M. Lahmann, J. Thiem / Tetrahedron 67 (2011) 1654e1664
1663
CH3-4a’, -8a’, -12a’, -130); J1,2¼7.0, J2,3¼9.0, J3,4¼9.0, J4,5¼9.0,
hygroscopic solid; mp 45e47 ꢀC (decomposition); [
CH2Cl2).
1H NMR (CDCl3)
a
]
20 þ31.8 (c 1.2,
D
J5a,gem¼12.0 Hz.
d
¼5.98 (m, 2H, H-c); 5.35 (m, 2H, H-d); 5.30 (m,
4.2.34. 6-O-Allyl-5-[2,3,4-tri-O-allyl-1-O-(3,3-dimethoxypropyl)-
D
b
-
2H, H-d0); 4.95 (m, 2H, H-b); 4.71 (d, 1H, H-4); 4.59 (m, 2H, H-b0);
3.97 (wdt,1H, H-5); 3.85 (dd,1H, H-6a); 3.79 (dd,1H, H-6b); 2.78 (s,
2H, 2ꢂOH); J4,5¼2.6, J5,6a¼5.9, J5,6b¼4.6, J6a,6b¼11.5 Hz. 13C NMR
-glucopyranos-6-oxy]-methyl-2,20,7,8-tetramethyl-chroman-6-ol
44. Compound 42 (900 mg, 1.45 mmol) dissolved in anhydrous THF
(10 mL) was treated with NaH (60%, 650 mg, 16.0 mmol) for 30 min,
and then allylbromide (1.4 mL, 16.0 mmol) was added and the
mixture kept at room temperature for 18 h. Workup as for com-
pound 8 followed by flash chromatographic purification (pet. ether/
(100 MHz, CDCl3)
d
¼169.11 (1C, C]O, C-1); 156.33 (1C, C-3);
132.36, 131.34 (2C, ]CH, C-all-c); 120.81 (1C, C-2); 119.04e118.70
(2C, ]CH2, C-all-d); 75.28 (1C, C-4); 72.32e71.55 (2C, OCH2, C-all-
b); 69.51 (1C, C-5); 62.93 (1C, C-6). EI-MS: 256 (Mþ). Anal. Calcd for
C12H16O8(256.3): C, 56.24; H, 6.29. Found: C, 55.57; H, 6.43.
ethyl acetate 3:1) gave 44: 690 mg (72%) pale rose crystals; mp
20
52e53 ꢀC; [
a
]
D
ꢁ2.5 (c 0.9, CH2Cl2).
1H NMR (CDCl3)
d
¼6.12 (m, 1H, CH-all-c); 5.96 (m, 2H, CH-all-
4.2.37. 6-O-Allyl-5-[2-(5,6-O-metylidene-2,3-di-O-allyl-
L-ascorbyl)-
c); 5.84 (m, 1H, CH-all-c); 5.47 (mc, 1H, CH2-all-d); 5.33e5.11 (m,
7H, CH2-all-d); 4.63 (d, 1H, CH2-5a); 4.55 (d, 1H, CH2-5a); 4.53 (t,
1H, CH-c-Sp); 4.38e4.15 (m, 8H, 7ꢂCH2-all-b, H-1b); 3.96 (m, 2H,
CH2-all-b, CH2-a-Sp); 3.76 (dd, 1H, H-6a); 3.66 (dd, 1H, H-6b); 3.54
(m, 1H, CH2-a’-Sp); 3.40e3.32 (m, 8H, H-3, H-5, 2ꢂOCH3); 3.26 (m,
1H, H-4); 3.17 (dd, 1H, H-2); 2.85 (m, 2H, CH2-4); 2.19, 2.11 (s, 6H,
CH3-7a and -8a); 1.90 (m, 2H, CH2-b-Sp); 1.78 (m, 2H, CH2-3); 1.32
(s, 6H, CH3-2a, -2a’); J1,2¼8.2, J2,3¼9.5, J3,4¼9.5, J4,5¼9.5, J5,6a¼1.9,
J5,6b¼5.0, J6a,6b¼10.7, J5a,gem¼10.1, Jc,b-Sp¼5.7 Hz. 13C NMR
ethyl-2,3,4-tri-O-allyl-
b-D
-glucopyranos-6-oxy]-methyl-2,20,7,8-tet-
ramethyl-chroman-6-ol 47. Compounds 44 (200 mg, 0.3 mmol) and
46 (80 mg, 0.31 mmol) dissolved in a mixture of n-hexane (5 mL)
and dichloromethane (5 mL) were treated with p-TsOH (1 mg) and
heated at a water separator for 1.5 h. After cooling dichloromethane
(30 mL) was added, neutralised with saturated NaHCO3 solution,
washed with NaCl solution, dried (Na2SO4), evaporated and puri-
fied by flash chromatography (pet. ether/ethyl acetate 5:1) to give
47: 238 mg (93%) as a pale rose oil consisting of two diastereomers,
which could be partly separated. Upper diastereomer: 110 mg (43%),
(100 MHz, CDCl3)
d
¼135.66, 135.59, 135.12, 134.73 (4C, ]CH, C-all-
c); 117.33, 117.17, 117.06 (3C, ]CH2, C-all-d); 103.62 (1C, C-c-Sp);
102.49 (1C, C-1); 81.98 (1C, C-3); 78.21 (1C, C-2); 76.82e75.69 (3C,
C-4, C-5, C-all-b); 71.70, 68.11, 67.66 (3C, C-6, C-a-Sp, C-5a); 55.57
(2C, 2ꢂOMe); 35.54, 35.05 (2C, C-b-Sp, CH2-3); 29.50, 29.14 (1C, C-
2a, C-2a’); 22.14 (1C, CH2-4); 14.50 (2C, C-7a, 8a). EI-MS: 660 (Mþ).
Anal. Calcd for C37H56O10(660.8): C, 67.14; H, 8.54. Found: C, 67.14;
H, 8.54.
lower diastereomer: 91 mg (36%), mixed fraction: 37 mg (14%).
20
Upper diastereomer:
(400 MHz, CDCl3)
[a
]
D
þ4.1 (c 0.3, CH2Cl2). 1H NMR
d
¼6.08 (m, 1H, CH-all-c); 5.94 (m, 4H, CH-all-c);
5.81 (m, 1H, CH-all-c); 5.48e5.06 (m, 10H, CH2-d-all); 5.03 (m, 1H,
CH-c-Sp); 4.91 (m, 2H, CH2-d-all); 4.67e4.49 (m, 5H, CH2-b-all, H-
4-aa, CH2-5a); 4.35e4.09 (m, 10H, H-1b, CH2-b-all, H-6a-aa, H-5-
aa); 3.94 (m, 3H, CH2-a-Sp, CH2-b-all, H-6b-aa); 3.72 (m, 1H, H-6a);
3.63 (m, 1H, H-6b); 3.56 (m, 1H, CH2-a’-Sp); 3.33 (m, 2H, H-3, H-5);
3.22 (t, 1H, H-4); 3.14 (t, 1H, H-2); 2.82 (m, 2H, CH2-4); 2.15, 2.08 (s,
6H, CH3-7a and -8a); 1.93 (m, 2H, CH2-b-Sp); 1.74 (m, 2H, CH2-3);
4.2.35. 6-O-Allyl-5-[2,3,4-tri-O-allyl-1-O-(3,3-dimethoxypropyl)-
b-
D
-glucopyranos-6-oxy]-methyl- -tocopherol 45. Compound 43
g
(920 mg, 1.11 mmol) in anhydrous THF (10 mL) was treated with
NaH (60%, 650 mg, 16.0 mmol) for 30 min, and then allylbromide
(2.0 ml, 23.0 mol) was added and the mixture kept at room tem-
perature for 24 h. Workup as for compound 8 and purification by
flash chromatography (pet. ether/ethyl acetate 5:1) gave 45:
730 mg (76%) as a pale yellow oil.
1.29, 1.28 (s, 6H, CH3, 20, -2a’). 13C NMR (100 MHz, CDCl3)
d¼168.15
(1C, C-1-aa); 155.29 (1C, C-3-aa); 148.78 (1C, C-6); 147.77 (1C, C-
8a); 134.90, 134.77, 134.36, 133.92, 132.39, 131.36 (6C, ]CH, C-c-
all); 127.63, 125.86, 125.15 (3C, C-5, C-7, C-8); 120.89 (1C, C-2-aa);
118.86e116.10 (2C, C-4a and ]CH2 C-d-all); 103.37 (1C, C-c-Sp);
102.92 (1C, C-1b); 83.68 (1C, C-3); 81.04 (1C, C-2); 77.35 (1C, C-4);
1H NMR (400 MHz, CDCl3)
d¼6.10 (m, 1H, CH-all-c); 5.92 (m, 2H,
74.99 (1C, CH2 C-b-all); 74.43 (1C, C-4-aa); 74.37e73.05 (2C, CH2 C-
b-all and C-5-aa); 72.93 (1C, C-5); 72.60 (1C, C-2); 72.12, 71.96 (2C,
CH2, C-b-all); 68.89 (1C, C-6); 65.80 (1C, C-6-aa); 64.88 (1C, C-5a);
64.59 (1C, CH2, C-a-Sp); 33.83 (1C, CH2, C-b-Sp); 32.25 (1C, C-3);
26.66, 26.35 (2C, CH3, C-20, -2a’); 19.34 (1C, C-4); 12.34 (1C, CH3, C-
CH-all-c); 5.81 (m, 1H, CH-all-c); 5.44 (m, 1H, CH2-all-d); 5.31e5.08
(m, 7H, CH2-all-d); 4.62e4.68 (m, 3H, CH2-5a, CH-c-Sp); 4.37e4.11
(m, 8H, CH2-b-all, H-1b); 3.99e3.87 (m, 2H, CH2-b-all, CH2-a-Sp);
3.74 (m, 1H, H-6a); 3.64 (m, 1H, H-6b); 3.52 (m, 1H, CH2-a’-Sp);
3.38e3.28 (m, 8H, H-3, H-5, 2ꢂOMe); 3.23 (m, 1H, H-4); 3.15 (t, 1H,
H-2); 2.81 (m, 2H, CH2-4); 2.16, 2.08 (s, 6H, CH3-7a and -8a); 1.88
(m, 2H, CH2-b-Sp); 1.74 (m, 2H, CH2-3); 1.59e0.99 (m, 24H, CH3-2a,
CH-40, -80, -120, CH2-h10-110i); 0.87e0.83 (m, 12H, CH3-4a’, -8a’,
7a); 11.67 (1C, CH3, C-8b).
20
Lower diastereomer: [
(400 MHz, CDCl3)
a
]
þ15.3 (c 2.5, CH2Cl2). 1H NMR
D
d
¼6.09 (m, 1H, CH-all-c); 5.93 (m, 4H, CH-all-
c); 5.80 (m, 1H, CH-all-c); 5.47e5.06 (m, 10H, CH2-d-all); 5.03 (t,
1H, CH-c-Sp); 4.92 (m, 2H, CH2-d-all); 4.66e4.50 (m, 5H, H-4-aa,
CH2-b-all h2Hi, CH2-5a); 4.34e4.18 (m, 10H, H-1b, H-5-aa, CH2-b-
all h8Hi); 4.12 (m, 1H, CH2-b-all); 4.06 (dd, 1H, H-6a-aa); 3.94 (m,
3H, H-6b-aa, CH2-a-Sp, CH2-b-all); 3.72 (m, 1H, H-6a); 3.64 (m,
1H, H-6b); 3.57 (m, 1H, CH2-a’-Sp); 3.33 (m, 2H, H-3, H-5); 3.23
(t, 1H, H-4); 3.13 (t, 1H, H-2); 2.83 (m, 2H, CH2-4); 2.16, 2.08 (s,
6H, CH3-7a and -8a); 1.97 (m, 1H, CH2-b-Sp); 1.88 (mc, 1H, CH2-b-
Sp); 1.75 (m, 2H, CH2-3); 1.29, 1.28 (s, 6H, CH3, 20, -2a’); J1,2¼8.2,
J2,3¼8.8, J3,4¼9.1, J4,5¼9.5, J5,6b¼5.1, J6a,6b¼10.7, J5,6a-aa¼4.7, J6a,b-
-12a’, -130); J1,2¼8.1 Hz. 13C NMR (100 MHz, CDCl3)
¼148.73 (2C, C-
d
6, C-8a); 134.84, 134.67, 134.30, 133.94 (4C, ]CH C-all-c); 127.64,
125.90, 125.09, 118.34 (4C, C-4a, C-5, C-7, C-8); 116.47, 116.32, 116.21
(3C, ]CH2 C-all-d); 102.80, 101.65 (2C, C-1, C-c-Sp); 83.74, 81.16,
77.39, (3C, C-2, C-3, C-4); 74.99e73.14 (4C, C-2, C-5, C-6, C-all-b);
65.30, 64.90 (2C, C-a-Sp, C-5a); 52.70 (2C, CH3, 2ꢂOMe); 38.93,
37.03, 36.99, 36.86, 32.73 (8C, C-b-Sp, CH2-3, C-10, -30, -50, -70, -90,
-110); 32.36, 27.54 (3C, C-40, -80, -120); 24.38, 24.03 (2C, C-60, -100);
23.56e22.2 (3C, CH3, C-2a,-12a’, -130); 20.57 (1C, CH2-4); 13.32,
19.24 (2C, CH3, C-4a’, -8a’); 18.99 (1C, C-20); 12.34, 11.67 (2C, CH3, C-
7a, -8a). EI-MS: 871 (Mþ).
¼8.5, Jb,c-Sp¼5.4 Hz. 13C NMR (CDCl3)
¼168.22 (1C, C-1-aa);
d
aa
155.10 (1C, C-3-aa); 148.78 (1C, C-6); 147.78 (1C, C-8a);
134.89e131.41 (6C, ]CH, C-c-al1); 127.62, 125.82, 125.14 (3C, C-5,
C-7, C-8); 121.16 (1C, C-2-aa); 118.88e116.11 (12C, ]CH2, C-d-
all); 118.20 (1C, C-4a); 102.83 (2H, C-c-Sp and C-1b); 83.69 (1H,
C-3); 81.15 (1C, C-2); 77.33 (1C, C-4); 74.99 (1C, CH2, C-b-all);
74.46 (1C, C-4-aa); 74.37e71.96 (12C, CH2, C-b-all, C-5-aa and CH,
C-5); 72.60 (1C, C-2); 68.78 (1C, C-6); 65.42 (1C, C-6-aa); 64.94
(1C, C-5a); 64.86 (1C, C-a-Sp); 33.65 (1C, C-b-Sp); 32.25 (1C, C-3);
4.2.36. 2,3-Di-O-allyl- -ascorbic acid 46. L-Ascorbic acid (3.0 g,
L
17.0 mmol) and allylbromide (3.03 mL. 36 mmol) dissolved in an-
hydrous dimethylformamide (10 mL) were treated with sodium
hydride (60%, 1.44 g 36.0 mmol) for 3 h at room temperature.
Workup as for compound 8 was followed by chromatography
(diethylether) to give 46: 1.0 g (23%) as a pale yellow waxy