HETEROCYCLES

Note | Regular issue | Vol. 81, No. 10, 2010, pp. 2323-2334
Received, 10th June, 2010, Accepted, 23rd August, 2010, Published online, 24th August, 2010.
DOI: 10.3987/COM-10-11993

■ Ozonolyses of Isophorone and of 3-Methyl-2-cyclohexen-1-one and Subsequent Reactions of the Respective Ozonides to Afford Di-, Tri- and Tetraozonides

In Chan Jung,* Sad Alam Sheikh, Byong-Mun Jon, Wei Li, Bon-Suk Goo, and In-Soo Jeong

Department of Chemistry, Hanseo University, Seosan 356-706, Korea

Abstract

Ozonolyses of isophorone (1a) and 3-methyl-2-cyclohexen-1-one (1b) in pentane, followed by treatment of the ozonolyses products with O-methyl- hydroxylamine afforded the ozonides 3,3,5-Trimethyl-6,7,8-trioxabicycle[3.2.1]octane-1-carbaldehyde-O-methyloxime (5a) and 5-Methyl-6,7,8-trioxabicyclo[3.2.1]octane-1-carbaldehyde-O-methyloxime (5b), respectively. Coozonolyses of ozonides 5 with selected carbonyl compounds resulted in the formation of diozonides (9, 11), triozonides (12) and tetraozonides (14).

Ozonolyses of isophorone (1a) have been reported previously1, 2 but neither the structure of peroxidic products nor the direction of cleavage have been described, since the primary reaction products were immediately converted into non-peroxidic compounds by acid catalyzed1 or by oxidative2 post treatment. The goal of the present investigation was the clarification of the reaction course and the identification of peroxidic products of the ozonolyses of 1a, and subsequently also of 1b. Based on previous experience with ozonolyses of cyclic α-oxo olefins,3 ozone cleavage of these substrates were expected to provide intermediates of structure 2 in which the carbonyl oxide moiety has a choice to undergo cycloaddition with either one of the two carbonyl groups of 2 to give ozonides of structures 3 and 4.

Treament of 1a with one molar equivalent of ozone in pentane at -78 °C provided a peroxidic reaction product. However, attempts at isolating the peroxidic species by chromatograpy failed because it decomposed on silica gel. Since it is known, that α-oxo-ozonides are very labile4 but can be stabilized by converting them into the corresponding O-methyloximes,5 ozonolyses of 1a was repeated and the crude reaction product was treated with O-methyl hydroxylamine. From the ensuing mixture, ozonide 5a has been isolated in a yield of 45%. In a smilar manner, ozonolyses of 1b, provided the ozonide 5b in a yield of 70%. Ozonides 5a and 5b are stable compounds. They have been characterized by their 1H and 13C NMR spectra and by their reaction with triphenylphosphane which, as expected, provided the corresponding diketones 6 as the sole reduction products.

The isolation of 5a and of 5b proves that the corresponding ozonides 3 have been formed and persisted in the crude reaction mixture at low temperatures. On the other hand, 1H NMR analyses of the crude ozonolysis products prior to their treatment with O-methyl hydroxylamine indicated, that ozonides of structure 4 were apparently not formed in noticeable quantities since the spectra did not exhibit any signals between 5.0 and 5.5 ppm which would be the expected range for the signals of the CH-groups in the ozonide rings of 4a and 4b. The preferred formation of ozonides of structure 3 is in line with the experience that the formation of cyclopentene-ozonides is favored over the formation of cyclohexene-ozonides.3

It has been reported that ozonolyses of O-methyloximes in the presence of carbonyl compounds provides an alternate access to ozonides.6 We have applied this so-called coozonolyses reaction to ozonides 5a and 5b. They proceeded via the corresponding carbonyl oxide intermediates 7 and gave the results depicted in scheme 3: Coozonolyses of 5a and of 5b with acetone (8) afforded the corresponding diozonides 9. Similarly, coozonolyses of 5a and of 5b with cyclopentanone (10c) and with cyclohexanone (10d) provided the corresponding diozonides 11. Coozonolyses of 5a and of 5b with ozonides 3a and 3b provided the corresponding triozonides of structure 12, and coozonolyses of 5a and of 5b with 1,4-cyclohexadiene(13) afforded the corresponding tetraozonides of structure 14. All of the isolated polyozonides were stable at room temperature.

The diozonides of structures 9 and 11 exist as mixtures of two diastereomers. These isomers have been individually isolated, but not stereochemically assigned. and, hence, denoted as isomer 1 and isomer 2. The triozonides of structures 12 exist as mixtures of cis- and trans-isomers which have been individually isolated. Their stereochemical assignment is based on the experience that in the 1H NMR spectra of ozonides the signals of the hydrogen atoms attached to the ozonide rings of trans-isomers appear downfield from those of the corresponding cis-isomers.7,8 Ozonide 14a consisted of three diastereomers of which two, denoted as isomer 1 and isomer 2 which were individually isolated. Ozonide 14b consisted of two diastereomers, denoted as isomer 1 and isomer 2, which were individually isolated.

In summary, the present investigation has revealed the direction of ozone cleavage and the structures of the peroxidic products 5a and 5b from the ozonolyses of isophorone (1a) and of 3-methyl-2-cyclohenen-1-one (1b). Furthermore, coozonolyses reactions of the stable ozonides 5 and suitable carbonyl compounds have provided access to stable di-, tri- and tertaozonides, a class of compounds of which only few examples have been described.

EXPERIMENTAL
General: All reagents and solvents were of commercial grade. 1H and 13C NMR spectra were obtained in CDCl3 with TMS as internal reference on a Bruker AC-300 instrument. GC analyses were carried out on a Shimadzu GC-14B instrument using the following conditions: column J&W-DB-5, 30 m; 60-180 °C at 10 °C/min. Chromatographic separations were performed by flash chromatography on silica gel 60.

Caution: All reactions with ozone or ozonides and chromatographic separations were carried out behind protective safety-glass shiels in a hood. Safety glasses and gloves must be worn at all times when working with ozone or ozonides.

Ozonolyses of 1a: A solution of 1a (0.50 g, 3.6 mmol) in pentane (80 mL) was treated with ozone (3.6 mmol) at -78 °C to provide a peroxidic solution. It was warmed up to room temperature and the solvent was distilled off at reduced pressure to leave 0.80 g of a colorless liquid residue. Chromatographic separation of the residue afforded no peroxidic product.

Preparation of 5a: The above described ozonolysis was repeated and the liquid residue of 0.80 g was admixed with O-methylhydroxylamine (360 mg, 4.32 mmol) and pyridine (341 mg, 4.32 mmol) in MeOH (20 mL). The solution was stirred for 12 h and extracted with Et2O (20 mL). The extract was washed with an aqueous sodium hydrogen carbonate (20 mL), dried with magnesium sulfate, and filtered. The solvent was distilled off at reduced pressure at room temperature to leave 0.6 g of a yellow liquid residue from which of ozonide 5a (348 mg, 45%) was isolated by flash chromatography (column 2.5 x 60 cm; pentane/Et2O, 8:2).

3,3,5-Trimethyl-6,7,8-trioxabicyclo[3.2.1]octane-1-carbaldehyde-O-methyloxime (5a): Yellow liquid. 1H NMR: δ 1.02 (s, 3H), 1.33 (s, 3H), 1.52 (s, 3H), 1.68-2.11 (m, 4H), 3.89 (s, 3H), 7.26 (s, 1H) ppm; 13C NMR(BB): δ 21.47, 29.35, 31.22, 34.83, 42.24, 46.93, 62.75, 106.36, 109.84, 144.87 ppm; 13C NMR (DEPT): δ 21.47, 31.22, 34.83, 42.24, 46.93, 62.75, 144.87 ppm; GC: tR = 9.2 min.; Anal. Calcd for C10H17NO4 (215.25): C, 55.80; H, 7.96; N, 6.51. Found : C, 55.72; H, 7.90; N, 6.69.

Reduction of 5a: A solution of 5a (0.13 g, 0.6 mmol) in Et2O (50 mL) was admixed with triphenylphosphane (0.21 g, 0.80 mmol) and left standing for one day. The solvent was distilled off at reduced pressure to leave 0.35 g of a colorless liquid from which 6a (0.11 g, 92%) has been isolated by flash chromatography (column 2.5 x 60 cm; pentane/Et2O, 7:3).

4, 4-Dimethyl-2,6-dioxoheptanal-O-methyloxime (6a): 1H NMR δ 1.08 (s, 6H), 2.08 (s, 3H), 2.59 (s, 2H), 2.94 (s, 2H), 4.03 (s, 3H), 7.29 (s, 1H) ppm; 13C NMR(BB) δ 28.86, 32.29, 33.26, 46.66, 52.91, 63.69, 148.89, 198.47, 208.67 ppm; 13C NMR (DEPT) δ 28.86, 32.29, 46.66, 52.91, 63.69, 148.89 ppm.

Preparation of 5b: A solution 1b (0.50 g, 4.5 mmol) in pentane (80 mL) was treated with ozone (4.5 mmol) at -78 °C. The mixture was warmed up to room temperature and the solvent was distilled of at reduced pressure to leave 0.60 g of a colorless liquid residue. It was admixed with O-methylhydroxylamine (292 mg, 3.5 mmol) and pyridine (276 mg, 3.5 mmol) in MeOH (20 mL). The solution was stirred for 6 h and extracted with Et2O (20 mL). The extract was washed with an aqueous sodium bicarbonate (20 mL), dried with magnesium sulfate and filtered. The solvent was distilled off at reduced pressure and room temperature to leave 0.75 g of a colorless liquid residue from which of ozonide 5b (593 mg, 70%) was isolated by flash chromatography (column 2.5 x 60 cm; pentane/Et2O, 7:3).

5-Methyl-6,7,8-trioxabicyclo[3.2.1]octane-1-carbaldehyde-O-methyloxime (5b): Colorless liquid .1H NMR δ 1.52 (s, 3H), 1.76-1.92 (m, 4H), 2.11-2.18 (m, 2H), 3.90 (s, 3H), 7.27 (s, 1H) ppm; 13C NMR(BB) δ 16.79, 21.29, 29.45, 33.83, 62.86, 106.97, 110.61, 144.71 ppm; 13C NMR (DEPT) δ 16.79, 21.29, 29.44, 33.83, 62.86, 144.71 ppm; GC: tR = 8.0 min. Anal. Calcd for C8H13NO4 (187.19): C, 51.33; H, 7.00; N,7.48. Found: C, 50.58; H, 7.00; N, 7.58

Reduction of 5b: A solution of 5b (0.10 g, 0.5 mmol) in Et2O (50 mL) was admixed with triphenylphosphane (0.18 g, 0.70 mmol) and left standing for one day. The solvent was distilled off at reduced pressure to leave 0.30 g of a colorless liquid from which 6b (90 mg, 90%) has been isolated by flash chromatography (column 2.5 x 60 cm; pentane/Et2O, 7:3).

2,6-Dioxoheptanal-O-methyloxime (6b): 1H NMR δ 1.84-1.91 (m, 2H), 2.10 (s, 3H), 2.45-2.50 (m, 2H), 2.76-2.81 (m, 2H), 3.99 (s, 3H), 7.36 (s, 1H) ppm; 13C NMR(BB) δ 17.94, 30.20, 37.08, 42.79, 63.67, 147.72, 198.06, 208.40 ppm; 13C NMR (DEPT) δ 17.94, 30.20, 37.08, 42.79, 63.67, 147.71 ppm.

Coozonolyses of Ozonides 5 with acetone(8), cyclopentanone(10c) and cyclohexanone (10d):

a) General procedure: A solution of one of the ozonides 5 and a ketone in pentane or in CH2Cl2 was treated with ozone at -78 °C until it turned slightly blue. Residual ozone was flushed off with nitrogen and the mixture was warmed up to room temperature. The solvent was distilled off at room temperature and reduced pressure and the liquid residue was separated by flash chromatography (column 2 x 55 cm; pentane/Et2O, 9:1) to provide mixtures of the stereoisomeric ozonides in a first step and the individual isomers in a second separation step.

b) Coozonolyses of 5a with 8: Ozone treatment of 5a (0.5 g, 2.32 mmol) and an excess of 8 (10 mL) in pentane (70 mL) provided 0.7 g of a colorless liquid residue from which diozonide 9a (171 mg, 28%, mixture of isomer 1 and isomer 2) and subsequently isomer 1 (21 mg, 3.4%) and isomer 2 (30 mg, 5%) were isolated.

1-(5,5-Dimethyl-1,2,4-trioxolan-3-yl)-3,3,5-trimethyl-6,7,8-trioxabicyclo[3.2.1]octane (9a, isomer 1): Colorless liquid. 1H NMR δ 1.02 (s, 3H), 1.32 (s, 3H), 1.51 (s, 3H), 1.53 (s, 3H), 1.56 (s, 3H), 1.74-1.81 (m, 4H), 5.21 (s, 1H) ppm; 13C NMR(BB) δ 21.24, 23.10, 24.00, 29.29, 31.56, 34.86, 38.65, 46.98, 102.08, 107.54, 109.87, 110.29 ppm; 13C NMR (DEPT) δ 21.24, 23.10, 24.00, 31.56, 34.86, 38.65, 46.98, 102.08 ppm; Anal. Calcd for C12H20O6 (260.28): C, 55.37; H, 7.74. Found: C, 55.72; H, 7.51.

1-(5,5-Dimethyl-1,2,4-trioxolan-3-yl)-3,3,5-trimethyl-6,7,8-trioxabicyclo[3.2.1]octane (9a, isomer 2): Colorless liquid. 1H NMR δ 1.02 (s, 3H), 1.32 (s, 3H), 1.51 (s, 3H), 1.53 (s, 3H), 1.56 (s, 3H), 1.74-1.82 (m, 4H), 5.21 (s, 1H) ppm; 13C NMR(BB) δ 21.25, 23.17, 24.10, 29.26, 31.40, 34.91, 38.76, 46.98, 101.80, 107.64, 109.85, 110.24 ppm; 13C NMR (DEPT) δ 21.25, 23.17, 24.09, 31.40, 34.91, 38.76, 46.98, 101.80 ppm; Anal. Calcd for C12H20O6 (260.28): C, 55.37; H, 7.74. Found: C, 55.52; H, 7.71.

c) Coozonolyses of 5a with 10c: Ozone treatment of 5a (0.50 g, 2.32 mmol) and 10c (0.20 g, 2.32 mmol) in pentane (70 mL) provided 0.7 g of a colorless liquid residue from which diozonide 11ac (237 mg, 35%, mixture of isomer 1 and isomer 2) and subsequently isomer 1 (45 mg, 6.8%) and isomer 2 (40 mg, 6%) were isolated.

3-(3,3,5-Trimethyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.4]nonane (11ac, isomer 1): Colorless liquid. 1H NMR δ 1.02 (s, 3H), 1.32 (s, 3H), 1.52 (s, 3H), 1.65-1.83 (m, 8H), 1.90-1.96 (m, 3H), 2.07-2.10 (m, 1H), 5.19 (s, 1H) ppm; 13C NMR(BB) δ 21.27, 23.94, 24.42, 29.31, 31.56, 33.11, 34.89, 35.56, 38.51, 47.04, 101.94, 107.80, 109.95, 119.99 ppm; Anal. Calcd for C14H22O6 (286.32): C, 58.73; H, 7.74. Found: C, 58.64; H, 7.68.

3-(3,3,5-Trimethyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.4]nonane (11ac, isomer 2): Colorless liquid. 1H NMR δ 1.02 (s, 3H), 1.32 (s, 3H), 1.53 (s, 3H), 1.68-1.81 (m, 8H), 1.93-1.95 (m, 3H), 2.06-2.08 (m, 1H), 5.19 (s, 1H) ppm; 13C NMR(BB) δ 21.26, 23.96, 24.40, 29.19, 31.43, 33.27, 34.91, 35.56, 38.54, 46.97, 101.69, 107.82, 109.80, 119.88 ppm; 13C NMR (DEPT) δ 21.26, 23.96, 24.40, 31.43, 33.27, 34.91, 35.57, 38.53, 47.00, 101.69 ppm; Anal. Calcd for C14H22O6 (286.32): C, 58.73; H, 7.74. Found: C, 58.59; H, 7.76.

d) Coozonolyses of 5a with 10d: Ozone treatment of 5a (0.6 g, 2.78 mmol) and 10d (0.5 g, 3.1 mmol) in pentane (70 mL) provided 0.76 g of a colorless liquid residue from which diozonide 11ad (182 mg, 22%, mixture of isomer 1 and isomer 2) and subsequently isomer 1 (37 mg, 4.4%) and isomer 2 (32 mg, 3.8%) were isolated.

3-(3,3,5-Trimethyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.5]decane (11ad, isomer 1): Colorless liquid. 1H NMR δ 1.02 (s, 3H), 1.32 (s, 3H), 1.52 (s, 3H), 1.53-1.85 (m, 14H), 5.20 (s, 1H) ppm; 13C NMR(BB) δ 21.29, 23.91, 24.26, 25.18, 29.30, 31.61, 32.98, 33.53, 34.89, 38.64, 47.03, 101.90, 107.66, 109.90, 111.09 ppm; 13C NMR (DEPT) δ 21.30, 23.91, 24.26, 25.18, 31.61, 32.98, 33.53, 34.89, 38.64, 47.02, 101.90 ppm; Anal. Calcd for C15H24O6 (300.35): C, 59.98; H, 8.05. Found: C, 60.25; H, 7.96.

3-(3,3,5-Trimethyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.5]decane (11ad, isomer 2): Colorless liquid. 1H NMR δ 1.02 (s, 3H), 1.32 (s, 3H), 1.52 (s, 3H), 1.53-1.81 (m, 14H), 5.21 (s, 1H) ppm; 13C NMR(BB) δ 21.29, 23.91, 24.26, 25.17, 29.25, 31.40, 33.04, 33.59, 34.92, 38.77, 46.99, 101.63, 107.73, 109.84, 111.02 ppm; 13C NMR (DEPT) δ 21.29, 23.91, 24.26, 25.16, 31.40, 33.04, 33.59, 34.92, 38.76, 46.99, 101.63 ppm; Anal. Calcd for C15H24O6 (300.35): C, 59.98; H, 8.05. Found: C, 60.10; H, 8.06.

e) Coozonolyses of 5b with 8: Ozone treatment of 5b (0.50 g, 2.67 mmol) and an excess of 8 (10 mL) in pentane (70 mL) provided 0.8 g of a colorless liquid residue from which diozonide 9b (215 mg, 34%, mixture of isomer 1 and isomer 2) and subsequently isomer 1 (49 mg, 8%) and isomer 2 (45 mg, 7%) were isolated.

1-(5,5-Dimethyl-1,2,4-trioxolan-3-yl)-5-methyl-6,7,8-trioxabicyclo[3.2.1]octane (9b, isomer 1): Colorless liquid. 1H NMR δ 1.50-1.54 (m, 9H), 1.74-1.90 (m, 5H), 2.20-2.23 (m, 1H), 5.22 (s, 1H) ppm; 13C NMR(BB) δ 16.59, 21.02, 23.01, 24.09, 25.91, 33.78, 102.02, 108.03, 110.32, 110.64 ppm; 13C NMR (DEPT) δ 16.59, 21.03, 23.01, 24.09, 25.90, 33.78, 102.02 ppm; GC: tR =10.4 min. Anal. Calcd for C10H16O6 (232.23): C, 51.72 ; H, 6.94. Found: C, 51.75; H, 7.05.

1-(5,5-Dimethyl-1,2,4-trioxolan-3-yl)-5-methyl-6,7,8-trioxabicyclo[3.2.1]octane (9b, isomer 2): Colorless liquid. 1H NMR δ 1.51-1.56 (m, 9H), 1.78-1.92 (m, 5H), 2.21-2.25 (m, 1H), 5.23 (s, 1H) ppm; 13C NMR(BB) δ 16.54, 20.98, 23.04, 24.11, 26.15, 33.79, 101.65, 108.10, 110.18, 110.60 ppm; 13C NMR (DEPT) δ 16.54, 21.00, 23.04, 24.12, 26.15, 33.79, 101.65 ppm; GC: tR = 11.3 min. Anal. Calcd for C10H16O6 (232.23): C, 51.72 ; H, 6.94. Found: C, 51.77; H, 6.98.

f) Coozonolyses of 5b with 10c: Ozone treatment of 5b (0.6 g, 3.21 mmol) and 10c (0.27 g, 3.21 mmol) in CH2Cl2 (70 mL) provided 0.9 g of a yellowish liquid residue from which diozonide 11bc (173 mg, 19%, mixture of isomer 1 and isomer 2) and subsequently isomer 1 (34 mg, 8%) and isomer 2 (28 mg, 7%) of were isolated.

3-(5-Methyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.4]nonane (11bc, isomer 1): Colorless liquid. 1H NMR δ 1.52 (s, 3H), 1.62-1.94 (m, 12H), 2.16
-2.25 (m, 2H), 5.20 (s, 1H) ppm; 13C NMR(BB) δ 16.23, 20.63, 23.53, 24.02, 25.38, 32.58, 33.42, 35.27, 101.46, 107.86, 110.30, 119.57 ppm; 13C NMR (DEPT) δ 16.23, 20.63, 23.53, 24.02, 25.38, 32.58, 33.42, 35.27, 101.46 ppm; Anal. Calcd for C12H18O6 (258.26): C, 55.80 ; H, 7.03. Found: C, 55.57; H, 7.28.

3-(5-Methyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.4]nonane (11bc, isomer 2): Colorless liquid. 1H NMR δ 1.52 (s, 3H), 1.64-1.99 (m,12H), 2.05-2.26 (m,2H), 5.20(s,1H) ppm; 13C NMR(BB) δ 16.12, 20.63, 23.55, 24.03, 25.51, 32.77, 33.40, 35.23, 101.14, 107.88, 110.16, 119.45 ppm; 13C NMR (DEPT) δ 16.12, 20.63, 23.55, 24.03, 25.51, 32.77, 33.40, 35.23, 101.14 ppm; Anal. Calcd for C12H18O6 (258.26): C, 55.80 ; H, 7.03. Found: C, 55.62; H, 7.27.

g) Coozonolyses of 5b with 10d: Ozone treatment of 5b (0.6 g, 3.21 mmol) and 10d (0.31 g, 3.21 mmol) in CH2Cl2 (70 mL) provided 1.0 g of a yellowish liquid residue from which diozonide 11bd (186 mg, 19%, mixture of isomer 1 and isomer 2) and subsequently isomer 1 (31 mg, 3.1%) and isomer 2 (30 mg, 3.0%) were isolated.

3-(5-Methyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.5]decane (11bd, isomer 1): Colorless liquid. 1H NMR δ 1.52 (s, 3H), 1.64-1.94 (m, 12H), 2.18-2.27(m, 2H, 5.20 (s,1H) ppm; 13C NMR(BB) δ 16.21, 20.64, 23.51, 23.84, 24.78, 25.50, 32.56, 33.17, 33.40, 101.43, 107.39, 110.24, 110.68 ppm; 13C NMR (DEPT) δ 16.21, 20.64, 23.51, 23.84, 24.78, 25.50, 32.56, 33.17, 33.40, 101.43 ppm; Anal. Calcd for C13H20O6 (272.29): C, 57.34 ; H, 7.40. Found: C, 57.22; H, 7.31.

3-(5-Methyl-6,7,8-trioxabicyclo[3.2.1]oct-1-yl)-1,2,4-trioxaspiro[4.5]decane (11bd, isomer 2): Colorless liquid. 1H NMR δ 1.52 (s, 3H), 1.38-1.48 (m, 2H), 1.57-1.90 (m, 13H), 2.17-2.26(m,1H), 5.22 (s, 1H) ppm; 13C NMR(BB) δ 16.15, 20.66, 23.50, 23.85, 24.76, 25.77, 32.57, 33.20, 33.40, 101.08, 107.80, 110.20, 110.57 ppm; 13C NMR(DEPT) δ 16.15, 20.66, 23.50, 23.85, 24.76, 25.77, 32.57, 33.20, 33.40 ppm; Anal. Calcd for C13H20O6 (272.29): C, 57.34 ; H, 7.40. Found: C, 57.17; H, 7.29.

Coozonolyses of 5a with 3a:

A solution of 1a (0.5 g, 3.6 mmol) in pentane (80 mL) was treated with ozone at -78 °C until it turned blue. Residual ozone was flushed off with nitrogen and the solvent was distilled off at room temperature and reduced pressure. The liquid residue was admixed with ozonide 5a (0.78 g, 3.6 mmol) in pentane (80 mL) and the solution was treated with ozone at -75 °C until it turned blue. Residual ozone was flushed off and the solvent was distilled off to leave 0.76 g of a colorless liquid residue from which triozonide 12a (253 mg, 18%, mixture of cis-trans isomers) and subsequently cis-12a (36 mg, 2.6%) and trans-12a (30 mg, 2,1%) were isolated by flash chromatography (column 2.5 x 60 cm; pentane/Et2O, 99:1 ).

cis-3,5-bis(3,3,5-Trimethyl-6,7,8-trioxabicyclo[3.2.1]octane-1-yl)-1,2,4-trioxolane (cis-12a): Colorless liquid. 1H NMR δ 1.02 (s, 6H), 1.32 (s, 6H), 1.53 (s, 6H), 1.69-1.90 (m, 8H), 5.23 (s, 2H) ppm; 13C NMR(BB) δ 21.17, 29.35, 31.57, 34.83, 39.61, 46.92, 102.38, 107.06, 110.07 ppm; 13C NMR (DEPT) δ 21.17, 31.57, 34.83, 39.61, 46.92, 102.38 ppm; Anal. Calcd for C18H28O9 (388.41): C, 55.66; H, 7.27. Found: C, 55.61; H, 7.12.

trans-3,5-bis(3,3,5-Ttrimethyl-6,7,8-trioxabicyclo[3.2.1]octane-1-yl)-1,2,4-trioxolane (trans-12a): Colorless liquid. 1H NMR δ 1.02 (s, 6H), 1.32 (s, 6H), 1.53 (s, 6H), 1.69-1.82 (m, 8H), 5.25 (s, 2H) ppm; 13C NMR(BB) δ 21.16, 29.36, 31.36, 34.74, 39.76, 46.94, 102.00, 107.07, 109.95 ppm; 13C NMR (DEPT) δ 21.16, 31.35, 34.75, 39.76, 46.93, 102.00 ppm; Anal. Calcd for C18H28O9 (388.41): C, 55.66; H, 7.27. Found: C, 55.55; H, 7.24.

Coozonolyses of 5b with 3b:

A solution of 1b (0.30 g, 2.7 mmol) in pentane (80 mL) was treated with ozone at -78 °C until it turned blue. Residual ozone was flushed off with nitrogen and the solvent was distilled off at room temperature and reduced pressure. The liquid residue was admixed with ozonide 5b (0.50 g, 2.7 mmol) in pentane (80 mL) and the solution was treated with ozone at -75 °C until it turned blue. Residual ozone was flushed off with nitrogen and the solvent was distilled off to leave 0.9 g of a yellow, viscous residue from which triozonide 12b (275 mg, 31%, mixture of cis-trans-isomers) and subsequently cis-12b (37 mg, 4,2%) and trans-12b (27 mg, 3.0%) were isolated by flash chromatography (column 1.0 x 60 cm; pentane/Et2O, 99.5:4.5).

cis-3,5-bis(5-Methyl-6,7,8-trioxabicyclo[3.2.1]octane-1-yl)-1,2,4-trioxolane (cis-12b): Yellowish liquid. 1H NMR δ 1.52 (s, 6H), 1.74-2.10 (m, 12H), 5.23 (s, 2H) ppm; 13C NMR(BB) δ 16.52, 20.91, 26.68, 33.70, 102.33, 107.44, 110.84 ppm; 13C NMR (DEPT) δ 16.51, 20.92, 26.68, 33.70, 102.32 ppm; Anal. Calcd for C14H20O9 (332.3): C, 50.60; H, 6.07. Found: C, 50.07; H, 6.20.

trans-3,5-bis(5-Methyl-6,7,8-trioxabicyclo[3.2.1]octane-1-yl)-1,2,4-trioxolane (trans-12b): Yellowish liquid. 1H NMR δ 1.52 (s, 6H), 1.77-2.12 (m, 12H), 5.25 (s, 2H) ppm; 13C NMR(BB) δ 16.52, 20.87, 26.92, 33.72, 102.02, 107.49, 110.73 ppm; 13C NMR (DEPT) δ 16.51, 20.86, 26.92, 33.72, 102.01 ppm; Anal. Calcd for C14H20O9 (332.3): C,50.60; H, 6.07. Found : C, 50.42; H, 6.16.

Coozonolyses of 5a with 1,4-cyclohexanedione(13):

A solution of 5a (0.80 g, 3.72 mmol) and 13 (0.12 g, 1.24 mmol) in CH2Cl2 (80 mL) was treated with ozone at -58 °C until it turned blue. Residual ozone was flushed off with nitrogen, the mixture was warmed up to room temperature and the solvent was distilled off at reduced pressure to leave 1.8 g of a yellowish liquid residue. From this residue tetraozonide 14a (165 mg, 9%, mixture of three diastereomers) were isolated by flash chromatography (column 1 x 50 cm; pentane/Et2O, 95:5). Subsequent chromatographic separation of this mixture of 14a-isomers under the same conditions afforded isomer 1 (55 mg, 2.9%) and isomer 2 (35 mg, 1.8%) but not isomer 3, probably due to its low yield.

Tetraozonide 14a (isomer 1): Yellowish liquid. 1H NMR δ 1.02 (s, 6H), 1.32 (s, 6H), 1.53 (s, 6H), 1.68-1.84 (m, 8H), 1.99-2.07 (m, 8H), 5.25 (s, 2H) ppm; 13C NMR(BB) δ 21.25, 29.32, 30.23, 31.39, 34.91, 39.15, 46.95, 101.71, 107.41, 109.35, 109.96 ppm; 13C NMR (DEPT) δ 21.24, 29.83, 30.21, 31.39, 34.88, 39.13, 46.94, 101.68 ppm; Anal. Calcd for C24H36O12 (516.54): C, 55.81; H, 7.02. Found: C, 55.68; H, 7.14.

Tetraozonide 14a (isomer 2): Yellowish liquid. 1H NMR δ 1.02 (s, 6H), 1.32 (s, 6H), 1.53 (s, 6H), 1.68-1.84 (m, 8H), 1.99-2.07 (m, 8H), 5.24 (s, 2H) ppm; 13C NMR(BB) δ 21.26, 29.32, 30.24, 31.39, 34.92, 39.26, 46.96, 101.72, 107.42, 109.35, 109.95 ppm; 13C NMR (DEPT) δ 21.27, 30.25, 31.39, 34.92, 39.25, 46.95, 101.72 ppm; Anal. Calcd for C24H36O12 (516.54): C, 55.81; H, 7.02. Found: C, 55.87; H, 7.09.

Coozonolyses of 5b with 13:

A solution of 5b (0.50 g, 2.67 mmol) and 13 (0.10 g, 0.89 mmol) in CH2Cl2 (80 mL) was treated with ozone at -60 °C until it turned blue. Residual ozone was flushed off with nitrogen, the mixture was warmed up to room temperature and the solvent was distilled off at reduced pressure to leave 0.80 g of yellowish liquid residue. From this residue tetraozonide 14b (105 mg, 9%, mixture of two diastereomers) were isolated by flash chromatography (column 1 x 50 cm; pentane/Et2O, 95:5). Subsequent chromatographic separation of this mixture of isomers under the same conditions afforded isomer 1 (25 mg, 2.0%) and isomer 2 (20 mg, 1.6%).

Tetraozonide 14b (isomer 1): Yellowish liquid. 1H NMR δ 1.51 (s, 6H), 1.84-2.17 (m, 20H), 5.24 (s, 2H) ppm; 13C NMR(BB) δ 16.53, 20.99, 26.36, 30.23, 33.74, 101.95, 107.87, 109.25, 110.71 ppm; 13C NMR(DEPT) δ 16.53, 20.99, 26.34, 30.24, 33.73, 102.02 ppm; Anal. Calcd for C20H28O12 (460.43): C, 52.17; H, 6.13. Found: C, 51.98; H, 6.15.

Tetraozonide 14b (isomer 2): Yellowish liquid. 1H NMR δ 1.53 (s, 6H), 1.85-2.20 (m, 20H), 5.25 (s, 2H) ppm; 13C NMR(BB) δ 16.53, 20.96, 26.49, 30.52, 33.74, 101.60, 107.86, 109.27, 110.71 ppm; 13C NMR (DEPT) δ 16.54, 21.00, 26.50, 30.52, 33.74, 101.60 ppm; Anal. Calcd for C20H28O12 (460.43): C, 52.17; H, 6.13. Found: C, 52.28; H, 6.18.

ACKNOWLEDGEMENTS
This work was supported by Grant (No. R05-2002-000-01426-0) from the Basic Research Program of the Korean Science & Engineering Foundation(KOSEF). We also thank the Hanseo University for financial support of this Work.

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