(3aS,4R,5R,7aS) - 4 - (Benzyloxy) - 2,2,4 - trimethyl - 3a,4,5,7a-
tetrahydro-1,3-benzodioxol-5-yl benzoate 4Bz. White crystalline
solid (1.0 g, 41%); mp 111–112 ◦C (from hexane); Rf 0.29 (25%
EtOAc in hexane); [a]D +146 (c 0.99, CHCl3); (Found: C 70.45,
H 5.6; C24H24O6 requires C 70.6, H 5.9%); dH(500 MHz, CDCl3)
1.36, 1.38 [3 H × 2, s, C(Me)2], 1.42 (3 H, s, Me), 4.23 (1 H, d,
a solution of the diol acetonide (1 mmol), in a mixture of THF
(4 cm3), water (1 cm3) and TFA (0.5 cm3), was heated at 50 ◦C
until the starting material had reacted completely.
(1R,2R,3S,4S)-5-Fluoro-5-cyclohexene-1,2,3,4-tetraol 5a. Re-
moval of the acetonide group of diol 3a (method a) gave tetraol
5a as colourless crystals (0.7 g, 90%); mp 152–155 ◦C (from
MeOH–acetone); [a]D −3.0 (c 0.5, MeOH); (Found: C 43.6, H
5.5; C6H9FO4 requires C 43.9, H 5.5%); dH(500 MHz, CD3OD)
3.54 (1 H, dd, J3,2 10.3, J3,4 4.4, 3-H), 3.68 (1 H, dd, J2,3 10.3,
J2,1 4.7, 2-H), 4.07 (1 H, dd, J1,6 5.3, J1,2 4.7, 1-H), 4.12 (1 H,
dd, J4,F 8.0, J4,3 4.4, 4-H), 5.25 (1 H, dd, J6,F 13.8, J6,1 5.3, 6-H);
dC(125 MHz, CD3OD) 64.88, 66.80, 68.23, 68.56, 106.38, 160.99;
m/z (EI) 164 (M+, 2%), 146 (2), 128 (4), 129 (33), 117 (8), 113 (12),
111 (21), 104 (43), 85 (31), 71 (74), 57 (79), 43 (100), 39 (17), 32
(13) and 29 (27).
J
3a,7a 5.2, 3a-H), 4.73 (1 H, dd, J7a,3a 5.2, J7a,7 3.9, 7a-H), 5.65 (1 H,
d, J5,6 3.9, 5-H), 5.70 (1 H, m, J7,6 10.3, J7,7a 3.9, 7-H), 5.99 (1 H,
dd, J6,7 10.3, J6,5 3.9, 6-H), 7.46–7.49 (4 H, m, Ar-H), 7.60–7.62
(2 H, m, Ar-H), 8.07–8.13 (4 H, m, Ar-H); m/z (EI) 409 [(M +
H)+, 0.2%], 289 (12), 231 (5), 203 (6), 125 (11), 115 (19), 105 (100),
86 (22), 84 (35) and 77 (24).
(3aS,4R,5R,7aR)- and (3aR,4S,5S,7aS)-2,2,7-Trimethyl-3a,4,
5,7a-tetrahydro-1,3-benzodioxole-4,5-diol 3e.
A
solution of
dibenzoate 3eBz (1.5 g, 3.7 mmol) in MeOH (30 cm3) was treated
with aqueous NaOH (5%, 15 cm3) and the mixture stirred at room
temperature until the starting material had reacted completely
(TLC analysis). A saturated aqueous solution of NH4Cl (5 cm3)
was◦then added and the mixture heated (15 min) on a water bath
(60 C). The solvents were removed under reduced pressure and
the residue obtained was purified by flash column chromatography
(50% EtOAc in hexane). Diol acetonide 3e was obtained as a white
crystalline solid (0.7 g, 95%); mp 90 ◦C; [a]D −96 (c 0.58, CHCl3);
(Found: M+, 200.1042. C10H16O4 requires 200.1048); dH(500 MHz,
CDCl3) 1.39, 1.44 [3 H × 2, s, C(Me)2], 1.87 (3 H, s, Me), 3.89 (1 H,
dd, J4,5 3.7, J4,3a 7.1, 4-H), 4.26 (1 H, dd, J5,4 3.7 J5,6 3.2, 5-H), 4.34
(1 H, dd, J3a,4 7.1, J3a,7a 6.0, 3a-H), 4.48 (1 H, d, J7a,3a 6.0, 7a-H),
5.63 (1 H, d, J6,5 3.2, 6-H); dC(125 MHz, CDCl3) 20.39, 25.99,
27.95, 66.41, 71.20, 75.42, 75.91, 109.45, 124.29, 136.04; m/z (EI)
200 (M+, 18%), 185 (90), 167 (61), 125 (91), 112 (27), 109 (38), 107
(90), 100 (93), 86 (32), 84 (100), 82 (89), 77 (93), 73 (95), 66 (92),
60 (87), 57 (93), 50 (87), 44 (72), 42 (95), 39 (93), 30 (47) and 27
(86).
(1R,2R,3S,4S)-5-Chloro-5-cyclohexene-1,2,3,4-tetraol
5b.
Cleavage of acetonide group of diol 3b (metho◦d b) yielded tetraol
5b, a white solid, (0.56 g, 92%); mp 147–149 C (from acetone);
[a]D −161 (c 0.47, MeOH); (Found: M+ − H2O, 162.0091.
C6H7ClO3 requires 162.0084); dH(500 MHz, D2O) 4.01 (1 H, dd,
J3,2 9.9, J3,4 4.4, 3-H), 4.14 (1 H, dd, J2,3 9.9, J2,1 5.1, 2-H), 4.44
(1 H, d, J4,3 4.4, 4-H), 4.47 (1 H, t, J1,2 = J1,6 5.1, 1-H), 6.19 (1 H,
d, J6,1 5.1, 6-H); dH(75 MHz, D2O) 66.73, 68.21, 68.99, 71.22,
127.37, 135.47; m/z (EI) 162 (M+ − H2O, 13%), 133 (22), 122
(75), 120 (100), 93 (42), 91 (82), 60 (40), 39 (36) and 29 (40).
(1R,2R,3S,4S)-5-Bromo-5-cyclohexene-1,2,3,4-tetraol
5c.
Cleavage of acetonide group of diol 3c (method b) gave tetraol
5c as colourless crystals (0.32 g, 94%); mp 99–102 ◦C (from
MeOH–acetone); [a]D −74 (c 0.47, MeOH); (Found: C 32.3, H
3.9; C6H9BrO4 requires C 32.1, H 4.0%); dH(500 MHz, D2O) 3.95
(1 H, dd, J3,2 9.8, J3,4 4.3, 3-H), 4.09 (1 H, dd, J2,3 9.8, J2,1 4.4,
2-H), 4.36 (1 H, m, 1-H), 4.44 (1 H, d, J4,3 4.3, 4-H), 6.36 (1 H,
d, J6,1 5.1, 6-H); dC(75 MHz, D2O) 67.45, 68.28, 69.34, 72.70,
126.51, 131.76; m/z (EI) 206 (M+ − H2O, 4%), 177 (5), 164 (100),
135 (28), 127 (7), 109 (12), 81 (31), 69 (22), 60 (55).and 57 (26).
(3aR,4S,5S,7aS) Enantiomer, mp 85 ◦C, [a]D +76.0 (c 0.51,
CHCl3).
(3aS,4S,5S,7aS) - 2,2,4 - Trimethyl - 3a,4,5,7a - tetrahydro - 1,3-
benzodioxole-4,5-diol 4. Alkaline hydrolysis of the dibenzoate 4Bz
(0.9 g, 2.2 mmol) under similar conditions, yielded diol acetonide 4
as white crystalline solid (0.4 g, 91%); mp 59–60 ◦C (from EtOAc–
hexane); [a]D +79 (c 0.62, CHCl3); (Found: M+ − Me, 184.9923.
C9H13O4 requires 184.9937); dH(500 MHz, CDCl3) 1.36 (3 H, s,
Me), 1.36, 1.46 [3 H × 2, s, C(Me)2], 2.63 (1 H, br s, OH), 2.87
(1 H, br s, OH), 4.13 (1 H, s, 5-H), 4.18 (1 H, d, J3a,7a 5.0, 3a-H),
4.64 (1 H, dd, J7a,3a 5.0, J7a,7 2.7, 7a-H), 5.67 (1 H, m, J7,6 10.3, 7-H),
5.75 (1 H, d, J6,7 10.3, 6-H); dC(125 MHz, CDCl3) 23.82, 26.57,
27.78, 69.29, 72.50, 73.31, 79.82, 109.59, 127.67, 129.62; m/z (EI)
185 (M+ − Me, 39%), 157 (7), 127 (31), 125 (54), 115 (98), 107
(27), 100 (7), 97 (66), 87 (12), 83 (24), 81 (62), 74 (33), 69 (28), 59
(62), 53 (25), 45 (17), 43 (98), 41 (68), 32 (100) and 28 (90).
(1R,2R,3R,4R)- and (1S,2S,3S,4R)-5-Methyl-5-cyclohexene-
1,2,3,4-tetraol 5e. Deprotection of the acetonide group of diol
3e (method a) yielded tetraol 5e (0.8 g, 80%), as a white crystalline
solid, mp 176–178 ◦C (from MeOH); [a]D −280 (c 0.86, H2O) (lit.37
[a]D −272, H2O); (Found: C 52.5, H 7.4; C7H12O4 requires C 52.5,
H 7.5%); dH(500 MHz, D2O) 1.73 (3 H, s, Me), 3.76 (1 H, dd, J2,3
10.5, J2,1 4.0, 2-H), 3.80 (1 H, dd, J3,2 10.5, J3,4 3.9, 3-H), 4.02 (1
H, d, J4,3 3.9, 4-H), 4.15 (1 H, dd, J1,6 5.0, J1,2 4.0, 1-H), 5.55 (1
H, d, J6,1 5.0, 6-H); dC(125 MHz, D2O) 20.06, 66.91, 68.69, 69.07,
70.82, 124.38, 138.77; m/z (EI) 142 (M+ − H2O, 10%), 124 (16),
133 (11), 100 (97), 96 (34), 81 (11), 71 (100), 69 (17), 60 (10), 57
(18), 55 (25), 43 (59), 41 (49), 39 (34) and 31 (15).
(1S,2S,3S,4R) Enantiomer, white solid, mp 178–180 ◦C, [a]D
−220 (c 0.89, H2O).
Syntheses of tetraols 5a–5c, 5e, 11 and 19
(1S,2S,3S,4S)-2-Methyl-5-cyclohexene-1,2,3,4-tetraol
11.
Method (a): a solution of the diol acetonide (1.5–5.0 mmol) in
MeOH (25 cm3) was treated with aqueous HCl solution (1.5 M,
10 cm3) and the mixture heated at 50 ◦C until the starting
material had reacted completely (TLC analysis). The crude tetraol,
obtained after removal of the solvents, was purified either by
chromatography or by crystallization. Method (b): alternatively,
Deprotection of the acetonide group of diol 4 (method a) yielded
tetraol 11 as colourless viscous oil (1.6 g, 82%); [a]D +43 (c
0.58, MeOH); (Found: M+ − H2O, 142.0634. C7H10O3 requires
142.0630); dH(500 MHz, D2O) 1.21 (3 H, s, Me), 3.67 (1 H, d, J3,4
3.3, 3-H), 3.98 (1 H, d, J1,6 2.7, 1-H), 4.33 (1 H, dd, J4.5 = J4,3 3.3,
4-H), 5.52–5.54 (2 H, br s, 5-H, 6-H); dC(125 MHz, D2O) 22.83,
This journal is The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 2208–2217 | 2213
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