 9H), 0.05(s, 3H), 0.04 (s, 3H) ppm; 13C NMR
(75MHz, CDCl 3): d 169.7, 133.3, 118.1, 108.8, 79.5, 78.7, 75.0, 72.2, 62.0,
27. 25.8, 25.2, 21.1, 18.3, À5.48 ppm; IR (film): nÄ 2933 (s), 1747 (s), 1372
(m), 1234 (brs), 1123 (m), 1058 (s), 837 (s) cmÀ1; HRMS: calcd for
Enzymatic resolution of tert-butyl 3-hydroxypent-4-enoate (7): Compound
7 (22 g, 0.128 mol) and vinyl acetate (23.6 mL, 0.256 mol, 2 equiv) were
dissolved in pentane (800 mL). Amano PS lipase (10 g) was added, and the
suspension was heated at reflux for 45h. The mixture was filtered and
evaporated, and the acetylated S isomer was removed by silica gel
chromatography (cyclohexane/ethyl acetate 8:2) to give (R)-7 (9.53 g,
43%) with ee > 95% (measured by 1H NMR in the presence of Eu(hfc)3).
(R)-Pent-4-ene-1,3-diol (8): Lithium aluminium hydride (2.31 g, 61 mmol,
1.1 equiv) was suspended in dry THF (300 mL) at 08C. A solution of (R)-7
(9.53 g, 55 mmol) in dry THF (20 mL) was then added dropwise at 08C.
After 20 min at room temperature, the reaction mixture was quenched with
water until evolution of hydrogen ceased, followed by few drops of conc.
aq. HCl. The solution was dried (MgSO4), filtered, and concentrated.
Chromatography on silica gel (cyclohexane/ethyl acetate 3:7) afforded 8
(4.2 g, 74%) as a colorless liquid. 1H NMR (300 MHz, CDCl3): d 1.8 (m,
C17H32O5Si: 345.2097; found: 345.2108 [MH] .
5-O-Acetyl-6-O-tert-butyldimethylsilyl-2-deoxy-3,4-O-isopropylidene-d-
ribo-hexitol (14): Compound 13 (790 mg, 2.3 mmol) was dissolved in THF
(40 mL), and BH3 ¥ THF (ꢀ1m solution in THF, 23 mL) was added at 08C.
The mixture was kept at 08C for 1 h and was allowed to warm to 258C and
stirred for a further 12 h. NaOH (5n, 4.1 mL), H2O2 (30%, 2.6 mL), and
ethanol (13 mL) were then added, and the mixture was stirred at 558C for
2 h. Aqueous workup (water/EtOAc) and FC (hexane/EtOAc 8:2 to 1:1)
gave 14 (376 mg, 45%) as a colorless oil. [a]2D0 À20.2 (CHCl3, c 0.37);
1H NMR (300 MHz, CDCl3): d 4.92 4.87 (m, 1H), 4.40 4.29 (m, 2H),
3.92 3.77 (m, 4H), 2.28 (brs, 1H), 2.07 (s, 3H), 1.85 1.60 (m, 2H), 1.45(s,
3H), 1.35(s, 3H), 0.89 (s, 9H), 0.05(s, 3H), 0.04 (s, 3H) ppm; 13C NMR
(75MHz, CDCl 3): d 169.9, 108.4, 75.7, 74.6, 72.1, 62.2, 60.5, 31.7, 27.9, 25.7,
25.5, 21.1, 18.5, À5.54 ppm; IR (film): nÄ 3447 (brm), 2933 (s), 1740 (s),
1473 (m), 1370 (s), 1252 (s), 1055 (s), 835(s) cmÀ1; HRMS: calcd for
2H; C2H2), 2.5(brs, 2H; 2 Â OH), 3.85(m, 2H; C1H ), 4.4 (m, 1H; CH),
2
5.1 (d, J 10.4 Hz, 1H; CH trans), 5.3 (d, J 17.1 Hz, 1H; CH cis), 5.9
(ddd, J 5.7, 10.4, 17.1 Hz, 1H; CH) ppm; 13C NMR (300 MHz, CDCl3):
d 38.1 (C2), 61.1 (C1), 72.8 (C3), 114.7 (C5), 140.5 (C4) ppm.
(3R)-1-Iodopent-4-en-3-ol (9): Compound 7 (4.8 g, 47 mmol), imidazole
(4.8 g, 70.6 mmol, 1.5equiv), and triphenylphosphine (18.5g, 70.6 mmol,
1.5equiv) were dissolved in dry CH 2Cl2 (200 mL). The solution was cooled
to 08C, and iodine (23.9 g, 94.1 mmol, 2 equiv) was added in small portions,
with the temperature maintained below 08C. After 30 minutes the mixture
was allowed to warm to room temperature, the Ph3PO precipitate was
filtered off, and the filtrate was evaporated. The residue was purified by
double flash chromatography on silica gel (CH2Cl2/MeOH 99:1, then
cyclohexane/EtOAc 8:2) to give 9 (6.4 g, 64%) as a slightly yellow liquid.
1H NMR (300 MHz, CDCl3): d 1.7 (brs, 1H; OH), 2.0 (m, 2H; CH2), 3.2
(m, 2H; CH2), 4.2 (m, 1H; CH), 5.1 (d, J 10.4 Hz, 1H; CH trans), 5.25 (d,
J 17.2 Hz, 1H; CH cis), 5.8 (ddd, J 6.2, 10.4, 17.2 Hz, 1H; CH) ppm;
13C NMR (300 MHz, CDCl3): d 2.2 (C1), 40.2 (C2), 73.0 (C3), 115.8 (C5),
139.9 (C4) ppm.
C17H34O6Si: 363.2203; found: 363.2193 [MH] .
6-O-tert-Butyldimethylsilyl-2-deoxy-3,4-O-isopropylidene-d-ribo-hexitol
(15): Compound 14 (37 mg, 0.10 mmol) and K2CO3 (28 mg, 0.20 mmol)
were dissolved in aq. MeOH (50%, 1.2 mL) and stirred overnight at 258C.
Aqueous workup (water/AcOEt) and evaporation of the residue quanti-
tatively gave 15 as a colorless oil. [a]2D0 À17.2 (CH3OH, c 0.27);
1H NMR (300 MHz, CDCl3): d 4.41 4.37 (m, 1H), 4.00 3.95(m, 1H),
3.78 3.17 (m, 3H), 3.69 3.62 (m, 2H), 2.67 (brs, 1H), 2.11 2.02 (m, 1H),
1.94 1.89 (m, 1H), 1.42 (s, 3H), 1.33 (s, 3H), 0.91 (s, 9H), 0.09 (s, 6H) ppm;
13C NMR (75MHz, CDCl 3): d 108.3, 77.5, 77.3, 69.3, 64.8, 61.3, 31.9, 28.4,
26.0, 25.8, 18.9, À5.20 ppm; IR (film): nÄ 3403 (brs), 2933 (s), 1472 (m),
1381 (m), 1255 (s), 1058 (s), 837(s) cmÀ1; HRMS: calcd for C15H32O5Si:
(3'R)-7-(3'-Hydroxypent-4'-enoxy)-chromen-2-one (10): A solution of 9
(2 g, 9.4 mmol) and umbelliferone (1.53 g, 9.4 mmol) in acetone (100 mL)
was treated with K2CO3 (1.43 g, 10.4 mmol), and the mixture was heated at
reflux overnight. After cooling to room temperature, the solution was
filtered and concentrated. The crude yellow product was purified by flash
chromatography on silica gel (CH2Cl2/MeOH 99:1) to give 10 (2.16 g, 93%)
as a colorless liquid. 1H NMR (300 MHz, CDCl3): d 2.05(m, 2H; C2 'H2),
2.1 (brs, 1H; OH), 4.2 (m, 2H; C1'H2), 4.45(m, 1H; CH), 5.2 (d, J
10.5Hz, 1H; CH trans), 5.3 (d, J 17.2 Hz, 1H; CH cis), 5.95 (ddd, J 6.1,
321.2097; found: 321.2087 [MH] .
6-O-tert-Butyldimethylsilyl-2-deoxy-3,4-O-isopropylidene-1-O-(p-tosyl)-
d-ribo-hexitol (16): A solution of compound 15 (460 mg, 1.44 mmol) and p-
toluenesulfonyl chloride (410 mg, 190.6 mmol) in dry pyridine (8 mL) was
stirred at 08C for 12 h. Aqueous workup (water/AcOEt) and FC (hexane/
EtOAc 8:2 to 1:1) gave compound 16 (300 mg, 44%) as a yellowish oil.
1
[a]2D0 À4.4 (CH3OH, c 0.27); H NMR (300 MHz, CDCl3): d 7.80 (d,
J 8.1 Hz, 2H), 7.34 (d, J 8.1 Hz, 2H), 4.26 4.19 (m, 3H), 3.92 3.87 (m,
1H), 3.80 (dd, J 9.9, 3.3 Hz, 1H), 3.66 3.55 (m, 2H), 2.52 (brs, 1H), 2.45
(s, 3H), 2.26 2.15(m, 1H), 1.93 1.81 (m, 1H), 1.33 (s, 3H), 1.26 (s, 3H),
0.90 (s, 9H), 0.08 (s, 6H) ppm; 13C NMR (75MHz, CDCl 3): d 145.3,
133.9, 130.5, 128.7, 109.1, 77.3, 74.4, 69.8, 68.9, 65.1, 30.1, 28.9, 26.6, 26.2,
22.2, 18.9, À4.65ppm; IR (film): nÄ 3549 (w), 2932 (s), 1364 (s), 1178 (s),
837 (s) cmÀ1; HRMS: calcd for C22H38O7SiS: 475.2185; found: 475.2204
10.4, 17.2 Hz, 1H; CH), 6.2 (d, J 9.5Hz, 1H; C3H), 6.85(m, 2H; C6H
C8H), 7.35(d, J 8.5Hz, 1H; C5H), 7.65(d, J 9.5Hz, 1H; C4H) ppm;
13C NMR (300 MHz, CDCl3): d 36.0 (C2'), 65.5 (C1'), 70.1 (C3'), 101.6
(C6), 112.7 (C10), 113.0 (C8), 113.1 (C3), 115.3 (C5'), 140.5(C4 '), 144.0
(C4), 155.9 (C7), 161.5 (C9), 162.2 (C2) ppm.
6-O-tert-Butyldimethylsilyl-1,2-dideoxy-3,4-O-isopropylidene-d-ribo-hex-
1-enitol (12): In a modification of an established method,[20a] a yellow
[MH] .
898
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0898 $ 20.00+.50/0
Chem. Eur. J. 2003, 9, No. 4