ϩ
ϩ
(
ϩ) (Found: M , 202.1033. C H SO requires M , 202.1027);
The filtrate and combined washings were evaporated under
10
18
2
ϩ
ϩ
m/z 202 (M ,13%), 147 (87), 118 [M Ϫ C(᎐O)C(Me) CH , 30]
reduced pressure and the crude material was filtered through a
plug of silica to give a 95:5 mixture (by NMR) of the syn- and
anti-diols, 9.
2
2
and 56 [C(Me) CH , 100].
2
2
Stereoselective reductions of the á-hydroxy ketone 4: syn-
,3,6,6-tetramethylthiacycloheptane-4,5-diol, syn-9
3
anti-3,3,6,6-Tetramethylthiacycloheptane-4,5-diol, anti-9
Sodium borohydride (75 mg, 19.5 mmol) was added to a stirred
Reduction with DIBAL and ZnCl . Zinc chloride (0.5 mol
2
Ϫ3
3
solution of the hydroxy ketone 4 (80 mg, 3.9 mmol) in dry
dm solution in THF; 3 cm ) was added to a stirred solution of
the hydroxy ketone 4 (300 mg, 1.49 mmol) in dry THF. The
solution was cooled to Ϫ78 ЊC and treated with a solution of
3
ethanol (1 cm ). The reaction mixture was stirred at room tem-
perature for 2 h, after which it was treated with dilute hydro-
chloric acid and concentrated by evaporation of most of the
ethanol under reduced pressure. The residue was dissolved in
Ϫ3
3
DIBAL (1 mol dm in THF; 1.5 cm , 1.5 mmol), added drop-
wise. The reaction mixture was allowed to warm to room tem-
perature and then stirred overnight. After this, methanol was
added to the mixture which was then stirred for a further 30
min. The resulting inorganic precipitate was filtered off and
washed several times with dichloromethane. The filtrate and
organic washings were combined and evaporated under
reduced pressure. The crude material (a 39:61 ratio of syn- and
anti-diols 9 by NMR) was chromatographed on silica eluting
with hexane–ethyl acetate (5:2) to give the syn-diol (105 mg,
3
dichloromethane (5 cm ) and the solution was washed with
3
3
water (5 cm ), aqueous sodium hydrogen carbonate (5 cm ) and
water and then dried (MgSO ) and evaporated under reduced
4
pressure to give a colourless solid. This was purified by chroma-
tography (SiO , hexane–ethyl acetate, 3:1), to remove any
2
remaining starting material, to give the syn-diol 9 as prisms (75
4
7
mg, 92%), mp 180–182 ЊC (from hexane) (lit., 179–180 ЊC, lit.,
83–185 ЊC); R [hexane–ethyl acetate (3:1)] 0.19; νmax(Nujol)/
1
f
Ϫ1
cm 3406 (OH) and 2922 (CH); δ (250 MHz; CDCl ) 3.73 (2
35%) and the anti-diol 9 (160 mg, 54%), R [hexane–ethyl acet-
H
3
f
H, d, J 6.2, 2 × CHOH), 2.83 (2 H, d, J 14.5, 2 × SCH H ),
ate (3:1)] 0.33 (Found: C, 58.75; H, 9.89. C H SO requires C,
A
B
10 20
2
Ϫ1
2
2
2
4
.28 (2 H, d, J 14.5, 2 × SCH H ), 1.78 (2 H, d, J 6.3,
58.78; H, 9.87%); νmax(CH Cl )/cm 3614–3495 (OH) and
A
B
2 2
× CHOH), 1.08 (6 H, s, 2 × CMe Me ) and 1.07 (6 H, s,
2958–2871 (CH); δ (250 MHz; CDCl ) 3.56 (2 H, br s,
H 3
A
B
× CMe Me ); δ (100 MHz; CD COCD ) 82.9 (ϩ), 46.3 (Ϫ),
2 × CHOH), 2.76 (2 H, br s, 2 × CHOH), 2.52 (2 H, d, J 14.7,
2 × SCH CH ), 2.27 (2 H, d, J 14.7, 2 × SCH CH ), 1.09 (6 H,
A
B
C
3
3
ϩ
0.5 (Ϫ), 27.6 (ϩ) and 19.6 (ϩ) (Found: M , 204.1185.
A
B
A
B
ϩ
ϩ
C H O S requires M , 204.1184); m/z 204 (M , 48), 120 (78),
s, 2 × CMe Me ) and 0.95 (6 H, s, 2 × CMe Me ); δ (63 MHz;
10
20
2
A B A B C
8
6 [CH CMe C(OH)H, 69] and 56 [CH CMe , 52].
CDCl ) 73.6 (ϩ), 47.1 (Ϫ), 38.8 (Ϫ), 28.3 (ϩ) and 19.7 (ϩ)
2
2
2
2
3
ϩ
ϩ
(
2
Found: M , 204.1181. C H SO requires M , 204.1184); m/z
04 (M , 11%), 186 (M Ϫ H O, 20), 139 (76) and 130
2
ϩ
10
20
2
ϩ
ϩ
Luche Reduction
Sodium borohydride (10 mg, 0.26 mmol), the hydroxy ketone 8
16 mg, 0.08 mmol) and CeCl ؒ7H O (33 mg, 0.09 mmol) in dry
[
M Ϫ H O Ϫ CH C(Me) , 100], 86 [CH C(Me) C(OH)H, 40]
2 2 2 2 2
(
3
2
and 56 [CH C(Me) , 52].
2 2
3
ethanol (0.5 cm ) at Ϫ78 ЊC gave, after purification by washing
through a plug of silica eluting with hexane–ethyl acetate (1:1)
and recrystallisation, the syn-diol 9 (12 mg, 74%).
4-Acetoxy-5-chloro-3,3,6,6-tetramethylthiacycloheptane 17
3
Trimethyl orthoacetate (0.138 cm , 1.1 mmol) was added to a
solution of the syn-diol 9 (170 mg, 0.83 mmol) and toluene-p-
2
0
3
Preparation of Zn(BH ) solution
4
2
sulfonic acid (2 mg) in dry CH Cl (2 cm ). After the mixture
2
2
Ϫ3
3
Zinc chloride (1 mol dm solution in diethyl ether; 27.5 cm )
was added dropwise to a stirred solution of sodium boro-
hydride (2 g, 52.8 mmol) in dry ether (150 cm ). The reaction
mixture was stirred at room temperature for 2 days. The solid
material was then allowed to settle and the supernatant solution
transferred by cannula to a bottle. The solution was stored at
had been stirred at room temperature for 1 h, volatile material
was removed under reduced pressure and most of the residual
methanol was removed by subjecting the sample to high
vacuum for 1 min. The residue was then dissolved in dichloro-
3
3
methane and trimethylsilyl chloride (0.160 cm , 1.25 mmol)
was added to the solution. The reaction mixture was stirred at
room temperature for 4 days after which it was evaporated
under reduced pressure. The residue was chromatographed
5
ЊC under argon.
Reduction with Zn(BH4)2
(
SiO , hexane–ether, 10:1) to give the α-chloro acetate 17 (141
2
Zinc borohydride solution in Et O (prepared as above) and the
hydroxy ketone 4 (88 mg, 0.43 mmol) in dry ether (1.5 cm ) at
ЊC for 6 h (with further reducing agent added until all the
starting material was consumed) gave after acidification, extrac-
tion with ethyl acetate (3 × 5 cm ), washing with saturated
aqueous sodium hydrogen carbonate, drying (MgSO ) and
chromatography (SiO , hexane–ethyl acetate, 6:1) the syn-diol 9
50 mg, 62%) and the anti-diol 9 (30 mg, 38%) (see below).
2
mg, 64%) as a colourless oil; R [hexane–ethyl acetate (3:1)]
f
3
Ϫ1
0
.52; νmax(CDCl )/cm 2962–2890 (CH) and 1732 (C᎐O);
3
0
δ (250 MHz; CDCl ) 5.18 (1 H, d, J 3.5, CHOAc), 3.78 (1 H, d,
H
3
J 3.5, CHCl), 3.40 (2 H, AB quartet, J 11.1, SCH CH ), 2.89 (1
A
B
3
H, d, J 10.1, SCH CH ), 2.52 (1 H, d, J 10.1, SCH CH ), 2.11
C
D
C
D
4
(
3 H, s, CO Me), 1.12 (3 H, s, Me ), 1.08 (6 H, s, Me Me ) and
2 C A B
2
0
5
.97 (3 H, s, Me ); δ (100 MHz; CDCl ) 170.2 (Ϫ), 82.6 (ϩ),
D C 3
(
6.7 (ϩ), 55.4 (Ϫ), 47.7 (Ϫ), 41.2 (Ϫ), 38.1 (Ϫ), 25.4 (ϩ), 24.4
ϩ
(
ϩ), 24.2 (ϩ), 22.8 (ϩ) and 21.3 (ϩ) (Found: M , 264.0954.
Reduction with LiAlH4
ϩ
ϩ
C H O SCl requires M , 264.0951); m/z 266 (M , 15%), 264
3
12 21
ϩ
2
The hydroxy ketone 4 (20 mg, 0.1 mmol) in dry ether (0.5 cm )
and a solution of lithium aluminium hydride (5 mg, 0.13 mmol)
in dry ether (1.5 cm ) was refluxed for 4 h and quenched by the
ϩ
ϩ
(
M , 45), 221 [M Ϫ C(᎐O)Me, 2], 204 (M Ϫ HCO Me, 4)
2
ϩ
and 173 [M Ϫ Cl Ϫ C(Me) CH , 100].
3
2
2
careful addition of water and then dilute aq. HCl. The organic
Acknowledgements
We thank Zeneca Fine Chemicals and EPSRC for CASE
awards (to M. J. G., S. O’S and P. W.).
layer was separated and the aqueous layer extracted with ether
3
(
3 × 5 cm ) to give, after work-up, the syn- and anti-diols 9 in a
1
6:3 ratio (by NMR).
Reduction with DIBAL
References
Ϫ3
A mixture of diisobutylaluminium hydride (1 mol dm in
3
1 A. de Groot and H. Wynberg, J. Org. Chem., 1966, 31, 3954.
H. Wynberg and A. de Groot, J. Chem. Soc., Chem. Commun., 1965,
CH Cl ; 0.22 cm ) and the hydroxy ketone 4 (9 mg, 0.044 mmol)
2
2
2
in dry CH Cl was stirred at Ϫ78 ЊC for 3 h, and then warmed
2
2
1
71.
to room temperature and treated with methanol. After the mix-
ture had been stirred for a further 30 min the precipitate was
filtered off and washed several times with dichloromethane.
3
4
A. Krebs and H. Kimling, Tetrahedron Lett., 1970, 761.
A. de Groot, J. A. Boerma and H. Wynberg, Rec. Trav. Chim. Pays-
Bas., 1969, 88, 994.
3
482
J. Chem. Soc., Perkin Trans. 1, 1997