10072
M. O’Brien, E.J. Thomas / Tetrahedron 67 (2011) 10068e10081
under reduced pressure. Chromatography of the residue eluting
with light petroleum to light petroleum/ether (1:1) gave the title
HRMS (CIþ): MþþNH4, found 464.2653. C25H38NO7 requires
464.2648.
compound 8 (1.9 g, 61%) as a colourless oil, [
a]
D þ12 (c 0.2 in Et2O);
nmax/cmꢀ1 3010, 2975, 2912, 2872, 1741, 1707, 1455, 1369, 1237 and
1068; dH (3000 MHz, CDCl3) 1.04 (3H, s, 30-CH3), 1.23 (5H, s, 3-Heq, 5-
Heq, 30-CH3 ), 1.74 (1H, dd, J 13.5 and 11.7, 5-Hax), 1.91 (1H, dd, J 13.5
and 12.0, 3-Hax), 2.09 (3H, s, COCH3), 2.58 (1H, dd, J 17.2 and 6.6, 10-
H), 2.66 (1H, d, J 4.5, 100-H), 2.70 (1H, d, J 4.5, 100-H0), 2.96 (1H, dd, J
17.2 and 5.6, 10-H0), 3.98 (2H, m, 2-H, 40-H), 4.08 (2H, m, 2-CH2), 4.18
(1H, m, 6-H), 4.28 and 4.57 (each 1H, d, J 11.8, HCHAr), 5.32 (1H, d, J
17.2, 60-H), 5.40 (1H, dd, J 10.4 and 1.6, 60-H0), 5.76 (1H, ddd, J 17.3,
10.4 and 8.1, 50-H) and 7.20e7.40 (5H, m, ArH); dC (75 MHz, CDCl3)
18.72, 20.79, 21.84, 30.86, 34.37, 37.96, 44.76, 51.17, 52.77, 55.86,
70.44, 71.89, 73.09, 85.93, 120.21, 127.30, 127.47, 128.12, 134.14,
138.35, 170.79 and 212.05; m/z (CIþ) 434 (Mþþ18, 100%), 417 (19),
309 (30) and 108 (28); HRMS (CIþ): MþþH, found 417.2288.
C24H33O6 requires 417.2278.
4.2.4. (7R,9S,)-9-[(4S)-4-Benzyloxy-3,3-dimethyl-2-oxohex-5-enyl]-
7-hydroxymethyl-1,4,8-trioxaspiro[4.5]decane (11). Potassium car-
bonate (20 g) was added to an emulsion of the acetate 10 (2.08 g,
4.66 mmol) in methanol (20 mL) and water (20 mL) and the mixture
stirred vigorously for 1.5 h. Water (100 mL) was added, the mixture
was extracted with ether and the organic extracts werewashed with
water then dried over magnesium sulfate. Concentration under re-
duced pressure gave the title compound 11 (1.6 g, 85%) as a colourless
oil, Rf¼0.3 (1:1 light petroleum/ethyl acetate), [
a]
þ8.8 (c 1.5 in
D
Et2O); nmax/cmꢀ1 3480, 3064, 2966, 2923, 2878, 1706, 1469, 1455,
1384,1367,1209,1151,1068,1003, 944 and 737; dH (300 MHz, CDCl3)
0.95 and 1.09 (each 3H, 30-CH3), 1.25 (1H, dd, J 12.8 and 11.5,10-Hax),
1.46 (1H, t, J 12.9 and 6-Hax), 1.51 (1H, m, 6-Heq), 1.73 (1H, dt, J 12.9
and 2.1, 10-Heq), 1.89 (1H, m, OH), 2.48 (1H, dd, J 17.5 and 6.7, 10-H),
2.79 (1H, dd, J 17.5 and 5.9,10-H0), 3.40 and 3.52 (each 1H, m, 7-HCH),
3.65 (1H, m, 7-H), 3.88 (5H, m, 40-H, 2-H2, 3-H2), 4.00 (1H, m, 9-H),
4.19 and 4.46 (each 1H, d, J 11.7, HCHAr), 5.21 (1H, ddd, J 18.0,1.9 and
0.8, 60-H), 5.29 (1H, ddd, J 10.4, 1.9 and 0.7, 60-H0), 5.64 (1H, m, 50-H)
and 7.15e7.35 (5H, m, ArH); dC (75 MHz, CDCl3) 18.80, 21.87, 36.75,
40.56, 44.51, 51.24, 64.21, 64.37, 65.68, 70.38, 71.33, 75.47, 85.53,
106.85, 120.26, 127.35, 127.53, 128.15, 134.15, 138.24 and 211.69; m/z
(CIþ) 422 (Mþþ18,100%), 405 (63) and 344 (49); HRMS (CIþ): MþþH,
found 405.2277. C23H33O6 requires 405.2279.
4.2.2. (2R,4RS,6S)-2-Acetoxymethyl-6-[(4S)-4-benzyloxy-3,3-
dimethyl-2-oxohex-5-enyl]tetrahydropyran-4-one (9). Periodic acid
(1.28 g, 5.6 mmol) was added to the epoxide 8 (2.33 g, 5.6 mmol) in
ether (50 mL) and the mixture stirred at room temperature for 18 h.
Saturated aqueous sodium thiosulfate (20 mL) was added after
which the mixture gave a negative result with starch/potassium
iodide paper. The mixture was extracted with ether (3ꢂ20 mL) and
the organic extracts were washed with water (20 mL) and brine
(20 mL), then dried over magnesium sulfate and concentrated un-
der reduced pressure. Chromatography of the residue eluting with
light petroleum to light petroleum/ether (1:1) gave the title com-
4.2.5. (7R,9S,)-9-[(4S)-4-Benzyloxy-3,3-dimethyl-2-oxohex-5-enyl]-
7-tert-butyldimethysilyloxymethyl-1,4,8-trioxaspiro[4.5]-decane
(12). The alcohol 11 (1.6 g, 3.96 mmol) and imidazole (1.35 g,
19.8 mmol) were dissolved in DCM (20 mL) and tert-butyldime-
thylsilyl chloride (658 mg, 4.36 mmol) in DCM (20 mL) was added.
The mixture was stirred at room temperature for 30 min then water
(20 mL) was added. Following extraction with ether (3ꢂ20 mL), the
organic extracts were washed with water (20 mL) and brine
(20 mL), then dried over magnesium sulfate. After concentration
under reduced pressure, chromatography eluting with light pe-
troleum to light petroleum/ether (1:1) gave the title compound 12
(1.5 g, 72%) as a colourless oil, Rf¼0.7 (9:1 light petroleum/ethyl
pound 9 (2.1 g, 91%) as a colourless oil, [
a
]
D þ4.6 (c 1.4 in Et2O); nmax
/
cmꢀ1 2963, 2920, 2855, 1741, 1719, 1455, 1367, 1234 and 1067; dH
(300 MHz, CDCl3) 1.05 and 1.23 (each 3H, s, 30-CH3), 2.10 (4H, m,
COCH3, 5-Hax), 2.30 (1H, dd, J 14.8 and 11.3, 3-Hax), 2.39 (1H, ddd, J
14.8, 3.4 and 1.6, 3-Heq), 2.49 (1H, dt, J 14.6 and 1.8, 5-Heq), 2.67 (1H,
dd, J 17.6 and 6.5, 10-H), 3.06 (1H, dd, J 17.4 and 5.9, 10-H0), 3.90 (1H,
m, 2-H), 3.96 (1H, d, J 8.1, 40-H), 4.14 (3H, m, 6-H, 2-CH2), 4.24 and
4.57 (each 1H, d, J 11.5, HCHAr), 5.33 (1H, d, J 17.2, 60-H), 5.42 (1H,
dd, J 10.3, 60-H0), 5.77 (1H, ddd, J 17.2, 10.3 and 8.1, 50-H) and
7.20e7.40 (5H, m, ArH); dC (75 MHz, CDCl3) 18.65, 20.70, 21.92,
43.34, 45.08, 46.81, 51.14, 65.86, 70.49, 73.04, 74.26, 86.03, 120.45,
127.44, 127.55, 128.18, 133.96, 138.16, 170.55, 205.16 and 211.42; m/z
(CIþ) 420 (Mþþ18, 100%) and 403 (27); HRMS (CIþ): MþþH, found
403.2131. C23H31O6 requires 403.2120.
acetate), [
a
]
ꢀ5.0 (c 1.0 in DCM); nmax/cmꢀ1 2953, 2927, 2855,
D
1709, 1638, 1470, 1384, 1363, 1253, 1115, 1069, 1027, 1006, 942, 837
and 778; dH (300 MHz, CDCl3) 0.00 (6H, s, 2ꢂ SiCH3), 0.84 [9H, s,
SiC(CH3)3], 0.98 and 1.14 (each 3H, s, 30-CH3), 1.27 (1H, t, J 11.8, 10-
Hax), 1.45 (1H, dd, J 13.0 and 10.8, 6-Hax), 1.69 (1H, dt, J 13.0 and 1.9,
6-Heq), 1.77 (1H, dt, J 12.8 and 2.3, 10-Heq), 2.51 (1H, dd, J 17.4 and
7.1, 10-H), 2.91 (1H, dd, J 17.4 and 5.6, 10-H0), 3.48 (1H, m, 7-H), 3.61
(2H, m, 7-CH2), 3.92 (5H, m, 40-H, 2-H2, 3-H2), 4.02 (1H, m, 9-H),
4.23 and 4.49 (each 1H, d, J 11.7, HCHAr), 5.26 (1H, dd, J 17.2 and 1.1,
60-H), 5.33 (1H, dd, J 10.3 and 1.5, 60-H0), 5.69 (1H, ddd, J 17.2, 10.3
and 8.0, 50-H) and 7.15e7.30 (5H, m, ArH); dC (75 MHz, CDCl3)
ꢀ5.35, ꢀ5.31, 18.27, 18.77, 21.79, 25.84, 37.53, 40.58, 44.68, 51.24,
64.11, 64.32, 66.11, 70.43, 71.31, 75.67, 85.64, 107.10, 120.11, 127.29,
127.46, 128.12, 134.22, 138.32 and 212.02; m/z (CIþ) 536 (Mþþ18,
4%), 519 (Mþþ1, 4), 373 (16), 108 (96) and 91 (100%); HRMS (CIþ):
MþþH, found 519.3133. C29H47O6Si requires 519.3142.
4.2.3. (7R,9S,)-7-Acetoxymethyl-9-[(4S)-4-benzyloxy-3,3-dimethyl-
2-oxohex-5-enyl]-1,4,8-trioxaspiro[4.5]decane (10). Ketone 9 (2.1 g,
5.24 mmol), ethylene glycol (30 mL) and PPTS (50 mg) were dis-
solved in benzene (150 mL) and the solution heated under reflux in
a DeaneStark apparatus for 2 h before being cooled to room tem-
perature. Water (100 mL) was added, the mixture was extracted
with ether and the organic extracts were washed with water then
dried over magnesium sulfate. Concentration under reduced pres-
sure gave the title compound 10 (2.08 g, 89%) as a colourless oil, [a]
D
þ5.7 (c 0.7 in Et2O); nmax/cmꢀ1 2964, 2924, 2879, 1740, 1706, 1454,
1382, 1369, 1245, 1069, 1044, 1004, 945 and 700; dH (300 MHz,
CDCl3) 1.04 and 1.21 (each 3H, s, 30-CH3), 1.36 (1H, t, J 11.7, 10-Hax),
1.57 (1H, t, J 12.8, 6-Hax), 1.66 (1H, dt, J 12.8 and 2.5, 6-Heq), 1.85 (1H,
dt, J 12.9 and 2.2, 10-Heq), 2.05 (3H, s, COCH3), 2.59 (1H, dd, J 17.3
and 7.1, 10-H), 2.95 (1H, dd, J 17.3 and 5.6, 10-H0), 3.86 (1H, m, 7-H),
3.99 (5H, m, 2-H2, 3-H2, 40-H), 4.08 (3H, m, 7-CH2, 9-H), 4.29 and
4.56 (each 1H, d, J 11.8, HCHAr), 5.31 (1H, dd, J 17.2 and 1.0, 60-H),
5.40 (1H, dd, J 10.3 and 1.7, 60-H0), 5.75 (1H, ddd, J 17.2, 10.3 and 8.0,
50-H) and 7.20e7.40 (5H, m, ArH); dC (75 MHz, CDCl3) 18.74, 20.82,
21.77, 37.16, 40.37, 44.55, 51.24, 64.26, 64.41, 66.59, 70.37, 71.73,
73.03, 85.69, 106.64, 120.24, 127.32, 127.48, 128.13, 134.17, 138.29,
170.83 and 212.08; m/z (CIþ) 464 (Mþþ18, 24%) and 108 (100);
4.2.6. (7R,9R)-9-[(2R,4S)- and (7R,9R)-9-[(2S,4S)-4-Benzyloxy-3,3-
dimethyl-2-hydroxyhex-5-enyl]-7-tert-butyldimethylsilyloxymethyl-
1,4,8-trioxaspiro[4.5]decane (13). Ketone 12 (1.1 g, 2.12 mmol) was
dissolved in THF (6.5 mL) and the solution was cooled to ꢀ78ꢁ C.
Lithium triethylborohydride (‘super HydrideÒ’) (1 M in THF, 6.4 mL)
was added dropwise and the mixture allowed to warm to room
temperature. After 30 min, saturated aqueous sodium-potassium
tartrate (10 mL) was added and the mixture extracted with ether
(3ꢂ10 mL) The organic extracts were washed with water (10 mL)
and brine (10 mL), then dried over magnesium sulfate. After