100
M. G. Banwell et al.
Stirring was continued overnight during which time the ice bath and
reaction mixture were allowed to warm to ca. 18°C. The resulting
mixture was then washed with sodium metabisulfite (3 × 60 mL of an
15% w/v aqueous solution), sodium bicarbonate (1 × 60 mL of a
saturated aqueous solution) and water (1 × 60 mL) before being dried
(MgSO4), filtered and concentrated under reduced pressure. The
ensuing light-yellow oil was subjected to flash chromatography (silica
gel, gradient elution using 2–3% v/v ethyl acetate/hexane) thereby
affording two fractions, A and B.
129.8, 128.5, 128.0, 127.5, 74.4, 72.3, 70.8, 70.4, 27.0, 20.5, 19.8. νmax
(KBr) 3429, 2931, 2857, 1747, 1227, 1159, 1112, 1040, 738, 703, 508
• +
cm–1. EI-MS m/z (70 eV) 405 (2%) and 403 (7) [M – C4H9 ] , 267 (20)
and 265 (50), 241 (60), 199 (100), 181 (60).
(1S,2S,3S,6R)-4,6-Dichloro-2-{[(1,1-dimethylethyl)diphenylsilyl]-
oxy}-4-cyclohexene-1,3-diol 3-Acetate and (1R,2S,3S,4S)-5-Chloro-3-
{[(1,1-dimethylethyl)diphenylsilyl]oxy}-5-cyclohexene-1,2,4-triol 4-
Acetate (9)
Concentration of fraction A (RF 0.5) afforded compound (6) (1.25 g,
58%) as a clear colourless oil, [α]D +34.6 (c, 1.1) (Found: M+•,
442.1363. C24H2735ClO4Si requires M+•, 442.1367). 1H NMR (CDCl3,
300 MHz) δ 7.75–7.65, complex m, 4H; 7.50–7.40, complex m, 6H;
6.30, dd, J 4.1 and 2.2 Hz, 1H; 5.38, m 1H; 4.55, m, 1H; 3.41, m 1H;
3.35, m, 1H; 1.94, s, 3H; 1.11, s, 9H. 13C NMR (CDCl3, 75 MHz) δ
170.1, 136.5, 136.3, 135.9, 133.6, 133.3, 130.7, 130.5, 128.4, 128.1,
122.8, 69.4, 68.4, 53.7, 48.6, 27.3, 21.0, 20.0; νmax (KBr) 2957, 2858,
2932, 1751, 1369, 1225, 1112, 703, 506 cm–1. EI-MS m/z (70 eV) 444
and 442 (M+•, both < 1%), 241 (100), 199 (80).
A solution of compound (7) (457 mg, 1.03 mmol) and water (2 mL) in
THF (6 mL) was treated with HCl (1 mL of a 1 M aqueous solution) and
the ensuing mixture allowed to stand at 18°C for 24 h and then treated
with NaOH (2.5 mL of a 1 M aqueous solution) and dichloromethane
(10 mL). The separated aqueous phase was extracted with
dichloromethane (3 × 8 mL) and the combined organic phases were
washed with brine (1 × 10 mL) then dried (MgSO4), filtered and
concentrated under reduced pressure to give a light-yellow oil.
Subjection of this material to flash chromatography (silica gel, gradient
elution using 3 to 30% v/v ethyl acetate/hexane) afforded three
fractions, A–C.
Concentration of fraction B (RF 0.3) afforded compound (7) (0.38 g,
18%) as a white crystalline solid, melting point (m.p.) 156–158°C, [α]D
Concentration of fraction A (RF 0.6 in 1 : 2.5 : 5.5 v/v/v ethyl
acetate/dichloromethane/hexane) afforded starting material (7) (68 mg,
15% recovery), identical, in all respects, with authentic material.
Concentration of fraction B (RF 0.5 in 1 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) afforded (1S,2S,3S,6R)-4,6-dichloro-2-
{[(1,1-dimethylethyl)diphenylsilyl]oxy}-4-cyclohexene-1,3-diol 3-ace-
tate (231 mg, 47 at 85% conversion) as a white crystalline solid, m.p.
135.5–137°C, [α]D –131.4 (c, 0.9) (Found: C, 59.6; H, 5.8; Cl, 14.7%;
• +
–156.9 (c, 1.1) (Found: C, 64.8; H, 6.1; Cl, 7.9%; [M – C4H9 ] ,
385.0663. C24H2735ClO4Si requires C, 65.1, H, 6.1, Cl, 8.0%; [M –
C4H9• ]+, 385.0663). 1H NMR (CDCl3, 300 MHz) δ 7.81, m, 2H; 7.77,
m, 2H; 7.50–7.37, complex m, 6H; 6.25, d, J 4.4 Hz, 1H; 5.86, dd, J 5.7
and 1.9 Hz, 1H; 4.31, dd, J 5.7 and 1.2 Hz, 1H; 3.17, t, J 4.2 Hz, 1H;
3.03, m, 1H; 2.24, s, 3H; 1.09, s, 9H. 13C NMR (CDCl3, 75 MHz) δ
170.7, 135.9, 135.8, 134.9, 134.7, 133.3, 132.1, 130.3, 130.2, 129.6,
128.1, 128.0, 127.7, 126.7, 70.6, 70.0, 54.9, 47.8, 26.7, 21.2, 19.2. νmax
(KBr) 2931, 2858, 1743, 1427, 1370, 1233, 1112, 706, 507 cm–1. EI-
MS m/z (70 eV) 444 and 442 (M+•, both < 1%), 241 (53), 199 (100).
• +
[M – C4H9 ] , 421.0427. C24H2835Cl2O4Si requires C, 60.1; H, 5.9; Cl,
• +
14.8%; [M – C4H9 ] , 421.0430). 1H NMR (CDCl3, 300 MHz) δ 7.75–
7.65, complex m, 4H; 7.50–7.38, complex m, 6H; 6.07, d, J 4.4 Hz, 1H;
5.70, d, J 4.4 Hz, 1H; 4.56, br t, J 4.4 Hz, 1H; 4.37, m, 1H; 3.72, m, 1H;
2.70, br s, 1H; 1.98, s, 3H; 1.09, s, 9H. 13C NMR (CDCl3, 75 MHz) δ
169.5, 136.1, 136.0, 132.6, 132.5, 130.4, 130.2, 128.1, 127.9, 126.8,
73.4, 70.2, 69.2, 56.6, 27.0, 20.7, 19.5 (one signal obscured or
overlapping). νmax (KBr) 2932, 2858, 1751, 1226, 1113, 1048,
736, 702, 508 cm–1. EI-MS m/z (70 eV) 425 (< 1%), 423 (2) and 421
(1S,2S,3S,6R)-4-Chloro-2-{[(1,1-dimethylethyl)diphenylsilyl]oxy}-6-
(4´-hydroxybutoxy)-4-cyclohexene-1,3-diol 3-Acetate (8) and (1R,2S,-
3S,4S)-5-Chloro-3-{[(1,1-dimethylethyl)diphenylsilyl]oxy}-5-cyclo-
hexene-1,2,4-triol 4-Acetate (9)
A magnetically stirred solution of epoxide (7) (1.08 g, 2.44 mmol) in
THF (15 mL) and water (5 mL) was treated with phosphoric acid
(0.5 mL of a 93% aqueous solution, M & B) whilst being maintained
under a nitrogen atmosphere. The resulting mixture was stirred at 18°C
for 40 h then concentrated under reduced pressure and the residue
partitioned between ethyl acetate (30 mL) and brine (30 mL). The
separated aqueous phase was extracted with ethyl acetate (3 × 30 mL)
and the combined organic phases were then dried (MgSO4), filtered and
concentrated under reduced pressure. The resulting light-yellow oil was
subject to flash chromatography (silica gel, gradient elution using 30 to
50% v/v ethyl acetate/hexane) thereby affording two fractions, A and B.
Concentration of fraction A (RF 0.5 in 8 : 2.5 : 5.5 v/v/v ethyl
acetate/dichloromethane/hexane) then afforded compound (8) (265 mg,
• +
(4) [M – C4H9 ] , 250 (35) and 248 (78), 241 (88), 199 (100).
Concentration of fraction C (RF 0.7 in 8 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) afforded diol (9) (50 mg, 10 at 85%
conversion), identical, in all respects, with material obtained as
described immediately above.
3-O-[(1,1-Dimethylethyl)diphenylsilyl]-D-talonic acid γ-Lactone 2-
Acetate (10)
A magnetically stirred solution of diol (9) (830 mg, 1.80 mmol) and
pyridine (2 mL) in methanol (35 mL) was cooled to –78°C (acetone/
dry-ice bath) then treated with a stream of ca. 40% ozone in oxygen
(produced by a Wallace & Tiernan ozonator) for 1.0 h, at which point
TLC analysis indicated the complete consumption of the starting
material. The reaction mixture was purged with nitrogen and then
treated with sodium iodide (840 mg, 5.60 mmol). After 3 h the now red-
brown reaction mixture was warmed to –66°C and treated with sodium
borohydride (1.35 g, 35.69 mmol). The reaction mixture was
maintained between –60 and –40°C for 6 h and then treated with
sufficient 2 M HCl in methanol so as to reduce the pH to ca. 3.5. The
ensuing mixture was concentrated under reduced pressure and the
residue partitioned between ethyl acetate (25 mL) and brine (25 mL).
The separated aqueous phase was extracted with ethyl acetate
(3 × 20 mL) and the combined organic phases were dried (MgSO4),
filtered and concentrated under reduced pressure. Subjection of the
resulting light-yellow oil to flash chromatography (silica gel, 60% v/v
ethyl acetate/hexane elution) and concentration of the appropriate
fractions (RF 0.4) then afforded lactone (10) (450 mg, 54%) as a clear,
• +
20%) as a light-yellow oil, [α]D –87.2 (c, 1.0) (Found: [M – C4H9 ] ,
• +
475.1345. C28H3735ClO6Si requires [M – C4H9 ] , 475.1344). 1H NMR
(CDCl3, 300 MHz) δ 7.75–7.70, complex m, 4H; 7.45–7.38, complex
m, 6H; 6.07, br d, J 4.0 Hz, 1H; 5.61, br d, J 4.0 Hz, 1H; 4.28, m, 1H;
4.03, br, t, J 4.0 Hz, 1H; 3.64–3.54, complex m, 3H; 3.41, m, 1H; 3.25,
m, 1H; 2.43, s, 2H; 1.88, s, 3H; 1.52, m, 4H; 1.08, s, 9H. 13C NMR
(CDCl3, 75 MHz) δ 169.8, 136.1, 136.0, 132.9, 132.8, 131.7, 130.2,
129.9, 127.9, 127.7, 126.5, 77.4, 70.8, 70.5, 69.9, 62.5, 29.5, 26.9, 26.5,
20.7, 19.5 (one signal obscured or overlapping). νmax (KBr) 3429, 2932,
2858, 1747, 1370, 1228, 1112, 1045, 740, 704, 507 cm–1. EI-MS m/z
• +
(70 eV) 477 (1%) and 475 (2) [M – C4H9 ] , 241 (78), 199 (100), 181
(52), 101 (90).
Concentration of fraction B (RF 0.7 in 8 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) then afforded compound (9) (795 mg, 71%)
• +
as a clear, colourless oil, [α]D –59.1 (c, 1.0) (Found: [M – C4H9 ] ,
• +
1
• +
403.0763. C24H2935ClO5Si requires[M– C4H9 ] , 403.0769). H NMR
(CDCl3, 300 MHz) δ 7.75–7.65, complex m, 4H; 7.50–7.38, complex
m, 6H; 6.02, m 1H; 5.48, m, 1H; 4.50, m, 1H; 4.30, m, 1H; 3.51, dd, J
6.5 and 1.6 Hz, 1H; 2.74, s, 2H; 1.69, s, 3H; 1.08, s, 9H. 13C NMR
(CDCl3, 75 MHz) δ 170.0, 136.2, 136.1, 132.9, 132.5, 130.9, 130.3,
colourless oil, [α]D +19.1 (c, 0.6) (Found: [M – C4H9 ] , 401.1041.
• +
1
C24H30O7Si requires [M – C4H9 ] , 401.1057). H NMR (CDCl3, 300
MHz) δ 7.62–7.58, complex m, 4H; 7.50–7.37, complex m, 6H; 5.62,
d, J 5.6 Hz, 1H; 4.61, d, J 5.6 Hz, 1H; 4.13, br s, 1H; 3.42, dd, J 11.3
and 8.0 Hz, 1H; 3.31, dd, J 11.3 and 4.1 Hz, 1H; 3.15, m, 1H; 2.55, br