The Journal of Organic Chemistry
Article
2H, CH), 4.41−4.51 (m, 4H, CH), 4.82−4.92 (m, 2H, CH); 13C
NMR (75 MHz, CDCl3) δC 27.1 (CH3), 27.6 (CH2), 28.0 (CH2),
28.7 (CH2), 31.9 (CH2), 38.8 (C), 69.0 (CH), 69.0 (CH), 74.4 (CH),
75.6 (CH), 108.7 (C), 177.8 (C); mp = 211−212 °C; IR 3470, 2959,
1720, 1639, 1479, 1378, 1282, 1170, 1101, 1045, 951 cm−1; HRMS
(ESI) calcd for C28H45O10 [M + H]+, 541.3013; found, 541.2965.
Note: The letters a−d in the context of compounds 6−8 refer to
different diastereomers. After oxidation, all diastereomers of 8 (8a−8d)
provide the same compound 9.
(3a′R,4a′R,7a′S,8a′S)-4′,8′-Bis(prop-2-en-1-yloxy)-
hexahydrodispiro[cyclohexane-1,2′-benzo[1,2-d:4,5-d′]bis-
[1,3]dioxole-6′,1″-cyclohexane]-4,4″-diyl Bis(2,2-dimethylpro-
panoate) (6a−6d). 5 (1315 mg, 2.43 mmol) was dissolved in anhyd
DMF (40 mL), and NaH (60% in mineral oil, 330 mg, 8.25 mmol, 3.4
equiv) was added and the mixture stirred for 30 min at room
temperature. Allyl bromide (700 μL, 8.10 mmol, 3.3 equiv) was added,
and the resulting mixture was stirred overnight. CH2Cl2 was added,
and the mixture was washed with 1N HCl and brine. The organic layer
was dried over MgSO4, evaporated, and purified by flash
chromatography (CHCl3 > CHCl3/EtOAc 10:1), yielding four
diastereomers 6a−6d (1403 mg, 2.26 mmol, 93%). Diastereomers
6a and 6b could be separated by flash chromatography. Diastereomers
6c and 6d could be obtained only as a mixture. 6a: colorless crystals; Rf
(CHCl3/EtOAc 20:1) = 0.4; 1H NMR (300 MHz, CDCl3) δH 1.18 (s,
18H, CH3), 1.57−2.02 (m, 16H, CH2), 3.90 (dd, 3J = 4.4 Hz, 3J = 2.9
Hz, 2H, CH), 4.21 (dt, 3J = 5.6 Hz, 4J = 1.2 Hz, 4H, CH2), 4.40 (dd, 3J
= 7.6 Hz, 3J = 4.8 Hz, 2H, CH), 4.52 (dd, 3J = 7.6 Hz, 3J = 2.9 Hz, 2H,
CH), 4.83−4.94 (m, 2H, CH), 5.18 (ddd, 3J = 10.4 Hz, 2J = 2.8 Hz, 4J
= 1.2 Hz, 2H, CH2), 5.29 (ddd, 3J = 17.2 Hz, 2J = 3.3 Hz, 4J = 1.6 Hz,
2H, CH2), 5.92 (ddt, 3J = 17.2 Hz, 3J = 10.6 Hz, 3J = 5.4 Hz, 2H, CH);
13C NMR (75 MHz, CDCl3) δC 27.1 (CH3), 27.7 (CH2), 28.1 (CH2),
conversion monitored by TLC, the reaction mixture was filtered
over Celite, evaporated, and purified by flash chromatography
(CHCl3/EtOAc 20:1), yielding 7a (219 mg, 351 μmol, 94%) as
1
white foam. Rf (CHCl3/EtOAc 20:1) = 0.5; H NMR (300 MHz,
CDCl3) δH 0.92 (t, 3J = 7.4 Hz, 6H, CH3), 1.19 (s, 18H, CH3), 1.53−
3
1.96 (m, 4H, CH2, 16H, CH2), 3.60 (t, J = 6.8 Hz, 4H, CH2), 3.80
(dd, 3J = 4.5 Hz, 3J = 2.9 Hz, 2H, CH), 4.38 (dd, 3J = 7.6 Hz, 3J = 4.7
Hz, 2H, CH), 4.48 (dd, 3J = 7.6 Hz, 3J = 2.9 Hz, 2H, CH), 4.76−4.88
(m, 2H, CH); 13C NMR (75 MHz, CDCl3) δC 10.5 (CH3), 23.1
(CH2), 27.1 (CH3), 27.8 (CH2), 28.1 (CH2), 29.0 (CH2), 31.5 (CH2),
38.8 (C), 68.9 (CH), 73.2 (CH2), 74.0 (CH), 75.3 (CH), 77.0 (CH),
108.7 (C), 177.9 (C); IR 2961, 1723, 1478, 1377, 1281, 1165, 1107,
951 cm−1; HRMS (ESI) calcd for C34H56O10Na [M + Na]+, 647.3771;
found, 647.3797.
(3a′R,4a′R,7a′S,8a′S)-4′,8′-Dipropoxyhexahydrodispiro-
[cyclohexane-1,2′-benzo[1,2-d:4,5-d′]bis[1,3]dioxole-6′,1″-cy-
clohexane]-4,4″-diyl Bis(2,2-dimethyl-propanoate) (7b). 6b
(139 mg, 224 μmol) was prepared according to 7a, yielding 7b (135
mg, 216 μmol, 97%) as white foam. Rf (CHCl3/EtOAc 20:1) = 0.4; 1H
3
NMR (300 MHz, CDCl3) δH 0.92 (t, J = 7.4 Hz, 6H, CH3), 1.19 (s,
18H, CH3), 1.55−1.93 (m, 4H, CH2, 16H, CH2), 3.60 (t, 3J = 6.8 Hz,
4H, CH2), 3.80 (dd, 3J = 2.9 Hz, 3J = 4.8 Hz, 2H, CH), 4.38 (dd, 3J =
3
4.7 Hz, 3J = 7.6 Hz, 2H, CH), 4.48 (dd, J = 2.9 Hz, 3J = 7.6 Hz, 2H,
CH), 4.77−4.87 (m, 2H, CH); 13C NMR (75 MHz, CDCl3) δC 10.5
(CH3), 23.1 (CH2), 27.1 (CH3), 27.9 (CH2), 28.3 (CH2), 29.6 (CH2),
32.0 (CH2), 38.8 (C), 68.6 (CH), 73.0 (CH2), 73.8 (CH), 75.2 (CH),
76.9 (CH), 108.6 (C), 177.9 (C); IR 2961, 1723, 1477, 1377, 1280,
1165, 1109, 950 cm−1; HRMS (ESI) calcd for C34H56O10Na [M +
Na]+, 647.3771; found, 647.3784.
(3a′R,4a′R,7a′S,8a′S)-4′,8′-Dipropoxyhexahydrodispiro-
[cyclohexane-1,2′-benzo[1,2-d:4,5-d′]bis[1,3]dioxole-6′,1″-cy-
clohexane]-4,4″-diyl Bis(2,2-dimethyl-propanoate) (7c−7d).
6c−6d (270 mg, 757 μmol) was prepared according to 7a, yielding
7c−7d (227 mg, 715 μmol, 95%) as white foam. Rf (CHCl3/EtOAc
20:1) = 0.3; 1H NMR (300 MHz, CDCl3) δH 0.92 (t, 3J = 7.4 Hz, 6H,
29.0 (CH2), 31.5 (CH2), 38.8 (C), 68.9 (CH), 72.1 (CH2), 74.1
(CH), 75.4 (CH), 76.0 (CH), 108.9 (C), 117.0 (CH2), 134.8 (CH),
177.8 (C); mp = 120−122 °C; IR 2957, 1723, 1478, 1376, 1281, 1166,
1106, 952 cm−1; HRMS (ESI) calcd for C34H52O10 [M]+, 620.3560;
found, 620.3618. 6b: colorless crystals; Rf (CHCl3/EtOAc 20:1) = 0.3;
1H NMR (300 MHz, CDCl3) δH 1.18 (s, 18H, CH3), 1.52−1.99 (m,
16H, CH2), 3.90 (dd, 3J = 4.5 Hz, 3J = 2.8 Hz, 2H, CH), 4.21 (dt, 3J =
5.5 Hz, 4J = 1.3 Hz, 4H, CH2), 4.40 (dd, 3J = 7.6 Hz, 3J = 4.7 Hz, 2H,
CH), 4.49 (dd, 3J = 7.6 Hz, 3J = 2.8 Hz, 2H, CH), 4.77−4.88 (m, 2H,
CH), 5.17 (ddd, 3J = 10.4 Hz, 2J = 2.9 Hz, 4J = 1.2 Hz, 2H, CH2), 5.29
(ddd, 3J = 17.2 Hz, 2J = 3.3 Hz, 4J = 1.6 Hz, 2H, CH2), 5.91 (ddt, 3J =
3
CH3), 0.93 (t, J = 7.4 Hz, 6H, CH3), 1.19 (s, 18H, CH3), 1.19 (s,
18H, CH3), 1.51−2.06 (m, 4H + 4H, CH2, 16H + 16H, CH2), 3.60 (t,
3J = 6.9 Hz, 4H, CH2), 3.62 (t, 3J = 6.9 Hz, 4H, CH2), 3.76−3.84 (m,
2H + 2H, CH), 4.36 (dd, 3J = 7.6 Hz, 3J = 4.8 Hz, 2H, CH), 4.39 (dd,
3
3J = 7.6 Hz, 3J = 4.7 Hz, 2H, CH), 4.47 (dd, J = 7.6 Hz, 3J = 2.8 Hz,
2H, CH), 4.51 (dd, 3J = 7.6 Hz, 3J = 2.9 Hz, 2H, CH), 4.76−4.95 (m,
2H + 2H, CH); 13C NMR (75 MHz, CDCl3) δC 10.5 (CH3), 10.5
(CH3), 23.1 (CH2), 27.1 (CH3), 27.7 (CH2), 27.9 (CH2), 28.1 (CH2),
28.3 (CH2), 29.0 (CH2), 29.6 (CH2), 31.4 (CH2), 32.1 (CH2), 38.8
(C), 38.8 (C), 68.9 (CH), 69.6 (CH), 73.1 (CH2), 73.1 (CH2), 73.9
(CH), 74.0 (CH), 75.2 (CH), 75.2 (CH), 76.9 (CH), 77.0 (CH),
108.6 (C), 108.7 (C), 177.9 (C), 177.9 (C); IR: 2957, 1723, 1478,
1377, 1281, 1166, 1108, 951 cm−1; HRMS (ESI) calcd for
C34H56O10Na [M + Na]+, 647.3771; found, 647.3792.
3
3
17.2 Hz, J = 10.6 Hz, J = 5.4 Hz, 2H, CH); 13C NMR (75 MHz,
CDCl3) δC 27.1 (CH3), 27.9 (CH2), 28.2 (CH2), 29.5 (CH2), 32.0
(CH2), 38.7 (C), 69.5 (CH), 72.0 (CH2), 74.0 (CH), 75.4 (CH), 76.0
(CH), 108.8 (C), 116.9 (CH2), 134.8 (CH), 177.8 (C); mp = 130−
131 °C; IR 2954, 1721, 1478, 1377, 1281, 1167, 1109, 933 cm−1;
HRMS (ESI) calcd for C34H52O10 [M]+, 620.3560; found, 620.3613.
1
6c−6d: colorless oil; Rf (CHCl3/EtOAc 20:1) = 0.2; H NMR (600
(3a′R,4a′R,7a′S,8a′S)-4′,8′-Dipropoxyhexahydrodispiro-
[cyclohexane-1,2′-benzo[1,2-d:4,5-d′]bis[1,3]dioxole-6′,1″-cy-
clohexane]-4,4″-diol (8a). 7a (204 mg, 327 μmol) was dissolved in
anhyd CH2Cl2 (20 mL) and cooled to −78 °C. DIBAL (1 M in
hexanes, 1.80 mL, 1.80 mmol, 5.5 equiv) was added, and the reaction
was stirred for 1 h. CH2Cl2 was added, and resulting mixture was
washed with 1N HCl, aqueous saturated NaHCO3, and brine. The
organic layer was dried over MgSO4, evaporated, and purified by flash
chromatography (CH2Cl2/MeOH 100:3), yielding 8a (132 mg, 290
μmol, 89%) as a ductile colorless oil. Rf (CH2Cl2/MeOH 100:4) = 0.1;
1H NMR (300 MHz, CDCl3) δH 0.91 (t, 3J = 7.4 Hz, 6H, CH3), 1.44−
1.97 (m, 2H, OH, 4H, CH2, 16H, CH2), 3.52−3.64 (m, 4H, CH2),
3.78 (dd, 3J = 4.7 Hz, 3J = 2.9 Hz, 2H, CH), 3.74−3.87 (m, 2H, CH),
4.35 (dd, 3J = 7.6 Hz, 3J = 4.8 Hz, 2H, CH), 4.48 (dd, 3J = 7.6 Hz, 3J =
2.9 Hz, 2H, CH); 13C NMR (75 MHz, CDCl3) δC 10.5 (CH3), 23.1
(CH2), 29.4 (CH2), 31.4 (CH2), 31.8 (CH2), 31.9 (CH2), 67.6 (CH),
72.9 (CH2), 73.7 (CH), 75.2 (CH), 76.9 (CH), 108.8 (C); IR 3386,
2933, 1372, 1103, 1074, 1039, 939, 752 cm−1; HRMS (ESI) calcd for
C24H40O8Na [M + Na]+, 479.2621; found, 479.2622.
MHz, CDCl3) δH 1.18 (s, 18H, CH3), 1.18 (s, 18H, CH3), 1.54−2.00
3
(m, 16H + 16H, CH2), 3.84−3.95 (m, 2H + 2H, CH), 4.19 (dt, J =
5.6 Hz, 4J = 1.4 Hz, 4H, CH23), 4.23 (dt, 3J = 5.6 Hz, 4J = 1.4 Hz, 4H,
3
3
CH2), 4.38 (dd, J = 7.6 Hz, J = 4.7 Hz, 2H, CH), 4.41 (dd, J = 7.7
Hz, 3J = 4.7 Hz, 2H, CH), 4.48 (dd, 3J = 7.7 Hz, 3J = 2.7 Hz, 2H, CH),
4.52 (dd, 3J = 7.6 Hz, 3J = 2.9 Hz, 2H, CH), 4.77−4.93 (m, 2H + 2H,
CH), 5.13−5.21 (m, 2H + 2H, CH2), 5.23−5.35 (m, 2H + 2H, CH2),
5.82−6.00 (m, 2H + 2H, CH); 13C NMR (300 MHz, CDCl3) δC 27.1
(CH3), 27.7 (CH2), 27.9 (CH2), 28.1 (CH2), 28.2 (CH2), 29.0 (CH2),
29.5 (CH2), 31.5 (CH2), 32.0 (CH2), 38.7 (C), 38.8 (C), 68.9 (CH),
69.5 (CH), 72.1 (CH2), 74.0 (CH), 74.1 (CH), 75.4 (CH), 76.0
(CH), 76.0 (CH), 108.7 (C), 108.9 (C), 116.8 (CH2), 117.0 (CH2),
134.8 (CH), 134.8 (CH), 177.8 (C), 177.8 (C); IR 2954, 1721, 1477,
1377, 1281, 1166, 1106, 951, 934 cm−1; HRMS (ESI) calcd for
C34H52O10 [M]+, 620.3560; found, 620.3567.
(3a′R,4a′R,7a′S,8a′S)-4′,8′-Dipropoxyhexahydrodispiro-
[cyclohexane-1,2′-benzo[1,2-d:4,5-d′]bis[1,3]dioxole-6′,1″-cy-
clohexane]-4,4″-diyl Bis(2,2-dimethyl-propanoate) (7a). 6a
(231 mg, 372 μmol) was dissolved in EtOH (25 mL), and Pd(OH)2
on charcoal (20%, spatula tip) was added. The resulting mixture was
stirred under a hydrogen atmosphere (1 bar). After complete
(3a′R,4a′R,7a′S,8a′S)-4′,8′-Dipropoxyhexahydrodispiro-
[cyclohexane-1,2′-benzo[1,2-d:4,5-d′]bis[1,3]dioxole-6′,1″-cy-
3916
dx.doi.org/10.1021/jo300266b | J. Org. Chem. 2012, 77, 3907−3920