C. Singh et al. / Bioorg. Med. Chem. 12 (2004) 5745–5752
5749
(m, 2H), 3.76 (dd, 1H, J = 11.8, 3.2Hz), 3.96 (dd, 1H,
J = 11.8, 10.3Hz), 4.73 (dd, 1H, J = 10.3, 3.2Hz), 4.86
and 4.92 (2 · s, 2H); 13C NMR (50MHz, CDCl3): d
6.35, 6.75, 14.07, 22.48, 22.61, 29.73, 30.16, 31.35,
38.67, 63.10, 81.71, 107.27, 111.06, 145.81; FABMS
(m/z) 239 (M+H)+. Anal. Calcd for C14H22O3Æ0.3H2O:
C 68.98; H 9.34. Found: C 68.63; H 9.36.
J = 10.4, 2.92Hz), 5.01 and 5.04 (2 · s, 2H); 13C NMR
(50MHz, CDCl3): d 26.49, 26.89, 27.59, 29.72, 32.59,
33.39, 33.65, 33.86, 33.97, 36.76, 37.63, 43.54, 62.92,
80.59, 104.74, 112.90, 150.05; FABMS (m/z) 319
(M+H)+. Anal. Calcd for C20H30O3ÆH2O: C 71.39; H
9.58. Found: C 71.70; H 9.29.
6.17. 6-(Cyclopropyl-cyclopropylidene-methyl)-3,3-
dimethyl-[1,2,4]trioxane (22)
6.12. Trioxane 11
Yield 75%, white solid: mp82–84 ꢁC; FT-IR (KBr,
cmÀ1) 1641.9; 1H NMR (200MHz, CDCl3): d 0.42–
0.49 (m, 2H), 0.67–0.74 (m, 2H), 1.26–1.40 (m, 1H),
1.61–2.09 (m, 13H), 2.93 (br s, 1H), 3.77 (dd, 1H,
J = 11.7, 3.1Hz), 3.99 (dd, 1H, J = 11.7, 10.4Hz), 4.75
(dd, 1H, J = 10.4, 3.1Hz), 4.87 and 4.93 (2 · s, 2H);
13C NMR (50MHz, CDCl3): d 6.43, 6.79, 14.25, 27.58,
29.71, 33.39, 33.66, 33.86, 33.95, 36.65, 37.63, 62.45,
81.74, 104.87, 111.31, 145.86; FABMS (m/z) 277
(M+H)+. Anal. Calcd for C17H24O3Æ0.1H2O: C 73.39;
H 8.77. Found: C 73.38; H 9.10.
Yield 8%, oil: FT-IR (neat, cmÀ1) 1452.0; 1H NMR
(200MHz, CDCl3): d 0.52–0.70 (m, 5H), 1.09 (s, 4H),
1.38 (s, 3H), 1.67 (s, 3H), 3.70 (dd, 1H, J = 11.8,
2.8Hz), 4.30 (dd, 1H, J = 11.8, 10.9Hz), 4.84 (dd, 1H,
J = 10.9, 2.8Hz); 13C NMR (50MHz, CDCl3): d 1.67,
2.1, 5.7, 6.1, 13.7, 20.4, 25.9, 62.4, 82.0, 102.4, 122.2,
124.5; FABMS (m/z) 211 (M+H)+.
6.18. 3-(Cyclopropyl-cyclopropylidene-methyl)-1,2,5-tri-
oxa-spiro[5.5]undecane (23)
Yield 8%, oil: FT-IR (neat, cmÀ1) 1448.9; 1H NMR
(200MHz, CDCl3): d 0.53–0.69 (m, 5H), 0.96–1.08 (m,
4H), 1.48–1.59 (m, 8H), 1.93–2.06 (m, 1H), 2.19–2.29
(m, 1H), 3.67 (dd, 1H, J = 11.7, 2.9Hz), 4.33 (dd, 1H,
J = 11.7, 10.8Hz), 4.85 (dd, 1H, J = 10.8, 2.9Hz); 13C
NMR (50MHz, CDCl3): d 1.72, 2.15, 5.73, 6.22, 13.81,
22.70, 22.77, 26.00, 29.34, 35.26, 61.70, 82.15, 102.67,
122.27, 124.68; FABMS (m/z) 251 (M+H)+.
6.13. 6-(1-Cyclohexyl-vinyl)-3,3-dimethyl-[1,2,4]trioxane
(12)
1
Yield 57%, oil: FT-IR (neat, cmÀ1) 1639.4; H NMR
(200MHz, CDCl3): d 1.10–1.31 (m, 5H), 1.37 (s, 3H),
1.45–1.93 (m, 6H), 1.65 (s, 3H), 3.70 (dd, 1H, J = 11.9,
2.9Hz), 3.91 (dd, 1H, J = 11.9, 10.3Hz), 4.69 (dd, 1H,
J = 10.3, 2.9Hz), 5.03 (s, 2H); FABMS (m/z) 227
(M+H)+.
6.19. Trioxane 16
6.14. 8-(1-Cyclohexyl-vinyl)-6,7,10-trioxa-spiro[4,5]de-
cane (13)
To a magnetically stirred mixture of trioxane 11 (2.00g,
7.24mmol) and NaHCO3 (2.20g, 26.19mmol) in dichlo-
romethane (100mL) was added mCPBA (2.18g,
26.03mmol) portion wise over 30min and stirred at rt
for 24h. Reaction mixture was diluted with water
1
Yield 78%, oil: FT-IR (neat, cmÀ1) 1641.6; H NMR
(200MHz, CDCl3): d 1.10–1.31 (m, 5H), 1.60–1.92 (m,
13H), 2.45–2.52 (m, 1H), 3.77–3.81 (m, 2H), 4.76 (dd,
1H, J = 8.5, 4.5Hz), 5.00 and 5.03 (2 · s, 2H); 13C
NMR (50MHz, CDCl3): d 23.65, 25.10, 26.47, 26.90,
32.65, 33.01, 37.44, 43.28, 65.72, 80.79, 112.89, 114.64,
149.75; FABMS (m/z) 253 (M+H)+.
(50mL)
and
extracted
with
dichloromethane
(3 · 75mL). Combined organic layer was washed first
with 10% aq NaOH solution (50mL), then with water
(2 · 25mL) and dried over anhyd Na2SO4. Solvent
was removed under vacuum at rt to furnish the crude
product, which on column chromatography over silica
gel using EtOAc–hexane (0.5:99.5) as eluant furnished
16 (1.40g, 66% yield) as mixtures of diastereomers as
6.15. 3-(1-Cyclohexyl-vinyl)-1,2,5-trioxa-spiro[5,5]unde-
cane (14)
1
viscous oil: H NMR (200MHz, CDCl3): d 0.16–0.55
1
Yield 80%, oil: FT-IR (neat, cmÀ1) 1640.6; H NMR
(m, 4H), 1.16–1.42 (m, 1H), 1.55–2.03 (m, 13H), 2.53
(d, 1H, J = 5.0Hz), 2.71, and 2.91 (2 · d, 1H,
J = 5.0Hz each), 2.59 and 2.86 (2 · br m, 1H), 3.75–
4.53 (m, 3H); 13C NMR (50MHz, CDCl3): d 0.11,
0.27, 2.29, 2.76, 10.65, 12.28, 27.51, 30.04, 31.21,
33.39, 33.63, 33.79, 34.90, 36.14, 37.55, 49.33, 50.34,
57.08, 57.36, 58.22, 58.91, 76.82, 77.45, 78.09, 80.03,
81.86, 105.22; FABMS (m/z) 293 (M+H)+. Anal. Calcd
for C17H24O4Æ0.3H2O: C 68.56, H 8.33. Found: C 68.48,
H 8.56.
(200MHz, CDCl3): d 1.10–1.31 (m, 5H), 1.46–2.01 (m,
15H), 2.15–2.29 (m, 1H), 3.67 (dd, 1H, J = 11.8,
2.96Hz), 3.94 (dd, 1H, J = 11.8, 10.4Hz), 4.70 (dd,
1H, J = 10.4, 2.96Hz), 5.02 and 5.04 (2 · s, 2H); 13C
NMR (50MHz, CDCl3): d 22.67, 22.71, 25.95, 26.47,
26.89, 29.34, 32.61, 35.17, 43.39, 63.36, 80.76, 102.65,
112.87, 149.98; FABMS (m/z) 267 (M+H)+. Anal. Calcd
for C16H26O3Æ0.8H2O: C 68.43; H 9.90. Found: C 68.77;
H 10.20.
6.16. Trioxane 15
6.20. Trioxane 17
1
Yield 83%, oil: FT-IR (neat, cmÀ1) 1640.0; H NMR
To an ice cooled magnetically stirred solution of 16
(1.0g, 3.42mmol) in 1,4-dioxane (15mL) was added
25% aq HClO4 (7.2mL) and stirred at 0ꢁC for 2h.
Reaction mixture was diluted with water (50mL) and
(200MHz, CDCl3): d 1.11–1.32 (m, 5H), 1.55–2.09 (m,
19H), 2.94 (br s, 1H), 3.67 (dd, 1H, J = 11.8, 2.92Hz),
3.91 (dd, 1H, J = 11.8, 10.4Hz), 4.72 (dd, 1H,