Catalytic cis-dihydroxylation of cis-dihydrodiols 2aS–dS
(1S,2S,3R,4R)-2-Methyl-5-cyclohexene-1,2,3,4-tetraol 9eR
To a solution of the diols 2aS (ca. 60% ee), 2bS–dS (>98% ee,
8 mmol), in CH2Cl2 (160 cm3), was added trimethylamine-N-oxide
dihydrate (11 mmol) and a catalytic amount of osmium tetroxide
(ca. 0.002 g). The reaction mixture was left stirring at room
temperature until the dihydroxylation was completed (3 days,
TLC analysis). A saturated solution of sodium metabisulfite
(5 cm3) was added and the reaction mixture stirred (0.5 h) at
room temperature. The solvents were removed in vacuo, and the
residual crude product purified by charcoal–celite (1 : 1, w/w)
column chromatography (H2O → 10% EtOH in H2O). The
pure tetraols 6aS–dS were obtained in the early eluting fractions.
Catalytic cis-dihydroxylation (OsO4) of cis-diol 2eS (>98% ee)
gave a mixture of diastereoisomeric tetraols 6e and 9e. This
was also separated by charcoal–celite column, tetraol 9e eluted
before tetraol 6e. An enantioenriched (ca. 60% ee) sample of cis-
dihydrodiol 2eR, available from earlier studies, was treated in a sim-
ilar manner to cis-diol 2eS.34,35 Compound 6cS had been reported
earlier.37
[a]D −4.0 (c 0.67, MeOH); ca. 60% ee.
Syntheses of bis-bromoacetates 7a–e and 10e
To a stirred suspension of the tetraol (3 mmol), in dry acetonitrile
(10 cm3) at 0 ◦C under a nitrogen atmosphere, 1-bromocarbonyl-
1-methylethylacetate (2.5 mol equiv.) was added drop-wise. The
reaction mixture was kept stirring at 0 ◦C for 15 min and then
at room temperature for another 2 h. The solvent was removed
under reduced pressure and the residue thoroughly partitioned
by shaking with a mixture of diethyl ether (50 cm3) and 3%
aqueous NaHCO3 (40 cm3). The ether extract was washed with
water, dried (Na2SO4), and concentrated to afford a crude sample
of bis-bromoacetate which was purified by PLC (15% EtOAc in
hexane) or by recrystallisation.
(1R,2R,5R,6S)-6-(Acetyloxy)-2,5-dibromo-3-fluoro-3-
cyclohexenyl acetate 7a
Colourless oil (0.756 g, 80%); Rf 0.40; [a]D +32 (c 0.78, CHCl3);
(found: M+ − OAc, 314.9883. C8H8Br2FO2 requires 314.9875);
dH(500 MHz, CDCl3) 2.11 (3 H, s, OCOMe), 2.13 (3 H, s,
OCOMe), 4.52 (1 H, br s, 5-H), 4.76 (1 H, dd, J2,F 9.9, J2,1 6.3,
2-H), 5.62 (2 H, m, 1-H and 6-H), 5.68 (1 H, dd, J4,F 11.9, J4,5
3.4, 4-H); dC(125 MHz, CDCl3) 20.64, 20.66, 39.40, 41.19, 71.08,
71.96, 108.00, 154.57, 169.28, 169.42; m/z (EI) 315 (M+ − OAc,
57%), 297 (11), 295 (12), 235 (18), 233 (19), 193 (43), 129 (52), 112
(49), 101 (81), 70 (33), 59 (72), 43 (100).
(1S,2S,3S,4S)-5-Fluoro-5-cyclohexene-1,2,3,4-tetraol 6aS
Colourless oil (1.05 g, 80%); [a]D −3.0 (c 0.80, MeOH); ca. 60%
ee, (found: M+ − H2O, 146.0378. C6H7FO3 requires 146.0379);
dH(500 MHz, CD3OD) 3.92–3.94 (2 H, m, 2-H and 3-H), 4.32–
4.34 (2 H, m, 1-H and 4-H), 5.43 (1 H, dd, J6,F 15.3, J6,1 3.7, 6-H);
dC(125 MHz, CD3OD) 66.66, 66.75, 68.23, 69.91, 69.99, 106.20,
160.08; m/z (EI) 146 (M+ − H2O, 91%), 128 (80), 1117 (82), 104
(100), 75 (82), 60 (29), 55 (31), 51 (18), 41 (48), 31 (18).
(1S,2S,5R,6R)-6-(Acetyloxy)-2,5-dibromo-3-methyl-3-
cyclohexenyl acetate 7e
(1S,2S,3R,4R)-5-Methyl-5-cyclohexene-1,2,3,4-tetraol 6eS
Colourless oil (0.64 g, 50%); [a]D −1.0 (c 0.94, MeOH); (found: M+,
160.0729. C7H12O4 requires 160.0736); dH(500 MHz, D2O) 1.62
(3 H, s, Me), 4.12 (1 H, ddd, J1,6 3.2, J1,2 4.5, J1,3 1.8, 1-H), 4.22
(1 H, ddd, J1,4 0.6, J3,2 3.3, J3,1 1.5, 3-H), 4.32 (1 H, dd, J4,6 0.7,
J4,3 1.7, 4-H), 4.47 (1 H, ddd, J2,1 4.4, J2,3 3.0, J2,6 1.6, 2-H), 5.80
(1 H, ddd, J6,1 3.2, J6,2 1.5, J6,4 0.7, 6-H); dC(125 MHz, D2O) 19.56,
68.22, 70.19, 70.73, 71.62, 123.96, 137.17. m/z 160 (M+, 6%), 142
(33), 124 (89), 118 (90), 113 (87), 111 (84), 109 (42), 98 (89), 87
(60), 82 (87), 77 (91), 73 (99), 71 (85), 65 (87), 59 (92), 55 (90), 50
(96), 45 (93), 40 (91), 38 (100).
A small portion of the diastereoisomeric mixture 7e and 12e
(0.87 g, 82%), on separation by PLC (15% EtOAc in hexane),
gave a pure sample of bis-bromoacetate 7e as a light yellow oil,
Rf 0.35; [a]D −17 (c 0.86, CHCl3); (found: M+ − Me, 354.8991.
C10H11Br2O4 requires 354.9003); dH(500 MHz, CDCl3) 1.96 (3 H,
s, Me), 2.10 (6 H, s, 2 × OCOMe), 4.41 (1 H, d, J2,1 4.0, 2-H),
4.75 (1 H, dd, J5,6 7.7, J5,4 3.1, 5-H), 5.55 (1 H, dd, J1,2 4.1, J1,6
2.5, 1-H), 5.67 (1 H, dd, J6,5 7.7, J6,1 2.5, 6-H), 5.77 (1 H, d, J4,5
3.1, 4-H); dC(125 MHz, CDCl3) 20.74, 20.75, 21.60, 44.62, 47.30,
71.50, 72.43, 127.15, 133.98, 169.58, 169.74; m/z (EI) 355 (M+ −
Me, 70%), 311 (78), 253 (84), 231 (80), 229 (81) 185 (19), 187 (20),
108 (61), 57 (16), 43 (100).
(1R,2R,3S,4S)-5-Methyl-5-cyclohexene-1,2,3,4-tetraol 6eR
[a]D +0.7 (c 0.44, MeOH); ca. 60% ee.
(1R,2R,5S,6S)-6-(Acetyloxy)-2,5-dibromo-3-methyl-3-
cyclohexenyl acetate 7eꢀ
[a]D +11.0 (c 0.3, CHCl3); ca. 60% ee.
(1R,2R,3S,4S)-2-Methyl-5-cyclohexene-1,2,3,4-tetraol 9eS
Colourless viscous oil (0.515 g, 40%); [a]D +6 (c 0.82, MeOH);
(found: M+, 160.0726. C7H12O4 requires 160.0736); dH(500 MHz,
D2O) 1.11 (3 H, s, Me), 3.53 (1 H, d, J3,4 4.5, 3-H), 3.82 (1 H,
d, J1,6 3.0, 1-H), 4.09 (1 H, dd, J4.3 4.5, J4,5 2.5, 4-H), 5.77 (1 H,
dd, J5,6 10.2, J5,4 2.5, 6-H); dC(125 MHz, D2O) 21.5, 67.39, 71.98,
72.80, 73.96, 128.19, 130.46; m/z (EI) 160 (M+, 4%), 142 (32), 124
(82), 87 (87), 81 (79), 71 (80), 69 (85), 58 (87), 56 (82), 45 (93),
42 (88), 40 (81), 53 (44), 45 (25), 43 (83), 41 (71), 39 (66), 21 (50),
29 (100).
(1R,2R,5S,6S)-6-(Acetyloxy)-2,5-dibromo-6-methyl-3-
cyclohexenyl acetate 10e
Colourless oil (0.85 g, 80%); [a]D −123 (c 0.56, CHCl3); (found: M+,
369.9254. C11H14Br2O4 requires 369.9238); dH(500 MHz, CDCl3)
1.45 (3 H, s, Me), 1.97 (3 H, s, OCOMe), 2.16 (3 H, s, OCOMe),
4.57 (1 H, dd, J2,1 8.1, J2,3 3.2, 2-H), 5.79 (1 H, dd, J3,4 12.5, J3,2
3.2, 3-H), 5.86 (1 H, dd, J4,3 12.5, J4,5 5.2, 4-H), 6.09 (1 H, d, J1,2
8.1, 1-H), 6.26 (1 H, m, J5,4 5.2, 5-H); m/z (EI) 370 (M+, 100%),
This journal is
The Royal Society of Chemistry 2007
Org. Biomol. Chem., 2007, 5, 2267–2273 | 2271
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