K. Krohn, D. Gehle, U. Flörke
FULL PAPER
freshly distilled dry diethyl ether (30 mL) was treated under argon
at –78 °C with methyllithium (5.6 mL, 2.5 equiv., 1.6 m solution in
diethyl ether), which was added via syringe over a period of 5 min.
Upon warming up to 0 °C the solution became clear. The mixture
was kept for 10 min at 0 °C, then cooled to –78 °C and treated with
a solution of ketone 9 (500 mg, 3.6 mmol) in dry THF (30 mL) by
addition over a period of 1 h. The resulting solution was stirred
at –78 °C for 1 h and then warmed up to 20 °C. After complete
conversion of the starting material (1 h), water was added dropwise
until the vigorous hydrolysis was finished. Saturated NH4Cl solu-
tion (20 mL) was added and the biphasic mixture was stirred for
1 h. The precipitate was filtered and washed with diethyl ether. Ex-
traction of the aqueous phase with diethyl ether (3×10 mL) and
concentration of the dried combined organic phases gave 12
(496 mg, 3.17 mmol, 89%). [α]2D0 = –17.0 (c = 1.21, MeOH). 1H
NMR (500 MHz, CDCl3): δ = 1.08 (s, 3 H, 7-H), 1.09 (s, 3 H, 8-
H), 2.20 (ddd, J3a,3b = 16.6, J3a,1 = 1.6, J3a,5 = 1.6 Hz, 1 H, 3a-H),
tain 14 as an oil (1.31 g, 8.34 mmol, 98%). [α]2D0 = +53.4 (c = 0.79,
MeOH). H NMR (500 MHz, CDCl3): δ = 1.44 (s, 3 H, 8-H), 1.71
(d, J7,3 = 1.5 Hz, 3 H, 7-H), 1.90 (br. s, 1 H, OH), 3.86 (dd, J6a,6b
1
= 8.1, J6a,5 = 6.0 Hz, 1 H, 6a-H), 4.12 (dd, J6b,6a = 8.1, J6b,5
=
1.8 Hz, 1 H. 6b-H), 4.22 (ddd, J5,6b = 1.8, J5,6a = 6.0, J5,3 = 1.8 Hz,
1 H, 5-H), 5.18 (dd, J3,7 = 1.5, J3,5 = 1.8 Hz, 1 H, 3-H), 5.25 (s,
1 H, 1-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 18.2 (q, C-7),
27.1 (q, C-8), 62.8 (t, C-6), 71.2 (s, C-4), 79.2 (d, C-5), 99.6 (d, C-
1), 126.1 (d, C-3), 135.0 (s, C-2) ppm. IR (film): ν = 3446 cm–1 (s,
˜
O–H), 2965 (s, C–H), 2924 (s, C–H), 2893 (m, C–H), 1734 (s, C=C),
1450 (m, C–H), 1377 (m, C–H), 1310 (m, C–H), 1248 (m, C–O),
1089 (s, C–O), 1015 (m, C–O). MS (EI, 70 eV): m/z (%) = 156 (32)
[M+], 113 (90), 111 (33), 95 (29), 86 (38), 85 (22), 84 (54), 71 (47),
67 (31), 67 (31), 55 (26), 47 (14), 43 (100), 41 (28), 29 (12), 27 (13).
HREIMS calcd. for C8H12O3: 156.0786; found 156.0786. C8H12O3
(156.18): calcd. C 61.52, H 7.74; found C 61.38, H 7.92.
4-O-Acetyl-1,6-anhydro-2,3-dideoxy-2,4-dimethyl-β-D-threo-hex-2-
2.32 (d, J3b,3a = 16.6 Hz, 1 H, 3b-H), 3.92 (dd, J6a,6b = 8.3, J6a,5
=
enopyranose (15): A solution of 14 (620 mg, 3.97 mmol in anhy-
drous CH2Cl2 (20 mL) was acetylated at 0 °C by addition of trieth-
ylamine (2.1 mL, 15.6 mmol), Ac2O (1.6 mL, 15.6 mmol), and
DMAP (cat.). After 1 h the solution was warmed to 20 °C and was
kept at that temperature for an additional 5 h, and was then
quenched by pouring into ice-water. The phases were separated and
the organic phase was extracted with water (2×30 mL), sat.
NaHCO3 (2×10 mL) and brine. After drying (Na2SO4) the com-
bined organic phases were concentrated at reduced pressure and
the crude product was purified by flash chromatography (PE/
EtOAc, 9:1–3:1) to yield 15 as a colorless oil (747 mg, 3.77 mmol,
95%). 1H NMR (500 MHz, CDCl3): δ = 1.69 (s, 3 H, 8-H), 1.72
5.3 Hz, 1 H, 6a-H), 3.97 (dd, J6b,6a = 8.3, J6b,5 = 0.9 Hz, 1 H, 6b-
H), 4.45 (ddd, J5,6a = 5.3, J5,6b = 0.9, J5,3a = 1.6 Hz, 1 H, 5-H), 5.12
(d, J1,3 = 1.6 Hz, 1 H, 1-H) ppm. 13C NMR (125 MHz, CDCl3): δ
= 24.8, 25.1 (2×q, C-7, C-8), 41.6 (s, C-2), 47.0 (t, C-3), 67.0 (t,
C-6), 78.4 (d, C-5), 107.7 (d, C-1), 204.2 (s, C-4). IR (film): ν =
˜
2970 cm–1 (s, C–H), 2893 (s, C–H), 1729 (s, C=O), 1465 (m, C–H),
1418 (m, C–H), 1377 (m, C–H), 1315 (m, C–H), 1289 (s, C–O),
1118 (s, C–O), 1085 (s, C–O) ppm. MS (EI, 70 eV): m/z (%) = 156
(44) [M+], 113 (100), 111 (26), 95 (24), 85 (16), 71 (34), 67 (19), 55
(20), 43 (48), 41 (12). HREIMS calcd. for C8H12O3: 156.0786;
found 156.0786. C8H12O3 (156.18): calcd. C 61.52, H 7.74; found
C 61.40, H 7.83.
(d, J7,3 = 1.7 Hz, 3 H, 7-H), 2.02 (s, 3 H, Ac-H), 3.88 (dd, J6a,6b
=
1,6-Anhydro-2,3-dideoxy-2-dimethyl-4-methyl-β-
D
-threo-pyranose
8.0, J6a,5 = 6.0 Hz, 1 H, 6a-H), 3.97 (dd, J6b,6a = 8.0, J6b,5 = 2.0 Hz,
1 H, 6b-H), 4.83 (dd, J5,6b = 2.0, J5,6a = 6.0 Hz, 1 H, 5-H), 5.25 (s,
1 H, 1-H), 5.57 (br. s, 1 H, 3-H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 18.2 (q, C-7), 22.0 (q, Ac-CH3), 22.9 (q, C-8), 63.1 (t,
C-6), 77.3 (d, C-5), 81.4 (s, C-4), 99.6 (d, C-1), 122.4 (d, C-3), 136.6
(s, C-2), 170.3 (s, Ac-CO) ppm. MS (EI, 70 eV): m/z (%) = 156 (32)
[M+], 113 (90), 111 (33), 95 (29), 86 (38), 85 (22), 84 (54), 71 (47),
67 (31), 67 (31), 55 (26), 47 (14), 43 (100), 41 (28), 29 (12), 27 (13).
HREIMS calcd. for C10H14O4: 198.0892; found 198.0891.
(13): A solution of 12 (138 mg, 0.88 mmol) in dried diethyl ether
(15 mL) was treated at 0 °C with MeMgCl (0.35 mL, 1.2 equiv. 3 m
in THF) by dropwise addition. After 30 min the conversion was
complete and water was added to quench the reaction. The aque-
ous phase was extracted with diethyl ether (3×10 mL), the com-
bined organic phases were washed with water, dried (Na2SO4) and
evaporated at reduced pressure. The residue was purified by flash
chromatography (CH2Cl2/acetone, 95:5) to afford 13 (139 mg,
0.81 mmol, 92%) as a colorless oil. [α]2D0 = –84 (c = 0.75, CDCl3).
1H NMR (500 MHz, CDCl3): δ = 0.93 (s, 3 H, 7-H), 1.06 (s, 3 H,
8-H), 1.47 (d, J3a,3b = 13.6 Hz, 1 H, 3a-H), 1.54 (s, 3 H, 9-H), 1.59
4-O-Acetyl-1,6-anhydro-2-methyl-β-D-gulopyranose (17): A solution
of 6b (250 mg, 1.36 mmol) in acetone/water, (1:2, 3 mL) was treated
with a mixture of OsO4 (0.1 mL of a solution of 0.5 g in 5 mL
tBuOH) and NMO (202 mg, 1.5 mmol, 1.1 equiv.) and the mixture
was stirred at 20 °C for 4 h. After complete conversion of the start-
ing material (TLC monitoring), solid NaHSO3 (50 mg) was added
and the mixture was stirred for 1 h. The suspension was filtered
through a pad of Florisil and eluted with EtOAc (100 mL). The
ethyl acetate solution was washed with water (5 mL), dried
(Na2SO4), filtered and purified by silica gel column chromatog-
raphy (CH2Cl2/MeOH, 95:5) to yield 17 as a single isomer (oil,
213 mg, 0.98 mmol, 72%). [α]2D0 = +18.4 (c = 0.74, MeOH). 1H
NMR (500 MHz, CDCl3): δ = 1.29 (s, 3 H, 7-H), 2.13 (s, 3 H, Ac-
H), 2.89 (br. s, 2 H, 2×OH), 3.56 (d, J3,4 = 9.0 Hz, 1 H, 3-H), 3.69
(ddd, J6a,6b = 8.0, J6a,5 = 4.7, J6a,4 = 0.8 Hz, 1 H, 6a-H), 3.98 (d,
J6b,6a = 8.0 Hz, 1 H. 6b-H), 4.53 (dd, J5,6a = 4.7, J5,4 = 4.6 Hz, 1 H,
5-H), 4.94 (ddd, J4,5 = 4.6, J4,3 = 9.0, J4,6a = 0.8 Hz, 1 H, 4-H),
5.16 (s, 1 H, 1-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.4 (q,
C-7), 21.0 (q, Ac-CH3), 64.6 (t, C-6), 71.6 (d, C-3), 72.3 (d, C-5),
73.1 (d, C-4), 74.4 (s, C-2), 104.6 (d, C-1), 171.3 (s, Ac-CO) ppm.
(d, J3b,3a = 13.6 Hz, 1 H, 3b-H), 3.70 (dd, J6a,6b = 7.8, J6a,5
=
5.4 Hz, 1 H, 6a-H), 4.04 (dd, J5,6a = 5.4, J5,6b = 0.6 Hz, 1 H, 5-H),
4.18 (dd, J6b,6a = 7.8, J6b,5 = 0.6 Hz, 1 H, 6b-H), 4.90 (s, 1 H, 1-H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 24.3, 27.0 (2×q, C-7, C-
8), 28.7 (q, C-9), 37.5 (s, C-2), 44.7 (t, C-3), 64.7 (t, C-6), 68.3 (s,
C-4), 79.6 (d, C-5), 107.4 (d, C-1) ppm. IR (film): ν = 3451 cm–1
˜
(m, O–H), 2960 (s, C–H), 2924 (C–H), 2893 (s, C–H), 1486 (m, C–
H), 1448 (m, C–H), 1377 (m, C–H), 1367 (m, C–H), 1289 (w, C–
O), 1196 (m, C–O), 1103 (s, C–O), 1062 (m, C–O), 1015 (m, C–O).
MS (EI, 70 eV): m/z (%) = 172 (4) [M+], 157 (8), 129 (49), 116 (22),
111 (20), 99 (14), 95 (9), 85 (18), 71 (42), 70 (100), 55 (79), 43 (64),
41 (24). HREIMS calcd. for C9H16O3: 172.1099; found 172.1100.
C9H16O3 (172.22): calcd. C 62.77, H 9.36; found C 62.51, H 9.21.
1,6-Anhydro-2,3-dideoxy-2,4-dimethyl-β-D-threo-hex-2-enopyranose
(14): A solution of ketone 9 (1.2 g, 8.56 mmol) in dry THF (80 mL)
was treated at –78 °C with MeMgCl (3.4 mL, 10.3 mmol,
1.2 equiv., 3 m in THF) by dropwise addition. The solution was
warmed up to 20 °C and was quenched with water (20 mL) after
30 min (TLC monitoring) followed by extraction of the aqueous
phase with diethyl ether (3×50 mL). The combined organic phases
were dried (Na2SO4) and concentrated at reduced pressure to ob-
IR (film): ν = 3472 cm–1 (s, OH), 2986 (m, C–H), 2908 (m, C–H),
˜
1739 (w, C=O), 1344 (m, C–H), 1243 (s, C–H), 1118 (s, C–O), 1036
(s, C–O), 968 (s, C–O). MS (CI, iBu, 70 eV): m/z (%) = 219 (12)
[M++1], 201 (3), 89 (9), 59 (8), 57 (100), 55 (7), 43 (14), 41 (4), 39
2846
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 2841–2848