First exclusive regioselective fragmentation of primary ozonides controlled by remote carbonyl groups and a new method for determining the regiochemistry of carbonyl oxide formation

Article abstract of DOI:10.1021/jo952284p

The first exclusive regioselective fragmentation of primary ozonides controlled by remote carbonyl groups on ozonolysis of norbornene derivatives and reaction of final ozonides with triethylamine as a new probe for determining the regiochemistry of carbonyl oxide formation from primary ozonide fragmentation are reported. Ozonolysis of the endo adducts 3a-d and the deuterated compounds 8a and 8b in CDCl₃ at -78°C gave the final ozonides 4a-d, 9a, and 9b as the sole products (>95%), respectively. No detectable amount of the isomeric final ozonides 5, 10, 11, and 12 was obtained. A mechanism is proposed to account for the exclusive regioselective fragmentation of the primary ozonides. Ozonolysis of 3a-d, 8a, and 8b in CH₂Cl₂ at -78°C followed by treatment with triethylamine exclusively gave the convex tetraquinane oxa cage compounds 16a-d, 19a, and 19b in 85-90% yields, respectively. No detectable amount of the other regioisomers 17a-d, 20a, and 20b was obtained. Ozonolysis of 3a-d, 8a, and 8b in CH₂Cl₂ at -78°C followed by reduction with dimethyl sulfide gave the tetraacetal tetraoxa cage compounds 21a-d, 23a, and 23b in 85% yields, respectively. The difference in function between triethylamine and dimethyl sulfide in reaction with final ozonide is demonstrated. Ozonolysis of the endo adducts 24a and 24b in CDCl₃ at -78°C exclusively gave the final ozonides 27a and 27b, respectively. The order of the preference of various remote carbonyl groups to control the fragmentation of the primary ozonides formed by ozonolysis of norbornene derivatives is investigated. Ozonolysis of the endo esters 32a-c in CH₂Cl₂ at -78°C followed by reduction with dimethyl sulfide gave the new tetraacetal oxa cages 35a-c, with an alkoxyl group directly on the skeleton, and the novel triacetal oxa cages 36b and 36c, respectively. The structures of triacetal oxa cages are proven for the first time by X-ray analysis of the crystalline compound 36c.

Full text of DOI:10.1021/jo952284p

3820
J . Org. Chem. 1996, 61, 3820-3828
F ir st Exclu sive Regioselective F r a gm en ta tion of P r im a r y
Ozon id es Con tr olled by Rem ote Ca r bon yl Gr ou p s a n d a New
Meth od for Deter m in in g th e Regioch em istr y of Ca r bon yl Oxid e
F or m a tion
Hsien-J en Wu* and Chu-Chung Lin
Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan, China
Received December 28, 1995X
The first exclusive regioselective fragmentation of primary ozonides controlled by remote carbonyl
groups on ozonolysis of norbornene derivatives and reaction of final ozonides with triethylamine
as a new probe for determining the regiochemistry of carbonyl oxide formation from primary ozonide
fragmentation are reported. Ozonolysis of the endo adducts 3a -d and the deuterated compounds
8a and 8b in CDCl3 at -78 °C gave the final ozonides 4a -d , 9a , and 9b as the sole products
(>95%), respectively. No detectable amount of the isomeric final ozonides 5, 10, 11, and 12 was
obtained. A mechanism is proposed to account for the exclusive regioselective fragmentation of
the primary ozonides. Ozonolysis of 3a -d , 8a , and 8b in CH2Cl2 at -78 °C followed by treatment
with triethylamine exclusively gave the convex tetraquinane oxa cage compounds 16a -d , 19a ,
and 19b in 85-90% yields, respectively. No detectable amount of the other regioisomers 17a -d ,
20a , and 20b was obtained. Ozonolysis of 3a -d , 8a , and 8b in CH2Cl2 at -78 °C followed by
reduction with dimethyl sulfide gave the tetraacetal tetraoxa cage compounds 21a -d , 23a , and
23b in 85% yields, respectively. The difference in function between triethylamine and dimethyl
sulfide in reaction with final ozonide is demonstrated. Ozonolysis of the endo adducts 24a and
24b in CDCl3 at -78 °C exclusively gave the final ozonides 27a and 27b, respectively. The order
of the preference of various remote carbonyl groups to control the fragmentation of the primary
ozonides formed by ozonolysis of norbornene derivatives is investigated. Ozonolysis of the endo
esters 32a -c in CH2Cl2 at -78 °C followed by reduction with dimethyl sulfide gave the new
tetraacetal oxa cages 35a -c, with an alkoxyl group directly on the skeleton, and the novel triacetal
oxa cages 36b and 36c, respectively. The structures of triacetal oxa cages are proven for the first
time by X-ray analysis of the crystalline compound 36c.
In tr od u ction
tive fragmentation of the PO controlled by remote car-
bonyl groups has not yet been demonstrated.2 We report
here the first observation of exclusive regioselective
fragmentation of primary ozonides controlled by remote
different carbonyl groups and stereoselective formation
of final ozonides on ozonolysis of norbornene derivatives.
Also, we wish to demonstrate that reaction of final
ozonides with triethylamine can act as a new method for
determining the regiochemistry of carbonyl oxide forma-
tion from PO fragmentation. Usually, ozonolysis in a
protic solvent, such as in methanol, is used to determine
the regiochemistry of carbonyl oxide formation from PO
fragmentation.2,4
Extensive investigation of the mechanism of alkene
ozonolysis has confirmed the essential features of the
pathway originally proposed by Criegee.1 Apart from the
long-established utility of ozonolysis in synthesis and
structure determination, much of the current interest in
this process centers on the factors affecting the direction
of cleavage of the primary ozonide (PO) and the nature
of the transient carbonyl oxide intermediate formed along
with a carbonyl group by fragmentation of the PO.2
Substituent effects on the regioselectivity of the PO
fragmentation have been reported in cases in which the
substituents are directly placed on the ozonation alkene
bond.3 The cleavage of the PO tends to occur along the
path which results in the placement of electron-donating
substituents on the carbonyl oxide fragment, while
electron-withdrawing substituents are incorporated in
the carbonyl product. To our knowledge, the regioselec-
Resu lts a n d Discu ssion
Oxidation of 2-methylfuran (1a ) (commercially avail-
able) with m-chloroperoxybenzoic acid (m-CPBA)5 in
dichloromethane at 0 °C gave the cis-enedione 2a . Di-
els-Alder reaction of 2a with cyclopentadiene at room
temperature gave the endo product 3a as major product
in 80% yield. Metalation6 of furan with n-BuLi in dry
tetrahydrofuran (THF) followed by addition of 1 equiv
X Abstract published in Advance ACS Abstracts, May 1, 1996.
(1) (a) Criegee, R.; Wenner, G. Ann. 1949, 564, 9. (b) Criegee, R.
Ann. 1953, 583, 1. (c) Criegee, R. Angew. Chem., Int. Ed. Engl. 1975,
11, 745.
(2) (a) Bailey, P. S. Ozonation in Organic Chemistry; Academic
Press: New York, 1978, Vol. 1; 1982, Vol. 2. (b) Bunnelle, W. H. Chem.
Rev. 1991, 91, 335. (c) McCullough, K. J .; Nojima, M. In Organic
Peroxides; Ando, W., Ed.; Wiley: New York, 1992. (d) Sander, W.
Angew. Chem., Int. Ed. Engl. 1990, 29, 344.
(3) (a) Fliszar, S.; Renard, J .; Simon, D. Z. J . Am. Chem. Soc. 1971,
93, 6953. (b) Griesbaum, K.; Greunig, H. J .; Volpp, W.; J ung, I. C.
Chem. Ber. 1991, 124, 947. (c) Griesbaum, K.; Zwick, G. Chem. Ber.
1986, 119, 229. (d) Griesbaum, K.; Zwick, G.; Agarwal, S.; Keul, H.;
Pfeffer, B.; Murray, R. W. J . Org. Chem. 1985, 50, 4194. (e)
Wojciechowski, B. J .; Chiang, C. Y.; Kuczkowski, R. L. J . Org. Chem.
1990, 55, 1120.
(4) (a) Griesbaum, K.; Kiesel, G. Chem. Ber. 1989, 122, 145. (b)
Paryzek, Z.; Martynow, J .; Swoboda, W. J . Chem. Soc., Perkin Trans.
1 1990, 1222. (c) Bunnelle, W. H.; Isbell, T. A. J . Org. Chem. 1992,
57, 729. (c) Teshima, K.; Kawamura, S. I.; Ushigoe, Y.; Nojima, M.;
McCullough, K. J . J . Org. Chem. 1995, 60, 4755.
(5) (a) Williams, P. D.; LeGoff, E. J . Org. Chem. 1981, 46, 4143. (b)
Williams, P. D.; LeGoff, E. Tetrahedron Lett. 1985, 26, 1367.
(6) (a) Ramanathan, V.; Levine, R. J . Org. Chem. 1962, 27, 1216.
(b) Gschwend, H. W.; Rodriguez, H. R. Org. React. 1979, 26, 31.
S0022-3263(95)02284-5 CCC: $12.00 © 1996 American Chemical Society

Regioselective Fragmentation of Primary Ozonides
J . Org. Chem., Vol. 61, No. 11, 1996 3821
Sch em e 1
Sch em e 3
n-BuLi
R–X
n-BuLi
R–X
THF
25 °C
1a, 1c
D
R
R
O
O
O
THF
25 °C
1b: R = n-C4H9
c: R = n-C8H17
d: R = CH2Ph
6a: R = CH3
b: R = n-C8H17
m-CPBA
CH2Cl2
O
O
6
m-CPBA
CH2Cl2
O
O
D
R
R
O
H
O
R
7
1
2
O
7 +
O
2 +
R
O
D
R
H
8
3
O
O
O3
Sch em e 2
O
O
O
O
O
O
8
O
CDCl3
–78 °C
O
D
R
O
O
R
D
O
O
O3
O
R
O
R
O
R
10
9
O
CDCl3
–78 °C
O
O
O
H
O
O
4
O
O
O
O
O
O
3a: R = CH3
O
b: R = n-C4H9
c: R = n-C8H17
d: R = CH2Ph
R
R
O
O
O
O
O
D
D
O
O
O
11
12
O
O
O
R
O
Sch em e 4
R
O
5
O
O
–O
+O
O
O3
O
O
4
3
of n-butyl bromide, n-octyl bromide, and benzyl bromide
at 25 °C for 4 h gave 2-n-butylfuran (1b), 2-n-octylfuran
(1c), and 2-benzylfuran (1d ) in 70-80% yields, respec-
tively. Compounds 3b, 3c, and 3d were prepared from
1b, 1c, and 1d in a similar sequence, Scheme 1.
CDCl3
or CH2Cl2
–78 °C
R
R
O
O
13
14
–O
+O
O
Ozonolysis of the endo adducts 3a -d in CDCl3 at -78
°C gave the final ozonides 4a -d as the sole product
(>95%) on the basis of their 1H and 13C NMR spectra,
O
5
O
R
1
respectively, Scheme 2. The H and 13C NMR spectra of
15
4a -d were taken at -30 °C right after the ozonation
process without purification. No detectable amount of
the isomeric final ozonides 5a -d was observed from the
1H and 13C NMR spectra of the crude products of the
ozonation reaction of compounds 3a -d . The 1H NMR
spectrum of 4a revealed two singlets at δ 6.45 and 5.70
for the 1,2,4-trioxolane ring protons and a singlet at δ
2.21 for the methyl ketone protons, consistent with
structure 4a rather than 5a . The 13C NMR spectrum of
4a showed two peaks (CH) at δ 103.7 and 101.6 for the
two tertiary bridgehead carbons of the 1,2,4-trioxolane
ring indicating that there is no quaternary carbon
present at the ozonide ring bridgehead.
In order to confirm the structure of the final ozonides
4 to be intramolecular cross ozonides, the deuterated
compounds 8a and 8b were prepared for ozonolysis study.
Metalation of methylfuran (1a ) and 2-n-octylfuran (1c)
with n-BuLi in THF followed by addition of D2O at 0 °C
gave the deuterated furans 6a and 6b in 80-85% yields,
respectively. Oxidation of 6a and 6b with m-CPBA in
dichloromethane at 0 °C gave the cis-endiones 7a and
7b in 75% yields, respectively. Diels-Alder reaction of
7a and 7b with cyclopentadiene at 25 °C gave the endo
adducts 8a and 8b as the major products in 85% yields,
respectively.
the sole product (>95%) respectively, Scheme 3. No
detectable amount of the isomeric final ozonides 10a and
10b was observed. The crude 1H NMR spectra of 9a and
9b revealed that the deuterium atom locates on the
bridgehead of the trioxolane ring rather than on the
aldehyde group. Thus, these experiments rule out the
possibility of the final ozonides being 11 or 12.
A mechanism is proposed for the exclusive formation
of the final ozonides 4 from ozonation of 3, Scheme 4.
1,3-Dipolar cycloaddition of an ozone molecule with the
alkene bond of 3 via the exo face gave the 1,2,3-trioxolane
13. A least-motion fragmentation7 of the 1,2,3-trioxolane
ring of the primary ozonides 13 affected by the carbonyl
groups led exclusively to the syn-oriented carbonyl oxides
14. Rapid intramolecular 1,3-dipolar cycloaddition of the
syn carbonyl oxide group of 14 with the endo formyl group
gave the final ozonides 4 with endo stereochemistry.
Since no detectable amount of the isomeric final ozonides
5 was obtained, formation of the isomeric carbonyl oxides
15 from 13 would be excluded. The exclusively regiose-
lective fragmentation of the primary ozonides 13 to form
(7) (a) Bailey, P. S.; Ferrell, T. M. J . Am. Chem. Soc. 1978, 100,
899. (b) Lattimer, R. P.; Kuczkowski, R. L.; Gillies, C. L. J . Am. Chem.
Soc. 1974, 96, 348. (c) Kuczkowski, R. L. 1,3-Dipolar Cycloaddition
Chemistry; Padwa, A., Ed.; Wiley: New York, 1984; pp 197-276. (d)
Cremer, D. J . Am. Chem. Soc. 1981, 103, 3619.
Ozonolysis of the deuterated endo adducts 8a and 8b
in CDCl3 at -78 °C gave the final ozonides 9a and 9b as

3822 J . Org. Chem., Vol. 61, No. 11, 1996
Wu and Lin
Sch em e 5
Sch em e 6
H
H
H
H
O
OH
O
OH
O
NEt3
O3
H
NEt3
H H
O
H H
9a, 9b
H
H
O
O
O
OH
O
CH2Cl2
–78 °C
O
O
O3
Et3N
H H
O
3a–d
O
D
O
R
D
R
CH2Cl2
O
O
R
19
20
H
R
O
O
16a–d
4a–d
The structure of the stereochemistry of the final
ozonides formed by ozonolysis of 3a -d in CH2Cl2 or
CDCl3 at -78 °C is deduced to be the endo isomer 4
instead of the exo isomer 18 (Scheme 5). If the final
ozonides were the isomers 18a -d , with an exo stereo-
chemistry, proton abstraction of the trioxolane ring
proton of 18 by triethylamine followed by heterolytic
cleavage of the peroxide bond could not give the observed
products 16a -d since the sequential nucleophilic addi-
tion of the newly-formed alkoxide ions to the carbonyl
groups is stereochemically impossible.
O
R
O
O
H
H
O
OH
HO
O
O
H H
O
O
R
O
H
R
O
O
H
H
O
O
17
18
the carbonyl oxides 14 is controlled by the two different
carbonyl groups. According to the above results, it is the
formyl group rather than the acyl group that induces the
space-closed trioxolane carbon to form the carbonyl oxide
group. If the fragmentation of the primary ozonides 13
was not preferentially controlled by the endo formyl
group, both the carbonyl oxides 14 and 15 should be
formed. Consequently, both the final ozonides 4 and 5
should be obtained. Since both the formyl group and the
acyl group are three σ bonds remote to the primary
ozonide ring, we propose here that the fragmentation of
the trioxolane ring of 13 is induced by the endo formyl
group through space rather than through bond. We also
propose that it is the oxygen atom of the formyl group
rather than the oxygen atom of the acyl group that adopts
a conformation in proximity to the 1,2,3-trioxolane ring
of 13.
Similarly, ozonolysis of 8a and 8b in dichloromethane
at -78 °C followed by reaction with triethylamine
exclusively gave the convex tetraquinane oxa cages 19a
and 19b in 85-90% yields, respectively, Scheme 6. No
detectable amount of the other regioisomers 20a and 20b
was obtained in both cases.
Ozonolysis of 3a -d in dichloromethane at -78 °C
followed by reduction with dimethyl sulfide gave the
tetraacetal oxa cage compounds 21a -d in 85-90% yields,
respectively. Electron donation from dimethyl sulfide to
the sterically less hindered oxygen atom of the endo
peroxide bond of the final ozonides followed by heterolytic
cleavage of the peroxide bond via 22A and sequential
nucleophilic addition of the newly-formed alkoxide ions
to the adjacent carbonyl groups gave the intermediates
22B or 22C. Loss of a neutral dimethyl sulfoxide
molecule from 22B or 22C followed by intramolecular
nucleophilic addition of the alkoxide ion to the oxonium
ion gave the tetraoxa cage compounds 21, Scheme 7.
Nevertheless, we cannot rule out the possibility that
reaction of 4 with dimethyl sulfide proceeded via 22E.
Similarly, oznolysis of 8a and 8b under the same reaction
conditions gave the deuterated tetraacetal oxa cages 23a
and 23b in 85% yields, respectively.
Ozonolysis of 3a -d in dichloromethane at -78 °C
followed by reaction with triethylamine regioselectivity
gave the convex tetraquinane oxa cage compounds 16a -d
in 85-90% yields, respectively, Scheme 5. No detectable
amount of the other regioisomers 17a -d was obtained
in each case. These results indicate that ozonolysis of
3a -d in CH2Cl2 or CDCl3 at -78 °C exclusively gives
the corresponding final ozonides 4a -d , which, in reaction
with triethylamine, give 16a -d as the sole products,
respectively. The regiochemistry of the angular alkyl
groups of 16a -d was assigned by H-H COSY 2D
spectral analysis. A mechanism is proposed for formation
of 16 from 4, Scheme 5. Proton abstraction of the
trioxolane ring proton of 4 by triethylamine followed by
heterolytic cleavage of the peroxide bond and sequential
nucleophilic addition of the newly-formed alkoxide ions
to the adjacent carbonyl groups gave the sole product 16.
If both the isomeric final ozonides 4 and 5 were formed
from ozonolysis of 3, both isomeric compounds 16 and
17 should be obtained via reaction of triethylamine with
4 and 5. These experimental results support the regi-
oselective fragmentation of primary ozonides, shown as
Scheme 2. Thus, we have demonstrated for the first time
that ozonolysis of alkenes in CH2Cl2 at -78 °C followed
by treatment with triethylamine can act as a new probe
to determine the regiochemistry of carbonyl oxide forma-
tion from fragmentation of primary ozonide. Usually,
ozonolysis of alkenes in a protic solvent, such as in
methanol, is used to determine the regiochemistry of
carbonyl oxide formation because the structures of the
solvent-derived products provide direct information on
the mode of interaction of a carbonyl oxide with the
solvent, and the product composition reflects the regi-
oselectivity in the primary ozonides cleavage.2,4
In the reaction of final ozonides with triethylamine,
Razumovskii et al.8 reported that an oxidation-reduction
electron transfer process occurred between the amine and
the ozonides. In our experimental results, reaction of the
final ozonides 4 and 9 with triethylamine gave the convex
tetraquinane oxa cages 16 and 19 whereas reaction of
the final ozonides 4 and 9 with dimethyl sulfide gave the
tetraacetal oxa cages 21 and 23. Thus, our result
indicated that the reaction between the final ozonides and
triethylamine proceeded via an acid-base proton transfer
process.9 In other words, triethylamine acts as a base
rather than as a reducing agent in the reaction with final
ozonides if there is at least one proton present at the final
ozonide ring.
To determine the relative ability between a thioester
group and a ketone or aldehyde carbonyl group to control
the fragmentation of the primary ozonides, we prepared
(8) (a) Razumovskii, S. D.; Zaikov, G. E. Ozone and its Reaction with
Organic Compounds; Elsevier: The Netherlands, 1984; Chapter 9, p
370. (b) Pobedimskii, D. G.; Razumovskii, S. D. Izv. Akad. Nauk SSSR,
Ser. Khim 1970, 3, 602; Chem. Abstr. 1970, 73, 13853n.
(9) Hon, Y. S.; Yan, J . L. Tetrahedron Lett. 1993, 34, 6591.

Regioselective Fragmentation of Primary Ozonides
J . Org. Chem., Vol. 61, No. 11, 1996 3823
Sch em e 7
O
Me2S+ O–
O
–O
Me2S+
Me2S
O
O
O
O3
Me2S
O
3a–d
4
–O
–Me2S
O
CH2Cl2
–78 °C
R
R
O
R
or
O
O
+O
O
R
O
O
O
O
O
22D
22A
22B
22C
O
Me2S+
O
O
–O
O
O
O
R
Me2S
R
O3
O
O
R
8a, 8b
9
O
CH2Cl2
–78 °C
O
D
O
O
21a: R = CH3
22E
23a: R = CH3
b: R = n-C4H9
c: R = n-C8H17
d: R = CH2Ph
b: R = n-C4H17
Sch em e 8
O
O
–O
+O
O
O
O
O
O3
O3
O
O
O
R
O
CDCl3
or CH2Cl2
–78 °C
24
O
O
O
O
O
O
CDCl3
–78 °C
SCH3
SCH3
O
O
R
SCH3
R
SCH3
SCH3
O
R
O
R
24a: R = H
b: R = CH3
27
28
26
25
O
Me2S
SCH3
27
O
O
O
R
29a: R = H
b: R = CH3
Sch em e 9
compounds 24a and 24b from furan and 2-methylfuran,10
respectively. Ozonolysis of 24a and 24b in CDCl3 at -78
°C exclusively gave the final ozonides 27a and 27b,
respectively. No detectable amount of the isomeric final
PCC
O
OCH3
CH2Cl2
O
OMe
1
ozonides 28a and 28b was observed from the H and 13C
O
NMR spectra of the crude products of the ozonolysis of
compounds 24a and 25b, Scheme 8. 1,3-Dipolar cycload-
dition of an ozone molecule with the alkene bond of 24
gave the PO 25. A least-motion fragmentation of the
1,2,3-trioxolane ring of 25 controlled by the carbonyl
groups rather than by the thioester group led exclusively
to the carbonyl oxide 26. Intramolecular 1,3-dipolar
cycloaddition of the carbonyl oxide group of 26 with the
endo acyl group gave the final ozonide 27. According to
the above results, it is the formyl group and the acetyl
group rather than the thioester group that induces the
space-closed trioxolane carbon of 25 to form the carbonyl
oxide group. Thus, the order of the preference of various
carbonyl groups to control through space the fragmenta-
tion of the primary ozonides formed by ozonolysis of
norbornene derivatives is as follow: aldehyde carbonyl
> ketone carbonyl > thioester. Ozonolysis of 24a and
24b in CH2Cl2 at -78 °C followed by reduction with
dimethyl sulfide gave the tetraacetal oxa cage compounds
29a and 29b in 65-70% yields, respectively.10
32a
O
hv (300 nm)
EtOH
R
O
O
OR′
O
OR′
R
30
31
31
O
OR′
O
R
32b: R = R′ =CH3
c: R = Ph, R′ = Et
cially available) with pyridinium dichlorochromate (PCC)
in dichloromethane at 25 °C followed by addition of
cyclopentadiene gave the endo adduct 32a as major
product in 50% yield. Photoisomerization of compounds
30b and 30c (commercially available) with ultraviolet
light (300 nm) in absolute ethanol at 25 °C gave the cis
isomers 31b and 31c in 60% and 80% yields, respectively.
Diels-Alder reaction of 31b and 31c with cyclopentadi-
ene at room temperature gave the endo adducts 32b and
32c as major products, Scheme 9.
Ozonolysis of the endo adduct 32a in CDCl3 at -78 °C
gave the final ozonides 33a and 34a in a ratio of 85:15,
Scheme 10. On the other hand, ozonolysis of 32b in
CDCl3 at -78 °C gave the final ozonides 33b and 34b in
a ratio of 30:70. Ozonolysis of 32c in CDCl3 at -78 °C
To determine the relative ability between an ester
group and carbonyl group to control the fragmentation
of the primary ozonides, we prepared compounds 32a ,
32b, and 32c. Oxidation of 2-methoxyfuran (commer-
(10) (a) Wu, H. J .; Huang, F. J .; Lin, C. C. J . Chem. Soc., Chem.
Commun. 1991, 770. (b) Wu, H. J .; Lin, C. C.; Huang, F. J .; Lin, J . C.
Submitted for publication.

3824 J . Org. Chem., Vol. 61, No. 11, 1996
Wu and Lin
Sch em e 10
the tetraacetal oxa cages 35a -c, which possess an
alkoxyl group directly on the skeleton, has been ac-
complished. Ozonolysis of the endo esters 32b and 32c
followed by reductive workup afforded the triacetal oxa
cages 36b and 36c in addition to the tetraacetal oxa cages
35b and 35c, respectively. The structures of novel
triacetal oxa cages are proven for the first time by X-ray
analysis of the crystalline compound 36c.
O
O
O
O
R
O
O
R′O
O3
32
CDCl3
–78 °C
R′O
R
O
O
O
O
33
34
a: R = H, R′ =CH3
b: R = R′ = CH3
c: R = Ph, R′ = Et
Exp er im en ta l Section
Gen er a l. Melting points were determined in capillary
tubes with a Laboratory Devices melting point apparatus and
uncorrected. Infrared spectra were recorded in CHCl3 solu-
tions or on neat films between NaCl disks. 1H NMR spectra
were determined at 300 MHz, and 13C NMR were determined
at 75 MHz on Fourier transform spectrometers. Chemical
shifts are reported in ppm relative to TMS in the solvents
specified. The multiplicities of 13C signals were determined
by DEPT techniques. High-resolution mass values were
obtained with a high-resolution mass spectrometer at the
Department of Chemistry, National Tsing Hua University.
X-ray analyses were carried out on a diffractometer at the
Department of Chemistry, National Chung Hsing University.
For thin-layer chromatography (TLC) analysis, precoated TLC
plates (Kieselgel 60 F254) were used, and column chromatog-
raphy was done by using Kieselgel 60 (70-230 mesh) as the
stationary phase. THF was distilled immediately prior to use
from sodium benzophenone ketyl under nitrogen. CH2Cl2 was
distilled from CaH2 under nitrogen.
Sch em e 11
O
Me2S
O3
32a
OCH3
O
CH2Cl2
–78 °C
O
O
35a
O
O
Me2S
O3
32b, 32c
O
OR′
O
CH2Cl2
–78 °C
+
O
O
OR′
O
O
R
R
36b: R = R′ =CH3
36c: R = Ph, R′ = Et
35b: R = R′ =CH3
35c: R = Ph, R′ = Et
gave 33c and 34c in a ratio of 25:75. These results may
indicate that the ability of an ester group to affect the
primary ozonide fragmentation to form a carbonyl oxide
group is in between that of an aldehyde carbonyl group
and a ketone carbonyl group.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2-Alk yl-
fu r a n s 1b-d . To a solution of furan (2.0 g, 24.4 mmol) in
dry THF (40 mL) was added n-BuLi (10.2 mL, 25.6 mmol) at
0 °C. The reaction mixture was stirred at room temperature
for 4 h. To this solution was added n-butyl bromide (4.1 g,
24.4 mmol) at 0 °C, and the reaction mixture was stirred at
room temperature for 4 h. After addition of saturated NH4Cl
(20 mL) and extraction with ether (3 × 30 mL), the organic
layer was washed with brine, dried over MgSO4, and evapo-
rated, and the residue was purified by column chromatography
to give 1b: pale yellow oil; yield 85%; IR (neat) 2980, 2940,
Ozonolysis of 32a in CH2Cl2 at -78 °C followed by
reduction with dimethyl sulfide gave the tetraacetal oxa
cage compound 35a in 70% yield, Scheme 11. Ozonolysis
of 32b in CH2Cl2 at -78 °C followed by reduction with
dimethyl sulfide gave the tetraacetal oxa cage 35b (66%)
and the triacetal oxa cage 36b (9%). Ozonolysis of 32c
under the same reaction conditions gave 35c (67%) and
36c (8%). Thus, we have achieved for the first time the
synthesis of tetraacetal tetraoxa cage compounds 35a -
c, which possess an alkoxyl group directly on the skel-
eton. The structure of the novel triacetal trioxa cage
compounds is proven for the first time by X-ray single-
crystal analysis of the crystalline compound 36c.
1
2880, 2870, 1610 cm-1; H NMR (300 MHz, CDCl3) δ 7.25 (d,
J ) 1.0 Hz, 1H), 6.24 (dd, J ) 2.7 Hz, J ) 1.0 Hz, 1H), 5.94 (d,
J ) 2.7 Hz, 1H), 2.60 (t, J ) 7.5 Hz, 2H), 1.66-1.56 (m, 2H),
1.42-1.31 (m, 2H), 0.92 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 156.53 (C), 140.57 (CH), 109.95 (CH), 104.44 (CH),
30.08 (CH2), 29.76 (CH2), 22.19 (CH2), 13.77 (CH3); LRMS m/z
(rel inten) 124 (M+, 100).
The same reaction conditions and procedure were applied
to the preparation of 1c and 1d .
2-n -Octylfu r a n (1c): pale yellow oil; yield 90%; IR (neat)
2980, 2940, 2880, 2870, 1610 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.28 (brs, 1H), 6.26 (brs, 1H), 5.96 (d, J ) 2.1 Hz, 1H), 2.61
(t, J ) 7.8 Hz, 2H), 1.65-1.60 (m, 2H), 1.42-1.15 (m, 10H),
0.97-0.85 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 156.60 (C),
140.58 (CH), 109.98 (CH), 104.48 (CH), 31.84 (CH2), 29.33
(CH2), 29.22 (CH2), 29.10 (CH2), 28.02 (CH2), 27.96 (CH2), 22.66
(CH2), 14.07 (CH3); LRMS m/z (rel inten) 138 (M+, 100).
2-Ben zylfu r a n (1d ): pale yellow oil; yield 89%; IR (neat)
Con clu sion
In summary, we have reported the first exclusive
regioselective fragmentation of primary ozonides con-
trolled by remote carbonyl groups on ozonolysis of nor-
bornene derivatives. To account for the exclusive regi-
oselective fragmentation of the primary ozonides, we
propose that the conformation of the endo formyl and acyl
groups may play an important role. The order of the
preference of various carbonyl groups to control through
space the fragmentation of the primary ozonides formed
by ozonolysis of norbornene derivatives is as follows:
aldehyde carbonyl > ketone carbonyl > thioester. The
ability of an ester group to control the fragmentation of
the primary ozonides may be compared to that of ketone
carbonyl group. We have also demonstrated for the first
time that reaction of final ozonide with triethylamine can
act as a probe to determine the regiochemistry of carbonyl
oxide formation from fragmentation of a primary ozonide.
In reaction with the final ozonides, triethylamine is found
to act as a base instead of a reducing agent, a different
function from that of dimethyl sulfide. The synthesis of
3010, 2980, 2885, 1620 cm-1 1H NMR (300 MHz, CDCl3) δ
;
7.32-7.21 (m, 6H), 6.28 (d, J ) 1.5 Hz, 1H), 5.99 (brs, 1H),
3.97 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 154.53 (C), 141.45
(CH), 138.10 (C), 128.66 (2CH), 128.46 (2CH), 126.46 (CH),
110.22 (CH), 106.20 (CH), 34.43 (CH2); LRMS m/z (rel inten)
180 (M+, 100).
Gen er a l P r oced u r e for th e Oxid a tion of 2-Alk ylfu r a n s
1a -d w ith m -Ch lor op er oxyben zoic Acid (m -CP BA). To
a solution of 2-methylfuran (2.0 g, 24.4 mmol) in dichlo-
romethane (180 mL) was added m-CPBA (4.2 g, 24.4 mmol)
at 0 °C. The reaction mixture was stirred at 0 °C for 30 min.
To this solution was added saturated Na2CO3 (50 mL). After
separation, the water layer was extracted with dichlo-
romethane (3 × 40 mL). The combined organic layer was
washed with brine, dried over MgSO4, and evaporated to give
2a (0.9 g, 75%). Compounds 2a -d were used for the next step,
a Diels-Alder reaction, without purification, since 2a -d were

Regioselective Fragmentation of Primary Ozonides
J . Org. Chem., Vol. 61, No. 11, 1996 3825
1H), 3.15 (brs, 1H), 2.98-2.92 (m, 1H), 1.53-1.35 (m, 2H); 13
sensitive to cis-trans isomerization upon heat or silica gel
treatment. Spectral data for 2a : IR (CHCl3) 2920, 2860, 1770,
1720 cm-1; 1H NMR (300 MHz, CDCl3) δ 10.19 (d, J ) 7.2 Hz,
1H); 7.02 (d, J ) 11.7 Hz, 1H), 6.18 (dd, J ) 11.7 Hz, J ) 7.2
Hz, 1H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ
198.21 (CdO), 192.29 (CHO), 140.31 (CH), 137.37 (CH), 30.47
(CH3); LRMS m/z (rel inten) 98 (M+, 18), 81 (57), 69 (100).
(Z)-2-Octen e-1,4-d ion e (2b): IR (CHCl3) 2930, 2870, 1770,
1720 cm-1; 1H NMR (300 MHz, CDCl3) δ 10.21 (d, J ) 7.2 Hz,
1H), 6.95 (d, J ) 12.3 Hz, 1H), 6.16 (dd, J ) 12.3 Hz, J ) 7.2
Hz, 1H), 2.64 (t, J ) 7.5 Hz, 2H), 1.73-1.42 (m, 4H), 0.91 (t,
J ) 5.6 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 200.61
(CdO), 192.30 (CHO), 140.28 (CH), 137.56 (CH), 43.61 (CH2),
31.81 (CH2), 24.15 (CH2), 13.63 (CH3); LRMS m/z (rel inten)
140 (M+, 100).
C
NMR (75 MHz, CDCl3, DEPT) δ 206.40 (CdO), 202.70 (CHO),
136.09 (CH), 133.90 (CH), 133.61 (C), 129.27 (2CH), 128.60
(2CH), 127.03 (CH), 58.62 (CH), 55.88 (CH), 49.18 (CH2), 48.68
(CH2), 47.49 (CH), 45.36 (CH); LRMS m/z (rel inten) 240 (M+,
30), 143 (65), 105 (100); HRMS (EI) calcd for C16H16O2
240.1150, found 240.1131.
1
Ta k in g th e H a n d 13C NMR Sp ectr a l Da ta of th e F in a l
Ozon id es 4a -d . The solution of 3a (0.050 g, 0.3 mmol) in
CDCl3 (1.0 mL) was cooled to -78 °C, and ozone was bubbled
through it at -78 °C until the solution turned light blue. The
solution was then transferred to an NMR tube, and the 1H
and 13C NMR spectra were taken at -30 °C. Spectral data
for 4a : 1H NMR (300 MHz, CDCl3) δ 9.47 (s, 1H), 6.45 (s, 1H),
5.70 (s, 1H), 3.13-3.07 (m, 1H), 2.94 (dd, J ) 7.8 Hz, J ) 7.5
Hz, 1H), 2.83 (dd, J ) 6.9 Hz, J ) 7.2 Hz, 1H), 2.75-2.69 (m,
1H), 2.67-2.01 (m, 2H), 2.20 (s, 3H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 205.29 (CdO), 200.71 (CHO), 103.64 (CH), 101.55
(CH), 56.20 (CH), 52.82 (CH), 47.48 (CH), 44.99 (CH), 29.40
(CH3), 28.19 (CH2).
(Z)-2-Dod ecen e-1,4-d ion e (2c): IR (CHCl3) 2930, 2860,
1
1770, 1720 cm-1; H NMR (300 MHz, CDCl3) δ 10.22 (d, J )
7.2 Hz, 1H), 6.96 (d, J ) 12.6 Hz, 1H), 6.18 (dd, J ) 12.6 Hz,
J ) 7.2 Hz, 1H), 2.63 (t, J ) 7.5 Hz, 2H), 1.71-1.63 (m, 2H),
1.42-1.22 (m, 10H), 0.88 (t, J ) 5.7 Hz, 3H); 13C NMR (75
MHz, CDCl3, DEPT) δ 200.74 (CdO), 192.53 (CHO), 140.26
(CH), 137.75 (CH), 43.58 (CH2), 31.69 (CH2), 29.22 (CH2), 29.13
(CH2), 28.98 (CH2), 23.53 (CH2), 22.54 (CH2), 13.98 (CH3);
LRMS m/z (rel inten) 196 (M+, 15), 141 (100).
Spectral data for 4b: 1H NMR (300 MHz, CDCl3) δ 9.45 (s,
1H), 6.50 (s, 1H), 5.74 (s, 1H), 3.20-3.15 (m, 1H), 2.95-2.72
(m, 3H), 2.57-2.16 (m, 4H), 1.61-1.51 (m, 2H), 1.28-1.22 (m,
2H), 0.85 (t, J ) 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT)
δ 208.70 (CdO), 201.91 (CHO), 103.43 (CH), 101.62 (CH), 54.51
(CH), 52.70 (CH), 46.61 (CH), 43.96 (CH), 41.34 (CH2), 27.67
(CH2), 25.60 (CH2), 22.11 (CH2), 14.07 (CH3).
(Z)-4-Ben zyl-2-p en ten e-1,4-d ion e (2d ): IR (CHCl3) 2950,
1
2850, 1760, 1730 cm-1; H NMR (300 MHz, CDCl3) δ 9.98 (d,
J ) 7.3 Hz, 1H), 7.37-7.18 (m, 5H), 6.97 (d, J ) 12.3 Hz, 1H),
6.21 (dd, J ) 12.3 Hz, J ) 7.3 Hz, 1H), 3.68 (brs, 2H); 13C
NMR (75 MHz, CDCl3, DEPT) δ 200.50 (CdO), 193.15 (CHO),
141.32 (CH), 138.61 (CH), 134.65 (C), 129.51 (2CH), 128.41
(2CH), 127.67 (CH), 49.81 (CH2); LRMS m/z (rel inten) 174
(M+, 100).
Spectral data for 4c: 1H NMR (300 MHz, CDCl3) δ 9.47 (s,
1H), 6.48 (s, 1H), 5.69 (s, 1H), 3.05 (dd, J ) 8.7 Hz, J ) 2.1
Hz, 1H), 2.97 (dd, J ) 7.8 Hz, J ) 7.8 Hz, 1H), 2.83 (dd, J )
6.9 Hz, J ) 7.4 Hz, 1H), 2.74-2.68 (m, 1H), 2.52-2.10 (m,
4H), 1.62-1.57 (m, 2H), 1.36-1.17 (m, 10H), 0.84 (t, J ) 6.3
Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 208.56 (CdO),
200.89 (CHO), 103.66 (CH), 101.62 (CH), 55.24 (CH), 52.82
(CH), 47.63 (CH), 44.95 (CH), 42.15 (CH2), 31.78 (CH2), 29.36
(CH2), 29.16 (CH2), 29.07 (CH2), 28.25 (CH2), 23.91 (CH2), 22.57
(CH2), 14.04 (CH3).
Gen er a l P r oced u r e for th e Diels-Ald er Rea ction of
2a -d w ith Cyclop en ta d ien e. To a solution of 2a (2.0 g, 20.4
mmol) in dichloromethane (3 mL) was added 1,3-cyclopenta-
diene (2.69 g, 40.8 mmol) at 25 °C. The reaction mixture was
stirred at 25 °C for 2 h. The solvent was evaporated and the
crude product was purified by column chromatography to give
the endo adduct 3a as major product (2.6 g, 14.6 mmol, 82%).
Spectral data for 4d : 1H NMR (300 MHz, CDCl3) δ 9.50 (s,
1H), 7.41-7.17 (m, 5H), 6.51 (s, 1H), 5.71 (s, 1H), 3.78 (ABq,
J ) 16.2 Hz, δA 3.85, δB 3.71, 2H), 3.12-3.00 (m, 2H), 2.79-
2.66 (m, 2H), 2.26-2.06 (m, 2H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 205.61 (CdO), 201.27 (CHO), 134.02 (C), 129.36
(2CH), 128.72 (2CH), 127.14 (CH), 103.60 (CH), 101.59 (CH),
54.07 (CH), 52.79 (CH), 49.18 (CH2), 47.54 (CH), 44.63 (CH),
28.05 (CH2).
Gen er a l P r oced u r e for th e P r ep a r a tion of 2-Deu ter io-
5-a lk ylfu r a n s 6a a n d 6b. To a solution of 2-octylfuran (2.0
g, 11.1 mmol) in dry THF (40 mL) was added 2.5 M m-BuLi
(4.8 mL, 12.1 mmol) at 0 °C. The reaction mixture was stirred
at room temperature for 4 h. To this solution was added D2O
(0.3 g, 16.8 mmol) at 0 °C, and the reaction mixture was stirred
at room temperature for 1 h. After addition of saturated NH4-
Cl (20 mL) and extraction with ether (3 × 30 mL), the organic
layer was washed with brine, dried over MgSO4, and evapo-
rated, and the residue was purified by column chromatography
to give 6b: Spectral data for 6b: pale yellow oil; yield 87%;
1H NMR (300 MHz, CDCl3) δ 6.26 (d, J ) 2.7 Hz, 1H), 5.96 (d,
J ) 2.7 Hz, 1H), 2.60 (t, J ) 8.1 Hz, 2H), 1.68-1.58 (m, 2H),
1.40-1.22 (m, 10H), 0.96-0.83 (s, 3H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 156.51 (C), 139.75 (CD), 109.75 (CH), 104.45
(CH), 31.93 (CH2), 31.84 (CH2), 29.33 (CH2), 29.22 (CH2), 28.02
(CH2), 27.96 (CH2), 22.66 (CH2), 14.07 (CH3).
Spectral data for 3a : IR (CHCl3) 2925, 2840, 1710 cm-1; H
1
NMR (300 MHz, CDCl3) δ 9.47 (d, J ) 3.3 Hz, 1H), 6.41 (dd,
J ) 6.0 Hz, J ) 2.7 Hz, 1H), 6.11 (dd, J ) 6.0 Hz, J ) 2.7 Hz,
1H), 3.68 (dd, J ) 9.8 Hz, J ) 3.6 Hz, 1H), 3.36 (brs, 1H), 3.17
(brs, 1H), 3.02-2.96 (m, 1H), 2.17 (s, 3H), 1.60-1.42 (m, 2H);
13C NMR (75 MHz, CDCl3, DEPT) δ 206.75 (CdO), 202.99
(CHO), 136.44 (CH), 133.70 (CH), 60.36 (CH), 55.73 (CH),
47.31 (CH), 45.53 (CH), 29.62 (CH2), 28.75 (CH3); LRMS m/z
(rel inten) 164 (M+, 4), 98 (36), 66 (100); HRMS (EI) calcd for
C10H12O2 164.0837, found 164.0837.
Spectral data for 3b: IR (CHCl3) 2920, 2840, 1710 cm-1; 1H
NMR (300 MHz, CDCl3) δ 9.46 (d, J ) 3.3 Hz, 1H), 6.40 (dd,
J ) 5.6 Hz, J ) 2.7 Hz, 1H), 6.06 (dd, J ) 5.6 Hz, J ) 3.0 Hz,
1H), 3.68 (dd, J ) 9.5 Hz, J ) 3.9 Hz, 1H), 3.34 (brs, 1H), 3.17
(brs, 1H), 3.00-2.94 (m, 1H), 1.58-1.25 (m, 6H), 0.90 (t, J )
7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 209.11 (CdO),
203.02 (CHO), 136.24 (CH), 133.79 (CH), 59.69 (CH), 55.76
(CH), 49.35 (CH2), 47.43 (CH), 45.45 (CH), 41.05 (CH2), 25.63
(CH2), 22.17 (CH2), 13.74 (CH3); LRMS m/z (rel inten) 206 (M+,
7), 150 (100); HRMS (EI) calcd for C13H18O2 206.1307, found
206.1309.
Spectral data for 3c: IR (CHCl3) 2920, 2840, 1710 cm-1; 1H
NMR (300 MHz, CDCl3) δ 9.46 (d, J ) 3.3 Hz, 1H), 6.40 (dd,
J ) 5.4 Hz, J ) 3.0 Hz, 1H), 6.06 (dd, J ) 5.4 Hz, J ) 2.7 Hz,
1H), 3.68 (dd, J ) 9.3 Hz, J ) 3.3 Hz, 1H), 3.34 (brs, 1H), 3.17
(brs, 1H), 3.00-2.94 (m, 1H), 2.44 (t, J ) 6.9 Hz, 2H), 1.58-
F or m a tion of 7a a n d 7b. The same reaction conditions
and procedure for the synthesis of 2a -d from the oxidation of
1a -d were applied to the oxidation of 6a and 6b. Compounds
7a and 7b were used for the next step, a Diels-Alder reaction,
without purification, since 7a and 7b were sensitive to cis-
trans isomerization upon heat or silica gel treatment. Spectral
data for 7a : pale yellow oil; yield 78%; IR (CHCl3) 2925, 2860,
1.32 (m, 4H), 1.35-1.22 (m, 10H), 0.87 (t, J ) 6.9 Hz, 3H); 13
C
NMR (75 MHz, CDCl3, DEPT) δ 209.11 (CdO), 202.99 (CHO),
136.26 (CH), 133.82 (CH), 59.69 (CH), 55.79 (CH), 49.38 (CH2),
47.46 (CH), 45.50 (CH), 41.40 (CH2), 31.72 (CH2), 29.30 (CH2),
29.13 (CH2), 29.04 (CH2), 23.59 (CH2), 22.54 (CH2), 14.01 (CH3);
LRMS m/z (rel inten) 262 (M+, 52), 141 (100); HRMS (EI) calcd
for C17H26O2 262.1933, found 262.1942.
1
1770, 1720 cm-1; H NMR (300 MHz, CDCl3) δ 7.01 (d, J )
11.7 Hz, 1H), 6.19 (d, J ) 11.7 Hz, 1H), 2.41 (s, 3H); 13C NMR
(75 MHz, CDCl3, DEPT) δ 198.56 (CdO), 192.31 (CDO), 140.20
(CH), 137.65 (CH), 30.47 (CH3); LRMS m/z (rel inten) 99 (M+,
21), 82 (59), 70 (100).
Spectral data for 3d : IR (CHCl3) 2980, 1775, 1720 cm-1
;
1H NMR (300 MHz, CDCl3) δ 9.44 (d, J ) 3.0 Hz, 1H), 7.36-
7.17 (m, 5H), 6.36 (dd, J ) 5.4 Hz, J ) 3.0 Hz, 1H), 5.99 (dd,
J ) 5.7 Hz, J ) 3.0 Hz, 1H), 3.76-3.68 (m, 3H), 3.28 (brs,
Spectral data for 7b: pale yellow oil; yield 78%; IR (CHCl3)
2930, 2860, 1770, 1720 cm-1 1H NMR (300 MHz, CDCl3) δ
;

3826 J . Org. Chem., Vol. 61, No. 11, 1996
Wu and Lin
6.98 (d, J ) 12.6 Hz, 1H), 6.19 (d, J ) 12.6 Hz, 1H), 2.63 (t, J
) 7.5 Hz, 2H), 1.73-1.63 (m, 2H), 1.42-1.21 (m, 10H), 0.88
(t, J ) 5.7 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 200.53
(CdO), 192.63 (CDO), 140.14 (CH), 137.45 (CH), 43.19 (CH2),
31.58 (CH2), 29.32 (CH2), 29.03 (CH2), 28.77 (CH2), 23.46 (CH2),
22.38 (CH2), 13.98 (CH3); LRMS m/z (rel inten) 197 (M+, 14),
142 (100).
178.31 (CdO), 121.84 (C), 106.69 (CH), 104.18 (CH), 57.36
(CH), 52.53 (CH), 51.83 (CH), 46.84 (CH), 38.34 (CH2), 36.79
(CH2), 26.16 (CH2), 22.63 (CH2), 13.92 (CH3); LRMS m/z (rel
inten) 254 (M+, 11), 197 (49), 166 (100); HRMS (EI) calcd for
C13H18O5 254.1154, found 254.1154.
Spectral data for 16c: white waxy solid; yield 88%; mp 110-
111 °C; IR (CHCl3) 3500-3300, 2920, 1775 cm-1; 1H NMR (300
MHz, CDCl3) δ 6.00 (d, J ) 5.7 Hz, 1H), 5.24 (d, J ) 2.7 Hz,
1H), 3.68-3.59 (m, 1H), 3.33 (dd, J ) 8.7 Hz, J ) 8.7 Hz, 1H),
3.13 (dd, J ) 9.6 Hz, J ) 8.7 Hz, 1H), 2.71-2.30 (m, 3H), 1.98-
Diels-Ald er Rea ction of 7a a n d 7b w ith Cyclop en ta -
d ien e. The same reaction conditions and procedure as for the
synthesis of 3a -d from the Diels-Alder reaction of 2a -d were
applied to the Diels-Alder reaction of 7a and 7b. Spectral
data for 8a : pale yellow oil; yield 84%; IR (CHCl3) 2920, 2840,
1.76 (m, 2H), 1.46-1.14 (m, 13H), 0.83 (t, J ) 5.7 Hz, 3H); 13
C
NMR (75 MHz, CDCl3, DEPT) δ 178.54 (CdO), 121.70 (C),
106.75 (CH), 104.10 (CH), 57.22 (CH), 52.50 (CH), 51.83 (CH),
46.84 (CH), 38.57 (CH2), 36.68 (CH2), 31.75 (CH2), 29.51 (CH2),
29.39 (CH2), 29.13 (CH2), 24.00 (CH2), 22.54 (CH2), 13.98 (CH3);
LRMS m/z (rel inten) 310 (M+, 2), 197 (100); HRMS (EI) calcd
for C17H26O5 310.1780, found 310.1780.
1
1710 cm-1; H NMR (300 MHz, CDCl3) δ 6.42-6.39 (m, 1H),
6.12-6.09 (m, 1H), 3.69 (dd, J ) 8.7 Hz, J ) 3.6 Hz, 1H), 3.37
(brs, 1H), 3.17 (brs, 1H), 2.98 (dd, J ) 8.8 Hz, J ) 3.0 Hz,
1H), 2.17 (s, 3H), 1.59-1.43 (m, 2H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 206.83 (CdO), 202.75 (CDO), 136.44 (CH), 133.64
(CH), 60.36 (CH), 55.53 (CH), 49.35 (CH), 47.28 (CH), 45.47
(CH2), 28.69 (CH3); LRMS m/z (rel inten) 165 (M+, 12), 139
(100); HRMS (EI) calcd for C10H11DO2 165.0897, found 165.0896.
Spectral data for 8b: pale yellow oil; yield 80%; IR (CHCl3)
2920, 2840, 1720 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.40 (dd,
J ) 5.6 Hz, J ) 2.4 Hz, 1H), 6.06 (dd, J ) 5.1 Hz, J ) 2.4 Hz,
1H), 3.68 (dd, J ) 9.5 Hz, J ) 3.9 Hz, 1H), 3.34 (brs, 1H), 3.16
(brs, 1H), 2.96 (dd, J ) 9.5 Hz, J ) 3.0 Hz, 1H), 2.45 (t, J )
7.2 Hz, 2H), 1.61-1.22 (m, 14H), 0.89-0.83 (m, 3H); 13C NMR
(75 MHz, CDCl3, DEPT) δ 209.11 (CdO), 202.64 (CDO), 136.29
(CH), 133.73 (CH), 59.69 (CH), 55.59 (CH), 49.35 (CH2), 47.43
(CH), 45.42 (CH), 41.31 (CH2), 31.69 (CH2), 29.27 (CH2), 29.07
(CH2), 29.01 (CH2), 23.53 (CH2), 22.52 (CH2), 13.98 (CH3);
LRMS m/z (rel inten) 263 (M+, 38), 142 (100); HRMS (EI) calcd
for C17H25DO2 263.1992, found 263.1988.
Spectral data for 16d : white waxy solid; yield 84%; mp 192-
193 °C; IR (CHCl3) 3500-3300, 1760, 1080 cm-1; 1H NMR (300
MHz, CD3COCD3) δ 7.33-7.20 (m, 5H), 5.92 (d, J ) 6.3 Hz,
1H), 4.99 (d, J ) 3.0 Hz, 1H), 3.51-3.01 (m, 7H), 2.34-2.18
(m, 2H); 13C NMR (75 MHz, CD3COCD3, DEPT) δ 178.98
(CdO), 136.41 (C), 130.55 (CH), 127.87 (2CH), 126.44 (2CH),
119.33 (C), 106.46 (CH), 103.66 (CH), 56.43 (CH), 52.09 (CH),
51.77 (CH), 46.61 (CH), 44.10 (CH2), 35.60 (CH2); LRMS m/z
(rel inten) 288 (M+, 2), 271 (100); HRMS (EI) calcd for C16H16O5
288.0998, found 288.0997.
Syn th esis of th e Tetr a qu in a n e Oxa Ca ge Com p ou n d s
19a a n d 19b. The same reaction conditions and procedure
as for the synthesis of 16a -d from the ozonolysis of 3a -d were
applied to the ozonolysis of 8a a n d 8b. Spectral data for
19a : white waxy solid; yield 89%; mp 170-171 °C; IR (KBr)
3500-3300, 2950, 1770 cm-1; 1H NMR (300 MHz, CD3COCD3)
δ 5.46 (d, J ) 4.5 Hz, 1H), 5.15 (dd, J ) 4.5 Hz, J ) 3.3 Hz,
1H), 3.83 (dd, J ) 10.2 Hz, J ) 10.2 Hz, 1H), 3.40 (dd, J )
10.2 Hz, J ) 8.7 Hz, 1H), 3.22-3.15 (m, 1H), 2.71-2.66 (m,
1H), 2.40-2.36 (m, 2H), 1.55 (s, 3H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 179.00 (CdO), 119.86 (C), 106.45 (CD), 105.32 (CH),
59.69 (CH), 53.63 (CH), 53.34 (CH), 47.51 (CH), 30.57 (CH2),
26.49 (CH3); LRMS m/z (rel inten) 213 (M+, 7), 167 (100);
HRMS (EI) calcd for C10H11DO5 213.0744, found 213.0741.
Spectral data for 19b: white waxy solid; yield 88%; mp 110-
112 °C; IR (CHCl3) 3500-3300, 2980, 1770 cm-1; 1H NMR (300
MHz, CDCl3) δ 5.30 (brs, 1H), 3.81 (brs, 1H), 3.68 (dd, J )
10.5 Hz, J ) 10.8 Hz, 1H), 3.39 (dd, J ) 10.5 Hz, J ) 9.6 Hz,
1H), 3.18 (dd, J ) 9.6 Hz, J ) 9.6 Hz, 1H), 2.78-2.35 (m, 3H),
1.95-1.84 (m, 2H), 1.44-1.20 (m, 12H), 0.91-0.85 (m, 3H);
13C NMR (75 MHz, CDCl3, DEPT) δ 178.45 (CdO), 121.75 (C),
106.32 (CD), 104.10 (CH), 57.25 (CH), 52.38 (CH), 51.74 (CH),
46.81 (CH), 38.57 (CH2), 36.73 (CH2), 31.75 (CH2), 29.51 (CH2),
29.39 (CH2), 29.16 (CH2), 24.00 (CH2), 22.54 (CH2), 14.01 (CH3);
LRMS m/z (rel inten) 311 (M+, 7), 198 (100); HRMS (EI) calcd
for C17H25DO5 311.1836, found 311.1842.
1
Ta k in g th e H a n d 13C NMR Sp ectr a l Da ta of th e F in a l
Ozon id es 9a a n d 9b. The same reaction conditions and
procedure as for the synthesis of 4a -d from the ozonolysis of
3a -d were applied to the ozonolysis of 8a and 8b. Spectral
data for 9a : 1H NMR (300 MHz, CDCl3) δ 9.46 (s, 1H), 5.69
(s, 1H), 3.10-3.07 (m, 1H), 2.94 (dd, J ) 7.5 Hz, J ) 7.5 Hz,
1H), 2.82 (dd, J ) 7.5 Hz, J ) 7.2 Hz, 1H), 2.74-2.71 (m, 1H),
2.19 (s, 3H), 2.23-2.10 (m, 2H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 205.52 (CdO), 200.89 (CHO), 103.63 (CH), 101.69
(CD), 56.08 (CH), 52.76 (CH), 47.22 (CH), 44.83 (CH), 29.33
(CH3), 28.08 (CH2).
Spectral data for 9b: 1H NMR (300 MHz, CDCl3) δ 9.46 (s,
1H), 5.69 (s, 1H), 3.11-2.69 (m, 4H), 2.51-2.08 (m, 4H), 1.64-
1.56 (m, 2H), 1.30-1.20 (m, 10H), 0.90-0.76 (m, 3H); 13C NMR
(75 MHz, CDCl3, DEPT) δ 208.09 (CdO), 200.92 (CHO), 103.69
(CH), 101.33 (CD), 55.18 (CH), 52.79 (CH), 47.49 (CH), 44.89
(CH), 42.09 (CH2), 31.72 (CH2), 29.30 (CH2), 29.10 (CH2), 29.04
(CH2), 28.20 (CH2), 23.88 (CH2), 22.54 (CH2), 14.01 (CH3).
Gen er a l P r oced u r e for th e Syn th esis of th e Tet-
r a qu in a n e Oxa Ca ge Com p ou n d s 16a -d . A solution of 3a
(0.30 g, 1.8 mmol) in dichloromethane (20 mL) was cooled to
-78 °C, and ozone was bubbled through it at -78 °C until the
solution turned light blue. To this solution was added tri-
ethylamine (0.28 g, 2.8 mmol) at -78 °C. Then, the reaction
mixture was stirred at room temperature for 3 h. The solvent
was evaporated, and the crude product was purified by column
chromatography to give 16a (0.34 g, 90%). Spectral data for
16a : white waxy solid; mp 166-167 °C; IR (CHCl3) 3500-
Gen er a l P r oced u r e for th e Ozon olysis of 3a -d . F or -
m a tion of th e Tetr a a ceta l Oxa Ca ge Com p ou n d s 21a -
d . A solution of 3a (0.5 g, 3.0 mmol) in dichloromethane (20
mL) was cooled to -78 °C, and ozone was bubbled through it
at -78 °C until the solution turned light blue. To this solution
was added dimethyl sulfide (0.56 g, 9.0 mmol) at -78 °C.
Then, the reaction mixture was stirred at room temperature
for 5 h. The solvent was evaporated, and the crude product
was purified by column chromatography to give the tetraacetal
oxa cage compound 21a (0.5 g, 85%). Spectral data for 21a :
white waxy solid; mp 127.5-128.5 °C; IR (CHCl3) 2970, 1060
1
3300, 2950, 1770 cm-1; H NMR (300 MHz, CDCl3) δ 6.04 (d,
J ) 6.3 Hz, 1H), 5.57 (brs, 1H), 5.17 (d, J ) 2.4 Hz, 1H), 3.87-
3.83 (m, 1H), 2.64 (dd, J ) 11.1 Hz, J ) 8.7 Hz, 1H), 3.24-
3.18 (m, 1H), 2.75-2.68 (m, 1H), 2.42-2.37 (m, 2H), 1.57 (s,
3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 178.79 (CdO), 119.61
(C), 107.32 (CH), 105.07 (CH), 59.41 (CH), 53.50 (CH), 53.06
(CH), 47.26 (CH), 36.95 (CH2), 26.23 (CH3); LRMS m/z (rel
inten) 212 (M+, 15), 195 (100); HRMS (EI) calcd for C10H12O5
212.0685, found 212.0688.
1
cm-1; H NMR (300 MHz, CDCl3) δ 5.82 (d, J ) 5.4 Hz, 1H),
5.50 (d, J ) 6.3 Hz, 2H), 3.52-3.47 (m, 1H), 3.10 (dd, J ) 10.8
Hz, J ) 7.2 Hz, 1H), 2.94-2.88 (m, 1H), 2.83-2.76 (m, 1H),
2.00-1.83 (m, 2H), 1.54 (s, 3H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 117.59 (C), 109.46 (CH), 103.25 (CH), 102.82 (CH),
56.52 (CH), 54.19 (CH), 45.82 (CH), 45.30 (CH), 29.36 (CH2),
24.70 (CH3); LRMS m/z (rel inten) 196 (M+, 39), 79 (76), 43
(100); HRMS (EI) calcd for C10H12O4 196.0736, found 196.0736.
1-Bu tyl-2,4,6,13-tetr a oxa p en ta cyclo[5.5.1.0.3,110.5,908,12]-
tr id eca n e (21b): pale yellow oil; yield 87%; IR (CHCl3) 2975,
Spectral data for 16b: white waxy solid; yield 87%; mp 114-
1
115.5 °C; IR (CHCl3) 3500-3300, 2950, 1770 cm-1; H NMR
(300 MHz, CDCl3) δ 6.07 (d, J ) 6.6 Hz, 1H), 5.32 (d, J ) 2.0
Hz, 1H), 3.73-3.64 (m, 2H), 3.39 (dd, J ) 10.8 Hz, J ) 8.7
Hz, 1H), 3.19 (dd, J ) 9.0 Hz, J ) 9.0 Hz, 1H), 2.77-2.70 (m,
1H), 2.62-2.36 (m, 2H), 2.05-1.83 (m, 2H), 1.48-1.32 (m, 4H),
0.91 (t, J ) 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ
1
1060 cm-1; H NMR (300 MHz, CDCl3) δ 5.83 (d, J ) 5.4 Hz,
1H), 5.35 (d, J ) 6.6 Hz, 2H), 3.44 (ddd, J ) 10.4 Hz, J ) 7.4

Regioselective Fragmentation of Primary Ozonides
J . Org. Chem., Vol. 61, No. 11, 1996 3827
Hz, J ) 5.4 Hz, 1H), 3.10 (dd, J ) 10.4 Hz, J ) 7.5 Hz, 1H),
2.87-2.78 (m, 2H), 2.00-1.72 (m, 4H), 1.43-1.27 (m, 4H), 0.90
(t, J ) 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 119.74
(C), 109.43 (CH), 103.19 (CH), 102.82 (CH), 54.83 (CH), 53.87
(CH), 46.00 (CH), 45.36 (CH), 37.26 (CH2), 29.45 (CH2), 26.30
(CH2), 22.66 (CH2), 13.92 (CH3); LRMS m/z (rel inten) 238 (M+,
4), 209 (41), 196 (100); HRMS (EI) calcd for C13H18O4 238.1205,
found 238.1203.
104.56 (CH), 56.11 (CH), 52.18 (CH), 51.48 (CH), 46.79 (CH),
28.93 (CH2), 13.72 (CH3), 12.06 (CH3).
F or m a tion of 31b a n d 31c. The commercially available
compound 30b (1.0 g, 7.8 mmol) was dissolved in absolute
ethanol (50 mL) with heating in a Pyrex tube. The mixture
was irradiated with ultraviolet light (300 nm) at 25 °C for 8
h. Then, the solvent was evaporated and the crude product
was purified by column chromatography to give 31b (0.56 g,
4.4 mmol, 56%). Spectral data of 31b: pale yellow oil; IR
(CHCl3) 2980, 1770, 1725 cm-1; 1H NMR (300 MHz, CDCl3) δ
6.41 (d, J ) 12.0 Hz, 1H), 5.95 (d, J ) 12.0 Hz, 1H), 3.67 (s,
3H), 2.27 (s, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 201.21
(CdO), 165.55 (CdO), 141.83 (CH), 124.03 (CH), 51.88 (CH3),
29.74 (CH3).
1-Octyl-2,4,6,13-tetr a oxa p en ta cyclo[5.5.1.0.3,110.5,908,12]-
tr id eca n e (21c): white waxy solid; yield 86%; mp 74-75 °C;
IR (CHCl3) 2970, 1065 cm-1; 1H NMR (300 MHz, CDCl3) δ 5.69
(d, J ) 5.4 Hz, 1H), 5.37 (d, J ) 6.6 Hz, 1H), 5.35 (d, J ) 6.0
Hz, 1H), 3.38-3.30 (m, 1H), 2.99 (dd, J ) 10.7 Hz, J ) 8.1
Hz, 1H), 2.76-2.67 (m, 2H), 1.93-1.58 (m, 4H), 1.35-1.12 (m,
12H), 0.77 (t, J ) 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 119.48 (C), 109.20 (CH), 102.99 (CH), 102.61 (CH),
54.59 (CH), 53.63 (CH), 45.77 (CH), 45.13 (CH), 37.35 (CH2),
31.35 (CH2), 29.33 (CH2), 29.19 (2CH2), 28.90 (CH2), 23.91
(CH2), 22.31 (CH2), 13.77 (CH3); LRMS m/z (rel inten) 294 (M+,
7), 265 (33), 196 (100); HRMS (EI) calcd for C17H26O4 294.1831,
found 294.1823.
Spectra data of 31c: pale yellow oil; yield 76%; IR (CHCl3)
1
2980, 1725, 1675 cm-1; H NMR (300 MHz, CDCl3) δ 7.95-
7.92 (m, 2H), 7.60-7.43 (m, 3H), 6.89 (d, J ) 11.7 Hz, 1H),
6.27 (d, J ) 11.7 Hz, 1H), 4.02 (q, J ) 6.9 Hz, 2H), 1.05 (t, J
) 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 193.87
(CdO), 164.53 (CdO), 140.81 (CH), 135.59 (C), 133.38 (CH),
128.57 (2CH), 128.46 (2CH), 125.78 (CH), 60.74 (CH2), 13.42
(CH3); LRMS m/z (rel inten) 204 (M+, 19), 159 (15), 105 (100).
P r ep a r a tion of 32a . To a solution of 2-methoxyfuran (1.0
g, 10.2 mmol) in dichloromethane (80 mL) was added PCC (3.3
g, 15.3 mmol) at 0 °C. The reaction mixture was stirred at 25
°C for 1 h. Cyclopentadiene (1.4 g, 20.4 mmol) was added to
the solution, and the reaction mixture was stirred at 25 °C
for 10 h. Then, ether (30 mL) was added, and the reaction
mixture was filtered through silical gel and Celite. After
filtration, the solution was evaporated, and the residue was
purified by flash column chromatography to give the endo
adduct 32a (0.91 g, 50%): pale yellow oil; IR (CHCl3) 2950,
1-Ben zyl-2,4,6,13-tetr aoxapen tacyclo[5.5.1.0.3,110.5,908,12]-
tr id eca n e (21d ): white waxy solid; yield 83%; mp 90-90.5
°C; IR (CHCl3) 2970, 1500, 1050 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.36-7.21 (m, 5H), 5.82 (d, J ) 5.7 Hz, 1H), 5.47 (d,
J ) 6.3 Hz, 1H), 5.40 (d, J ) 6.3 Hz, 1H), 3.35 (ddd, J ) 10.8
Hz, J ) 7.5 Hz, J ) 5.7 Hz, 1H), 3.18 (d, J ) 13.5 Hz, 1H),
3.07 (dd, J ) 10.8 Hz, J ) 7.5 Hz, 1H), 2.97 (d, J ) 13.5 Hz,
1H), 2.97-2.72 (m, 1H), 2.34-2.23 (m, 1H), 2.04-1.69 (m, 2H);
13C NMR (75 MHz, CDCl3, DEPT) δ 136.03 (C), 130.17 (2CH),
127.87 (2CH), 126.47 (CH), 119.10 (C), 109.43 (CH), 103.19
(CH), 102.76 (CH), 54.07 (CH), 53.57 (CH), 45.74 (CH), 45.15
(CH), 43.00 (CH2), 29.19 (CH2); LRMS m/z (rel inten) 272 (M+,
39), 181 (100); HRMS (EI) calcd for C16H16O4 272.1049, found
272.1043.
Ozon olysis of 8a a n d 8b. F or m a tion of th e Tetr a a ceta l
Oxa Ca ge Com p ou n d s 23a a n d 23b. The same reaction
conditions and procedure as for the synthesis of 21a -d from
the ozonolysis of 3a -d were applied to the ozonolysis of 8a
a n d 8b. Spectral data for 23a : white waxy solid; yield 87%;
mp 122.5-123 °C; IR (CHCl3) 2970, 1065 cm-1; 1H NMR (300
MHz, CDCl3) δ 5.50 (d, J ) 6.6 Hz, 2H), 3.48 (dd, J ) 10.2 Hz,
J ) 7.2 Hz, 1H), 3.09 (dd, J ) 10.2 Hz, J ) 7.2 Hz, 1H), 2.94-
2.78 (m, 2H), 2.00-1.82 (m, 2H), 1.54 (s, 3H); 13C NMR (75
MHz, CDCl3, DEPT) δ 117.59 (C), 109.72 (CD), 103.25 (CH),
102.82 (CH), 56.55 (CH), 54.07 (CH), 45.82 (CH), 45.30 (CH),
29.36 (CH2), 24.67 (CH3); LRMS m/z (rel inten) 197 (M+, 49),
108 (93), 80 (100); HRMS (EI) calcd for C10H11DO4 197.0795,
found 197.0809.
1
2940, 1770, 1730 cm-1; H NMR (300 MHz, CDCl3) δ 9.30 (d,
J ) 3.9 Hz, 1H), 6.28-6.23 (m, 2H), 3.76-3.60 (m, 1H), 3.59
(s, 3H), 3.40 (dd, J ) 9.8 Hz, J ) 3.6 Hz, 1H), 3.27 (brs, 1H),
3.14-3.05 (m, 1H), 1.52-1.50 (m, 1H), 1.37-1.35 (m, 1H); 13
C
NMR (75 MHz, CDCl3, DEPT) δ 203.13 (CHO), 172.60 (CdO),
136.03 (CH), 134.98 (CH), 55.38 (CH), 51.80 (CH3), 49.32 (CH),
49.18 (CH2), 46.47 (CH), 46.14 (CH); LRMS m/z (rel inten) 180
(M+, 2), 119 (19), 66 (100); HRMS (EI) calcd for C10H12O3
180.0786, found 180.0780.
Gen er a l P r oced u r e for th e Diels-Ald er Rea ction of
31b a n d 31c w ith Cyclop en ta d ien e. The same reaction
conditions and procedure as for the synthesis of 3a -d from
the Diels-Alder reaction of 2a -d were applied to the Diels-
Alder reaction of 31b and 31c with cyclopentadiene to give
the endo adducts 32b and 32c in 80% yield, respectively.
Spectral data for 32b: pale yellow oil; IR (CHCl3) 2970, 1740,
1
1720, 1200 cm-1; H NMR (300 MHz, CDCl3) δ 6.25 (dd, J )
1-D e u t e r i o -7-o c t y l-2,4,6,13-t e t r a o x a p e n t a c y c lo -
5.4 Hz, J ) 3.0 Hz, 1H), 6.01 (dd, J ) 5.4 Hz, J ) 3.0 Hz, 1H),
3.52 (s, 3H), 3.41 (dd, J ) 9.9 Hz, J ) 3.3 Hz, 1H), 3.14-3.06
(m, 3H), 2.04 (s, 3H), 1.41-1.37 (m, 1H), 1.29-1.26 (m, 1H);
13C NMR (75 MHz, CDCl3, DEPT) δ 206.16 (CdO), 173.36
(CdO), 135.77 (CH), 133.26 (CH), 56.05 (CH), 51.24 (CH3),
48.42 (CH2), 47.75 (CH), 46.55 (CH), 46.09 (CH), 30.03 (CH3);
LRMS m/z (rel inten) 194 (M+, 2), 162 (27), 119 (68), 66 (100);
HRMS (EI) calcd for C11H14O3 194.0943, found 194.0942.
Spectral data for 32c: pale yellow oil; yield 78%; IR (CHCl3)
[5.5.1.03,110.5,908,12]tr id eca n e (23b): white waxy solid; yield
1
88%; mp 110-112 °C; IR (CHCl3) 2970, 1065 cm-1; H NMR
(300 MHz, CDCl3) δ 5.50 (d, J ) 6.0 Hz, 2H), 3.44 (dd, J )
10.5 Hz, J ) 7.5 Hz, 1H), 3.10 (dd, J ) 10.4 Hz, J ) 7.8 Hz,
1H), 2.87-2.76 (m, 2H), 2.05-1.67 (m, 4H), 1.44-1.20 (m,
12H), 0.94-0.82 (m, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ
119.66 (C), 109.05 (CD), 103.11 (CH), 102.76 (CH), 54.74 (CH),
53.66 (CH), 45.91 (CH), 45.27 (CH), 37.49 (CH2), 31.69 (CH2),
29.51 (CH2), 29.33 (2CH2), 29.07 (CH2), 24.09 (CH2), 22.49
(CH2), 13.95 (CH3); LRMS m/z (rel inten) 295 (M+, 8), 197 (100);
HRMS (EI) calcd for C17H25DO4 295.1887, found 295.1869.
3040, 2945, 1730, 1680 cm-1 1H NMR (300 MHz, CDCl3) δ
;
7.93-7.90 (m, 2H), 7.57-7.41 (m, 3H), 6.29 (dd, J ) 5.4 Hz, J
) 3.0 Hz, 1H), 6.22 (dd, J ) 5.4 Hz, J ) 3.0 Hz, 1H), 4.20 (dd,
J ) 9.9 Hz, J ) 3.0 Hz, 1H), 3.93-3.86 (m, 2H), 3.44 (dd, J )
9.9 Hz, J ) 3.0 Hz, 1H), 3.24 (brs, 2H), 1.54-1.47 (m, 2H),
1.02 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ
193.15 (CdO), 172.54 (CdO), 137.63 (C), 134.66 (2CH), 132.45
(CH), 128.43 (2CH), 127.73 (2CH), 60.10 (CH2), 51.74 (CH),
49.23 (CH), 48.50 (CH2), 47.34 (CH), 46.79 (CH), 13.83 (CH3);
LRMS m/z (rel inten) 270 (M+, 5), 197 (35), 159 (57), 105 (100);
HRMS (EI) calcd for C17H18O3 270.1256, found 270.1258.
1
Ta k in g th e H a n d 13C NMR Sp ectr a l Da ta of th e F in a l
Ozon id es 27a a n d 27b. The same reaction conditions and
procedure as for the synthesis of 4a -d from the ozonolysis of
3a -d were applied to the ozonolysis of 24a and 24b. Spectral
data for 27a : 1H NMR (300 MHz, CDCl3) δ 9.55 (s, 1H), 6.45
(s, 1H), 5.79 (s, 1H), 3.39 (dd, J ) 8.1 Hz, J ) 8.1 Hz, 1H),
3.10-2.92 (m, 2H), 2.80-2.68 (m, 1H), 2.34 (s, 3H), 2.26-2.02
(m, 2H); 13C NMR (75 MHz, CDCl3, DEPT) δ 201.15 (CHO),
197.77 (COS), 103.66 (CH), 101.13 (CH), 54.59 (CH), 52.79
(CH), 47.83 (CH), 45.10 (CH), 28.05 (CH2), 11.94 (CH3).
Spectral data for 27b: 1H NMR (300 MHz, CDCl3) δ 9.97
(s, 1H), 5.83 (s, 1H), 3.51 (dd, J ) 8.4 Hz, J ) 8.0 Hz, 1H),
3.29 (dd, J ) 8.4 Hz, J ) 7.8 Hz, 1H), 3.02-2.94 (m, 2H), 2.43
(s, 3H), 2.40-2.10 (m, 2H), 1.74 (s, 3H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 202.55 (CHO), 198.18 (COS), 109.98 (C),
1
Ta k in g th e H a n d 13C NMR Sp ectr a l Da ta of th e F in a l
Ozon id es 33a + 34a , 33b + 34b, a n d 33c + 34c. The same
reaction conditions and procedure as for synthesis of 4a -d
from the ozonolysis of 3a -d were applied to the ozonolysis of
32a -c. Spectral data for 33a + 34a : 1H NMR (300 MHz,
CDCl3) δ 9.93 (s, 15% of 1H), 9.86 (s, 15% of 1H), 9.59 (s, 85%
of 1H), 6.52 (s, 85% of 1H), 5.88 (s, 85% of 1H), 5.72 (s, 15% of

3828 J . Org. Chem., Vol. 61, No. 11, 1996
Wu and Lin
1H), 3.79 (s, 85% of 3H), 3.69 (s, 15% of 3H), 3.48-2.78 (m,
4H), 2.32-2.16 (m, 2H); 13C NMR (75 MHz, CDCl3, DEPT) δ
201.38 (15% of CHO), 200.83 (85% of 1CHO), 200.04 (15% of
1CHO), 171.52 (85% of 1CdO), 124.03 (15% of 1C), 103.89 (15%
of 1CH), 103.49 (85% of 1CH), 101.50 (85% of 1CH), 55.03 (15%
of 1CH), 53.89 (15% of 1CH3), 52.55 (85% of 1CH), 52.23 (85%
of CH3), 51.65 (15% of 1CH), 48.94 (15% of 1CH), 48.07 (15%
of 1CH), 47.43 (85% of 1CH), 46.12 (85% of 1CH), 45.01 (85%
of 1CH), 27.82 (15% of 1CH2), 27.82 (85% of 1CH2).
45.53 (CH), 44.60 (CH), 29.19 (CH2), 24.96 (CH3); LRMS m/z
(rel inten) 226 (M+, 6), 195 (100); HRMS (EI) calcd for C11H14O5
226.0841, found 226.0822.
Spectral data for 35c: white waxy solid; yield 67%; mp 123-
124.5 °C; IR (CHCl3) 2980, 1330, 1050 cm-1 1H NMR (300
;
MHz, CDCl3) δ 7.52-7.48 (m, 2H), 7.38-7.30 (m, 3H), 5.73
(d, J ) 6.3 Hz, 1H), 5.69 (d, J ) 6.6 Hz, 1H), 3.95-3.87 (m,
2H), 3.43-3.28 (m, 2H), 3.07-2.93 (m, 2H), 1.98-1.94 (m, 1H),
1.84-1.76 (m, 1H), 1.27 (t, J ) 6.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 140.61 (C), 131.28 (C), 128.19 (CH), 127.99
(2CH), 125.22 (2CH), 116.68 (C), 103.17 (CH), 102.93 (CH),
60.25 (CH2), 58.76 (CH), 54.62 (CH), 45.62 (CH), 44.66 (CH),
29.10 (CH2), 15.29 (CH3); LRMS m/z (rel inten) 302 (M+, 2),
197 (29), 105 (100); HRMS (EI) calcd for C17H18O5 302.1154,
found 302.1150.
Spectral data for 33b + 34b: 1H NMR (300 MHz, CDCl3) δ
9.92 (s, 70% of 1H), 9.90 (s, 30% of 1H), 5.76 (s, 30% of 1H),
5.65 (s, 70% of 1H), 3.81 (s, 30% of 3H), 3.63 (s, 70% of 3H),
3.48-2.80 (m, 4H), 2.37 (s, 70% of 3H), 2.29-2.00 (m, 2H),
1.68 (s, 30% of 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 206.08
(70% of 1CdO), 204.53 (70% of 1CHO), 202.58 (30% of 1CH),
171.02 (30% of 1CdO), 124.17 (70% of 1CdO), 110.07 (30% of
1C), 104.74 (30% of 1CH), 103.86 (70% of 1CH), 55.96 (70% of
1CH), 54.01 (70% of 1CH3), 52.15 (30% of 1CH), 50.31 (30% of
1CH), 49.64 (70% of 1CH), 49.52 (30% of 1CH3), 48.13 (70% of
1CH), 47.78 (70% of 1CH), 47.02 (30% of 1CH), 46.14 (30% of
1CH), 29.94 (70% of 1CH3), 29.77 (70% of 1CH2), 28.46 (30%
of 1CH2), 13.63 (30% of 1CH3).
Spectral data for 36b: pale yellow oil; yield 9%; IR (CHCl3)
1
2970, 1680, 1150 cm-1; H NMR (300 MHz, CDCl3) δ 5.50 (d,
J ) 4.8 Hz, 1H), 5.44 (d, J ) 6.9 Hz, 1H), 3.70 (s, 3H), 3.14-
2.97 (m, 3H), 2.51 (dd, J ) 5.3 Hz, J ) 2.4 Hz, 1H), 1.62-1.58
(m, 1H), 1.55 (s, 3H), 1.29-1.22 (m, 1H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 172.25 (CdO), 107.27 (C), 100.46 (CH), 95.71
(CH), 51.59 (CH3), 47.11 (CH), 45.56 (CH), 44.80 (CH), 40.49
(CH), 24.76 (CH2), 22.66 (CH3); LRMS m/z (rel inten) 226 (M+,
3), 180 (36), 127 (94), 99 (100); HRMS (EI) calcd for C11H14O5
226.0841, found 226.0872.
Spectral data for 33c + 34c: 1H NMR (300 MHz, CDCl3) δ
10.11 (s, 75% of 1H), 10.02 (s, 25% of 1H), 7.95-7.43 (m, 5H),
6.08 (s, 25% of 1H), 5.69 (s, 75% of 1H), 4.22-4.15 (m, 25% of
2H), 3.85-3.67 (m, 75% of 2H), 3.64-2.78 (m, 4H), 2.60-2.10
(m, 2H), 0.94-0.81 (m, 3H); 13C NMR (75 MHz, CDCl3, DEPT)
δ 204.30 (75% of 1CH), 202.49 (25% of 1CH), 198.12 (75% of
1CdO), 170.03 (25% of 1CdO), 136.96 (75% of 1C), 133.00 (75%
of 1CH), 130.47 (25% of 1CH), 128.43 (75% of 1CH), 128.28
(25% of 1CH), 128.22 (75% of 1CH), 127.96 (25% of 1CH),
126.82 (25% of 1C), 123.91 (75% of 1C), 110.80 (25% of 1C),
104.83 (25% of 1CH), 103.72 (75% of 1CH), 62.67 (75% of
1CH2), 60.57 (25% of 1CH2), 53.57 (25% of 1CH), 51.94 (75%
of 1CH), 51.01 (75% of 1CH), 50.81 (25% of 1CH), 49.76 (75%
of 1CH), 48.68 (75% of 1CH), 47.60 (25% of 1CH), 46.52 (25%
of 1CH), 29.86 (75% of 1CH2), 28.37 (25% of 1CH2), 14.04 (75%
of 1CH3), 13.25 (25% of 1CH3).
Spectral data for 36c: white waxy solid; yield 8%; mp 120-
121 °C; IR (CHCl3) 2990, 1730, 1225, 1050 cm-1; 1H NMR (300
MHz, CDCl3) δ 7.50-7.32 (m, 5H), 5.70 (d, J ) 6.9 Hz, 1H),
5.67 (d, J ) 4.8 Hz, 1H), 3.96-3.87 (m, 1H), 3.54-3.42 (m,
2H), 3.29-3.16 (m, 2H), 2.55-2.50 (m, 1H), 1.72-1.68 (m, 1H),
1.37-1.30 (m, 1H), 0.69 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 171.40 (CdO), 138.36 (C), 128.51 (CH), 127.84
(2CH), 125.02 (2CH), 106.78 (C), 101.13 (CH), 95.82 (CH),
60.04 (CH2), 48.83 (CH), 45.56 (CH), 44.95 (CH), 40.26 (CH),
24.85 (CH2), 13.16 (CH3); LRMS m/z (rel inten) 302 (M+, 7),
197 (100); HRMS (EI) calcd for C17H18O5 302.1154, found
302.1153.11
Ack n ow led gm en t. We thank the National Science
Council of the Republic of China for financial support
(Grant No. NSC84-2113-M009-008) and Dr. Chu-Chieh
Lin of the Department of Chemistry, National Chung
Hsin University, for carrying out the X-ray crystal-
lographic analysis.
F or m a tion of Tetr a a ceta l Tetr a oxa Ca ge Com p ou n d s
35a -c a n d Tr ia ceta l Tr ioxa Ca ges 36b a n d 36c. The same
reaction conditions and procedure as for the synthesis of
21a -d from the ozonolysis of 3a -d were applied to the
ozonolysis of 32a -c. Spectral data of 35a : white waxy solid;
yield 80% mp 77-78 °C; IR (CHCl3) 2970, 1100 cm-1; 1H NMR
(300 MHz, CDCl3) δ 5.86 (d, J ) 5.7 Hz, 1H), 5.59 (d, J ) 6.3
Hz, 1H), 5.46 (d, J ) 6.3 Hz, 1H), 3.72-3.63 (m, 1H), 3.46 (s,
3H), 3.13 (dd, J ) 10.7 Hz, J ) 7.5 Hz, 1H), 3.00-3.63 (m,
1H), 2.80-2.76 (m, 1H), 1.95-1.77 (m, 2H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 131.60 (C), 108.67 (CH), 103.19 (CH), 102.47
(CH), 53.40 (CH), 52.35 (CH3), 51.86 (CH), 45.04 (CH), 44.60
(CH), 29.33 (CH2); LRMS m/z (rel inten) 212 (M+, 13), 183
(100); HRMS (EI) calcd for C10H12O2 212.0685, found 212.0693.
Spectral data for 35b: pale yellow oil; yield 66%; IR (CHCl3)
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR
spectra of 4a -d , 9a , 9b, 16a -d , 19a , 19b, 27a , 27b, 35a -c,
36b and 36c and ORTEP diagram of 36C (20 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O952284P
1
2970, 1100 cm-1; H NMR (300 MHz, CDCl3) δ 5.63 (d, J )
6.3 Hz, 1H), 5.50 (d, J ) 6.3 Hz, 1H), 3.48 (s, 3H), 3.25-3.16
(m, 2H), 2.99-2.88 (m, 2H), 1.95-1.75 (m, 2H), 1.59 (s, 3H);
13C NMR (75 MHz, CDCl3, DEPT) δ 131.02 (C), 116.60 (C),
102.82 (CH), 102.55 (CH), 55.88 (CH), 54.36 (CH), 51.68 (CH3),
(11) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.