Synthesis of new type diacetal trioxa-cage compounds via an intramolecular nucleophilic addition of the hydroxy group to the carbonyl oxide group

Article abstract of DOI:10.1021/jo980632s

The synthesis of diacetal trioxa-cage compounds with a new type of skeleton is reported. Ozonolysis of the diols 2a-f, 21, 24, and 33 in CH2C12 at -78 C followed by reduction with Me2S gave the diacetal trioxa-cages 3a-f, 22, 25, and 34 in 70-80% yields, respectively. A mechanism via an intramolecular nucleophilic addition of the hydroxy group of the diols to the carbonyl oxide group is proposed for the formation of the diacetal trioxa-cages. The effect of the number of carbon atoms at the bridge of the diols on the formation of the diacetal trioxa-cage skeleton was examined. Ozonolysis of the diols 13 and 15 under the same reaction conditions gave compounds 16 and 18, respectively. No detectable amount of the trioxa-cages 17 and 19 was obtained. For the synthesis of the diacetal trioxa-cages 28a-c and 31, which possess an alkene bond intact, Ozonolysis of the diols 27a-c and 30 was performed by controlling the amount of ozone.

Full text of DOI:10.1021/jo980632s

J . Org. Chem. 1998, 63, 7687-7693
7687
Syn th esis of New Typ e Dia ceta l Tr ioxa -Ca ge Com p ou n d s via a n
In tr a m olecu la r Nu cleop h ilic Ad d ition of th e Hyd r oxy Gr ou p to th e
Ca r bon yl Oxid e Gr ou p
Hsien-J en Wu,* Ching-Shiun Chao, and Chu-Chung Lin
Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan, China
Received April 6, 1998
The synthesis of diacetal trioxa-cage compounds with a new type of skeleton is reported. Ozonolysis
of the diols 2a -f, 21, 24, and 33 in CH2Cl2 at -78 °C followed by reduction with Me2S gave the
diacetal trioxa-cages 3a -f, 22, 25, and 34 in 70-80% yields, respectively. A mechanism via an
intramolecular nucleophilic addition of the hydroxy group of the diols to the carbonyl oxide group
is proposed for the formation of the diacetal trioxa-cages. The effect of the number of carbon atoms
at the bridge of the diols on the formation of the diacetal trioxa-cage skeleton was examined.
Ozonolysis of the diols 13 and 15 under the same reaction conditions gave compounds 16 and 18,
respectively. No detectable amount of the trioxa-cages 17 and 19 was obtained. For the synthesis
of the diacetal trioxa-cages 28a -c and 31, which possess an alkene bond intact, ozonolysis of the
diols 27a -c and 30 was performed by controlling the amount of ozone.
In tr od u ction
class of heterocyclic cage compounds is synthesized by
intramolecular alkene-oxirane (2σ-2π) photocycloaddi-
tion,3 by transannular cyclization of suitable compounds,4
by tandem cyclization,5 by dehydration of diols having
the proper stereochemistry,6 by base-promoted rear-
rangement,7 and by intamolecular etherification of an
alkene bond with organoselenium reagents.8 Recently,
we utilized ozonolysis reaction for the synthesis of a
series of oxa-cage compounds, such as triacetal trioxa-
cages,9 tetraacetal tetraoxa-cages,10 tetraacetal pentaoxa-
cages,11 and pentaacetal pentaoxa-cages (the pentaoxa-
[5]peristylanes).12 Later on, we investigated the chemical
nature of the acetal group of tetraoxa-cages and discov-
ered a hydride rearrangement and an one-pot conversion
from oxa-cages to aza-cages.13 We also developed a
method for the synthesis of diacetal trioxa-cages C via
the iodo-cages B by iodine-induced sequential cyclization
of norbornene derivatives A (Scheme 1).14
The synthesis and chemistry of polycyclic cage com-
pounds have attracted considerable attention in recent
years.1 The vast majority of the work reported in this
area has dealt with carbocyclic cage compounds. These
cage compounds have played a key role in theoretical
organic chemistry by providing rigid and often symmetric
frameworks for evaluating theories put forth on the
physicochemical properties of organic molecules. In
addition, some precursors of these cage compounds are
important building blocks for the synthesis of polycyclic
unnatural and natural products. Heterocyclic cage com-
pounds have also received attention in recent years from
synthetic as well as mechanistic consideration. The main
purpose for the studies was the desire to compare the
reactivity pattern of carbon cage compounds with their
heterologues. We envision that studies on the synthesis
and chemistry of heterocyclic cage compounds can greatly
expand the scopes and utilities of cage compounds.
There are some reports regarding the chemistry2 and
synthesis3-8 of oxa-cage compounds in the literature. This
An intermolecular nucleophilic addition of a hydroxy
group to a carbonyl oxide, for instance, ozonolysis of an
olefin in an alcohol, affords an R-alkoxy hydroperoxide
and a carbonyl compound.15 This reaction is usually used
(1) For review, see: (a) Eaton, P. E.Angew. Chem., Int. Ed. Engl.
1992, 31, 1421. (b) Griffin, G. W.; Marchand, A. P. Chem. Rev. 1989,
89, 997. (c) Marchand, A. P. Chem. Rev. 1989, 89, 1011. (d) Paquette,
L. A. Chem. Rev. 1989, 89, 1051. (e) Klunder, A. J . H.; Zwanenburg,
B. Chem. Rev. 1989, 89, 1035. (f) Osawa, E.; Yonemitsu, O. Carbocylic
Cage Compounds; VCH: New York, 1992. (g) Olah, G. A. Cage
Hydrocarbons; J . Wiley & Sons, Inc.: New York, 1990.
(2) (a) Mehta, G.; Nair, M. S. J . Chem. Soc., Chem. Commun. 1983,
439. (b) Shen, K. W. J . Am. Chem. Soc. 1971, 93, 3064. (c) Allred, E.
L.; Beck, B. R. Tetrahedron Lett. 1974, 437. (d) Barborak, J . C.; Khoury,
D.; Maier, W. F.; Schleyer, P. V. R.; Smith, E. C.; Smith, J r. W. F.;
Wyrick, C. J . Org. Chem. 1974, 44, 4761.
(3) (a) Prinzbach, H.; Klaus, M. Angew. Chem., Int. Ed. Engl. 1969,
8, 276. (b) Marchand, A. P.; Reddy, G. M.; Watson, W. H.; Kashyap,
R. Tetrahedron 1990, 46, 3409.
(4) (a) Sasaki, T.; Eguchi, S.; Kiriyama, T.; Hiroaki, O. Tetrahedron
1974, 30, 2707. (b) Singh, P. J . Org. Chem. 1979, 44, 843. (c) Coxon, J .
M.; Fong, S. T.; McDonald, D. Q.; O‘Connell, M. J .; Steel, P. J .
Tetrahedron Lett. 1991, 32, 7115.
(7) (a) Marchand, A. P.; Chou, T. C. Tetrahedron 1975, 31, 2655.
(b) Mehta, G.; Reddy, K. R. J . Org. Chem. 1987, 52, 460.
(8) (a) Mehta, G.; Rao, H. S. P. J . Chem. Soc., Chem. Commun. 1986,
472. (b) Mehta, G.; Rao, H. S. P.; Reddy, K. R. J . Chem. Soc., Chem.
Commun. 1987, 78.
(9) (a) Wu, C. Y.; Lin, C. C.; Lai, M. C.; Wu, H. J . J . Chin. Chem.
Soc. 1996, 43, 187. (b) Wu, H.. J .; Wu, C. Y.; Lin, C. C. Chin. Chem.
Lett. 1996, 7, 15.
(10) (a) Wu, H. J .; Lin, C. C. J . Org. Chem. 1995, 60, 7558. (b) Wu,
H. J .; Lin, C. C. J . Org. Chem. 1996, 61, 3820. (c) Wu, H. J .; Chern, J .
H.; Wu, C. Y. Tetrahedron 1997, 53, 2401. (d) Wu, H. J .; Chern, J . H.
Tetrahedron 1997, 53, 17653. (e) Lin, C. C.; Wu, H. J . Tetrahedron
Lett. 1995, 36, 9353. (f) Wu, H. J .; Huang, F. J .; Lin, C. C. J . Chem.
Soc., Chem. Commun. 1991, 770. (g) Lin, C. C.; Wu, H. J . J . Chin.
Chem. Soc. 1995, 42, 815. (h) Lin, C. C.; Huang, F. J .; Lin, J . C.; Wu,
H. J . J . Chin. Chem. Soc. 1996, 43, 177. (i) Lin, R. L.; Wu, C. Y.; Chern,
J . H.; Wu, H. J . J . Chin. Chem. Soc. 1996, 43, 289. (j) Chern, J . H.;
Wu, H. J . J . Chin. Chem. Soc. 1998, in press.
(11) Lin, C. C.; Wu, H. J . Synthesis 1996, 715.
(5) Suri, S. C. J . Org. Chem. 1993, 58, 4153.
(12) (a) Wu, H. J .; Wu, C. Y. Tetrahedron Lett. 1997, 38, 2493. (b)
Mehta, G.; Vidya, R. Tetrahedron Lett. 1997, 38, 4173.
(13) (a) Wu, H. J .; Chern, J . H. J . Org. Chem. 1997, 62, 3208. (b)
Wu, H. J .; Chern, J . H. J . Chem. Soc., Chem. Commun. 1997, 547. (c)
Wu, H. J .; Chern, J . H. Tetrahedron Lett. 1997, 38, 2887. (d) Chern, J .
H.; Wu, H. J . J . Chin. Chem. Soc. 1997, 44, 71. (e) Chern, J . H.; Wu.
H. J . Tetrahedron 1998, 54, 5967.
(6) (a) Mehta, G.; Srikrishna, A.; Reddy, A. V.; Nair, M. S. Tetra-
hedron 1981, 37, 4543. (b) Mehta, G.; Nair, M. S. J . Am. Chem. Soc.
1985, 107, 7519. (c) Marchand, A. P.; LaRoe, W. D.; Sharma, G. V. M.;
Suri, S. C.; Reddy, D. S. J . Org. Chem. 1986, 51, 1622. (d) Fessner, W.
D.; Prinzbach, H. Tetrahedron 1986, 42, 1797. (e) Smith, E. C.;
Barborak, J . C. J . Org. Chem. 1976, 41, 1433.
10.1021/jo980632s CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/09/1998

7688 J . Org. Chem., Vol. 63, No. 22, 1998
Wu et al.
Sch em e 1
Sch em e 2
for the determination of the regiochemistry of carbonyl
oxide formation from primary ozonide fragmentation
because the product composition reflects the regioselec-
tivity in the primary ozonide cleavage.16 This reaction
has also been utilized for the synthesis of terminally
differentiated compounds.17 As part of a program that
involves the synthesis, chemistry, and applications of new
heterocyclic cages, we report here the synthesis of diac-
etal trioxa-cage compounds with a new type of skeleton
via an intramolecular nucleophilic addition of the hy-
droxy group to the carbonyl oxide which is generated by
ozonolysis of the alkene bond.
Sch em e 3
Resu lts a n d Discu ssion
Reduction of 2,3-bis-endo-diacylnorbornenes 1a -e14a
with NaBH4 in MeOH gave the diols 2a -e in 75-80%
yields.18 Compound 2f was prepared by reduction of
maleic anhydride-cyclopentadiene adduct with LiAlH4 in
dry THF. The stereochemistry of the hydroxy groups of
2a -e was difficult to assign at this stage and was
determined by the following chemical transformation.
Ozonolysis of 2a -f in CH2Cl2 at -78 °C followed by
reduction with Me2S gave the diacetal trioxa-cages 3a -f
in 60-70% yields (Scheme 2). Trioxa-cages 3a -f possess
a new type of skeleton which is different from the
previously synthesized diacetal trioxa-cages C.14 The 1H
NMR spectrum of 3d revealed a quartet at δ 4.49 for the
Sch em e 4
1
protons on C3 and C6 whereas the H NMR spectrum of
3e displayed a singlet at δ 5.14 for the same protons. The
coupling constants (J ) 0 Hz) suggest that there are zero
H-H coupling between H4 and Hb (or H5 and Ha). This
is consistent with our assignment that Ha and Hb are
endo (rather than exo) in compounds 3a -f. The stereo-
chemistry of the alkyl group of 3 was also determined
on the basis of NOE experiments of 3a . Irradiating the
C3 proton Hb (δ4.44) gives 9.9% enhancement for the Ha
proton absorptions on C6 and 4.3% enhancement for the
methyl proton peak. Irradiating the methyl protons
(δ1.19) gives 4.5% enhancement for the Hb proton ab-
sorptions, 3.2% enhancement for the C4 proton peak, and
no enhancement for the Ha proton absorptions on C6.
Irradiating the Ha proton on C6 (δ4.23) gives 10.2%
enhancement for the Hb proton peak, 3.1% enhancement
for the C5 proton peak, and no enhancement for the
methyl proton absorptions. Thus, we have accomplished
the synthesis of trioxa-cages with a new type of skeleton
in a short sequence.
To account for the high stereoselectivity of the reduc-
tion reaction of 1a -e with NaBH4 in MeOH, we propose
that compounds 1a -e may adopt conformation 4 in the
protic solvent by virtue of double hydrogen bonding
(Scheme 3). Nucleophilic attack of NaBH4 on the car-
bonyl groups of 4 from the sterically less hindered outside
face gives the major products 2a -e.
Ozonolysis of 2f in CH2Cl2 at -78 °C without reduction
gave the hydroperoxide 5 in 80% yield (Scheme 4). The
1H NMR spectrum of 5 displayed two singlets at δ5.34
and 5.30 for the two hemiacetal protons on C2 and C9.
The coupling constants (J ) 0 Hz) may imply that the
proton on C2 is trans to the C1 proton, and the proton on
C9 is trans to the C10 proton. Reduction of the purified 5
with Me2S gave the dihemiacetal 6 in 90% yield. Both
1H and 13C NMR spectra showed that compound 6
(14) (a) Wu, H. J .; Tsai, S. H.; Chern, J . H.; Lin, H. C. J . Org. Chem.
1997, 62, 6367. (b) Wu, H. J .; Tsai, S. H.; Chung, W. S. Tetrahedron
Lett. 1996, 37, 8209. (e) Wu, H. J .; Tsai, S. H.; Chung, W. S. J . Chem.
Soc., Chem. Commun. 1996, 375. (d) Tsai, S. H.; Wu, H. J .; Chung, W.
S. J . Chin. Chem. Soc. 1996, 43, 445.
(15) (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.
(16) (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. (d) Teshima, K.; Kawamura, S. I.; Ushigoe, Y.; Nojima, M.;
McCullough, K. J . J . Org. Chem. 1995, 60, 4755.
(17) (a) Schreiber, S. L.; Claus, R. E.; Geagan, J . Tetrahedron Lett.
1982, 23, 3867. (b) Hon, Y. S.; Yan, J . L. Tetrahedron Lett. 1993, 34,
6591.
(18) Lin, H. C.; Wu, C. Y.; Wu, H. J . J . Chin. Chem. Soc. 1997, 44,
609.

Diacetal Trioxa-Cage Compounds
J . Org. Chem., Vol. 63, No. 22, 1998 7689
Sch em e 5
Sch em e 6
possesses a symmetry plane. The stereochemistry of the
hydroxy groups of 6 was determined on the basis of NOE
experiments. Irradiating the hemiacetal protons (δ5.30)
gives 3.9% enhancement for the syn proton Ha absorp-
tions on C11 and 2.0% enhancement for the C1 and C10
proton peak. Also, the coupling constant (J ) 0 Hz) is
consistent with the assignment that the hemiacetal
protons on C2 and C9 are trans to the protons on C1 and
C10. Treatment of 6 with 10% HCl in CH2Cl2 gave the
trioxa-cages 3f in 70% yield. When the hydroperoxide 5
was dissolved in an ozonated CH2Cl2 solution and then
Me2S was added, the trioxa-cage 3f was obtained as the
major product. Also, addition of 6 in an ozonated CH2-
Cl2 solution gave 3f as the major product. These results
imply that the ozonated CH2Cl2 blank solution is acidic.
A mechanism is proposed for the ozonolysis of 2 to give
the trioxa-cages 3. 1,3-Dipolar cycloaddition of an ozone
molecule with the alkene bond of 2f via the exo face gave
the 1,2,3-trioxolane (primary ozonide) 7. Fragmentation
of 7 leading to the carbonyl oxide 8, which was followed
by intramolecular nucleophilic addition of the hydroxy
groups to the carbonyl oxide group and the aldehyde
group, gave the hydroperoxide 5. Reduction of 5 with
dimethyl sulfide gave 6. Acid-catalyzed anomerization
of 6, followed by dehydration, gave the trioxa-cages 3f
(Scheme 5).
To understand the effect of the number of carbon atoms
at the bridge on the formation of the diacetal trioxa-cage
skeleton, we prepared compounds 13 and 15. Diels-
Alder reaction of maleic anhydride with 1,3-cyclohexa-
diene followed by reduction of the cycloadduct 12 with
LiAlH4 gave the diol 13. Reduction of compound 14
(commerically available) with LiAlH4 gave the diol 15.
Ozonolysis of 13 in CH2Cl2 at -78 °C followed by
reduction with Me2S gave compound 16 in 70% yield
(Scheme 6). No detectable amount of the diacetal trioxa-
cage 17 was obtained. Ozonolysis of 15 under the same
reaction conditions gave compound 18 in 75% yield. No
detectable amount of the trioxa-cage 19 was obtained.
Thus, the number of carbon atoms at the bridge could
affect the formation of the diacetal trioxa-cage skeleton.
To extend the synthesis of diacetal trioxa-cages, the
cycloadducts of quinone derivatives were prepared. Re-
duction of the cyclopentadiene-naphthoquinone and
cyclohexadiene-naphthoquinone cycloadducts 20 and 23
Sch em e 7
with sodium borohydride in methanol gave the diols 21
and 24 in 87-90% yields, respectively. Nucleophilic
addition of NaBH4 on the carbonyl groups from the
sterically less hindered exo face gave the observed
products 21 and 24. Ozonolysis of the diols 21 and 24
in CH2Cl2 at -78 °C followed by reduction with Me2S
gave the diacetal trioxa-cages 22 and 25 in 70-80%
yields, respectively (Scheme 7). Thus, we have demon-
strated that the formation of the trioxa-cages 22 and 25
can be used as a probe for the determination of the
stereochemistry of the hydroxy groups of the diols 21 and
24. In the case of ozonolysis of 24, which possessess two
carbon atoms at the bridge and a benzo-group bound ring,
the formation of trioxa-cages 25 takes place, different
from the case of ozonolysis of 13.
Reduction of the cyclopentadiene-benzoquinone cy-
cloadducts 26a -c and the cyclohexadiene-benzoquinone
cycloadduct 29 with NaBH4 in the presence of CeCl319 in
MeOH at 0 °C gave diols 27a -c and 30 in 80-85% yields,
respectively. Ozonolysis of 27a -c and 30 in CH2Cl2 at
-78 °C with controlled amount of ozone, followed by

7690 J . Org. Chem., Vol. 63, No. 22, 1998
Wu et al.
Sch em e 8
2a -f, 21, 24, and 33 has been accomplished in a short
sequence in good yields. A mechanism via an intramo-
lecular nucleophilic addition of the hydroxy group of the
diols to the carbonyl oxide group generated by ozonolysis
reaction is proposed for the formation of the diacetal
trioxa-cages. The number of carbon atoms at the bridge
of the diols was found to affect the formation of the trioxa-
cage skeleton. Ozonolysis of the diols 13 and 15 under
the same reaction conditions did not give the correspond-
ing trioxa-cage compounds 17 and 19. The synthesis of
the diacetal trioxa-cage compounds 28a -c and 31, which
possess an alkene bond intact, has been accomplished by
ozonolysis of the diols 27a -c and 30, controlling the
amount of ozone.
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 thin films between NaCl disks. 1H NMR
spectra were determined at 300 MHz, and 13C NMR spectra
were determined at 75 MHz on Fourier transform spectrom-
eters. 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.
Elemental analyses were performed at the microanalysis
laboratory of this department. For thin-layer chromatography
(TLC) analysis, precoated TLC plates (Kieselgel 60 F254) were
used, and column chromatography 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.
Red u ction of Com p ou n d 1e w ith Sod iu m Bor oh yd r id e
in Meth a n ol. To a solution of compound 1e10a (0.83 g, 3.0
mmol) in MeOH (20 mL) was added NaBH4 (0.13 g, 3.3 mmol)
at 0 °C. The reaction mixture was stirred at 0 °C for 2 h. The
solvent was evaporated, and saturated NH4Cl (20 mL) was
added. After extraction with ether (5 × 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 the diol 2e (0.68 g, 80%). The diols 2a -d were prepared
from 1a -d by the same reaction conditions.18 Spectral data
for 2e: white solid; mp 146-147 °C; IR (CHCl3) 3500-3300,
1600, 750, 700 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.39-7.26
(m, 10H), 6.10 (brs, 2H), 4.54-4.51 (m, 2H), 2.83-2.80 (m, 2H),
2.12 (brs, 2H) 1.22-1.10 (m, 2H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 143.62 (2C), 134.99 (2CH), 128.53 (4CH), 127.86
(2CH), 126.84 (4CH), 75.44 (2CH), 51.66 (2CH), 48.93 (CH2),
47.53 (2CH); LRMS m/z (rel int) 282 (M+, 10), 77 (100); HRMS
(EI) calcd for C19H22O2 282.1619, found 282.1610.
Gen er a l P r oced u r e for th e Ozon olysis of 2a -f. F or -
m a tion of th e Dia ceta l Tr ioxa -Ca ge Com p ou n d s 3a -f.
A solution of 2a (0.50 g, 3.0 mmol) in CH2Cl2 (30 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
Me2S (0.52 g, 8.4 mmol) at -78 °C, and 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 diacetal trioxa-cage compound 3a
(0.38 g, 70%).
reduction with Me2S, gave the diacetal trioxa-cages
28a -c and 31 in 30-40% yields, respectively (Scheme
8). Thus, the synthesis of diacetal trioxa-cages with an
alkene bond intact could be accomplished by controlling
the amount of ozone. Treatment of 26a with Zn powder
in glacial HOAc20 at 25 °C gave compound 32 in 90%
yield. Reduction of 32 with NaBH4 in MeOH gave the
diol 33. Ozonolysis of 33 in CH2Cl2 at -78 °C followed
by reduction with Me2S gave the trioxa-cage 34 in 80%
yield. Ozonolysis of 33 in CH2Cl2 at -78 °C without
reduction gave the hydroperoxide 35 in 85% yield.
Reduction of purified 35 with Me2S gave the dihemiacetal
36 in 90% yield. Treatment of 35 with Et3N in CH2Cl2
at 25 °C gave 36 (60%) and the lactone 37 (33%). Thus,
in reaction with the hydroperoxide 35, Et3N acts as a
reducing agent to give 36 and acts as a base to give 37.
3b -Me t h y l-2,7,12-t r io x a t e t r a c y c lo [6.3.1.04 ,1 1 .05 .9 ]-
d od eca n e 3a : White waxy solid; mp 58-59 °C; IR (CHCl3)
2960, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ5.40 (d, J ) 6.6
Hz, 2H), 4.44 (q, J ) 6.6 Hz, 1H), 4.23 (d, J ) 9.6 Hz, 1H),
3.86 (dd, J ) 9.6, 5.2 Hz, 1H), 2.91-2.86 (m, 1H), 2.76-2.70
(m, 1H), 2.64-2.57 (m, 1H), 2.35-2.29 (m, 1H), 1.82-1.65 (m,
2H), 1.19 (d, J ) 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT)
δ 103.89 (CH), 103.86 (CH), 76.43 (CH), 69.40 (CH2), 47.88
(CH), 46.19 (CH), 45.17 (CH), 42.45 (CH), 23.81 (CH2), 23.49
Con clu sion
The synthesis of new type diacetal trioxa-cage com-
pounds 3a -f, 22, 25, and 34 via ozonolysis of the diols
(19) Luche, J . L. J . Am. Chem. Soc. 1978, 100, 2226.
(20) (a) Windaus, A. Ber. 1906, 39, 2249. (b) Fieser, L. F.; Herz, J .
E.; Huang, W. Y. J . Am. Chem. Soc. 1951, 73, 2397.

Diacetal Trioxa-Cage Compounds
J . Org. Chem., Vol. 63, No. 22, 1998 7691
(CH3); LRMS m/z (rel int) 182 (M+, 5), 81 (100); HRMS (EI)
calcd for C10H14O3 182.0943, found 182.0949. Anal. Calcd for
C10H14O3: C, 65.90; H, 7.75. Found: C, 65.78; H, 7.69..
3â-n -B u t y l-2,7,12-t r io x a t e t r a c y c lo [6.3.1.04 ,1 1 .05 .9 ]-
d od eca n e 3b: white waxy solid; mp 50-51 °C; IR (CHCl3)
2960, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ5.43 (d, J ) 6.6
Hz, 1H), 5.41 (d, J ) 6.6 Hz, 1H), 4.23-4.19 (m, 2H), 3.85 (dd,
J ) 9.6, 5.1 Hz, 1H), 2.82-2.75 (m, 1H), 2.74-2.70 (m, 1H),
2.62-2.58 (m, 1H), 2.40-2.30 (m, 1H), 1.77-1.69 (m, 2H),
1.50-1.25 (m, 6H), 0.89 (t, J ) 6.6 Hz, 3H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 103.77 (CH), 103.68 (CH), 80.47 (CH), 69.37
(CH2), 46.20 (CH), 46.08 (CH), 45.40 (CH), 42.48 (CH), 37.04
(CH2), 28.02 (CH2) 23.81 (CH2), 22.42 (CH2), 13.89 (CH3);
LRMS m/z (rel int) 224 (M+, 14), 109 (100); HRMS (EI) calcd
for C13H20O3 224.1413, found 224.1402. Anal. Calcd for
found 202.0847. Anal. Calcd for C9H14O5: C, 53.44; H, 6.98.
Found: C, 53.60; H, 7.10.
Red u ction of 5 w ith Dim eth yl Su lfid e. To a solution of
purified 5 (0.41 g, 2.0 mmol) in CH2Cl2 (20 mL) was added
excess Me2S (0.62 g, 10 mmol) at 25 °C. The reaction mixture
was stirred at 25 °C for 3 h. The solvent was evaporated, and
the crude product was purified by column chromatography to
give the dihemiacetal 6 (0.34 g, 90%): pale yellow oil; IR
(CHCl3) 3500-3300, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ
5.31 (s, 2H), 4.15-4.05 (m, 2H), 3.82-3.75 (m, 2H), 3.13 (brs,
2H), 3.06-3.00 (m, 2H), 2.76-2.65 (m, 2H), 2.22-2.12 (m, 1H),
1.32-1.17 (m, 1H); 13C NMR (75 MHz, CDCl3, DEPT) δ 102.45
(2CH), 68.41 (2CH2), 54.10 (2CH), 44.68 (2CH), 31.99 (CH2);
LRMS m/z (rel int) 186 (M+, 10), 79 (38), 109 (100); HRMS
(EI) calcd for C9H14O4 186.0892, found 186.0899. Anal. Calcd
for C9H14O4: C, 58.04; H, 7.58. Found: C, 58.17; H, 7.69.
Tr ea tm en t of 6 w ith 10% HCl. To a solution of 6 (0.37 g,
2.0 mmol) in CH2Cl2 (30 mL) was added 10% HCl (0.5 mL) at
25 °C. The reaction mixture was stirred at 25 °C for 1 h.
Saturated NaHCO3 (5 mL) was added, and the mixture was
extracted with CH2Cl2 (3 × 20 mL). The combined organic
layer was washed with brine, dried over MgSO4, and evapo-
rated, and the residue was purified by column chromatography
to give the diacetal trioxa-cage 3e in 70% yield.
Red u ction of 5 w ith Dim eth yl Su lfid e in a n Ozon a ted
Dich lor om eth a n e Solu tion . Dichloromethane (30 mL) was
cooled to -78 °C, and ozone was bubbled through it at -78
°C. Compound 5 (0.2 g, 1.0 mmol) was added to the solvent
at -78 °C. To this solution was then added Me2S (0.31 g, 5.0
mmol) at -78 °C, and the reaction mixture was stirred at room
temperature for 2 h. The solvent was evaporated, and the
crude product was purified by column chromatography to give
3e in 80% yield.
Tr ea tm en t of 6 w ith a n Ozon a ted Dich lor om eth a n e
Solu tion . Dichloromethane (30 mL) was cooled to -78 °C,
and ozone was bubbled through it at -78 °C. Compound 6
(1.86 g, 1.0 mmol) was added to the ozonated solvent at -78
°C, and the reaction mixture was stirred at -78 °C for 1 h.
The solvent was evaporated, and the crude product was
purified by column chromatography to give 3e in 85% yield.
C
13H20O3: C, 69.61; H, 8.99. Found: C, 69.72; H, 8.91..
3â-n -O c t y l-2,7,12-t r io x a t e t r a c y c lo [6.3.1.04 ,1 1 .05 .9 ]-
d od eca n e 3c: white waxy solid; mp 45-47 °C; IR (CHCl3)
2950, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ5.44 (d, J ) 6.6
Hz, 1H), 5.41 (d, J ) 6.6 Hz, 1H), 4.23-4.20 (m, 2H), 3.85 (dd,
J ) 9.6, 5.1 Hz, 1H), 2.81-2.75 (m, 1H), 2.73-2.68 (m, 1H),
2.61-2.54 (m, 1H), 2.37-2.32 (m, 1H), 1.81-1.66 (m, 2H),
1.38-1.26 (m, 14H), 0.88 (t, J ) 6.9 Hz, 3H); 13C NMR (75
MHz, CDCl3, DEPT) δ 103.89 (CH), 103.79 (CH), 80.61 (CH),
69.49 (CH2), 46.34 (CH), 46.21 (CH), 45.52 (CH), 42.63 (CH),
37.48 (CH2), 31.80 (CH2) 29.49 (2CH2), 29.19 (CH2), 26.00
(CH2), 23.94 (CH2) 22.59 (CH2), 14.04 (CH3); LRMS m/z (rel
int) 280 (M+, 10), 109 (100); HRMS (EI) calcd for C17H28O3
280.2038, found 280.2047. Anal. Calcd for C17H28O3: C, 72.82;
H, 10.06. Found: C, 72.74; H, 10.16.
3â,6â-Dim et h yl-2,7,12-t r ioxa t et r a cyclo[6.3.1.04,11.05.9]-
d od eca n e 3d : white waxy solid; mp 66-67 °C; IR (CHCl3)
2970, 1055 cm-1; 1H NMR (300 MHz, CDCl3) δ5.43 (d, J ) 6.3
Hz, 2H), 4.49 (q, J ) 6.3 Hz 2H), 2.89-2.84 (m, 2H), 2.33-
2.31 (m, 2H), 1.80-1.63 (m, 2H), 1.18 (d, J ) 6.3 Hz, 6H); 13
C
NMR (75 MHz, CDCl3, DEPT) δ 103.80 (2CH), 76.46 (2CH),
48.23 (2CH), 44.77 (2CH), 23.61 (CH2), 23.31 (2CH3); LRMS
m/z (rel int) 196 (M+, 10), 83 (100); HRMS (EI) calcd for
C
11H16O3 196.1099, found 196.1090. Anal. Calcd for C11H16O3:
C, 67.31; H, 8.22. Found: C, 67.41; H, 8.30.
3â,6â-Dip h en yl-2,7,12-t r ioxa t et r a cyclo[6.3.1.04,11.05.9]-
d od eca n e 3e: white waxy solid; mp 148-149 °C; IR (CHCl3)
3060, 1050, 750, 700 cm-1; 1H NMR (300 MHz, CDCl3) δ6.91-
6.74 (m, 10H) 5.71 (d, J ) 6.6 Hz, 2H), 5.14 (s, 2H), 3.11-3.08
(m, 2H), 3.04-3.01 (m, 2H), 1.92-1.90 (m, 2H); 13C NMR (75
MHz, CDCl3, DEPT) δ 138.74 (2C), 128.54 (2CH), 127.66
(4CH), 126.07 (4CH), 103.13 (2CH), 82.59 (2CH), 50.85 (2CH),
45.79 (2CH), 23.97 (CH2); LRMS m/z (rel int) 320 (M+, 10), 77
(100); HRMS (EI) calcd for C21H20O3 320.1421, found 320.1430.
Anal. Calcd for C21H20O3: C, 78.72; H, 6.30. Found: C, 78.80;
H, 6.42.
Ozon olysis of Com p ou n d 13 a n d 15. The same reaction
conditions and procedure as for the ozonolysis of 2a -f were
applied for the ozonolysis of 13 and 15 to give compounds 16
and 18 in 70-75% yields, respectively. No detectable amount
of the diacetal trioxa-cage compounds 17 and 19 was obtained.
Spectral data for 16: pale yellow oil; IR (CHCl3) 3500-3300,
1
2930, 1720, 1060 cm-1; H NMR (300 MHz, CDCl3) δ 9.71 (s,
1H), 5.15 (d, J ) 3.0 Hz, 1H), 4.12-4.08 (m, 1H), 4.00-3.88
(m, 2H), 3.54-3.50 (m, 1H), 2.48-2.42 (m, 1H), 2.26-2.22 (m,
1H), 2.20-2.13 (m, 4H), 1.97-1.80 (m, 4H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 203.70 (CHO), 101.14 (CH), 72.10 (CH2), 61.14
(CH2), 52.23 (CH), 39.48 (CH), 38.72 (CH), 32.16 (CH), 21.44
(CH2), 19.47 (CH2); LRMS m/z (rel int) 200 (M+, 20), 46 (100);
HRMS (EI) calcd for C10H16O4 200.1049, found 200.1062.
2,7,12-Tr ioxatetr acyclo[6.3.1.04,11.05,9]dodecan e 3f: white
waxy solid; mp 89-90 °C; IR (CHCl3) 2960, 1050 cm-1 1H
;
NMR(300 MHz, CDCl3) δ 5.44 (d, J ) 6.3 Hz, 2H), 4.18 (d, J
) 9.6 Hz, 2H), 3.90 (dd, J ) 9.6, 5.1 Hz, 2H), 2.78-2.73 (m,
2H), 2.67-2.61 (m, 2H), 1.85-1.70 (m, 2H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 103.97 (2CH), 69.34 (2CH2), 46.51 (2CH),
42.10 (2CH), 23.97 (CH2); LRMS m/z (rel int) 168 (M+, 10),
109 (100); HRMS (EI) calcd for C9H12O3 168.0786, found
168.0780. Anal. Calcd for C9H12O3: C, 64.26; H, 7.20.
Found: C, 64.38; H, 7.31.
Spectral data for 18: pale yellow oil; IR (CHCl3) 3600-3300,
1
2970, 1720, 1070 cm-1; H NMR (300 MHz, CDCl3) δ 9.82 (s,
1H), 5.34 (d, J ) 3.0 Hz, 1H), 4.11-4.02 (m, 2H), 3.94 (dd, J
) 8.1, 4.2 Hz, 1H), 3.38 (d, J ) 12 Hz, 1H), 2.90-2.60 (m, 2H),
2.47 (brs, 1H), 2.28-2.20 (m, 1H), 2.06 (d, J ) 12 Hz, 1H),
1.70 (brs, 2H), 1.51-1.40 (m, 1H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 200.87 (CHO), 99.18 (CH), 73.30 (CH2), 63.12 (CH2),
46.18 (CH2), 36.86 (CH), 32.95 (CH2), 32.05 (CH); LRMS m/z
(rel int) 174 (M+, 24), 46 (100); HRMS (EI) calcd for C8H14O4
174.0892, found 174.0881.
Ozon olysis of 2f With ou t Red u ction . A solution of 2e
(0.46 g, 3.0 mmol) in CH2Cl2 (30 mL) was cooled to -78 °C,
and ozone was bubbled through it at -78 °C until the solution
turned light blue. After 10 min stirring, the solvent was
evaporated, and the crude product was purified by column
chromatography to give the hydroperoxide 5 (0.53 g, 80%):
Red u ction of Com p ou n d 20 w ith Sod iu m Bor oh yd r id e
in Meth a n ol. The same reaction conditions and procedure
as for the reduction of 1e were applied for the reduction of 20
to give compound 21 in 87% yield. white solid; mp 148-150
1
pale yellow oil; IR (CHCl3) 3500-3300, 1050 cm-1; H NMR
(300 MHz, CDCl3) δ 9.47 (s, 1H), 5.34 (s, 1H), 5.30 (s, 1H),
4.14-4.00 (m, 2H), 3.90-3.78 (m, 2H), 3.58 (brs, 1H); 3.12-
2.94 (m, 2H), 2.76-2.62 (m, 2H), 2.30-2.20 (m, 1H), 1.40-
1.30 (m, 1H); 13C NMR (75 MHz, CDCl3, DEPT) δ 112.15 (CH),
102.30 (CH), 69.15 (CH2), 68.15 (CH2), 53.94 (CH), 49.84 (CH),
45.03 (CH), 44.73 (CH), 32.10 (CH2); LRMS m/z (rel int) 202
(M+, 20), 91 (100); HRMS (EI) calcd for C9H14O5 202.0841,
°C; IR (CHCl3) 3500-3300, 3030, 2980 cm-1 1H NMR (300
;
MHz, CDCl3) δ 7.25-7.13 (m, 4H), 5.07 (brs, 2H), 4.90 (brs,
2H), 4.87-4.83 (m, 2H), 3.04-2.90 (m, 4H), 1.32-1.17 (m, 2H);
13C NMR (75 MHz, CDCl3, DEPT) δ 139.99 (2C), 134.20 (2CH),
127.26 (2CH), 122.77 (2CH), 69.34 (2CH), 49.58 (CH2), 46.03
(2CH), 45.59 (2CH); LRMS m/z (rel int) 228 (M+, 7), 19 (100);

7692 J . Org. Chem., Vol. 63, No. 22, 1998
Wu et al.
HRMS (EI) calcd for C15H16O2 228.1151, found 228.1163. Anal.
Calcd for C15H16O2: C, 78.91; H, 7.07. Found: C, 78.80; H,
7.15.
found 192.1165. Anal. Calcd for C12H16O2: C, 74.96; H, 8.39.
Found: C, 75.10; H, 8.51.
Ozon olysis of 27a-c with Con tr olled Am ou n t of Ozon e.
Syn th esis of th e Tr ioxa -Ca ges 28a -c. A solution of 27b
(0.50 g, 2.0 mmol) in CH2Cl2 (40 mL) was cooled to -78 °C,
and ozone was bubbled through it at -78 °C until compound
27b was consumed by thin-layer chromatography tracing. To
this solution was added Me2S (0.36 g, 5.8 mmol) at -78 °C,
and 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 diacetal trioxa-
cage 28b (0.21 g, 40%).
Ozon olysis of Com p ou n d 21. F or m a tion of Tr ioxa -
Ca ge 22. The same reaction conditions and procedure as for
the ozonolysis of 2a -f were applied for the ozonolysis of 21 to
give the trioxa-cage 22 in 75% yield. Spectral data for 22:
white solid; mp 163-163.5 °C; IR (CHCl3) 3020, 2980, 1035
1
cm-1; H NMR (300 MHz, CDCl3) δ 7.40-7.30 (m, 4H), 5.48
(d, J ) 6.6 Hz, 2H), 5.12-5.08 (m, 2H), 3.01 (brs, 2H), 2.86-
2.81 (m, 2H), 1.89 (brs, 2H); 13C NMR (75 MHz, CDCl3, DEPT)
δ 135.10 (2C), 129.94 (2CH), 128.57 (2CH), 103.40 (2CH), 79.74
(2CH), 47.31 (2CH), 43.55 (2CH), 26.16 (CH2); LRMS m/z (rel
int) 242 (M+, 100); HRMS (EI) calcd for C15H14O3 242.0943,
found 242.0939; Anal. Calcd for C15H14O3: C, 74.35; H, 5.83.
Found: C, 74.47; H, 5.92.
8,10,12-Tr ioxa p e n t a cyclo[5.5.2.02,6.03,11.05,9]-13-t e t -
r a d ecen e 28a : white solid; mp 155-156 °C; IR (CHCl3) 2980,
1050 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.41 (dd, J ) 4.2, 2.4
Hz, 2H), 5.45 (d, J ) 6.3 Hz, 2H), 4.66-4.64 (m, 2H), 2.92-
2.88 (m, 2H), 2.78-2.72 (m, 2H), 1.98-1.84 (m, 2H); 13C NMR
(75 MHz, CDCl3, DEPT) δ 132.19 (2CH), 103.40 (2CH), 73.74
(2CH), 47.66 (2CH), 43.11 (2CH), 26.62 (CH2), LRMS m/z (rel
int) 192 (M+, 8), 117 (100); HRMS (EI) calcd for C11H12O3
192.0786, found 192.0798. Anal. Calcd for C11H12O3: C, 68.72;
H, 6.30. Found: C, 68.82; H, 6.39.
Red u ction of Com p ou n d 23 w ith Sod iu m Bor oh yd r id e
in Meth a n ol. The same reaction conditions and procedure
as for the reduction of 1e were applied for the reduction of 23
to give compound 24 in 90% yield: white solid; mp 181-182
1
°C; IR (CHCl3) 3500-3300, 3050, 1600, 1080 cm-1; H NMR
(300 MHz, CDCl3) δ 7.30-7.20 (m, 4H), 6.35 (brs, 2H), 4.68
(brs, 2H), 3.00 (brs, 2H), 2.76 (brs, 2H), 2.20 (brs, 2H), 1.61-
1.54 (m, 2H), 1.37-1.33 (m, 2H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 140.53 (2C), 132.52 (2CH), 128.34 (2CH), 128.06
(2CH), 72.22 (2CH), 46.00 (2CH), 33.63 (2CH), 26.32 (2CH2);
LRMS m/z (rel int) 242 (M+, 42), 166 (51), 76 (100); HRMS
(EI) calcd for C16H18O2 242.1307, found 242.1315. Anal. Calcd
for C16H18O2: C, 79.30; H, 7.49. Found: C, 79.45; H, 7.60.
Ozon olysis of Com p ou n d 24. F or m a tion of Tr ioxa -
Ca ge 25. The same reaction conditions and procedure as for
the ozonolysis of 2a -f were applied for the ozonolysis of 24 to
give the trioxa-cage 25 in 70% yield: white solid; mp 132-
133 °C; IR (CHCl3 3020, 2925, 1030 cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.43-7.36 (m, 4H), 5.39 (d, J ) 5.4 Hz, 2H), 4.97 (d,
J ) 2.4 Hz, 2H), 2.70-2.67 (m, 2H), 2.48-2.45 (m, 2H), 2.14-
1.90 (m, 4H); 13C NMR (75 MHz, CDCl3, DEPT) δ 135.10 (2C),
129.24 (2CH), 128.57 (2CH), 104.86 (2CH), 80.85 (2CH), 44.60
(2CH), 35.80 (2CH), 16.08 (2CH2); LRMS m/z (rel int) 256 (M+,
100); HRMS (EI) calcd for C16H16O3 256.1099, found 256.1091.
Anal. Calcd for C16H16O3: C, 74.97; H, 6.30. Found: C, 74.86;
H, 6.38.
13-P h en yl-8,10,12-tr ioxa p en ta cyclo[5.5.2.02,6.03,11.05,9]-
13-tetr a d ecen e 28b: white solid; mp 141-142 °C; IR (CHCl3)
1
2860, 1640, 1040, 750, 700 cm-1; H NMR (300 MHz, CDCl3)
δ 7.52-7.26 (m, 5H), 6.56 (d, J ) 6.6 Hz, 1H), 5.54 (d, J ) 6.6
Hz, 1H), 5.47 (d, J ) 6.6 Hz, 1H), 4.96 (d, J ) 6.0 Hz, 1H),
4.84 (dd, J ) 6.6, 6.0 Hz, 1H), 3.02-2.70 (m, 4H), 2.00-1.89
(m, 2H); 13C NMR (75 MHz, CDCl3, DEPT) δ 143.49 (C), 140.14
(C), 128.25 (2CH), 127.79 (CH), 126.36 (2CH), 125.92 (CH),
103.72 (CH), 103.22 (CH), 77.20 (CH), 74.90 (CH), 47.63 (CH),
47.57 (CH), 44.40 (CH), 42.12 (CH), 26.74 (CH2); LRMS m/z
(rel int) 268 (M+, 100); HRMS (EI) calcd for C17H16O3 268.1099,
found 268.1095. Anal. Calcd for C17H16O3: C, 76.09; H, 6.01.
Found: C, 76.21; H, 6.10.
13-Meth yl-8,10,12-tr ioxa p en ta cyclo[5.5.2.02,6.03,11.05,9]-
13-tetr a d ecen e 28c: white solid; mp 152-153 °C; IR (CHCl3)
2950, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.06-6.03 (m,
1H), 5.46 (d, J ) 6.6 Hz, 1H), 5.42 (d, J ) 6.3 Hz, 1H), 4.64
(dd, J ) 6.3, 6.3 Hz, 1H), 4.42 (d, J ) 6.0 Hz, 1H), 2.91-2.88
(m, 2H), 2.82-2.62 (m, 2H), 1.97 (s, 3H), 1.95-1.87 (m, 2H);
13C NMR (75 MHz, CDCl3, DEPT) δ 140.98 (C), 124.85 (CH),
103.55 (CH), 103.19 (CH), 78.84 (CH), 74.95 (CH), 47.67 (CH),
47.59 (CH), 43.72 (CH), 42.25 (CH), 26.71 (CH2), 23.33 (CH3);
LRMS m/z (rel int) 206 (M+, 11), 117 (100); HRMS (EI) calcd
for C12H14O3 206.0943, found 206.0937. Anal. Calcd for
Gen er a l P r oced u r e for th e Red u ction of 26a -c w ith
Sod iu m Bor oh yd r id e in th e P r esen ce of CeCl3. To a
solution of compound 26b (2.5 g, 10 mmol) in MeOH (50 mL)
were added NaBH4 (0.57 g, 15 mmol) and CeCl3‚7H2O (8.6 g,
23 mmol) at 0 °C. The reaction mixture was stirred at 0 °C
for 3 h. The solvent was evaporated, and saturated NH4Cl
(30 mL) was added. After extraction with ether (5 × 30 mL),
the organic layer was washed with brine, dried over MgSO4,
and evaporated, and the residue was purified by column
chromatography to give the diol 27b (2.04 g, 80%). The diol
27a is a known compound.6c
Spectral data for 27b: white solid; mp 190-191 °C; IR
(CHCl3) 3500-3300, 1640, 1600, 750, 700 cm-1; 1H NMR (300
MHz, CDCl3) δ 7.37-7.17 (m, 5H), 6.03-5.95 (m, 2H), 5.78-
5.76 (m, 1H), 4.84 (s, 1H), 4.74-4.71 (m, 1H) 4.49-4.44 (m,
1H), 3.34 (s, 1H), 3.00-2.93 (m, 2H), 2.80-2.68 (m, 2H), 1.38
(brs, 2H); 13C NMR (75 MHz, CDCl3, DEPT) δ 144.57 (C),
141.01 (C), 136.15 (CH), 134.84 (CH), 131.28 (CH), 128.95
(2CH), 128.31 (2CH), 127.87 (CH), 68.87 (CH), 67.27 (CH),
51.59 (CH2), 46.64 (CH), 46.49 (CH), 45.82 (CH), 45.21 (CH);
LRMS m/z (rel int) 254 (M+, 11), 222 (100); HRMS (EI) calcd
for C17H18O2 254.1367, found 254.1379. Anal. Calcd for
C
12H14O3: C, 69.87; H, 6.85. Found: C, 69.95; H, 6.92.
Red u ction of Com p ou n d 29 w ith Na BH4 in th e P r es-
en ce of CeCl3. The same reaction conditions and procedure
as for the reduction of 26a -c were applied for the reduction
of 29 to give the diol 30 in 90% yield. Spectral data for 30:
white solid; mp 174-175 °C; IR (CHCl3) 3500-3300, 1050
cm-1; 1H NMR (300 MHz, CDCl3) δ 6.31-6.25 (m, 2H), 6.01-
5.98 (m, 1H), 4.15 (d, J ) 6.3, 4.2 Hz, 1H), 3.90 (d, J ) 4.2 Hz,
1H), 2.70 (brs, 2H), 2.59 (brs, 2H), 2.12-1.98 (m, 2H), 1.86 (d,
J ) 1.5 Hz, 3H), 1.57-1.54 (m, 2H), 1.33-1.30 (m, 2H); 13C
NMR (75 MHz, CDCl3, DEPT) δ 146.16 (C), 132.44 (CH),
131.82 (CH), 128.44 (CH), 70.80 (CH), 66.35 (CH), 45.47 (CH),
45.22 (CH), 33.63 (CH), 33.48 (CH), 26.33 (CH), 26.15 (CH2),
22.05 (CH3); LRMS m/z (rel int) 206 (M+, 29), (100), 191 (58);
HRMS (EI) calcd for C13H18O2 206.1307, found 206.1316. Anal.
Calcd for C13H18O2: C, 75.68; H, 8.80. Found: C, 75.82; H,
8.92.
Ozon olysis of 30 w ith Con tr olled Am ou n t of Ozon e.
F or m a tion of th e Tr ioxa -Ca ge 31. The same reaction
conditions and procedure as for the ozonolysis of 27a -c were
applied for the ozonolysis of 30 to give the trioxa-cage 31 in
30% yield. Spectral data for 31: white solid; mp 132-133 °C;
IR (CHCl3) 2950, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.13
(d, J ) 6.3 Hz, 1H), 5.31 (d, J ) 5.4 Hz, 1H), 5.28 (d, J ) 5.4
Hz, 1H), 4.47 (dd, J ) 6.3, 4.8 Hz, 1H), 4.27 (d, J ) 4.8 Hz,
1H), 2.58-2.51 (m, 2H), 2.40-2.17 (m, 2H), 2.05-1.86 (m, 4H),
1.88 (s, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 142.13 (C),
125.62 (CH), 104.93 (CH), 104.71 (CH), 80.14 (CH), 76.31 (CH),
44.89 (CH), 44.80 (CH), 36.03 (CH), 34.94 (CH), 23.07 (CH),
C
17H18O2: C, 80.27; H, 7.14. Found: C, 80.40; H, 7.25.
Spectral data for 27c: white solid; mp 199-200 °C; IR
(CHCl3) 3500-3300, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ
5.82 (dd, J ) 5.7, 2.7 Hz, 1H), 5.77 (dd, J ) 5.7, 3.0 Hz, 1H),
5.01 (brs, 1H), 4.89 (brs, 2H), 4.38-4.35 (m, 1H), 4.28 (brs,
1H), 2.98-2.96 (m, 2H), 2.78-2.74 (m, 2H), 1.61 (d, J ) 1.5
Hz, 3H), 1.29-1.28 (m, 2H); 13C NMR (75 MHz, CD3COCD3,
DEPT) δ 137.43 (C), 137.37 (CH), 133.76 (CH), 126.44 (CH),
70.18 (CH), 67.94 (CH), 50.31 (CH2), 46.52 (CH), 46.41 (CH),
44.80 (CH), 44.08 (CH), 18.23 (CH3); LRMS m/z (rel int) 192
(M+, 5), 175 (100); HRMS (EI) calcd for C12H16O2192.1151,

Diacetal Trioxa-Cage Compounds
J . Org. Chem., Vol. 63, No. 22, 1998 7693
16.41 (CH2), 16.34 (CH2); LRMS m/z (rel int) 220 (M+, 26), 66
(100); HRMS (EI) calcd for C13H16O3 220.1099, found 220.1091.
Anal. Calcd for C13H16O3: C, 70.87; H, 7.33. Found: C, 70.75;
H, 7.41.
white solid; mp 149-150 °C; IR (CHCl3) 3500-3200, 1100
cm-1 1H NMR (300 MHz, CDCl3) δ 5.29 (s, 1H), 4.75-4.72
;
(m, 2H), 4.50 (brs, 2H), 3.00-2.88 (m, 2H), 2.78-2.68 (m, 2H),
2.10-1.63 (m, 6H); 13C NMR (75 MHz, CDCl3, DEPT) δ 99.90
(2CH), 74.71 (2CH), 55.29 (2CH), 41.63 (2CH), 33.34 (CH2),
24.31 (2CH2); LRMS m/z (rel int) 212 (M+, 4), 148 (100), 117
(76); HRMS (EI) calcd for C11H16O4 212.1049, found 212.1040.
Anal. Calcd for C11H16O4: C, 62.23; H, 7.60. Found: C, 62.36;
H, 7.71.
Ozon olysis of Com p ou n d 33. Syn th esis of Tr ioxa -
Ca ge 34. The same reaction conditions and procedure as for
the ozonolysis of 2a -f were applied for the ozonolysis of 33 to
give the trioxa-cage 34 in 80% yield: white solid; mp 161-
162 °C; IR (CHCl3) 2900, 1060 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 5.45 (d, J ) 6.3 Hz, 2H), 4.43-4.40 (m, 2H), 2.94-
2.84 (m, 2H), 2.42-2.36 (m, 2H), 2.17-2.09 (m, 2H), 1.76-
1.60 (m, 4H); 13C NMR (75 MHz, CDCl3, DEPT) δ 103.40
(2CH), 75.78 (2CH), 47.25 (2CH), 39.39 (2CH), 23.74 (CH2),
20.94 (2CH2); LRMS m/z (rel int) 194 (M+, 100); HRMS (EI)
calcd for C11H14O3 194.0943, found 194.0949. Anal. Calcd for
Rea ction of 35 w ith Tr ieth yla m in e. To a solution of pure
compound 35 (0.46 g, 2.0 mmol) in CH2Cl2 (40 mL) was added
Et3N (1.5 g, 15 mmol) at 25 °C. The reaction mixture was
stirred at 25 °C for 4 h. The solvent was evaporated, and the
crude product was purified by column chromatography to give
the dihemiacetal 36 (0.25 g, 60%) and the lactone 37 (0.138 g,
33%). Spectral data for 37: white solid; 158-159 °C; IR
C
11H14O3: C, 68.01; H, 7.27. Found: C, 68.12; H, 7.35.
(CHCl3) 3500-3300, 1770, 1250 cm-1 1H NMR (300 MHz,
;
Ozon olysis of 33 w ith ou t Red u ction . A solution of 33
(0.36 g, 2.0 mmol) in CH2Cl2 (30 mL) was cooled to -78 °C,
and ozone was bubbled through it at -78 °C until the solution
turned light blue. After 10 min stirring, the solvent was
evaporated, and the crude product was purified by column
chromatography to give the hydroperoxide 35 (0.38 g, 85%):
white solid; mp 108-109 °C; IR (CHCl3) 3500-3200, 1100
CDCl3) δ 5.30 (s, 1H), 4.74-4.72 (m, 1H), 4.52-4.46 (m, 1H),
3.21-2.88 (m, 4H), 2.38-2.33 (m, 1H), 1.85-1.63 (m, 6H); 13
C
NMR (75 MHz, CDCl3, DEPT) δ 178.24 (CO), 100.63 (CH),
76.91 (CH), 73.37 (CH), 56.14 (CH), 47.95 (CH), 42.65 (CH),
40.87 (CH), 33.69 (CH2), 24.05 (CH2), 23.16 (CH2); LRMS m/z
(rel int) 210 (M+, 6), 119 (100), 92 (94); HRMS (EI) calcd for
C11H14O4 210.0892, found 210.0899. Anal. Calcd for
1
cm-1; H NMR (300 MHz, CDCl3) δ 9.94 (s, 1H), 5.33 (s, 1H),
5.28 (s, 1H), 4.44-4.41 (m, 2H), 4.17 (brs, 1H), 2.97-2.86 (m,
2H), 2.76-2.67 (m, 2H), 2.14-2.05 (m, 1H), 1.68-1.60 (m, 4H),
1.12-1.00 (m, 1H); 13C NMR (75 MHz, CDCl3, DEPT) δ 109.37
(CH), 99.61 (CH), 76.02 (CH), 74.48 (CH), 54.99 (CH), 51.26
(CH), 41.91 (CH), 41.67 (CH), 33.59 (CH2), 24.29 (CH2), 24.03
(CH2); LRMS m/z (rel int) 228 (M+, 4), 119 (74), 91 (100);
HRMS (EI) calcd for C11H16O5 228.0997, found 228.0985. Anal.
Calcd for C11H16O5: C, 57.87; H, 7.07. Found: C, 57.98; H,
7.16.
Red u ction of 35 w ith Dim eth yl Su lfid e. To a solution
of pure compound 35 (0.23 g, 1.0 mmol) in CH2Cl2 (20 mL)
was added excess Me2S (0.62 g, 10 mmol) at 25 °C. The
reaction mixture was stirred at 25 °C for 3 h. The solvent
was evaporated, and the crude product was purified by column
chromatography to give the dihemiacetal 36 (0.20 g, 90%):
C
11H14O4: C, 62.83; H, 6.72. Found: C, 62.97; H, 6.84.
Ack n ow led gm en t. We thank the National Science
Council of the Republic of China for financial support
(Grant No. NSC86-2113-M009-001).
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra data of compounds 3a , 3d , 5, 6, 16, 18, 25, and 31 (9
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
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J O980632S