C-C bond formation at ozonide rings by substitution of chlorinated ozonides

Article abstract of DOI:10.1002/ejoc.200400167

The TiCl₄-mediated substitution of 3-chloro-3,5- bis(chloromethyl)-5-methyl-1,2,4-trioxolane (1) with 1-(trimethylsilyloxy) cyclopentene (4), 2-methyl-1-(trimethylsilyloxy)propene (6) and allyltrimethylsilane (12) gave the corresponding 2-oxocy

Full text of DOI:10.1002/ejoc.200400167

FULL PAPER
C؊C Bond Formation at Ozonide Rings by Substitution of Chlorinated
Ozonides
Karl Griesbaum,*[a] Ralf-Olaf Quinkert,[a] and Kevin J. McCullough[b]
Keywords: CϪC coupling / Ozonolysis / Substitution / Synthetic methods
The TiCl4-mediated substitution of 3-chloro-3,5-bis(chloro-
methyl)-5-methyl-1,2,4-trioxolane (1) with 1-(trimethylsilyl-
trimethylsilane (12) gave the diallyl-substituted ozonide 14.
Ozonolysis of the allyl-substituted ozonide 13 provided the
oxy)cyclopentene (4), 2-methyl-1-(trimethylsilyloxy)propene corresponding diozonide 17, and ozonolysis of the diallyl-
(6) and allyltrimethylsilane (12) gave the corresponding 2-
oxocyclopentyl-, 1,1-dimethyl-2-oxo-ethyl- and allyl-substi-
substituted ozonide 14 provided the corresponding diozonide
18 and triozonide 19.
tuted ozonides 5, 7 and 13, respectively. Substitution of 3,5- ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
dichloro-3,5-bis(chloromethyl)-1,2,4-trioxolane (2) with allyl-
Germany, 2004)
Introduction
In previous work we have shown that in certain 3-chloro-
substituted and 3,5-dichloro-substituted ozonides, such as
1 and 2, chlorine can be replaced by F,[1] O(CO)CH3,[1]
OCH3,[1]
OCH2CHϭCH2,[2]
OCH2CH2OH,[2]
and
OCH2CH2CH2OH.[2] Similarly, the Cl substituent in ozon-
ide 3a can be replaced by F to give ozonide 3b,[3] whereas
the AlCl3-mediated reaction of 3a with benzene gave non-
peroxidic decomposition products instead of the expected
ozonide 3c.[3] Since treatment of independently prepared
ozonide 3c with AlCl3 in benzene gave the same products
in the same proportions[3] it is possible that 3c may have
been formed in the reaction of 3a with benzene, but that it
subsequently decomposed. This would be consistent with
the experience that, with few exceptions,[4] reactions of
Lewis acids with ozonides lead to ring opening, either with
or without rupture of the peroxide bond.[5Ϫ9] More recently
it has been found, however, that TiCl4-mediated, low-tem-
perature reactions of 3-alkoxy-1,2-dioxolanes with trimeth-
ylsilyl enol ethers or with allyltrimethylsilane result in the
substitution of the alkoxy groups and concomitant forma-
tion of CϪC bonds at the dioxolane rings.[10] In contrast,
to the best of our knowledge, analogous CϪC-bond forma-
tion by substitution reactions at ozonide rings are not
known.
Results and Discussion
The reaction of ozonide 1[11] with equimolar amounts of
4 and TiCl4 in dichloromethane at Ϫ78 °C provided a prod-
uct from which a mixture of two diastereomers of ozonide
cis-5 and peroxy ester 8 could be isolated in yields of 9%
and 7%, respectively. The diastereomers of ozonide cis-5,
denoted as cis-5a and cis-5b, were individually isolated in
yields of 2% and 7%, respectively. From a similar reaction
of 1 with 6 we obtained ozonide cis-7 in 1.5% yield and
peroxy ester 8 in 13% yield. It is obvious from these results
that TiCl4-mediated reaction of ozonide 1 to give the
known acyclic isomerization product 8[11] is preferred over
CϪC bond formation to give the substituted ozonides 5
and 7.
Ozonides 5 and 7 are stable at room temperature. Their
structures were established by 1H and 13C NMR spec-
troscopy and were verified by the results of reduction reac-
tions with triphenylphosphane: ozonide 5 gave 9 and 10
(the latter was partly enolized) in a molar ratio of about
1:1, and ozonide 7 gave 9 and 11 in a molar ratio also of
about 1:1. The structure of peroxy ester 8 was readily as-
[a]
Engler-Bunte-Institut, Universität Karlsruhe (TH),
76128 Karlsruhe, Germany
[b]
Department of Chemistry, Heriot-Watt University,
Riccarton, Edinburgh, EH14 4AS, UK
Eur. J. Org. Chem. 2004, 3657Ϫ3662
DOI: 10.1002/ejoc.200400167
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3657

K. Griesbaum, R.-O. Quinkert, K. J. McCullough
FULL PAPER
signed by comparison of its 1H and 13C NMR spectro-
The structures of the isolated ozonides 13 and 14 were
1
scopic data with those reported previously.[11]
established by H, 13C and 17O NMR spectroscopy. As ex-
pected, the reduction of ozonides 13 with triphenylphos-
phane gave equimolar quantities of 9 and 16; reduction of
the diastereomeric ozonides 14 gave 16 as the sole product.
The availability of the unsaturated ozonides 13 and 14
prompted us to examine whether their ozonolyses can pro-
vide stable diozonides and triozonides. To this end, they
were ozonized in pentane at Ϫ78 °C. Ozonolysis of cis-13
provided a mixture consisting of two diastereomers of di-
ozonide cis-17 in 84%. Similarly, ozonolysis of trans-13 gave
a mixture of two diastereomers of trans-17 in 69%. Al-
though the individual diastereomers were not isolated, their
1
existence was obvious from their H, 13C and 17O NMR
spectra, in which the signals of some structural units ap-
peared in duplicate. The liquid diozonides 17 appear to be
stable at room temperature, whereas upon heating on a hot
plate trans-17 burns off and cis-17 bursts.
Ozonolysis of cis-14 and of trans-14 provided, in each
case, mixtures of the corresponding diozonides 18 and
triozonides 19, even though the passage of ozone was con-
tinued until the solutions had turned blue. The reason for
this is probably the fact that some of the diozonides 18
co-precipitated with the triozonides 19 and hence became
largely unreactive towards further ozonolysis.
The difference between the yields of ozonides 5 and 7
suggests that CϪC bond formation at an ozonide ring
should be more favored if the nucleophilic carbon atom of
the silicon-containing co-reactant were less highly substi-
tuted. Therefore, we continued our studies using allyltri-
methylsilane (12). Indeed, reaction of ozonide 1 (cis/trans ϭ
70:30) with approximately equimolar amounts of 12 and
TiCl4 in dichloromethane at Ϫ78 °C provided a 3:2 mixture
of ozonides cis-13 and trans-13 in a combined yield of 45%.
The stable liquid ozonides were isolated in yields of 21%
(cis-13) and 15% (trans-13). In a similar manner, TiCl4-me-
diated reaction of ozonide trans-2[11] with 2 mol-equiv. of
12 provided a 1:1 mixture of ozonides cis-14 and trans-14
in a combined yield of 68%, along with 10% of unchanged
ozonide 2. The stable liquid ozonides cis-14 and trans-14
were isolated in yields of 26% and 25%, respectively.
Despite the presence of unchanged substrate 2, there was
no evidence for the presence of a monosubstituted ozonide
in the crude reaction mixture. This can be rationalized by
analogy with the observation that monochloro-substituted
ozonides are less stable and react faster than dichloro-sub-
stituted ozonides.[11] Moreover, the fact that TiCl4-mediated
substitution of ozonide trans-2 provided both cis-14 and
trans-14 is consistent with the intermediacy of the ozonide
cation 15.[12]
The diozonides cis-18 and trans-18 were isolated in yields
of 35% and 21%, respectively. They are colorless oils and
consist of two diastereomers, the components of which were
not isolated. They appear to be stable at room temperature,
whereas upon heating on a hot plate trans-18 burns off and
cis-18 bursts. The triozonides cis-19 and trans-19 were iso-
lated in yields of 44% and 55%, respectively, as colorless oils
which consisted of mixtures of all three diastereomers.[13]
Although each of the three diastereomers of triozonide cis-
19 was isolated by HPLC separation, they were not stereo-
chemically assigned. They are denoted as cis-19a, cis-19b,
and cis-19c in the order of increasing retention times. Treat-
ment of a dichloromethane solution containing all isolated
diastereomers of triozonide trans-19 with pentane, at room
temperature, yielded crystalline material which was found
to consist of a mixture of trans-19a and trans-19b. The
triozonides 19 appear to be stable at room temperature, but
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Eur. J. Org. Chem. 2004, 3657Ϫ3662

CϪC Bond Formation at Ozonide Rings
FULL PAPER
upon heating on a hot plate trans-19 bursts and cis-19 exhibits one ABX and one A2X system for cis-18a,b but
explodes with a loud bang. The structural assignments of two ABX systems for trans-18a,b, and the CH2 group in the
1
ozonides 17Ϫ19 are based on their H, 13C and 17O NMR ozonide ring exhibits one singlet for cis-18a,b but two sing-
spectroscopic data.
lets for trans-18a,b. Since the spectra of ozonides 17a,b
Analysis of a crystal known to contain a mixture of the show the same differences in their patterns, their configura-
diastereomers 19a and 19b was attempted by X-ray crystal- tions were assigned accordingly, and these assignments were
lography. Although the crystal diffracted weakly and was extended to their precursors cis-13 and trans-13.
prone to decomposition in the X-ray beam during data col-
In the 13C NMR spectra, the signals for the CH3 groups
lection, the structure was solved and the central ozonide at the ozonide rings of cis-13 (δ ϭ 20.70 ppm) and cis-17a,b
ring was found to be unambiguously of the trans configura- (δ ϭ 20.19, 20.22 ppm) appear downfield from those of
tion[14] (Figure 1). The structural features of one of the trans-13 (δ ϭ 19.17 ppm) and trans-17a,b (δ ϭ 19.40 ppm).
monosubstituted 1,2,4-trioxolane rings were also clearly de- Since the corresponding signals for 5a,b (δ ϭ 20.95 ppm)
fined. The remaining trioxolane ring consisted of unequal and 7 (δ ϭ 20.26 ppm) also appear in the downfield range,
proportions of both configurations at the fourth chiral we have assigned them as cis compounds. This assignment
center (ca. 70:30), as expected, and there appeared to be a derives support from the observation that the signals for the
high degree of ring disorder. Nonetheless, on the basis of CH2Cl groups geminal to the CH3 groups for cis-13 (δ ϭ
these results the configuration of the parent monoozonide 45.61 ppm) and cis-17a,b (δ ϭ 45.59 ppm) appear upfield
trans-14 and of the intermediate diozonide trans-18, as well from those for trans-13 (δ ϭ 46.17 ppm) and trans-17a,b
as the configurations of cis-14, cis-18 and cis-19, were also (δ ϭ 46.01 ppm) and that the corresponding signals for 5a,b
established.
(δ ϭ 45.40, 45.44 ppm) and 7 (δ ϭ 45.75 ppm) also appear
in the upfield range.
Experimental Section
General: NMR spectra: Bruker AC 250. 1H and 13C NMR spectra
were obtained in CDCl3 with TMS as internal reference and 17O
NMR spectra in C6D6 by using H2O as external reference. Chroma-
tographic separations: Flash chromatography[15] on silica gel.
HPLC separations: Knauer EUROPREP Si60 and Merck
LICHROSORB Si60.
Caution: All reactions with ozone or ozonides and chromato-
graphic separations were carried out behind protective safety-glass
shields in a hood. Ozonides were invariably transported in thick-
walled steel containers. Safety glasses and gloves must be worn at
all times when working with ozone or ozonides.
Preparation of cis-3,5-Bis(chloromethyl)-3-methyl-5-(2-oxocyclopen-
tyl)-1,2,4-trioxolane (cis-5a,b): A solution of 1,2,4-trichloro-3-
methyl-2-butene (1.44 g, 8.3 mmol)[11] (65% cis, 35% trans) in 145
mL of pentane was treated with ozone at Ϫ78 °C until the solution
turned blue. Residual ozone was flushed off with nitrogen, the reac-
tion mixture was warmed up to 0 °C and stirred in the presence of
solid K2CO3 for 30 min. The mixture was filtered and from the
filtrate the solvent was distilled off at Ϫ10 °C under reduced press-
ure. Under nitrogen, and with stirring, the residue was dissolved in
5.5 mL of dichloromethane, cooled to Ϫ70 °C and admixed with
1-(trimethylsilyloxy)cyclopentene (4; 735 mg, 4.7 mmol). Then, 4.7
mL of a 1  solution of TiCl4 in dichloromethane was added within
5 min and the mixture was stirred for 2 h while the temperature rose
to Ϫ50 °C. The mixture was poured into ice/water with stirring, the
phases were separated, the aqueous phase was repeatedly extracted
with dichloromethane and the extracts were added to the organic
phase. The combined organic phases were extracted with an aque-
ous solution of NaHCO3 and dried with MgSO4. The solvent was
distilled off at room temperature under reduced pressure to leave
1.4 g of a yellow viscous residue, which was purified by flash chro-
matography (petroleum ether/diethyl ether, 4:1) to give 210 mg (9%)
of a mixture of ozonides cis-5a,b and 130 mg (7%) of peroxy ester
8. HPLC separation of the ozonides (LICHROSORB Si60; petro-
leum ether/diethyl ether, 75:25) provided 32 mg (1%) of cis-5a and
90 mg (4%) of cis-5b.
Figure 1. ORTEP diagram showing the X-ray structure of tri-
ozonide trans-19a/b
The configurations of ozonides 17a,b were assigned with
the help of ozonides 18a,b, based on the following similarit-
1
ies in the H NMR patterns of common structural units
(Table 1): the CH2 group between the two ozonide rings
1
Table 1. H NMR spectroscopic data of common structural units
in diozonides 17a,b and 18a,b
Chemical shifts (ppm) of structural units
ϪCH2Ϫ(CH)
OϪOϪCH2ϪO
cis-18a,b
ABX: δA ϭ 2.43, δB ϭ 2.36
A2X: δA ϭ 2.40
s: 5.14, 5.15
s: 5.11
cis-17a,b
ABX: δA ϭ 2.43, δB ϭ 2.36
A2X: δA ϭ 2.40
s: 5.14, 5.15
s: 5.12
trans-18a,b
trans-17a,b
ABX: δA ϭ 2.57, δB ϭ 2.31
ABX: δA ϭ 2.49, δB ϭ 2.38
ABX: δA ϭ 2.56, δB ϭ 2.29
ABX: δA ϭ 2.49, δB ϭ 2.36
s: 5.15, 5.17
s: 5.131, 5.134
s: 5.16, 5.17
s: 5.13, 5.14
Eur. J. Org. Chem. 2004, 3657Ϫ3662
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K. Griesbaum, R.-O. Quinkert, K. J. McCullough
FULL PAPER
cis-3,5-Bis(chloromethyl)-3-methyl-5-(2-oxocyclopentyl)-1,2,4-
trioxolane (cis-5a): Colorless viscous liquid. H NMR: δ ϭ 1.62 (s,
3 H), 1.67Ϫ2.45 (m, 6 H), 3.03 (ddd, J ϭ 11.0, 8.0, 1.0 Hz, 1 H);
repeatedly extracted with dichloromethane and the extracts were
added to the organic phase. The combined organic phases were
dried with MgSO4 and filtered. From the filtrate the solvent was
1
AB system: δA ϭ 3.71, δB ϭ 3.64 (J ϭ 12.2 Hz, 2 H); AB system: distilled off at room temperature and reduced pressure to leave
δ
A ϭ 4.20, δB ϭ 3.75 (J ϭ 11.8 Hz, 2 H) ppm. 13C NMR: δ ϭ 20.15,
4.59 g of a yellow liquid residue, which was separated by flash chro-
20.95, 25.95, 39.45, 44.06, 45.50, 50.58, 109.43, 109.74, 213.78 ppm. matography (petroleum ether/diethyl ether, 83:17) to give 290 mg
of impure ozonide 7 and 1.02 g (13%) of peroxy ester 8. HPLC
separation of the impure ozonide (EUROPREP 60; n-hexane/di-
cis-3,5-Bis(chloromethyl)-3-methyl-5-(2-oxocyclopentyl)-1,2,4-
trioxolane (cis-5b): Colorless viscous liquid. H NMR: δ ϭ 1.62 (s,
3 H), 1.66Ϫ2.44 (m, 6 H); A-part of an AMNX system: δA ϭ 3.06
1
ethyl ether, 82:18) provided 135 mg (1.5%) of cis-7 as a colorless
1
liquid. H NMR: δ ϭ 1.23 (s, 3 H), 1.25 (s, 3 H), 1.63 (s, 3 H); AB
(JAM ϭ 11.2, JAN ϭ 8.1, JAX ϭ 0.9 Hz, 1 H); AB system: δA
3.68, δB ϭ 3.62 (JAB ϭ 12.1 Hz, 2 H); AB system: δA ϭ 4.21, δB
ϭ
system: δA ϭ 3.77, δB ϭ 3.71 (J ϭ 12.1 Hz); AB system: δA ϭ 3.86,
δB ϭ 3.77 (J ϭ 12.7 Hz); 9.68 (s, 1 H) ppm. 13C NMR: δ ϭ 18.33,
18.64, 20.26, 42.54, 45.75, 52.13, 109.90, 111.18, 200.07 ppm.
C9H14Cl2O4 (257.11): calcd. C 42.04, H 5.49; found C 41.72, H
5.65.
ϭ
3.87 (JAB ϭ 11.8 Hz, 2 H) ppm. 13C NMR: δ ϭ 20.10, 20.95, 24.72,
38.84, 43.18, 45.43, 49.19, 109.21, 109.79, 213.52 ppm.
C10H14Cl2O4 (269.12): calcd. C 44.63, H 5.24; found C 44.69, H
5.10.
Reduction of Ozonide cis-7: A sample of cis-7 (7.3 mg, 29 µmol) in
CDCl3 was admixed with an excess of triphenylphosphane in an
NMR tube and kept at room temperature for 3 h. 1H NMR analy-
sis showed the presence of 9 [δ ϭ 2.31 (s), 4.09 (s) ppm] and 11
[δ ϭ 1.40 (s, 6 H), 4.28 (s, 2 H), 9.58 (s, 1 H) ppm] in a ratio
of about 1:1. The data for 11 were verified with the help of an
independently prepared sample.[17]
Chloroacetyl (1,2-Dichloro-1-methyl) Peroxide (8): Colorless liquid.
1H NMR: ABX3 system: δA ϭ 4.21, δB ϭ 3.93, δX ϭ 2.00 (JAB
ϭ
12.3, JAX ϭ 0.7 Hz); 4.17 (s) ppm. 13C NMR: δ ϭ 25.37, 37.81,
48.04, 104.41, 163.16 ppm.
Reduction of Ozonides cis-5a,b: A sample of a 1:2 mixture of cis-
5a and cis-5b (12 mg, 45 µmol) in CDCl3 was admixed with an
excess of triphenylphosphane in an NMR tube and kept at room
temperature for 5 d. 1H NMR analysis showed the presence of 9
[δ ϭ 2.31 (s), 4.09 (s) ppm] and 10 [δ ϭ 1.80Ϫ2.88 (m), 1.97 (quint,
J ϭ 7.2 Hz), 2.46 (t, J ϭ 7.9 Hz), 2.64 (t, J ϭ 7.9 Hz), 3.62 (t, J ϭ
8.5 Hz), 4.05 (s); AB system: δA ϭ 4.53, δB ϭ 4.32 (J ϭ 16.0 Hz)
ppm] in a ratio of about 1:1.
Preparation of 3-Allyl-3,5-bis(chloromethyl)-5-methyl-1,2,4-tri-
oxolanes (cis-13 and trans-13): A solution of 1,2,4-trichloro-3-
methyl-2-butene[11] (1.13 g, 6.5 mmol; 65% cis, 35% trans) in 110
mL of pentane was treated with ozone at Ϫ78 °C until it turned
blue. Residual ozone was flushed off with nitrogen, the reaction
mixture was warmed up to room temperature and the solvent was
distilled off at reduced pressure. Under nitrogen, and with stirring,
the residue was dissolved in 20 mL of dichloromethane, cooled to
Ϫ75 °C and admixed with allyltrimethylsilane (12; 795 µL,
5.0 mmol). Then 4.5 mL of a 1  solution of TiCl4 in dichlorometh-
ane was added within 5 min and the mixture was stirred at Ϫ75 °C
for 2 h. The mixture was poured into ice/water with stirring, the
phases were separated, the water phase was repeatedly extracted
with dichloromethane and the extracts were added to the organic
phase. The combined organic phases were sequentially washed with
a saturated aqueous solution of NaHCO3 and water, dried with
MgSO4 and filtered. From the filtrate the solvent was distilled off
at room temperature and reduced pressure to leave 2.0 g of a color-
less liquid residue, which was purified by flash chromatography
(petroleum ether/diethyl ether, 9:1) to give 670 mg (45%) of a mix-
ture consisting of cis-13 (60%) and trans-13 (40%). HPLC separ-
ation of this mixture (EUROPREP Si60; n-hexane/diethyl ether,
96:4) provided 237 mg (21%) of cis-13 and 174 mg (15%) of
trans-13. They were further purified by distillation at 60 °C and
5 ϫ 10Ϫ3 Torr.
Synthesis of 2-(Chloroacetyl)cyclopentanone (10): The synthesis was
performed according to a general procedure for the preparation of
β-diketones:[16] Under nitrogen, 20 mL of a 1  solution of TiCl4
in dichloromethane was cooled to 0 °C. Then chloroacetyl chloride
(9; 2.26 g, 20 mmol) and 1-(trimethylsilyloxy)cyclopentene (4;
3.13 g, 20 mmol) were successively added with stirring. After 1 h,
the mixture was poured into ice/water with vigorous stirring. The
aqueous phase was extracted with dichloromethane and the extract
was combined with the organic phase. The mixture was dried with
MgSO4 and filtered. From the filtrate the solvent was distilled off
at 40 °C and reduced pressure to leave 2.6 g of a yellow liquid
residue, which was purified by flash chromatography (n-hexane/
ethyl acetate/methanol, 60:32:8) and subsequent distillation at 80
°C and 10Ϫ3 Torr to give 33 mg of 10 as a yellow liquid. 1H NMR:
δ ϭ 1.81Ϫ2.88 (m), 1.99 (quint, J ϭ 7.5 Hz), 2.47 (t, J ϭ 7.9 Hz),
2.65 (t, J ϭ 7.2 Hz), 3.62 (t, J ϭ 8.6 Hz), 4.05 (s); AB system: δA ϭ
4.53, δB ϭ 4.32 (J ϭ 16.0 Hz) ppm. 13C NMR: δ ϭ 20.34, 20.76,
25.21, 25.34, 36.88, 38.67, 42.07, 48.39, 59.47, 110.59, 169.81,
196.06, 206.28, 211.89 ppm.
Preparation of cis-3,5-Bis(chloromethyl)-3-(1,1-dimethyl-2-oxo-
ethyl)-5-methyl-1,2,4-trioxolane (7): A solution of 1,2,4-trichloro-3-
methyl-2-butene[11] (6.06 g, 34.9 mmol; 65% cis, 35% trans) in 610
mL of pentane was treated with ozone at Ϫ78 °C until it turned
blue. Residual ozone was flushed off with nitrogen, the reaction
mixture was warmed up to room temperature, separated from an
oily precipitate and stirred in the presence of solid K2CO3 for 1 h.
The mixture was filtered and from the filtrate the solvent was dis-
tilled off at Ϫ10 °C and reduced pressure. Under nitrogen, and with
stirring, the residue was dissolved in 50 mL of dichloromethane,
cooled to Ϫ70 °C and admixed with 2-methyl-1-(trimethylsilyloxy)-
cis-3-Allyl-3,5-bis(chloromethyl)-5-methyl-1,2,4-trioxolane (cis-13):
Colorless liquid. 1H NMR: δ ϭ 1.63 (s, 3 H); AB part of an
ABMNX system: δA ϭ 2.74, δB ϭ 2.67 (JAB ϭ 14.5, JAX ϭ 7.5,
JBX ϭ 7.3, JAM ϭ JAN ϭ JBM ϭ JBN ϭ 1.1 Hz); AB system: δA
ϭ
3.70, δB ϭ 3.61 (J ϭ 12.2 Hz); AB system: δA ϭ 3.72 δB ϭ 3.61
(J ϭ 12.0 Hz); 5.29Ϫ5.29 (m, 2 H), 5.71 Ϫ5.87 (m, 1 H) ppm.
13C NMR: δ ϭ 20.70, 38.59, 43.46, 45.61, 109.18, 109.58, 120.52,
130.42 ppm. 17O NMR: δ ϭ 122, 297 ppm. C8H12Cl2O3 (227.09):
calcd. C 42.31, H 5.33; found C 42.17, H 5.39.
trans-3-Allyl-3,5-bis(chloromethyl)-5-methyl-1,2,4-trioxolane (trans-
1
propene (6; 2.16 g, 15 mmol). Then 15 mL of a 1  solution of 13): Colorless liquid. H NMR: δ ϭ 1.64 (s, 3 H); AB part of an
TiCl4 in dichloromethane was added within 5 min and the mixture
was stirred at Ϫ70 °C for 45 min. The mixture was poured into ice/
water with stirring, the phases were separated, the water phase was
ABMNX system: δA ϭ 2.76, δB ϭ 2.64 (JAB ϭ 14.6, JAX ϭ 7.4,
JBX ϭ 7.3, JAM ϭ JAN ϭ 1.0, JBM Ͻ 1, JBN Ͻ 1 Hz); AB system:
δA ϭ 3.63, δB ϭ 3.48 (J ϭ 11.6 Hz); AB system: δA ϭ 3.66, δB
ϭ
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CϪC Bond Formation at Ozonide Rings
FULL PAPER
3.50 (J ϭ 11.7 Hz); 5.17Ϫ5.31 (m, 2 H), 5.70 Ϫ5.87 (m, 1 H) ppm. in dichloromethane and the solution was combined with the pen-
13C NMR: δ ϭ 19.17, 36.07, 44.34, 46.17, 109.09, 109.73, 121.10,
tane solution. The solvents were distilled off at room temperature
129.57 ppm. 17O NMR: δ ϭ 122, 298 ppm. C8H12Cl2O3 (227.09): and reduced pressure to leave 260 mg of a colorless viscous oil.
calcd. C 42.31, H 5.33; found C 42.46, H 5.17.
Purification by flash chromatography (petroleum ether/diethyl
ether, 75:25) provided 232 mg (84%) of a mixture of the two dia-
stereomers of cis-17 as a colorless oil. H NMR: δ ϭ 1.66 (s), 1.67
Reduction of Ozonides cis- and trans-13: A sample of about 50Ϫ60
µmol of ozonide cis-13 or trans-13 in CDCl3 was admixed with
about 20 µmol of acetone (internal standard) and about 90 µmol
of triphenylphosphane in a sealed NMR tube and the solution was
heated to 50 °C for 90 min. 1H NMR analysis showed the presence
of 9 [δ ϭ 2.31 (s, 3 H), δ ϭ 4.08 (s, 2 H) ppm] and 16 [δ ϭ 3.36Ϫ3.40
(m, 2 H), 4.13 (s, 2 H), 5.16Ϫ5.28 (m, 2 H), 5.84Ϫ6.00 (m, 1 H)
ppm] in a molar ratio of about 1:1.
1
(s); AB part of an ABX system: δA ϭ 2.43, δB ϭ 2.36 (JAB ϭ 14.8,
JAX ϭ 5.6, JBX ϭ 4.9 Hz); A part of an A2X system: δA ϭ 2.40
(JAX ϭ 5.2 Hz); AB system: δA ϭ 3.75, δB ϭ 3.61 (JAB ϭ 11.9 Hz);
AB system: δA ϭ 3.81, δB ϭ 3.72 (JAB ϭ 12.6 Hz); AB system:
δA ϭ 3.81, δB ϭ 3.77 (JAB ϭ 12.7 Hz); 5.12 (s), 5.141 (s), 5.147 (s),
5.41 (t, J ϭ 5.1 Hz), 5.43 (t, J ϭ 5.2 Hz) ppm. 13C NMR: δ ϭ
20.19, 20.22, 36.77, 36.98, 43.69, 43.75, 45.59, 94.01, 94.10, 99.73,
99.75, 107.74, 107.80, 109.72 ppm. 17O NMR: δ ϭ 81, 121,
294 ppm. C8H12Cl2O6 (275.09): calcd. C 34.93, H 4.40; found C
34.91, H 4.43.
Preparation of 3,5-Diallyl-3,5-bis(chloromethyl)-1,2,4-trioxolanes
(cis-14 and trans-14): 10 mL of a 1  solution of TiCl4 in dichloro-
methane was added within 10 min to a stirred solution of ozonide
trans-2[12] (1.12 g, 4.6 mmol) in 20 mL of dichloromethane which
was kept at Ϫ78 °C under nitrogen. Subsequently, allyltrimethylsil-
ane (12; 1.60 mL, 10.0 mmol) was added and the mixture was
stirred at Ϫ40 °C for 6 h. The mixture was poured into 50 mL of
ice/water with stirring, the phases were separated, the water phase
was repeatedly extracted with dichloromethane and the extracts
were added to the organic phase. The combined organic phases
were dried with MgSO4 and filtered. From the filtrate the solvent
was distilled off at room temperature and reduced pressure to leave
1.13 g of a yellow liquid residue, which was purified by flash chro-
matography (petroleum ether/diethyl ether, 97:3) to give 800 mg of
a mixture consisting of 90% of ozonides cis-14 and trans-14 in a
ratio of about 1:1 and 10% of unchanged 2. HPLC separation of
this mixture (EUROPREP Si60; petroleum ether/diethyl ether,
98:2) provided 305 mg (26%) of cis-14 and 296 mg (25%) of trans-
14.
Ozonolysis of trans-3-Allyl-3,5-bis(chloromethyl)-5-methyl-1,2,4-
trioxolane (trans-13): A solution of trans-13 (230 mg, 1.0 mmol) in
100 mL of pentane was treated with ozone at Ϫ78 °C until it turned
blue. Residual ozone was flushed off with nitrogen, and the solvent
was distilled off at room temperature and reduced pressure to leave
265 mg of a colorless oil. Purification by flash chromatography
(petroleum ether/diethyl ether, 4:1) provided 190 mg (69%) of a
1
mixture of the two diastereomers of trans-17 as a colorless oil. H
NMR: δ ϭ 1.67 (s); AB part of an ABX system: δA ϭ 2.49, δB
2.36 (JAB ϭ 15.3, JAX ϭ 5.4, JBX ϭ 5.0 Hz); AB part of an ABX
system: δA ϭ 2.56, δB ϭ 2.29 (JAB ϭ 15.1, JAX ϭ 5.1, JBX
ϭ
ϭ
5.4 Hz); 3.76Ϫ3.53 (m), 5.49 (t, J ϭ 5.3 Hz) ppm. 13C NMR: δ ϭ
19.40, 34.38, 34.49, 44.80, 44.84, 46.01, 94.04, 99.47, 108.06,
109.60, 109.62 ppm. 17O NMR: δ ϭ 88, 128, 296 ppm. C8H12Cl2O6
(275.09): calcd. C 34.93, H 4.40; found C 34.89, H 4.45.
Ozonolysis of cis-3,5-Diallyl-3,5-bis(chloromethyl)-1,2,4-trioxolane
(cis-14): A solution of cis-14 (290 mg, 1.15 mmol) in 115 mL of
pentane was treated with ozone at Ϫ78 °C until it turned deep blue.
During this procedure, a voluminous precipitate was formed. The
suspension was flushed with nitrogen for 1 h and then warmed up
to room temperature. The pentane solution was decanted, the re-
sidual precipitate was dissolved in dichloromethane and the solu-
tion was combined with the pentane solution. The solvents were
distilled off at room temperature and reduced pressure to leave
432 mg of a colorless oil. HPLC separation (EUROPREP 60;
petroleum ether/diethyl ether, 70:30) of this oil provided 120 mg
(35%) of a mixture of two diastereomers of diozonide cis-18 and
176 mg (44%) of a mixture of the three diastereomeric triozonides
cis-19a,b,c. HPLC separation (LICHROSORB Si60; n-hexane/di-
ethyl ether, 70:30) of this mixture by the two-column-cycle tech-
nique[18] provided 40 mg of cis-19a, 78 mg of cis-19b and 39 mg of
cis-19c.
cis-3,5-Diallyl-3,5-bis(chloromethyl)-1,2,4-trioxolane (cis-14): Col-
orless liquid. 1H NMR: AB part of an ABMNX system: δA ϭ 2.68,
δB ϭ 2.67 (JAB ϭ 14.5, JAX ϭ 7.6, JBX ϭ 7.1, JAM ϭ JAN ϭ 1.0,
JBM Ͻ 1, JBN Ͻ 1 Hz); AB system: δA ϭ 3.73, δB ϭ 3.63 (J ϭ
12.2 Hz); 5.21Ϫ5.30 (m, 2 H), 5.71Ϫ5.88 (m, 1 H) ppm. 13C NMR:
δ ϭ 38.20, 43.53, 109.75, 120.64, 130.29 ppm. 17O NMR: δ ϭ 126,
295 ppm. C10H14Cl2O3 (253.13): calcd. C 47.45, H 5.57; found C
47.52, H 5.65.
trans-3,5-Diallyl-3,5-bis(chloromethyl)-1,2,4-trioxolane (trans-14):
1
Colorless liquid. H NMR: AB part of an ABMNX system: δA
2.77, δB ϭ 2.67 (JAB ϭ 14.6, JAX ϭ 7.3, JBX ϭ 7.4, JAM ϭ JAN
ϭ
ϭ
1.1, JBM Ͻ 1, JBN Ͻ 1 Hz); AB system: δA ϭ 3.65, δB ϭ 3.50 (J ϭ
11.6 Hz); 5.24Ϫ5.32 (m, 2 H), 5.70Ϫ5.87 (m, 1 H) ppm. 13C NMR:
δ ϭ 36.15, 44.51, 109.67, 121.15, 129.52 ppm. 17O NMR: δ ϭ 126,
297 ppm. C10H14Cl2O3 (253.13): calcd. C 47.45, H 5.57; found C
47.55, H 5.63.
Reduction of Ozonides cis- and trans-14: A sample of about 40 µmol
of ozonide cis-14 or trans-14 in CDCl3 was admixed with about 20
µmol of acetone (internal standard) and about 90 µmol of tri-
phenylphosphane in a sealed NMR tube and the solution was
heated to 50 °C for 90 min. 1H NMR analysis showed the presence
of 16 [δ ϭ 3.36Ϫ3.40 (m, 2 H), 4.13 (s, 2 H), 5.16Ϫ5.28 (m, 2 H),
5.84Ϫ6.00 (m, 1 H) ppm] in a yield of 98%.
cis-3-Allyl-3,5-bis(chloromethyl)-5-(1,2,4-trioxolanylmethyl)-1,2,4-
trioxolane (cis-18): Colorless oil. Mixture of two diastereomers. 1H
NMR: A part of an A2X system: δA ϭ 2.40 (JAX ϭ 5.0 Hz); AB
part of an ABX system: δA ϭ 2.43, δB ϭ 2.36 (JAB ϭ 14.8, JAX
5.8, JBX ϭ 4.6 Hz); AB part of an ABX system: δA ϭ 2.78, δB
ϭ
ϭ
2.69 (JAB ϭ 14.5, JAX ϭ 7.7, JBX ϭ 7.0 Hz); AB system: δA ϭ 3.76,
δB ϭ 3.63 (J ϭ 12.1 Hz, 4 H); AB system: δA ϭ 3.83, δB ϭ 3.73
(J ϭ 12.6 Hz); AB system: δA ϭ 3.84, δB ϭ 3.79 (J ϭ 12.4 Hz);
5.11 (s), 5.14 (s), 5.15 (s), 5.24Ϫ5.31 (m), 5.39Ϫ5.45 (m), 5.70Ϫ5.87
Ozonolysis of cis-3-Allyl-3,5-bis(chloromethyl)-5-methyl-1,2,4-tri-
oxolane (cis-13): A solution of cis-13 (230 mg, 1.0 mmol) in 100 mL
of pentane was treated with ozone at Ϫ78 °C until it turned blue. (m) ppm. 13C NMR: δ ϭ 36.53, 36.79, 37.61, 37.63, 43.68, 43.77,
Residual ozone was flushed off with nitrogen, the reaction mixture
was warmed up to room temperature and the pentane solution was
43.80, 92.99, 94.10, 99.71, 107.88, 107.95, 110.36, 121.15, 129.87,
129.90 ppm. 17O NMR: δ ϭ 92, 138, 291 ppm. C10H14Cl2O6
decanted from a viscous precipitate. The precipitate was dissolved (301.12): calcd. C 39.89, H 4.69; found C 39.57, H 4.77.
Eur. J. Org. Chem. 2004, 3657Ϫ3662
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3661

K. Griesbaum, R.-O. Quinkert, K. J. McCullough
FULL PAPER
cis-3,5-Bis(chloromethyl-3,5-bis(1,2,4-trioxolanylmethyl)-1,2,4-
trioxolane (cis-19a,b,c): Colorless oil. Mixture of three dia-
stereomers. 17O NMR: δ ϭ 89, 290 ppm. For safety reasons no
elemental analysis of ozonide 19 was attempted.
99.33, 108.53 ppm.17O NMR: δ ϭ 86, 292 ppm. For safety reasons
no elemental analysis of ozonide 19 was attempted.
Isolation of a Crystalline Mixture of Triozonides trans-19a and
trans-19b (trans-19a,b): In a test tube, a solution of trans-19a,b,c
(200 mg) in 500 µL of dichloromethane was layered with 4 mL of
n-pentane. The two-phase mixture was kept at room temperature
for 24 h, whereby colorless crystals precipitated. The liquid was de-
canted, the crystals were washed with n-pentane, dissolved in 500
µL of dichloromethane and the crystallization procedure was re-
peated, using 3 mL of n-pentane, to yield 50 mg of crystalline
trans-19ab.
1
cis-19a: Colorless oil. HPLC: tR ϭ 13.05 min. H NMR: AB sys-
tem: δA ϭ 3.86, δB ϭ 3.78 (J ϭ 12.5 Hz, 2 H); 5.15 (s, 1 H), 5.16
(s, 1 H); ABX system: δA ϭ 2.49, δB ϭ 2.36, δX ϭ 5.44 (JAB
ϭ
14.8, JAX ϭ 5.8, JBX ϭ 4.7 Hz, 3 H) ppm. 13C NMR: δ ϭ 36.16,
43.88, 94.12, 99.49, 108.52 ppm.
cis-19b: Colorless oil. HPLC: tR ϭ 13.35 min. 1H NMR: δ ϭ
2.32Ϫ2.55 (m, 4 H), 3.71Ϫ3.89 (m, 4 H, 5.12 (s, 1 H), 5.14 (s, 1
H), 5.16 (s, 1 H), 5.43Ϫ5.47 (m, 2 H) ppm. 13C NMR: δ ϭ 36.16,
43.88, 94.12, 99.49, 108.52 ppm.
trans-3,5-Bis(chloromethyl)-3,5-bis(1,2,4-trioxolanylmethyl)-1,2,4-
trioxolane (trans-19a,b): Colorless solid; m.p. 80Ϫ83 °C. Mixture
of two diastereomers. 1H NMR: AB part of an ABX system: δA
ϭ
1
cis-19c: Colorless oil. HPLC: tR ϭ 13.80 min. H NMR: AB sys-
2.505, δB ϭ 2.412 (JAB ϭ 15.1, JAX ϭ 5.1, JBX ϭ 5.4 Hz); AB part
tem: δA ϭ 3.85, δB ϭ 3.73 (J ϭ 12.5 Hz, 2 H), δ ϭ 5.12 (s, 1 H),
5.17 (s, 1 H); ABX system: δA ϭ 2.47, δB ϭ 2.42, δX ϭ 5.47 (JAB ϭ
15.1, JAX ϭ 5.8 Hz,, JBX ϭ 4.8 Hz, 3 H) ppm. 13C NMR: δ ϭ
36.34, 44.00, 94.03, 99.52, 108.48 ppm.
of an ABX system: δA ϭ 2.570, δB ϭ 2.342 (JAB ϭ 15.1, JAX
5.1, JBX ϭ 5.7 Hz); AB part of an ABX system: δA ϭ 2.570, δB
2.346 (JAB ϭ 15.1, JAX ϭ 5.1, JBX ϭ 5.5 Hz). AB system: δA
3.727, δB ϭ 3.698 (J ϭ 12.1 Hz,); AB system: δA ϭ 3.743, δB
ϭ
ϭ
ϭ
ϭ
Ozonolysis
of
trans-3,5-Diallyl-3,5-bis(chloromethyl)-1,2,4-tri-
3.652 (J ϭ 11.9 Hz); AB system: δA ϭ 3.743, δB ϭ 3.719 (J ϭ
12.1 Hz); 5.135 (s), 5.164 (s), 5.176 (s), 5.494 (t, J ϭ 5.3 Hz) ppm.
oxolane (trans-14): A solution of trans-14 (296 mg, 1.17 mmol) in
130 mL of pentane was treated with ozone at Ϫ78 °C until it turned
deep blue. During this procedure, a voluminous precipitate was
formed. The suspension was flushed with nitrogen for 1 h and
warmed up to room temperature. The pentane solution was de-
canted, the residual precipitate was dissolved in dichloromethane
and the solution was combined with the pentane solution. The sol-
vents were distilled off at room temperature and reduced pressure
to leave 446 mg of a colorless oil. HPLC separation (EUROPREP
60; petroleum ether/diethyl ether, 70:30) of this oil provided 73 mg
(21%) of a mixture of two diastereomers of diozonide trans-18 and
226 mg (55%) of a mixture of the three diastereomeric triozonides
trans-19a, 19b and 19c (trans-19a,b,c).
[1]
K. Griesbaum, K. Schlindwein, J. Org. Chem. 1995, 60,
8062Ϫ8066.
[2]
K. Griesbaum, R.-O. Quinkert, Liebigs Ann./Recueil 1997,
2518Ϫ2585.
K. Griesbaum, R. Greinert, unpublished results.
[3]
[4]
Y.-S. Hon, J.-L. Yan, Tetrahedron Lett. 1994, 35, 1743Ϫ1746.
[5]
M. Miura, M. Nojima, J. Am. Chem. Soc. 1980, 102, 288Ϫ292.
[6]
M. Miura, S. Nagase, M. Nojima, S. Kusabayashi, J. Org.
Chem. 1983, 48, 2366Ϫ2370.
K. J. McCullough, M. Nojima, in Organic Peroxides (Ed.: W.
[7]
Ando), John Wiley & Sons, Chichester, 1992, p. 661Ϫ728.
[8]
P. H. Dussault, X. Liu, Tetrahedron Lett. 1999, 40, 6553Ϫ6556.
trans-3-Allyl-3,5-bis(chloromethyl)-5-(1,2,4-trioxolanylmethyl)-
1,2,4-trioxolane (trans-18): Colorless oil. Mixture of two dia-
stereomers. 1H NMR: AB part of an ABX system: δA ϭ 2.49, δB ϭ
2.38 (JAB ϭ 15.2, JAX ϭ 5.3, JBX ϭ 5.2 Hz); AB part of an ABX
system: δA ϭ 2.57, δB ϭ 2.31 (JAB ϭ 15.1, JAX ϭ 5.0, JBX
5.6 Hz); AB part of an ABX system: δA ϭ 2.80, δB ϭ 2.69 (JAB
[9]
P. H. Dussault, H.-J. Lee, X. Liu, J. Chem. Soc., Perkin. Trans.
1 2000, 3006Ϫ3013.
[10]
P. H. Dussault, X. Liu, Org. Lett. 1999, 1, 1391Ϫ1393.
[11]
K. Griesbaum, K. Schlindwein, M. Hilß, Chem. Ber. 1993,
126, 1843Ϫ1848.
K. Griesbaum, R.-O. Quinkert, J. Prakt. Chem. 1997, 339,
650Ϫ651.
ϭ
[12]
ϭ
14.6, JAX ϭ 7.2, JBX ϭ 7.4 Hz); 3.54Ϫ3.75 (four overlapping AB
systems, 15 of 16 signals resolved), 5.13 (s), 5.14 (s), 5.15 (s), 5.17
(s), 5.24Ϫ5.26 (m), 5.29Ϫ5.33 (m), 5.49 (t, J ϭ 5.2 Hz), 5.70Ϫ5.87
(m) ppm. 13C NMR: δ ϭ 34.57, 34.67, 36.43, 44.33, 45.02, 45.06,
[13]
Ozonide cis-19 can exist as three diastereomers — two meso
forms and one chiral form — consistent with the three distinct
fractions isolated by chromatography and the NMR spectro-
scopic data obtained. Ozonide trans-19 can potentially exist
as four diastereomers — two with C2 symmetry and two of
lower symmetry.
94.04, 94.06, 99.46, 108.06, 110.21, 110.23, 121.44, 129.35 ppm. 17
O
NMR: δ ϭ 88, 122, 295 ppm. C10H14Cl2O6 (301.12): calcd. C 39.89,
H 4.69; found C 39.92, H 4.77.
[14]
CCDC-233569 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223-336-033;
E-mail: deposit@ccdc.cam.ac.uk].
W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43,
2923Ϫ2925.
R. E. Tirpak, M. W. Rathke, J. Org. Chem. 1982, 47,
5099Ϫ5102.
K. Ditgens, W. Krämer, H.-L. Elbe, DE Patent 1983, Nr.
3224130 AI (Bayer AG).
trans-3,5-Bis(chloromethyl-3,5-bis(1,2,4-trioxolanylmethyl)-1,2,4-
trioxolane (trans-19a,b,c): Colorless oil. Mixture of three dia-
stereomers. 1H NMR: AB part of an ABX system: δA ϭ 2.506,
δB ϭ 2.405 (JAB ϭ 15.1, JAX ϭ 5.2, JBX ϭ 5.3 Hz); AB part of an
ABX system: δA ϭ 2.505, δB ϭ 2.410 (JAB ϭ 15.1, JAX ϭ 5.2,
[15]
JBX ϭ 5.4 Hz); AB part of an ABX system: δA ϭ 2.570, δB ϭ 2.340
[16]
(JAB ϭ 15.1, JAX ϭ 5.1, JBX ϭ 5.5 Hz); AB part of an ABX system:
δA ϭ 2.570, δB ϭ 2.345 (JAB ϭ 15.1, JAX ϭ 5.1, JBX ϭ 5.6 Hz);
AB system: δA ϭ 3.727, δB ϭ 3.698 (J ϭ 12.0 Hz,); AB system:
δA ϭ 3.743, δB ϭ 3.651 (J ϭ 11.9 Hz); AB system: δA ϭ 3.744,
[17]
[18]
Handbuch der HPLC, part 2 (‘‘Präparative Säulenflüssig-Chro-
δ
B ϭ 3.719 (J ϭ 12.1 Hz); AB system: δA ϭ 3.757, δB ϭ 3.671 (J ϭ
matographie’’) (Ed.: K. K. Unger), GIT Verlag, Darmstadt,
1994, p. 89.
12.1 Hz); 5.129 (s), 5.134 (s), 5.164 (s), 5.176 (s), 5.494 (t, J ϭ
5.3 Hz) ppm. 13C NMR: δ ϭ 34.95, 35.07, 44.70, 44.74, 94.08,
Received March 14, 2004
3662
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3657Ϫ3662