Chromatographic separations: flash chromatography9 was
carried out on silica gel (Macherey and Nagel, type Si 60, 0.04–
0.063 mm) and preparative HPLC using a Merck/Hitachi 655
A-11 Chromatograph (stainless steel column, 25 × 3.2 cm,
stationary phase: Li Chrosorb Si 60].
But-2-yne 1 was supplied by Fluka AG and acetylenes 9a–d
were prepared from the corresponding alcohols and acyl
chlorides.
tion of 1 (1.60 g, 29.6 mmol) in CH2Cl2 (60 ml) in the presence
of methyl formate (1.78 g, 29.7 mmol) was followed by the
addition of a solution of 5 (2.63 g, 20.7 mmol) in pentane and
further ozonolysis to give an oily residue (2.73 g) from which a
mixture of 7c-I and 7c-II (0.65 g, 8%; isomer ratio 1:7) was
isolated (pentane–diethyl ether, 98:2) (Found: C, 52.33; H,
7.49. C12H20O7 requires C, 52.17; H, 7.30%). Further separation
by HPLC gave an initial fraction containing 7c-I (33% in
admixture with 67% of 7c-II) (0.13 g, 2%) [colourless oil; tR
26.1 min; δH 1.50 (s, 3 H), 1.64 (s, 3 H), 1.30–2.00 (m, 10 H), 3.42
(s, 3 H), 6.06 (s, 1 H); δC 17.83, 20.03, 23.80, 23.84, 24.91, 33.03,
34.37, 51.47, 108.82, 109.51, 110.26, 113.94] and a second pure
fraction of 7c-II (0.26 g, 3%) [colourless oil; tR 28.9 min; δH 1.51
(s, 3 H), 1.62 (s, 3 H), 1.30–2.00 (m, 10 H), 3.42 (s, 3 H), 6.04 (s,
1 H); δC 17.40, 19.87, 23.71, 23.88, 24.08, 32.80, 34.47, 51.42,
108.85, 109.41, 110.77, 113.91].
Co-ozonolyses of but-2-yne 1 and carbonyl compounds 3,
followed by ozonolyses of O-methylcyclohexanone oxime 5
Co-ozonolyses of but-2-yne 1 in the presence of carbonyl com-
pounds 3 were carried out in CH2Cl2 at Ϫ75 ЊC. The sol-
vent and residual carbonyl compounds 3 were distilled off
under reduced pressure at 10 ЊC. A cold (Ϫ20 ЊC) solution of
O-methylcyclohexanone oxime 5 in pentane (100 ml) was added
to the resulting residue and the ozonolysis was continued until
the solution turned blue. The crude product mixture was
washed with saturated aqueous NaHCO3, dried with MgSO4
and the solvent was distilled off at room temp. Flash chroma-
tography of the residue (eluent pentane–diethyl ether, 10:1)
gave mixtures of diastereoisomeric diozonides, which were
further separated by the HPLC methods.
Reduction of diozonide 7c. A solution of one drop of the
1:7 mixture of 7c-I and 7c-II in CDCl3 (0.8 ml) was treated
1
with excess triphenylphosphine. Immediate H NMR analysis
showed the presence of ozonide 8 [δH 1.53 (s), 2.29 (s)] in 28%
yield,2 28% of methyl formate [δH 3.77 (d), 8.06 (q)] and of
1
unreacted ozonide 7c. H NMR analysis after 2 days showed
the presence of methyl formate, butanedione, acetic anhydride
and cyclohexanone in a relative molar ratio of 5:1:5.5:5.
Preparation of 3-(5-ethoxy-3-methyl-1,2,4-trioxolan-3-yl)-
3-methyl-1,2,4-trioxaspiro[4.5]decane 7d. Ozonolysis of a solu-
tion of 1 (1.16 g, 21.5 mmol) in CH2Cl2 (70 ml) and in the
presence of ethyl formate (1.59 g, 29.7 mmol) was followed by
the addition of a solution of 5 (1.91 g, 15.0 mmol) in pentane
and further ozonolysis to give an oily residue (4.09 g), from
which a mixture of 7d-I and 7d-II (1.57 g, 25%; ratio 1:8) was
isolated (pentane–diethyl ether, 97:3) (Found: C, 54.15; H,
7.67. C13H22O7 requires C, 53.78; H, 7.64%). Further separation
by HPLC gave an initial fraction enriched in 7d-I (25% in
admixture with 75% of 7d-II) (0.53 g, 9%) [colourless oil; tR
49.5 min; δH 1.26 (t, 3 H), 1.50 (s, 3 H), 1.64 (s, 3 H), 1.20–2.00
(m, 10H), 3.70(m, 2H), 6.10(s, 1H);δC 14.90, 18.03, 20.03, 23.81,
23.84, 24.92, 33.05, 34.36, 60.61, 108.84, 109.39, 110.24, 113.53]
and a second pure fraction of 7d-II (0.45 g, 7%) [colourless oil;
tR 53.5 min; δH 1.26 (t, J 7.1, 3 H), 1.51 (s, 3 H), 1.62 (s, 3 H),
1.20–2.00 (m, 10 H), 3.70 (m, 2 H), 6.08 (s, 1 H); δC 14.90, 17.65,
19.90, 23.74, 23.90, 24.90, 32.83, 34.49, 60.53, 108.87, 109.32,
110.77, 113.51].
Preparation of 3-methyl-3-(3,5,5-trimethyl-1,2,4-trioxolan-3-
yl)-1,2,4-trioxaspiro[4.5]decane 7a. Ozonolysis of a solution of
1 (1.09 g, 20.2 mmol) in CH2Cl2 (40 ml) and in the presence of
acetone (1.17 g, 20.2 mmol) was followed by the addition of a
solution of 5 (1.79 g, 14.1 mmol) in pentane and further
ozonolysis to give a residue (2.52 g) from which was isolated
7a as a mixture of isomers (0.79 g, 14%; isomer ratio 1:2.5)
(Found: C, 56.54; H, 8.07. C13H22O6 requires C, 56.92; H,
8.08%). Subsequent separation by HPLC (pentane–diethyl
ether, 96:4) gave 7a-I as a colourless liquid (0.14 g, 3%) [tR 20.6
min; δH 1.51 (s, 3 H), 1.54 (s, 9 H), 1.30–2.00 (m, 10 H); δC 20.16,
20.40, 23.20, 23.77, 23.84, 24.90, 24.97, 32.76, 34.53, 108.52,
108.96, 109.53, 110.40] and 7a-II as a colourless liquid (0.43 g,
8%) [tR 21.6 min; δH 1.51, 1.53, 1.54 (overlapping s, total of 12
H), 1.30–2.00 (m, 10 H); δC 20.21, 20.36, 23.56, 23.73, 23.86,
24.87, 24.92, 32.97, 34.65, 108.35, 109.02, 109.72, 110.53].
Reduction of diozonide 7a. A solution of one drop of 7a
(mixture of isomers I and II) in CDCl3 (0.8 ml) was treated
1
with excess triphenylphosphine. H NMR analysis after 2 days
showed the presence of acetone [δH 2.18 (s)], butanedione [δH
2.33 (s)], acetic anhydride [δH 2.23 (s)] and cyclohexanone [δH
2.35 (t)] in a relative molar ratio of 2.7:1:2.3:3.3.
Reduction of diozonide 7d. A solution containing one drop of
the 1:8 mixture of 7d-I and 7d-II in CDCl3 (0.8 ml) was treated
1
Preparation of 3-(5-cyano-3,5-dimethyl-1,2,4-trioxolan-3-yl)-
3-methyl-1,2,4-trioxaspiro[4.5]decane 7b. Ozonolysis of a solu-
tion of 1 (1.17 g, 21.7 mmol) in CH2Cl2 (60 ml) in the presence
of acetyl cyanide (1.47 g, 21.3 mmol) was followed by the add-
ition of a solution of 5 (2.06 g, 16.2 mmol) in pentane and
further ozonolysis to give a residue (5.53 g) from which a mix-
ture of 7b-I and 7b-II as a colourless oil (1.22 g, 20%; isomer
ratio 3:1) was isolated by chromatography (pentane–diethyl
ether, 96:4) (Found: C, 55.12; H, 6.74; N, 5.23. C13H19NO6
requires C, 54.73; H, 6.71; N, 4.91%). Further separation by
HPLC gave 7b-I (0.55 g, 9%) [colourless liquid; tR 26.9 min; δH
1.30–1.90 (m, 10 H), 1.49 (s, 3 H), 1.70 (s, 3 H), 1.90 (s, 3 H); δC
18.28, 19.88, 19.92, 23.66, 23.85, 24.86, 32.57, 34.47, 98.49,
108.52, 107.90, 110.74, 111.49, 116.66] and 7b-II (0.20 g, 3%)
[colourless liquid; tR 30.1 min; δH 1.30–1.90 (m, 10 H), 1.50 (s, 3
H), 1.70 (s, 3 H), 1.89 (s, 3 H); δC 18.20, 19.92, 20.16, 23.62,
23.88, 24.82, 32.78, 34.58, 98.42, 107.78, 110.99, 111.42, 116.61].
Reduction of diozonide 7b. A solution of 7b (20 mg, mixture
of isomers I and II) in CDCl3 (0.8 ml) was treated with excess
with excess triphenylphosphine. Immediate H NMR analysis
showed the presence of ozonide 8 (36%), ethyl formate (29%)
[δH 1.31 (t), 8.05 (t)] and unreacted 7d. After 2 days, 7d had
disappeared and ethyl formate, butanedione, acetic anhydride
and cyclohexanone were present in a relative molar ratio of
2.3:1:1.5:2.5.
Sequential ozonolyses of acyloxy-substituted acetylenes 9 and
O-methylcyclohexanone oxime 5
Solutions of the acetylene derivatives 9a–d in CH2Cl2 were
ozonized at Ϫ30 ЊC. Without work-up, a cold (Ϫ20 ЊC) solution
of 5 in CH2Cl2 (10 ml) was added and the ozonolysis continued
at Ϫ20 ЊC until the reaction solution turned blue. The solvent
was removed by distillation and, unless mentioned otherwise,
the diozonide was isolated by flash chromatography.
Preparation of 9-benzoyloxymethyl-9,12-epoxy-12-phenyl-
7,10,11,13,15,16-hexaoxadispiro[5.1.6.2]hexadecane 12a. Fol-
lowing the initial ozonolysis of a solution of 9a (2.25 g, 7.7
mmol) in CH2Cl2 (60 ml), a solution of 5 (1.07 g, 8.4 mmol)
in CH2Cl2 (10 ml) was added and the reaction mixture ozonized
to completion. From the crude residue (3.20 g), diozonide
12a (0.91 g, 26%) was obtained by crystallization from diethyl
ether at 0 ЊC as a colourless crystalline solid, mp 99.5 ЊC (sharp)
(Found: C, 62.90; H, 5.37. C24H24O9 requires C, 63.16; H,
5.30%); δH 1.30–1.90 (m, 10 H), 4.19 (d, J 11.9, 1 H), 4.63 (d, J
1
triphenylphosphine. H NMR analysis after 3 days showed the
presence of acetyl cyanide [δH 2.56 (s)], butanedione, acetic
anhydride and cyclohexanone in a relative molar ratio of
4.5:1:4.5:5.
Preparation of 3-(5-methoxy-3-methyl-1,2,4-trioxolan-3-yl)-
3-methyl-1,2,4-trioxaspiro[4.5]decane 7c. Ozonolysis of a solu-
J. Chem. Soc., Perkin Trans. 1, 1997
1603