K. Plonska-Ocypa et al. / Bioorg. Med. Chem. 19 (2011) 7205–7220
7215
O-CH2CH2-O), 4.22 (1H, br dd, J = 11.3, 5.4 Hz, 7
a
-H), 4.79 and 5.04
Compound 21: ½a 2D4
ꢂ
ꢀ36 (c 1.55, CHCl3); 1H NMR (200 MHz,
(1H and 1H, each br s, C@CH2); 13C NMR (50 MHz) d ꢀ4.81 and
ꢀ4.76 [Si(CH3)2], 18.5 [SiC(CH3)3], 26.1 [SiC(CH3)3], 29.8 (9-C),
35.8 (10-C), 45.8 (6-C), 64.5 and 64.7 (O-CH2CH2-O), 70.5 (7-C),
106.2 (C@CH2), 109.5 (5-C), 149.5 (C@CH2); HRMS (ESI) exact mass
calcd for C15H28O3SiNa (M++Na) 307.1703, measured 307.1705.
CDCl3) d 0.10 [6H, s, Si(CH3)2], 0.93 (9H, s, Si-t-Bu), 1.67 (1H, t,
J ꢃ 12 Hz, 10b-H), 1.84 (1H, dd, J = 14.1, 3.9 Hz, 6b-H), 2.05 (1H,
dt, J = 14.1, 2.8 Hz, 6a-H), 2.11 (1H, ddd, J = 12.2, 5.1, 2.8 Hz, 10a-
H), 4.01 (4H, m, O-CH2CH2-O), 4.44 (1H, br t, J ꢃ 3.2 Hz, 7b-H),
4.61 (1H, ddt, J = 11.5, 5.1, 1.8 Hz, 9a-H), 5.01 and 5.16 (1H and
1H, each t, J ꢃ 2 Hz, C@CH2); 13C NMR (50 MHz) d ꢀ4.78 and
ꢀ4.81 [Si(CH3)2], 18.5 [SiC(CH3)3], 26.0 [SiC(CH3)3], 40.9 (10-C),
45.8 (6-C), 64.3 and 65.1 (O-CH2CH2-O), 67.2 (7-C), 72.2 (9-C),
109.1 (C@CH2), 109.8 (5-C), 150.6 (C@CH2); HRMS (ESI) exact mass
calcd for C15H28O4SiNa (M++Na) 323.1655, measured 323.1654.
4.1.6. (R)-7-[(tert-Butyldiphenylsilyl)oxy]-8-methylene-1,4-
dioxa-spiro[4.5]decane (19)
The Wittig reaction of ketone 16 (2.85 g, 6.93 mmol) in anhy-
drous THF was performed as described above for compound 15.
The reaction mixture was stirred at ꢀ78 °C for 4 h and then at
room temperature for 1 h. Then it was treated as described above
and the product was purified by flash chromatography on silica
gel. Elution with hexane/ethyl acetate (97:3) gave pure 8-methy-
Compound 22 : ½a 2D4
ꢂ
ꢀ2 (c 2.15, CHCl3); 1H NMR (200 MHz,
CDCl3) d 0.08 (6H, s, Si(CH3)2], 0.92 (9H, s, Si-t-Bu), 1.59 (1H, t,
J ꢃ 12 Hz, 6b-H), 1.67 (1H, t, J ꢃ 12 Hz, 10b-H), 2.00 (1H, ddd,
J = 12.4, 5.4, 2.4 Hz, 10a-H), 2.15 (1H, ddd, J = 12.1, 5.0, 2.6 Hz,
lene compound 19 (2.83 g, 97%) as a colorless oil; ½a D24
ꢂ
+3 (c 1.16,
6a-H), 3.98 (4H, m, O-CH2CH2-O), 4.2–4.3 (2H, m, 7a- and 9a-H),
CHCl3); 1H NMR (200 MHz, CDCl3) d 1.01 (9H, s, Si-t-Bu), 1.44
5.11 and 5.21 (1H and 1H, each narr m, C@CH2); 13C NMR
(50 MHz) d ꢀ4.88 and ꢀ4.81 [Si(CH3)2], 18.5 [SiC(CH3)3], 26.0
[SiC(CH3)3], 44.7 (10-C), 45.4 (6-C), 64.5 and 64.8 (O-CH2CH2-O),
68.4 (7-C), 68.9 (9-C), 103.5 (C@CH2), 107.3 (5-C), 152.8 (C@CH2);
(1H, t, J ꢃ 12 Hz, 6b-H), 1.54–1.72 (3H, br m, 6
2.12 (1H, br dt, J = 4.9, ꢃ13.2 Hz, 9 -H), 2.33 (1H, ddd, J = 13.7,
4.9, 2.7 Hz, 9b-H), 3.36 and 3.70 (1H and 3H, each m, O-CH2CH2-
a-H and 10-H2),
a
O), 4.30 (1H, dd, J = 11.0, 5.0 Hz, 7
a
-H), 4.88 and 5.31 (1H and
HRMS (ESI) exact mass calcd for
323.1655, measured 323.1655.
C
15H28O4SiNa (M++Na)
1H, each br s, @CH2), 7.35 (6H, m, Ar-H), 7.70 (4H, m, Ar-H); 13C
NMR (50 MHz, CDCl3) d 19.5 [SiC(CH3)3], 22.9 [SiC(CH3)3], 30.0
(9-C), 36.3 (10-C), 44.5 (6-C), 64.1 and 64.3 (O-CH2CH2-O), 71.2
(7-C), 106.6 (C@CH2), 109.2 (5-C), 127.8, 129.78, 129.84, 134.1,
134.8, 136.0 and 136.2 (Ar-C), 149.3 (C@CH2); HRMS (ESI) exact
4.1.9. (7R,9R)- and (7S,9R)-9-[(tert-Butyldiphenylsilyl)oxy]-8-
methylene-1,4-dioxa-spiro[4.5]decan-7-ols (23 and 24)
The hydroxylation of allylic ether 19 (167 mg, 0.41 mmol) was
performed as described above for compound 18. The products
were purified and separated by column chromatography on silica
gel. Elution with hexane/ethyl acetate (8:2) gave an oily mixture
of alcohols 23 and 24 (93 mg, 53%; ratio of 2:1). Separation of
the isomers was achieved by rechromatography using CH2Cl2 as
an eluent. Purity of compounds was confirmed by HPLC
(9.4 mm ꢁ 25 cm, Zorbax RX-Sil column, 4 mL/min) using a hex-
ane/2-propanol (93:7) solvent system. The main product 23 was
collected at RV 27 mL and the 7S-isomer 24 at RV 33 mL.
mass calcd for
431.2000.
C
25H32O3SiNa (M++Na) 431.2018, measured
4.1.7. (R)-8-Methylene-7-[20-(trimethylsilyl)ethoxymethoxy]-
1,4-dioxa-spiro[4.5]decane (20)
The Wittig reaction of ketone 17 (0.72 g, 2.38 mmol) in anhy-
drous THF was performed as described above for compound 15.
The reaction mixture was stirred at ꢀ78 °C for 4 h. Then it was
treated as described above and the product was purified by flash
chromatography on silica gel. Elution with hexane/ethyl acetate
(9:1) gave the pure 8-methylene compound 20 (521 mg, 73%) as
Compound 23 : ½a 2D4
ꢂ
ꢀ23 (c 1.1, CHCl3); 1H NMR (200 MHz,
CDCl3) d 1.01 (9H, s, Si-t-Bu), 1.48 (1H, br t, J ꢃ 12 Hz, 10b-H),
a colorless oil; ½a D24
ꢂ
+30 (c 0.75, CHCl3); 1H NMR (200 MHz, CDCl3)
d 0.02 [9H, s, Si(CH3)3], 0.93 [2H, t, J = 8.4 Hz, CH2-Si(CH3)3], 1.55–
1.8 (3H, br m, 10-H2 and 6b-H), 2.11 (1H, ddd, J = 12.6, 5.0, 2.0 Hz,
1.70 (1H, ddd, J = 12.4, 5.1, 1.7 Hz, 10
3.42 and 3.72 (1H and 3H, each m, O-CH2CH2-O), 4.44 (1H, t,
J = 3.3 Hz, 7b-H), 4.67 (1H, dm, J = 11.2 Hz, 9 -H), 5.09 (1H, t,
a-H), 1.89 (2H, m, 6-H2),
a
6
a
-H), 2.20 (1H, br dt, J ꢃ 5, ꢃ13 Hz, 9
4.9 Hz, 9b-H), 3.94 (2H, m, O-CH2-CH2-Si), 3.95 (4H, m, O-
CH2CH2-O), 4.22 (1H, br dd, J = 10.0, 5.0 Hz, 7 -H), 4.69 and 4.73
a
-H), 2.36 (1H, dt, J = 13.6,
J = 1.8 Hz, one of C@CH2), 5.40 (1H, t, J = 2.1 Hz, one of C@CH2),
7.39 (6H, m, Ar-H), 7.69 (4H, m, Ar-H); 13C NMR (50 MHz, CDCl3)
d 19.5 [SiC(CH3)3], 27.2 [SiC(CH3)3], 41.6 (6-C), 44.53 (10-C), 64.0
and 64.6 (O-CH2CH2-O), 68.2 (7-C), 72.1 (9-C), 109.2 (C@CH2),
109.4 (5-C), 127.8, 129.9, 135.9 and 136.1 (Ar-C), 150.6 (C@CH2);
a
(1H and 1H, each d, J = 13.4, Hz, O-CH2-O), 4.83 and 4.97 (1H
and 1H, each br s, C@CH2); 13C NMR (50 MHz) d ꢀ1.2 [Si(CH3)3],
18.3 [CH2-Si(CH3)3], 29.7 (9-C), 36.0 (10-C), 42.8 (6-C), 64.8 and
64.5 (O-CH2CH2-O), 65.3 (O-CH2-CH2-Si), 74.5 (7-C), 93.4 (O-CH2-
O), 109.1 (5-C), 107.7 (C@CH2), 146.8 (C@CH2); HRMS (ESI) exact
HRMS (ESI) exact mass calcd for
447.1968, measured 447.1977.
C
25H32O4SiNa (M++Na)
Compound 24: ½a 2D4
ꢂ
+9 (c 1.0, CHCl3); 1H NMR (200 MHz, CDCl3)
d 1.07 (9H, s, Si-t-Bu), 1.48 (1H, dd, J = 12.4, 10.7 Hz, 10b-H), 1.61
mass calcd for
323.1655.
C
15H28O4SiNa (M++Na) 323.1655, measured
(2H, br m, 6b- and 10
H), 3.39 and 3.73 (1H and 3H, each m, O-CH2CH2-O), 4.17 (1H,
dd, J = 11.0, 5.1 Hz, 7 -H), 4.29 (1H, dd, J = 10.7, 5.2 Hz, 9 -H),
a-H), 2.03 (1H, ddd, J = 12.0, 5.1, 2.2 Hz, 6a-
4.1.8. (7R,9R)- and (7S,9R)-9-[(tert-Butyldimethylsilyl)oxy]-8-
methylene-1,4-dioxa-spiro[4.5]decan-7-ols (21 and 22)
a
a
5.19 and 5.45 (1H and 1H, each br d, J = 1.7 Hz, C@CH2), 7.38 (6H,
m, Ar-H), 7.67 (4H, m, Ar-H); 13C NMR (50 MHz, CDCl3) d 19.5
[SiC(CH3)3], 27.2 [SiC(CH3)3], 44.0 (6-C), 45.1 (10-C), 64.27 and
64.33 (O-CH2CH2-O), 68.5 (7-C), 68.7 (9-C), 104.0 (C@CH2), 107.0
(5-C), 127.8, 129.7, 135.9 and 136.2 (Ar-C), 152.5 (C@CH2); HRMS
(ESI) exact mass calcd for C25H32O4SiNa (M++Na) 447.1968, mea-
sured 447.1960.
To a solution of allylic ether 18 (600 mg, 2.11 mmol) in freshly
distilled dioxane (17 mL) was added pyridine N-oxide (798 mg,
8.38 mmol) and SeO2 (282 mg, 2.52 mmol). The mixture was
heated at 90 °C for 2 h with stirring. Then it was poured into water
and extracted with ethyl acetate. The organic layer was washed
with saturated NaHCO3, dried (MgSO4) and evaporated. The resi-
due was subjected to column chromatography on silica gel. Elution
with hexane/ethyl acetate (85:15) gave an oily mixture of isomeric
alcohols 21 and 22 (325 mg, 51%; ratio of 2:1). Separation of both
isomers was achieved by HPLC (9.4 mm ꢁ 25 cm, Zorbax RX-Sil
column, 4 mL/min) using a hexane/2-propanol (9:1) solvent sys-
tem. The main product 21 (214 mg) was collected at RV 25.0 mL
and the 7S-isomer 22 (109 mg) at RV 25.5 mL.
4.1.10. (7R,9R)- and (7S,9R)-8-Methylene-7-[20-(trimethylsilyl)
ethoxymethoxy]-1,4-dioxa-spiro[4.5]decan-7-ols (25 and 26)
The hydroxylation of allylic ether 20 (521 mg, 1.7 mmol) in
dioxane was performed as described above for compound 18. The
crude products were subjected to column chromatography on sil-
ica gel. Elution with hexane/ethyl acetate (95:5?80:20) gave pure