6.1 and 2.1, 3-H), 4.52 (1 H, td, J 7.0 and 2.7, 5-H), 4.37 (1 H,
dt, J 7.0 and 2.1, 4-H), 2.91 (1 H, br s, OH), 2.78 (1 H, d, J 11.9,
2ax-H), 2.46 (1 H, ddd, J 15.1, 7.0 and 2.1, 6eq-H), 2.36 (1 H,
dd, J 15.1 and 2.7, 6ax-H) and 2.34 (1 H, ddt, J 11.9, 6.1 and
2.1, 2eq-H); δC(62 MHz; CDCl3) 178.9, 135.4, 129.9, 128.6,
126.6, 103.7, 75.5, 72.9, 72.7, 71.4, 37.7 and 34.4; m/z (EI+) 262
(M+), 261 [(M Ϫ H)+] and 105 [(PhCO)+] (Found: M+, 262.0820.
C14H14O5 requires M, 262.0841).
(Found: C, 54.21; H, 8.39. C13H24O5Si requires C, 54.17; H,
8.33%); [α]2D0 Ϫ24 (c 0.4 in CH3OH); νmax/cmϪ1 3480 (OH), 3380
(OH) and 1800 (C᎐O); δ (250 MHz; CDCl ) 4.65 (1 H, dd, J 6.0
᎐
H
3
and 4.2, 3-H), 4.08 (1 H, dd, J 4.8 and 4.2, 4-H), 3.80 (1 H,
dddd, J 4.9, 6.6, 11.1 and 11.3, 5-H), 2.99 (1 H, s, 1-OH), 2.50 (1
H, d, J 11.4, 2ax-H), 2.29 (1 H, ddd, J 2.9, 6.0 and 11.4, 2eq-H),
2.17 (1 H, ddd, J 2.9, 6.6 and 12.0, 6eq-H), 2.09 (1 H, d, J 11.3,
5-OH), 1.83 (1 H, dd, J 12.0 and 11.1, 6ax-H), 0.92 [9 H, s,
C(CH3)3], 0.15 (3 H, s, SiCH3) and 0.12 (3 H, s, SiCH3); δC(62
MHz; CDCl3) 177.9 (C), 76.3 (CH), 71.9 (C), 67.0 (CH), 65.8
(CH), 40.7 (CH2), 36.4 (CH2), 25.6 [C(CH3)3], 17.9 (C), Ϫ4.7
(SiCH3) and Ϫ5.0 (SiCH3).
(1S,3R,4R,5R)-1,4,5-Trihydroxycyclohexane-1,3-carbolactone 3
To 500 mg of palladium on charcoal (10%) under a hydrogen
atmosphere was added glacial acetic acid (10 cm3). After 10 min
a solution of the acetal 2 (5 g, 19.0 mol) in glacial acetic acid (40
cm3) was added. The system was evacuated and kept under a
hydrogen atmosphere until reduction was complete as judged
by TLC (48 h). The hydrogen was evacuated, the suspension
filtered over Celite and washed with acetic acid (50 cm3) and
methanol (50 cm3). The solvent was removed under reduced
pressure and the product was recrystallised from acetic acid to
afford 3.09 g (94%) of the hydroxylactone 3 as white prisms, mp
184–185 ЊC (lit.,8 185–189 ЊC); νmax/cmϪ1 3000–3560 (OH) and
(1R,3R,4S)-4-tert-Butyldimethylsiloxy-1-hydroxy-5-oxocyclo-
hexane-1,3-carbolactone 6
To a stirred suspension of the alcohol 5 (232 mg, 0.81 mmol)
and 4 Å activated molecular sieves (300 mg) in dry dichloro-
methane (6 cm3) was added pyridinium dichromate (606 mg,
1.61 mmol). The resultant suspension was stirred at room
temp. for 2 h and then diluted with diethyl ether (60 cm3) and
filtered over Celite. The solution was washed successively with
HCl (5%, 2 × 50 cm3) and brine (2 × 50 cm3), dried (MgSO4),
filtered and evaporated. The product was recrystallised from
hexane to afford 201 mg of the ketone 6 as white crystals (87%),
mp 92–93 ЊC (Found: C, 54.46; H, 7.84. C13H22SiO5 requires C,
54.54; H, 7.69%); [α]2D0 Ϫ46 (c 0.4 in CH3OH); νmax/cmϪ1 3350–
1780 (C᎐O); δ (250 MHz; CD OD) 4.91 (3 H, br s, OH), 4.75
᎐
H
3
(1 H, dd, J 4.9 and 6.0, 3-H), 4.02 (1 H, dd, J 4.5 and 4.9, 4-H),
3.74 (1 H, ddd, J 4.5, 6.6 and 11.3, 5-H), 2.51 (1 H, d, J 11.5,
2ax-H), 2.26 (1 H, ddd, J 2.9, 6.0 and 11.5, 2eq-H), 2.07 (1 H,
ddd, J 6.6, 2.9 and 11.6, 6eq-H) and 1.91 (1 H, dd, J 11.3 and
11.6, 6ax-H); δC(62 MHz; CD3OD) 179.5, 77.6, 73.1, 67.3, 66.8,
40.0 and 37.8.
3500 (OH), 1810 (C᎐O) and 1730 (C᎐O); δ (62 MHz; CDCl )
᎐
᎐
H
3
4.78 (1 H, dd, J 3.9 and 6.2, 3-H), 4.05 (1 H, ddd, J 0.6, 1.1 and
3.9, 4-H), 3.10 (1 H, d, J 16.2, 6ax-H), 2.95 (1 H, s, OH), 2.86 (1
H, d, J 12.1, 2ax-H), 2.78 (1 H, ddd, J 1.1, 3.1 and 16.2, 6eq-H),
2.66 (1 H, dddd, J 0.6, 3.1, 6.2 and 12.1, 2eq-H), 0.95 [9 H, s,
C(CH3)3], 0.20 (3 H, s, SiCH3) and 0.16 (3 H, s, SiCH3); δC(250
MHz; CDCl3) 202.7 (C), 177.0 (C), 75.1 (CH), 71.4 (C), 70.6
(CH), 50.0 (CH2), 35.8 (CH2), 25.5 [C(CH3)3], 16.0 (C), Ϫ4.7
(SiCH3) and Ϫ5.3 (SiCH3); m/z (FAB+ve) 287 (MH+) (Found:
MH+, 287.1328. C13H23SiO5 requires M, 287.1315).
Selective monosilylation of the trihydroxylactone 3
Method A. To a stirred solution of the hydroxylactone 3 (1.83
g, 10.52 mmol), 4-dimethylaminopyridine (DMAP) (180 mg,
1.47 mmol) and butylammonium iodide (194 mg, 0.53 mmol)
in dry DMF (17 cm3) and dry triethylamine (1.8 cm3, 12.62
mmol) at 0 ЊC under argon was added 1.82 g (12.1 mmol) of
tert-butyldimethylsilyl chloride. The solution was stirred at this
temperature for 30 min and then 5 h at room temp. The result-
ant suspension was diluted with ethyl acetate (100 cm3) and
filtered over Celite. The solution was washed successively with
1 HCl (100 cm3) and brine (3 × 100 cm3), dried (MgSO4),
filtered and evaporated. The crude product (yellow solid) was
purified by column chromatography on silica gel eluting with
diethyl ether–hexane (1:1) to yield 2.40 g (79%) of monosilyl
ether 4 and 82 mg (3%) of monosilyl ether 5 as white needles.
Method B. To a stirred solution of the hydroxylactone 3 (1.02
g, 5.86 mmol), DMAP (100 mg, 0.82 mmol) and butylammo-
nium iodide (108 mg, 0.29 mmol) in dry DMF (9.6 cm3) and dry
triethylamine (0.98 cm3, 7.03 mmol) at room temp. under
argon was added 1.01 g (6.73 mmol) of tert-butyldimethylsilyl
chloride. The resultant solution was heated at 90 ЊC for 24 h,
and after cooling was diluted with ethyl acetate (100 cm3) and
filtered over Celite. The solution was washed successively with
1 HCl (100 cm3) and brine (3 × 100 cm3), dried (MgSO4),
filtered and evaporated. The crude product was purified by
column chromatography on silica gel eluting with diethyl ether–
hexane (1:1 to 3:1) to yield 918 mg (54%) of monosilyl ether 5
and 505 mg (30%) of monosilyl ether 4 as white needles.
(1S,3R,4S,6R)-6-Bromo-4-tert-butyldimethylsiloxy-1-hydroxy-
5-oxocyclohexane-1,3-carbolactone 7
To a stirred solution of the ketone 6 (328 mg, 1.15 mmol) in dry
diethyl ether (30 cm3) under argon was added freshly made
dioxane dibromide10 (313 mg, 1.26 mmol). The red solution
was stirred at room temp. until decoloration (2 h), diluted with
diethyl ether (30 cm3) and washed successively with aqueous
sodium metabisulfite (5%, 30 cm3), aqueous sodium hydrogen
carbonate (5%, 30 cm3) and water (30 cm3). The organic layer
was dried (MgSO4), filtered and evaporated. The product was
recrystallised from hexane to afford the bromo ketone 7 as white
needles (371 mg, 89%), mp 124–125 ЊC (Found: C, 42.68; H,
5.78. C13H21BrSiO5 requires C, 42.74; H, 5.75%); [α]2D0 Ϫ203 (c
0.4 in CH3OH); νmax/cmϪ1 3540 (OH), 1820 (C᎐O) and 1725
᎐
(C᎐O); λmax(EtOH)/nm 238 and 339 (ε/dm3 molϪ1 cmϪ1 832 and
᎐
117); δH (250 MHz; CDCl3) 4.79 (1 H, dd, J 4.1 and 6.3, 3-H),
4.35 (1 H, dd, J 1.2 and 2.5, 6-H), 4.19 (1 H, ddd, J 0.9, 1.2 and
4.1, 4-H), 3.78 (1 H, s, OH), 3.33 (1 H, d, J 12.7, 2ax-H), 2.55 (1
H, dddd, J 0.9, 2.5, 6.3 and 12.7, 2eq-H), 0.95 [9 H, s, C(CH3)3],
0.26 (3 H, s, SiCH3) and 0.19 (3 H, s, SiCH3); δC(100 MHz;
CDCl3) 198.3 (C), 172.8 (C), 76.4 (CH), 74.7 (C), 74.0 (CH),
71.0 (CH), 51.9 (CH), 32.7 (CH2), 25.3 [C(CH3)3], 17.9 (C),
Ϫ5.3 (SiCH3) and Ϫ5.5 (SiCH3); m/z (FAB+ve) 365 (MH+)
(Found: MH+, 365.0420. C13H22BrSiO5 requires M, 365.0420).
(1R,3R,4S,5R)-5-tert-Butyldimethylsiloxy-1,4-dihydroxy-
cyclohexane-1,3-carbolactone 4. Mp 95–96 ЊC (from hexane)
(Found: C, 54.12; H, 8.45. C13H24SiO5 requires C, 54.17; H,
8.33%); [α]2D0 Ϫ34 (c 1.1 in CH3OH); νmax/cmϪ1 3300 (br, OH)
and 1780 (C᎐O); δ (250 MHz; CDCl ) 4.85 (1 H, dd, J 6.0 and
᎐
H
3
4.7, 3-H), 3.95 (1 H, dd, J 4.5 and 4.7, 4-H), 3.86 (1 H, ddd, J
4.5, 7.2 and 11.6, 5-H), 3.00 (1 H, s, OH), 2.96 (1 H, s, OH), 2.59
(1 H, d, J 11.6, 2ax-H), 2.28 (1 H, ddd, J 2.6, 6.0 and 11.6, 6eq-
H), 1.89–2.06 (2 H, m, 6ax-H and 2eq-H), 0.88 [9 H, s, C(CH3)3]
and 0.08 [6 H, s, Si(CH3)2]; δC(62 MHz; CDCl3) 178.1, 76.3,
71.7, 67.0, 65.6, 40.1, 36.4, 25.6, 17.9, Ϫ4.7 and Ϫ5.0.
(1S,2R,4S,5R)-2-Bromo-1,4,5-trihydroxy-3-oxocyclohexane-
carboxylic acid [(2R)-2-bromodehydroquinic acid] 8
To a solution of the bromo ketone 7 (400 mg, 1.10 mmol) in
acetic acid (4 cm3) was added water (1 cm3) and the solution
stirred at 40 ЊC for 72 h. The solution was lyophilised and the
residue partitioned between ethyl acetate (25 cm3) and water (25
cm3). The aqueous phase was washed with ethyl acetate (25
cm3) and lyophilised to give the crude product. Recrystallisation
(1S,3R,4R,5R)-4-tert-Butyldimethylsiloxy-1,5-dihydroxy-
cyclohexane-1,3-carbolactone 5. Mp 154–155 ЊC (from hexane)
J. Chem. Soc., Perkin Trans. 1, 1997
627