Synthesis of pentaoxa[5]peristylanes

Article abstract of DOI:10.1021/jo982049h

The synthesis of alkyl-substituted pentaoxa[5]peristylanes has been accomplished by ozonolysis of 2,3-bis-endo-7-anti-triacymorbornenes 6a-d and by direct chemical transformation of the tetraacetal tetraoxa cages 11 and 12. Various reaction conditions have been used to optimize the overall yield for the synthesis of methyl group substituted pentaoxa[5]peristylane 7d. Ozonolysis of 6d in CDCl₃ at -78°C without reduction was performed to study the ozonolysis chemistry of the triacylnorbornenes 6a-d. The synthesis of the parent (unsubstituted) compound 25 of pentaoxa[5]peristylane has been accomplished by a three-step efficient sequence with a maximum 45% overall yield via ozonolysis of the dihemiacetal 24. The structure of pentaoxa[5]peristylanes was proven by X-ray analysis of the parent compound 25. The syntheses of the triacetal tetraoxa cage 26, a new type of oxa cage, and a new entry for the synthesis of the parent compound 33 of tetraacetal tetraoxa cages were also demonstrated.

Full text of DOI:10.1021/jo982049h

1576
J . Org. Chem. 1999, 64, 1576-1584
Syn th esis of P en ta oxa [5]p er istyla n es
Hsien-J en Wu* and Chung-Yi Wu
Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan, China
Received October 12, 1998
The synthesis of alkyl-substituted pentaoxa[5]peristylanes has been accomplished by ozonolysis of
2,3-bis-endo-7-anti-triacylnorbornenes 6a -d and by direct chemical transformation of the tetraacetal
tetraoxa cages 11 and 12. Various reaction conditions have been used to optimize the overall yield
for the synthesis of methyl group substituted pentaoxa[5]peristylane 7d . Ozonolysis of 6d in CDCl3
at -78 °C without reduction was performed to study the ozonolysis chemistry of the triacylnor-
bornenes 6a -d . The synthesis of the parent (unsubstituted) compound 25 of pentaoxa[5]peristylane
has been accomplished by a three-step efficient sequence with a maximum 45% overall yield via
ozonolysis of the dihemiacetal 24. The structure of pentaoxa[5]peristylanes was proven by X-ray
analysis of the parent compound 25. The syntheses of the triacetal tetraoxa cage 26, a new type of
oxa cage, and a new entry for the synthesis of the parent compound 33 of tetraacetal tetraoxa
cages were also demonstrated.
In tr od u ction
reports regarding the chemistry12 and synthesis13-18 of
oxa cage compounds in the literature. This class of
heterocyclic cages is synthesized by intramolecular alk-
ene-oxirane (2σ-2π) photocycloaddition,13 by transan-
nular cyclization of suitable compounds,14 by tandem
cyclization,15 by dehydration of diols having the proper
stereochemistry,16 by base-promoted rearrangement,17
and by intramolecular etherification of the alkene bond
with organoselenium reagents.18
We visualized that elaboration of oxa cages from
carbocyclic cages might be achieved by replacing the
skeletal carbon atoms with oxygen atoms at the proper
positions and by extending the skeletal backbone. For
instance, starting with homopentaprismane (A), one
might be able to “create” the following three different
types of oxa cage compounds, types B, C, and D (Scheme
1). Also, we can elaborate pentaoxa[5]peristylane F from
[5]peristylane E. We viewed types C, D, and F oxa cages
as cage backboned diacetal, tetraacetal, and pentaacetal
crown ethers, respectively. Types D and F oxa cages, in
particular, can be viewed as a class of cage-backboned
coronands (crown ethers) containing a 2n-crown-n moiety
in which the ligand oxygen atoms are separated by one
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, such as
adamantane,2 triprismane,3 tetraprismane (cubane),4
pentaprismane,5 homopentaprismane,6 hexaprismane,7
heptacyclotetradecane (HCTD),8 pagodane,9 dodecahe-
drane,10 and fullerene (C60).11 On the other hand, the
synthesis and chemistry of heterocyclic cage compounds
have received less attention. However, there are some
(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 and Sons, Inc.: New York, 1990.
(2) Schleyer, P. v. R. J . Am. Chem. Soc. 1957, 79, 3292.
(3) Katz, T. J .; Acton, N. J . Am. Chem. Soc. 1973, 95, 2738.
(4) Eaton, P. E.; Cole, T. W. J . Am. Chem. Soc. 1964, 86, 3157.
(5) (a) Eaton, P. E.; Or, Y. S.; Branca, S. T.; Shankar, B. K.
Tetrahedron 1986, 42, 1621. (b) Eaton, P. E.; Or, Y. S.; Branca, S. T.
J . Am. Chem. Soc. 1981, 103, 2134. (c) Dauben, W. G.; Cunningham,
A. F. J . Org. Chem. 1983, 48, 2842.
(6) (a) Eaton, P. E.; Cassar, L.; Hudson, R. A.; Hwang, D. R. J . Org.
Chem. 1976, 41, 1445. (b) Marchand, A. P.; Chou, T. C.; Ekstrand, J .
D.; Van der Helm, D. J . Org. Chem. 1976, 41, 1438.
(7) (a) Mehta, G.; Padma, S. J . Am. Chem. Soc. 1987, 109, 2212. (b)
Mehta, G.; Padma, S. J . Am. Chem. Soc. 1987, 109, 7230. (c) Mehta,
G.; Reddy, S. H. K.; Padma, S. Tetrahedron 1991, 47, 7821. (d) Mehta,
G.; Padma, S. Tetrahedron 1991, 47, 7807.
(8) (a) Chow, T. J .; Liu, L. K.; Chao, Y. S. J . Chem. Soc., Chem.
Commun. 1985, 700. (b) Chow, T. J .; Chao, Y. S.; Liu, L. K. J . Am.
Chem. Soc. 1987, 109, 797.
(9) (a) Fessner, W. D.; Prinzbach, H.; Rihs, G. Tetrahedron Lett.
1983, 24, 5857. (b) Fessner, W. D.; Sedelmeier, G.; Spurr, P. R.; Rihs,
G.; Prinzbach, H. J . Am. Chem. Soc. 1987, 109, 4626.
(12) (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, W. F., J r.;
Wyrick, C. J . Org. Chem. 1979, 44, 4761.
(13) (13) (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.
(14) (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.
(10) (a) Ternansky, R. J .; Balogh, D. W.; Paquette, L. A. J . Am Chem.
Soc. 1982, 104, 4503. (b) Paquette, L. A.; Ternansky, R. J .; Balogh, D.
W.; Kentgen, G. J . Am. Chem. Soc. 1983, 105, 5446. (c) Paquette, L.
A.; Ternansky, R. J .; Balogh, D. W. J . Am. Chem. Soc. 1982, 104, 4502.
(d) Paquette, L. A.; Ternansky, R. J .; Balogh, D. W.; Taylor, W. J . J .
Am. Chem. Soc. 1983, 105, 5441. (e) Mehta, G.; Nair, M. S. J . Am.
Chem. Soc. 1985, 107, 7519. (f) Eaton, P. E.; Mueller, R. H.; Carlson,
G. R.; Cullison, D. A.; Cooper, G. F.; Chou, T. C.; Krebs, E. P. J . Am.
Chem. Soc. 1977, 99, 2751.
(15) Suri, S. C. J . Org. Chem. 1993, 58, 4153.
(16) (a) Mehta, G.; Srikrishna, A.; Reddy, A. V.; Nair, M. S.
Tetrahedron 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.
(17) (a) Marchand, A. P.; Chou, T. C. Tetrahedron 1975, 31, 2655.
(b) Mehta, G.; Reddy, K. R. J . Org. Chem. 1987, 52, 460.
(18) (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.
(11) (a) Kroto, H. W., Heath, J . R.; O′Brien, S. C.; Curl, R. F.;
Smalley, R. E. Nature 1985, 318, 162. (b) McLafferty, F. W.; Ed. Acc.
Chem. Res. 1992, 25, 5 (3); Special Issue on Buckminsterfullerenes.
10.1021/jo982049h CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/09/1999

Synthesis of Pentaoxa[5]peristylanes
J . Org. Chem., Vol. 64, No. 5, 1999 1577
Sch em e 1
ered a hydride rearrangement and a one-pot conversion
from oxa cages to aza cages.25 We also developed a
method for the synthesis of diacetal trioxa cages26 and
dioxa cages27 by iodine-induced cyclization reaction. As
part of a program that involves the synthesis, chemistry,
and applications of new heterocyclic cages, we report here
the full details of the synthesis of alkyl-substituted
pentaoxa[5]peristylanes28 via the ozonolysis of 2,3-bis-
endo-7-anti-triacylnorbornenes and via the chemical
transformation from tetraoxa cages to pentaoxa[5]-
peristylanes. We also wish to report the synthesis of the
parent (unsubstituted) compound29 of pentaoxa[5]peri-
stylanes and the parent compound of tetraacetal tetraoxa
cages via the ozonolysis of dihemiacetal derivatives of
norbornene and to report the X-ray structure of pentaoxa-
[5]peristylane 25. Also, we wish to report the synthesis
of triacetal tetraoxa cage 26, a new type of oxa cage.
Sch em e 2
Resu lts a n d Discu ssion
Syn th esis of P en ta oxa [5]p er istyla n es a n d Con -
ver sion of Tetr a oxa Ca ge to P en ta oxa Ca ge. Reac-
tion of 5-trimethylsilylcyclopentadiene 1 with trimethyl
orthoformate 2 in the presence of trimethylsilyl triflate
(TMSOTf) in dichloromethane at -45 °C gave compound
3,30 which was used for the next reaction without
purification. Diels-Alder reaction of compound 3 with
cis-enediones 4a -d 23,26 in dichloromethane at 0 °C for
72 h gave the anti-endo adducts 5a -d in 70-75% yields.
Treatment of 5a -d with Cu(BF4)2 or methanesulfonic
acid in dichloromethane at 25 °C gave the hydrolysis
products 6a -d in 75-80% yields. Ozonolysis of 6a -c in
dichloromethane at -78 °C, followed by reduction with
dimethyl sulfide, gave the pentaoxa[5]peristylanes 7a -c
in 75-80% yields (Scheme 3). The amounts of the
tetraoxa cages 8, 9, and 10 were too small to be isolated.
Ozonolysis of 6d under the same reaction conditions gave
the tetraoxa cage compounds 11 (34%) and 12 (32%) and
the pentaoxa[5]peristylane 7d (20%). Tetraoxa cage 11
leaves one acetyl group intact, not participating the
cyclization reaction, whereas tetraoxa cage 12 leaves one
formyl group intact. Thus, the synthesis of alkyl-
substituted pentaoxa[5]peristylanes was accomplished for
the first time in our lab.28
bridging carbon atom, whereas most known coronands
are composed of repeating ethyleneoxy units to give the
3n-crown-n moiety. All three types of oxa cages, C, D,
and F , might exhibit interesting cation-binding proper-
ties. Particularly, [5]peristylane19 and pentaoxa[5]peri-
stylane F (R ) R′ ) H) are a class of aesthetically
pleasing and topologically novel molecular entities which
possess bowl-shaped structures.
From the standpoint of retrosynthetic analysis, we
realized that pentaoxa[5]peristylane F can be regarded
as the cyclic acetal form of all-cis 1,2,3,4,5-pentacarbon-
ylcyclopentane G (Scheme 2). To access G, we decided to
utilize the rigid, stereochemically well-defined nor-
bornene framework through strategic positioning of ap-
propriate substituents that could serve as surrogates for
the carbonyl functionality. Accordingly, we chose the
norbornene derivatives H as the starting material for
synthesizing the pentaoxa[5]peristylanes F .
The utility of ozonolysis in organic synthesis usually
centers on the chemical transformation of an alkene bond
to carbonyl groups or to an R-alkoxy hydroperoxide if an
alcohol is present.20 Recently, we utilized the ozonolysis
reaction for the synthesis of a series of oxa cage com-
pounds, such as diacetal trioxa cages,21 triacetal trioxa
cages,22 tetraacetal tetraoxa cages,23 and tetraacetal
pentaoxa cages.24 Later on, we investigated the chemical
nature of the acetal group of tetraoxa cages and discov-
(23) (a) Wu, H. J .; Lin, C. C. J . Org. Chem. 1995, 60, 7558. (b) Lin,
C. C.; Wu, H. J . Tetrahedron Lett. 1995, 36, 9353. (c) Wu, H. J .; Lin,
C. C. J . Org. Chem. 1996, 61, 3820. (d) Wu, H. J .; Chern, J . H.; Wu, C.
Y. Tetrahedron 1997, 53, 2401. (e) Wu, H. J .; Chern, J . H. Tetrahedron
1997, 53, 17653. (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 . Chinese Chem.
Soc. 1995, 42, 815. (h) Lin, C. C.; Huang, F. J .; Lin, J . C.; Wu, H. J . J .
Chinese Chem. Soc. 1996, 43, 177. (i) Lin, R. L.; Wu, C. Y.; Chern, J .
H.; Wu, H. J . J . Chinese Chem. Soc. 1996, 43, 289. (j) Chern, J . H.;
Wu, H. J .; Wang, S. L.; Liao, F. L. J . Chinese Chem. Soc. 1998, 45,
139.
(24) Lin, C. C.; Wu, H. J . Synthesis 1996, 715.
(25) (a) Wu, H. J .; Chern, J . H. J . Org. Chem. 1997, 62, 3208. (b)
Wu, H. J .; Chern, J . H. Tetrahedron Lett. 1997, 38, 2887. (c) Chern, J .
H.; Wu. H. J . Tetrahedron 1998, 54, 5967. (d) Wu, H. J .; Chern, J . H.
J . Chem. Soc., Chem. Commun. 1997, 547.
(26) (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 . Chinese Chem. Soc. 1996, 43, 445.
(19) Eaton, P. E.; Mueller, R. H. J . Am. Chem. Soc. 1972, 94, 1014.
(20) Bailey, P. S. Ozonation in Organic Chemistry; Academic
Press: New York, 1978, Vol. 1; 1982, Vol. 2.
(21) Wu, H. J .; Chao, C. S.; Lin, C. C. J . Org. Chem. In press.
(22) (a) Wu, H. J .; Wu, C. Y.; Lin, C. C. Chinese Chem. Lett. 1996,
7, 15. (b) Wu, C. Y.; Lin, C. C.; Lai, M. C.; Wu, H. J . J . Chinese. Chem.
Soc. 1996, 43, 187.
(27) (a) Lin, H. C.; Wu, C. Y.; Wu, H. J . J . Chinese Chem. Soc. 1997,
44, 609. (b) Yen, C. H.; Tsai, S. H.; Wu, H. J . J . Chinese Chem. Soc. In
press.
(28) (a) Wu, C. Y. Masters Thesis, National Chiao Tung University,
1996. (b) Wu, H. J .; Wu, C. Y. Tetrahedron Lett. 1997, 38, 2493.
(29) Mehta, G.; Vidya, R. Tetrahedron Lett. 1997, 38, 4173.
(30) Sternbach, D. D.; Hobbs, S. H. Synth. Commun. 1984, 14, 1305.

1578 J . Org. Chem., Vol. 64, No. 5, 1999
Wu and Wu
Sch em e 3
Sch em e 4
carbonyl group on the apical carbon to the oxonium ion
gives the oxonium ion 16 (route a). Nucleophilic addition
of the alkoxide ion to the oxonium ion gives the pentaoxa
cage 7d . On the other hand, hydride rearrangement25
(route b) of 15 gives the product 13. A similar mechanism
can be applied for the conversion of 12 to 7d . These
results indicate that the nucleophilic addition of the
formyl group on the apical carbon to the oxonium ion 15
may be faster than that of the acetyl group. Also, the
nucleophilic addition of the acetyl group on the apical
carbon to the oxonium ion 15 may be faster than the
hydride rearrangement. Treatment of 11 and 12 with
Amberlyst-15 or concentrated hydrochloric acid in dichlo-
romethane at 25 °C gave the pentaoxa[5]peristylane 7d
in a quantitative yield. Thus, we have demonstrated for
the first time the direct conversion of tetraacetal tetraoxa
cage to pentaoxa[5]peristylane. Also, we have accom-
plished the synthesis of alkyl-substituted pentaoxa[5]-
peristylanes in 35-45% overall yields, starting from
compound 3.
We also performed the chemical transformations of
tetraoxa cages 11 and 12 to pentaoxa[5]peristylane 7d .
Treatment of 11 with a catalytic amount of TiCl4 in
dichloromethane at 25 °C for 4 h gave the pentaoxa[5]-
peristylane 7d in 75% yield and the hydride rearrange-
ment product 13 in 20% yield (Scheme 4). Reaction of 12
under the same reaction conditions gave 7d in 90% yield.
The amount of 14 was too small to be isolated. A
mechanism was proposed for the conversion of 11 to 7d
and 13. Coordination of TiCl4 regioselectively to the O4
oxygen atom of 11 followed by cleavage of the C3-O4 bond
gives the oxonium ion 15. Nucleophilic addition of the
Op tim iza tion of th e Over a ll Yield of 7d w ith
Va r iou s Rea ction Con d ition s. Ozonolysis of 5d in
dichloromethane at -78 °C, followed by reduction with
dimethyl sulfide, gave compound 17 in 20% yield with
several unidentified compounds. Ozonolysis of 5d in
dichloromethane at -78 °C in the presence of sodium

Synthesis of Pentaoxa[5]peristylanes
J . Org. Chem., Vol. 64, No. 5, 1999 1579
Sch em e 5
Sch em e 6
1
were obtained in a negligible amount. The H and 13C
NMR spectra of 19 were taken at -30 °C right after the
ozonation reaction without purification. The 1H NMR
spectrum of 19 revealed one singlet at δ 9.93 for the
aldehyde proton, two singlets at δ 6.53 and 6.37 for the
1,2,4-trioxolane ring protons, and two singlets at δ 2.29
and 2.03 for the two methyl ketone protons. The 13C NMR
spectrum of 19 displayed two singlets at δ 205.81 and
204.60 for the two methyl ketone carbons, one peak at
δ197.53 for the aldehyde carbon, and two peaks at δ
100.83 and 100.48 for the 1,2,4-trioxolane ring carbons.
These results are consistent with our previous report23d
in that it is the anti carbonyl group on the apical carbon
rather than the endo carbonyl group that reacts intra-
molecularly with the carbonyl oxide group to form the
final ozonide.
Syn th esis a n d Str u ctu r e of th e Un su bstitu ted
P en ta oxa [5]p er istyla n e 25 a n d New Oxa Ca ge 26.
In the course of synthesis of cage compounds, the
synthesis of the parent (unsubstituted) compound is also
important . Diels-Alder reaction of compound 3 with
maleic anhydride in dichloromethane at 0 °C for 24 h
gave the endo adduct 22 in 90% yield. Reaction of 22 with
LiAlH4 in dry THF at refluxing temperature gave the diol
23 in 70% yield. Swern oxidation of 23 in dichlo-
romethane gave the dihemiacetal 24 in 80% yield, which
is a mixture of stereoisomers. Ozonolysis of the crude
product 24 in dichloromethane at -78 °C, followed by
reduction with dimethyl sulfide, gave the parent pentaoxa-
[5]peristylane 25 in a low yield (20%) with unidentified
compounds. Ozonolysis of 24 in dichloromethane at -78
°C, followed by reduction with dimethyl sulfide and then
treatment of the reaction mixture with Amberlyst-15 or
concentrated HCl, gave 25 in 85% yield (Scheme 7).
Reaction of furan with dimethyldioxirane32 at -78 °C,
followed by addition of compound 3 at 0 °C, gave the endo
adduct 24 in 58% yield. Thus, the parent pentaoxa[5]-
peristylane 25 was obtained in 45% overall yield by a
three-step sequence, starting from compound 1. This is
the shortest and most efficient sequence for the synthesis
of 25.33 Ozonolysis of the diol 23 in dichloromethane at
-78 °C, followed by reduction with dimethyl sulfide and
then treatment of the reaction mixture with Amberlyst-
bicarbonate, followed by reduction with dimethyl sulfide,
gave 17 in 70% yield (Scheme 5). Treatment of 17 with
Amberlyst-15 or concentrated hydrochloric acid in dichlo-
romethane at 25 °C gave the pentaoxa[5]peristylane 7d
in a quantitative yield. Ozonolysis of 5d in dichlo-
romethane at -78 °C, followed by reduction with di-
methyl sulfide and then treatment of the mixture with
Amberlyst-15, gave the pentaoxa cage 7d in 68% yield.
Ozonolysis of 5d in methanol at -78 °C in the presence
of sodium bicarbonate, followed by reduction with dim-
ethyl sulfide, gave compound 18 in 84% yield. The
stereochemistry of the hydroxy and methoxy groups of
18 was not determined. Treatment of 18 with Amberlyst-
15 or concentrated hydrochloric acid in dichloromethane
at 25 °C gave the pentaoxa cage 7d in a quantitative
yield. Thus, we have optimized the overall yield of
pentaoxa[5]peristylane 7d up to 64%, starting from 3,
via compound 18.
Ozon olysis Ch em istr y on Com p ou n d 6d . We also
focused our attention on the ozonolysis chemistry to
clarify the site selectivity of the final ozonide formation.
Ozonolysis of 6d in CDCl3 at -78 °C gave the final
ozonide 19 (>95%) (Scheme 6). The isomers 20 and 21
(31) Ozonolysis of 6d in dichloromethane at -78 °C followed by
removal of the solvent at room temperature without reduction gave
oligomeric or polymeric products which were not soluble in CDCl3 for
taking NMR spectra.
(32) (a) Adam, W.; Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989,
22, 205. (b) Murray, R. W. Chem. Rev. 1989, 89, 1187.

1580 J . Org. Chem., Vol. 64, No. 5, 1999
Wu and Wu
Sch em e 7
F igu r e 1. ORTEP diagram of 25.
1
spectrum of 26 exhibited the correct value. The H NMR
spectrum of 25 revealed one broad singlet at δ 4.90 for
the five equivalent acetal protons and another broad
singlet at δ 2.76 for the five methine protons (with
DMSO-d6 as solvent). The 13C NMR spectrum of 25
displayed one peak at δ 113.33 for the five acetal carbons
and one peak at δ 57.45 for the five methine carbons.
The structure of pentaoxa[5]peristylanes was also proven
by X-ray analysis of the crystalline compound 25 (Figure
1).
Compound 25 crystallizes from dichloromethane-
hexane as colorless needles with crystal dimensions 0.50
× 0.12 × 0.12 mm. The molecule crystallizes in an
orthorhombic space group Pnma, with unit cell param-
eters a ) 13.3576(6), b ) 10.9486(5), and c ) 5.5123(3)
Å, V ) 806.2(3) Å3, Z ) 4, with high crystal density Dc )
1.732 g/cm3. Compound 25 does not possess the antici-
pated C5v symmetry in the solid state but displays Cs
symmetry in the crystal with the crystallographic mirror
plane passing through O2, C4, and C5. The distances from
O1 to C6a, O1 to O3a, and O2 to O3a are 4.25, 3.88, and
3.39 Å, respectively, on the basis of calculations with
Simens SHELXTL PLUS (VMS). These distances are
greater than the summation of the diameter of sodium
cation and the van der Waals radius of the carbon or
oxygen atom. Therefore, we estimate that the cavity of
pentaoxa[5]peristylanes is large enough for binding a
sodium cation or lithium cation. In other words, we expect
that pentaoxa[5]peristylanes may exhibit interesting
cation-binding properties. A study on the applications of
pentaoxa[5]peristylanes for their cation-binding proper-
ties is undertaken.
Syn th esis of Oth er Oxa Ca ges. Diels-Alder reaction
of compound 3 with trans-endione 2722 in dichloromethane
at 0 °C for 72 h gave the trans-adduct 28 in 75% yield.
Treatment of 28 with methanesulfonic acid in dichlo-
romethane at 25 °C gave the hydrolysis product 29 in
80% yield. Ozonolysis of 29 in dichloromethane at -78
°C, followed by reduction with dimethyl sulfide, gave the
tetraacetal tetraoxa cage 30 in 90% yield (Scheme 8).
Treatment of 30 with Amberlyst-15 or concentrated HCl
in dichloromethane at 25 °C remained unchanged. No
detectable amount of the pentaoxa[5]peristylane 7d was
obtained.
We have also utilized a sequence similar to that shown
in Scheme 7 to synthesize the parent compound of
tetraacetal tetraoxa cages. Reduction of cyclopentadiene-
maleic anhydride adduct with LiAlH4 in dry THF at
refluxing temperature gave the diol 31. Swern oxidation
15, gave the tetraoxa cage compound 26 in 85% yield.
Tetraoxa cage 26 possesses a new type of skeleton.
The IR spectrum of 26 showed no hydroxyl and
carbonyl absorptions. The 1H NMR spectrum of 26
revealed one doublet at δ 5.84 for the two acetal protons
on C-3 and C-7, one doublet at δ 5.70 for the acetal proton
on C-5, and two doublets of doublets at δ 4.29 and 4.02
for the methylene protons on C-1 and C-9. The 13C NMR
spectrum of 26 displayed one peak at δ 112.18 for the
acetal carbons C-3 and C-7, one peak at δ 111.50 for the
acetal carbon C-5, and one peak at δ 70.53 for the
secondary carbons C-1 and C-9. The high-resolution mass
(33) After we accomplished the synthesis of alkyl-substituted
pentaoxa[5]peristylanes,28 Prof. Mehta et al. reported the synthesis of
25 by a 10-step sequence in a 0.3% overall yield.29

Synthesis of Pentaoxa[5]peristylanes
J . Org. Chem., Vol. 64, No. 5, 1999 1581
Sch em e 8
7a -c in high yields. Ozonolysis of 7-anti-formyl-2,3-bis-
endo-diacetylbicyclo[2.2.1]-5-heptene 6d under the same
reaction conditions gave the tetraoxa cages 11 and 12
and the pentaoxa[5]peristylane 7d . The tetraoxa cages
11 and 12 can be converted into the pentaoxa[5]-
peristylane 7d by treatment with TiCl4 or Amberlyst-15
or concentrated HCl in dichloromethane. Optimization
of the overall yield of the pentaoxa cage 7d was per-
formed with various reaction procedures. We have also
demonstrated that it is the anti carbonyl group on the
apical carbon rather than the endo carbonyl group that
reacts intramolecularly with the carbonyl oxide group to
form the final ozonide, consistent with our previous
report.23d The synthesis of the parent compound of
pentaoxa[5]peristylanes was accomplished in a 45%
overall yield by a three-step sequence. The structure of
pentaoxa[5]peristylanes was proven by X-ray analysis of
the parent compound 25. The synthesis of a new type of
oxa cage, 26, was also accomplished. The synthesis of the
parent compound 33 of tetraacetal tetraoxa cages via a
new route was also performed.
Sch em e 9
Exp er im en ta l Section
Gen er a l. Melting points were determined in capillary tubes
and are uncorrected. Infrared spectra were recorded in CHCl3
1
solutions or as neat thin films between NaCl disks. H 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. X-ray analyses were carried out
on a diffractometer at the Department of Chemistry, National
Tsing Hua University. 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 nitro-
gen.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2,3-Bis-
en d o-d ia cyln or bor n en es 5a -d . To a solution of 5-trimeth-
ylsilylcyclopentadiene 1 (1.0 g, 7.3 mmol) in dichloromethane
(30 mL) was added trimethyl orthoformate (0.85 g, 8.0 mmol)
at 25 °C. The mixture was cooled to -40 °C, and a catalytic
amount of TMSOTf (0.16 g, 0.73 mmol) was added at -40 °C.
The reaction mixture was stirred at -40 °C for 0.5 h. The
mixture was quenched by addition of a saturated NaHCO3
aqueous solution. Extractive workup with dichloromethane
followed by an ice-water wash, drying over K2CO3, and
evaporating the solution at 0 °C afforded the crude product
3,30 which was kept at 0 °C without purification for the Diels-
Alder reaction. To this crude product 3 in dichloromethane (30
mL) was added the cis-enedione 4d 23 (0.89 g, 8.0 mmol) at 0
°C. The reaction mixture was stirred at 0 °C for 72 h. The
solvent was evaporated, and the crude product was purified
by column chromatography to give the endo adduct 5d (1.0 g)
in 55% overall yield. The same reaction conditions and
procedure were applied to the preparation of 5b-d in 70-
75% yields.
of 31 in dichloromethane gave the dihemiacetal 32 as the
major product and two other stereoisomers as the minor
products. The stereochemistry of the hydroxy groups of
32 was determined on the basis of NOE experiments.
Irradiating the alkene protons (δ 6.10) of 32 gives 3.8%
enhancement for the hemiacetal proton absorptions and
4.0% enhancement for the bridgehead proton absorptions.
Irradiating the hemiacetal protons (δ 4.97) of 32 gives
4.7% enhancement for the alkene proton absorptions and
4.8% enhancement for the bridgehead proton absorptions.
Ozonolysis of the mixture of 32 and its stereoisomers in
dichloromethane at -78 °C, followed by reduction with
dimethyl sulfide and then treatment with Amberlyst-15,
gave the parent compound 33 in 85% yield (Scheme 9), a
new entry for the synthesis of 33. The parent tetraoxa
cage 33 was also obtained by ozonolysis of 2-endo-7-anti-
diformylnorbornene 34.23d
2,3-Bis-en d o-d ia cetyl-7-a n ti-d im eth oxym eth ylbicyclo-
[2.2.1]-5-h ep ten e 5d : pale yellow oil liquid; IR (neat) 1710,
1
1050 cm-1; H NMR (300 MHz, CDCl3) δ 6.13 (brs, 2H), 4.22
Con clu sion
(δ, J ) 8.1 Hz, 1H), 3.42 (brs, 2H), 3.31 (s, 6H), 3.17 (brs, 2H),
2.05 (s, 6H), 2.00-1.97 (m, 1H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 205.99 (2CO), 132.07 (2CH), 102.99 (CH), 62.20 (CH),
57.45 (2CH), 53.90 (2CH3), 47.89 (2CH), 29.86 (2CH3); LRMS
m/z (rel int) 252 (M+, 10), 221 (100); HRMS (EI) calcd for
We have accomplished for the first time the synthesis
of alkyl-substituted pentaoxa[5]peristylanes. Ozonolysis
of 6a -c in dichloromethane at -78 °C followed by
reduction with Me2S gave the pentaoxa[5]peristylanes

1582 J . Org. Chem., Vol. 64, No. 5, 1999
Wu and Wu
C14H20O4 252.1362, found 252.1375. Anal. Calcd for C14H20O4:
C, 66.63; H, 7.99. Found: C, 66.55; H, 7.94.
195 (100); HRMS (EI) calcd for C12H14O5 238.0841, found
238.0849. Anal. Calcd for C12H14O5: C, 60.48; H, 5.93. Found:
C, 60.59; H, 5.97.
Hyd r olysis of 5a -d . To a solution of 5d (0.50 g, 2.00 mmol)
in dichloromethane (30 mL) was added methanesulfonic acid
(MeSO3H) (0.19 g, 2.00 mmol) at 25 °C. The reaction mixture
was stirred at room temperature for 15 min. After addition of
saturated NaHCO3 (20 mL) and extraction with CH2Cl2, the
organic layer was washed with brine, dried over MgSO4, and
evaporated, and the residue was purified by column chroma-
tography to give 6d (0.33 g, 80%). The same reaction conditions
and procedure were applied for the preparation of 6a -c in 80-
85% yields.
1,3-Dim eth yl-10-syn -for m yl-2,4,6,13-tetr aoxapen tacyclo-
[5.5.1.03,11.05,9.08,12]tr id eca n e 12: white solid; mp 187-188
1
°C; IR (neat) 1725, 1050 cm-1; H NMR (300 MHz, CDCl3) δ
9.96 (s, 1H), 5.85 (d, J ) 5.1 Hz, 1H), 5.68 (d, J ) 6.3 Hz, 1H),
3.56-3.48 (m, 1H), 3.24-3.16 (m, 3H), 3.03-3.00 (m, 1H), 1.56
(s, 3H), 1.48 (s, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 199.20
(CHO), 116.36 (C), 108.93 (CH), 107.92 (C), 101.06 (CH), 57.43
(CH), 56.04 (CH), 53.01 (CH), 50.95 (CH), 45.11 (CH), 27.48
(CH3), 25.06 (CH3); LRMS m/z (rel int) 238 (M+, 5), 195 (100);
HRMS (EI) calcd for C12H14O5 238.0841, found 238.0820. Anal.
Calcd for C12H14O5: C, 60.48; H, 5.93. Found: C, 60.41; H,
5.88.
2-en d o-7-a n ti-Difor m yl-3-en d o-a cet yln or b or n en e 6a :
-1
pale yellow oil liquid; IR (neat) 2820, 2720, 1710 cm
;
1H
NMR (300 MHz, CDCl3) δ 9.61 (d, J ) 2.1 Hz, 1H), 9.52 (d, J
) 2.4 Hz, 1H), 6.44 (dd, J ) 6.0, 3.0 Hz, 1H), 6.10 (dd, J )
6.0, 3.0 Hz, 1H), 3.81-3.77 (m, 1H), 3.69 (brs, 1H), 3.58 (brs,
1H), 3.14-3.09 (m, 1H), 2.47 (d, J ) 1.5 Hz, 1H), 2.21 (s, 3H);
13C NMR (75 MHz, CDCl3, DEPT) δ 205.20 (CO), 202.32
(CHO), 200.19 (CHO), 134.98 (CH), 131.78 (CH), 69.72 (CH),
59.05 (CH), 55.35 (CH), 48.27 (CH), 46.44 (CH), 28.75 (CH3);
LRMS m/z (rel int) 192 (M+, 12), 191 (58), 190 (63), 163 (100);
HRMS calcd for C11H12O3 192.0786, founf 192.0790. Anal.
Calcd for C11H12O3: C, 65.95; H, 10.07. Found: C, 65.87; H,
10.01.
1,9-Dim eth yl-2,4,6,8,15-p en ta oxa h exa cyclo[7.5.1.03,13.-
05,12.07,11.010,14]p en ta d eca n e 7d : white solid; mp 235-236 °C;
IR (CHCl3) 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ 5.90 (d, J
) 6.0 Hz, 1H), 5.85 (d, J ) 5.4 Hz, 2H), 3.68-3.65 (m, 3H),
3.39-3.35 (m, 2H), 1.51 (s, 6H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 120.30 (2C), 113.33 (CH), 112.46 (2CH), 62.72 (2CH),
58.91 (2CH), 58.53 (CH), 26.94 (2CH3); LRMS m/z (rel int) 238
(M+, 14), 223 (100); HRMS (EI) calcd for C12H14O5 238.0841,
found 238.0845. Anal. Calcd for C12H14O5: C, 60.48; H, 5.93.
Found: C, 60.60; H, 5.99.
2,3-Bis-en do-diacetyl-7-a n ti-for m yln or bor n en e 6d: pale
Rea ction of 11 w ith Ca ta lytic TiCl4 in CH2Cl2. To a
solution of 11 (0.24 g, 1.00 mmol) in dichloromethane (50 mL)
was added a catalytic amount of TiCl4 (0.010 g, 0.005 mmol)
at room temperature. The reaction mixture was stirred at 25
°C for 4 h. The reaction mixture was quenched by addition of
water (30 mL) and extracted with dichloromethane. The
organic layer was washed with brine, dried over MgSO4, and
evaporated, and the residue was purified by column chroma-
tography to give the pentaoxa[5]peristylane 7d (0.18 g) in 75%
yield and the hydride rearrangement product 13 (0.048 g) in
20% yield.
yellow oil liquid; IR (neat) 2820, 2720, 1710 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 9.60 (d, J ) 2.1 Hz, 1H), 6.23 (brs, 2H),
3.54 (brs, 2H), 3.32 (brs, 2H), 2.39 (d, J ) 2.1 Hz, 1H), 2.09 (s,
6H); 13C NMR (75 MHz, CDCl3, DEPT) δ 205.11 (2CO), 203.13
(CHO), 132.76 (2CH), 69.02 (CH), 56.74 (2CH), 47.91 (2CH),
29.93 (2CH3); LRMS m/z (rel int) 266 (M+, 15), 205 (45), 177
(100); HRMS (EI) calcd for C12H14O3 206.0943, found 206.0955.
Anal. Calcd for C12H14O3: C, 71.14; H, 8.54. Found: C, 71.22;
H, 8.59.
Gen er a l P r oced u r e for th e Ozon olysis of 6a -c. F or -
m a tion of th e P en ta oxa [5]p er istyla n es 7a -c. A solution
of 6a (0.50 g, 2.78 mmol) in dichloromethane (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
dimethyl sulfide (0.30 g, 4.86 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 pentaoxa[5]peristylane
7a (0.48 g) (78%).
Sp ectr a l d a ta for 13: white waxy solid; mp 143-145 °C;
1
IR (CHCl3) 2980, 1770, 1715, 1250, 1070 cm-1; H NMR (300
MHz, CDCl3) δ 6.07 (d, J ) 6.3 Hz, 1H), 5.96 (d, J ) 6.0 Hz,
1H), 3.92-3.50 (m, 5H), 2.47 (dd, J ) 9.0, 9.0 Hz, 1H), 2.29 (s,
3H), 1.39 (d, J ) 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT)
δ 205.90 (CO), 177.90 (CO), 111.12 (CH), 106.57 (CH), 78.43
(CH), 60.83 (CH), 56.08 (CH), 55.26 (CH), 50.49 (CH), 48.62
(CH), 27.67 (CH3), 19.46 (CH3); LRMS m/z (rel int) 238 (M+,
34), 195(100); HRMS (EI) calcd for C12H14O5 238.0841, found
238.0835. Anal. Calcd for C12H14O5: C, 60.48; H, 5.93. Found:
C, 60.59; H, 5.98.
Con ver sion of 12 to 7a . The same reaction conditions and
prodecure as for the reaction of 11 with TiCl4 in CH2Cl2 were
applied for the conversion of 12 to give 7d in 90% yield. The
amount of the hydride rearrangement product 14 was too
small to be isolated.
Ozon olysis of 5d . F or m a tion of Com p ou n d 17. Meth od
1. A solution of 5d (0.50 g, 1.98 mmol) in dichloromethane (80
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 (0.60 g, 9.9 mmol) at -78 °C. The
reaction mixture was stirred at room temperature for 6 h. The
solvent was evaporated, and the crude product was purified
by column chromatography to give compound 17 (0.11 g, 20%)
with several unidentified compounds. Meth od 2. A solution
of 5d (0.50 g, 1.98 mmol) in dichloromethane (80 mL) was
cooled to -78 °C, and ozone was bubbled through it at -78 °C
until the solution turned light blue. To this solution were
added solid NaHCO3 (2.5 g) and dimethyl sulfide (0.60 g, 9.9
mmol) at -78 °C. The reaction mixture was stirred at room
temperature for 6 h. The solvent was evaporated, and the
crude product was purified by column chromatography to give
compound 17 (0.39 g, 70%).
1-Meth yl-2,4,6,8,15-p en ta oxa h exa cyclo[7.5.1.03,13.05,12.-
07,11.010,14]p en ta d eca n e 7a : white solid; mp 254-255 °C; IR
(CHCl3) 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ 5.90 (d, J )
6.0 Hz, 2H), 5.87 (d, J ) 5.4 Hz, 2H), 3.69-3.64 (m, 3H), 3.35-
3.32 (m, 2H), 1.52 (s, 3H); 13C NMR (75 MHz, CDCl3, DEPT)
δ 123.57 (C), 113.49 (2CH), 112.79 (2CH), 59.92 (CH), 58.74
(2CH), 58.24 (2CH), 39.42 (CH3); LRMS m/z (rel int) 224 (M+,
8), 209 (100); HRMS (EI) calcd for C11H12O4 224.0685, found
224.0692. Anal. Calcd for C11H12O4: C, 63.44; H, 5.81. Found:
C, 63.58; H, 5.87.
Ozon olysis of 6d . F or m a tion of th e Tetr a a ceta l Tet-
r a oxa Ca ges 11 a n d 12 a n d th e P en ta oxa [5]p er istyla n e
7d . A solution of 6d (0.50 g, 2.43 mmol) in dichloromethane
(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 dimethyl sulfide (0.30 g, 4.86 mmol) at -78
°C. Then, the reaction mixture was stirred at room tempera-
ture for 5 h. The solvent was evaporated, and the crude product
was purified by column chromatography to give the tetraacetal
tetraoxa cages 11 (0.208 g) (36%) and 12 (0.185 g) (32%) and
the pentaoxa[5]peristylane 7d (0.115 g) (20%).
3-Met h yl-10-syn -a cet yl-2,4,6,13-t et r a oxa p en t a cyclo-
[5.5.1.03,11.05,9.08,12]tr id eca n e 11: white solid; mp 183-184
°C; IR (CHCl3) 1710, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ
5.85 (d, J ) 5.1 Hz, 1H), 5.79 (d, J ) 5.4 Hz, 1H), 5.69 (d, J )
4.5 Hz, 1H), 3.54-3.36 (m, 2H), 3.17-3.10 (m, 3H), 2.27 (s,
3H), 1.48 (s, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 204.83
(CO), 108.98 (C), 108.95 (CH), 107.90 (CH), 101.44 (CH), 56.84
(CH), 53.90 (CH), 51.94 (CH), 50.59 (CH), 45.56 (CH), 29.07
(CH3), 27.01 (CH3); LRMs m/z (rel int) 238 (M+, 17), 223 (56),
Sp ectr a l d a ta for 17: white waxy solid; mp 67-68 °C; IR
(CHCl3) 2980, 2880, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ
5.53 (d, J ) 5.7 Hz, 2H), 4.83 (d, J ) 9.6 Hz, 1H), 3.37 (s, 6H),
3.16-3.13 (m, 2H), 2.92-2.86 (m, 2H), 2.50-2.46 (m, 1H), 1.69
(s, 6H); 13C NMR (75 MHz, CDCl3, DEPT) δ 117.15 (2C), 102.55
(CH), 101.45 (2CH), 56.95 (2CH), 53.90 (2CH3), 46.42 (2CH),

Synthesis of Pentaoxa[5]peristylanes
J . Org. Chem., Vol. 64, No. 5, 1999 1583
46.39 (CH), 25.07 (2CH3); LRMS m/z (rel int) 284 (M+, 11),
253 (100); HRMS (EI) calcd for C14H20O6 284.1260, found
284.1268. Anal. Calcd for C14H20O6: C, 59.13; H, 7.09. Found:
C, 59.25; H, 7.20.
Ozon olysis of 5d in Meth a n ol. F or m a tion of Com -
p ou n d 18. A solution of 5d (0.50 g, 1.98 mmol) in methanol
(80 mL) was cooled to -78 °C, and ozone was bubbled through
it at -78 °C until the solution turned light blue. To this
solution were added dimethyl sulfide (0.60 g, 9.9 mmol) and
solid NaHCO3 (2.5 g,) at -78 °C. The reaction mixture was
stirred at room temperature for 6 h. The solvent was evapo-
rated, and the crude product was purified by column chroma-
tography to give compound 18 (0.53 g, 84%).
Sp ectr a l d a ta for 18: pale yellow oil liquid; IR (neat) 3450,
2960, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ 5.67(d, J ) 2.7
Hz, 1H), 5.19 (s, 1H), 4.75 (d, J ) 9.0 Hz, 1H), 3.42 (s, 3H),
3.38 (s, 3H), 3.35 (s, 3H), 3.23-3.12 (m, 2H), 2.77-2.75 (m,
2H), 2.64-2.60 (m, 1H), 1.74 (brs, 1H), 1.61 (s, 3H), 1.53 (s,
3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 117.68 (C), 116.49
(C), 105.76 (CH), 102.71 (CH), 99.69 (CH), 59.53 (CH), 58.02
(CH), 55.00 (CH3), 54.10 (CH), 53.93 (CH3), 52.67 (CH3), 52.52
(CH), 48.54 (CH), 26.51 (CH3), 26.42 (CH3); LRMS m/z (rel int)
316 (M+, 11), 75 (100); HRMS (EI) calcd for C15H24O7 316.1522,
found 316.1530.
Ozon olysis of 6d in CDCl3. F or m a tion of th e F in a l
Ozon id e 19. A solution of 6d (0.010 g, 0.048 mmol) in CDCl3
(1 mL) was cooled to -78 °C, and ozone was bubbled through
it at - 78 °C until the solution turned light blue to give the
final ozonide 19 (>95%). This solution was bubbled with N2
to get rid of excess ozone at -78 °C. The 1H and 13C NMR
spectra of 19 were taken at -30 °C right after the ozonation
reaction without purification.
Sp ectr a l d a ta for 19: 1H NMR (300 MHz, CDCl3) δ 9.93
(s, 1H), 6.53 (s, 1H), 6.37 (s, 1H), 3.69 (dd, J ) 6.9, 6.9 Hz,
1H), 3.1-3.00 (m, 2H), 2.92-2.87 (m, 2H), 2.29 (s, 3H), 2.03
(s, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 205.81 (CO),
204.60 (CO), 197.53 (CHO), 100.83 (CH), 100.48 (CH), 55.37
(CH), 55.09 (CH), 54.80 (CH), 45.26 (CH), 44.19 (CH), 29.98
(CH3), 29.39 (CH3).
P r ep a r a t ion of Com p ou n d 22. To a solution of 5-tri-
methylsilylcyclopentadiene 1 (0.50 g, 3.7 mmol) in dichlo-
romethane (25 mL) was added trimethyl orthoformate (0.43
g, 4.0 mmol) at 25 °C. The mixture was cooled to -40 °C, and
a catalytic amount of TMSOTf (0.12 g, 0.55 mmol) was added
at -40 °C. The reaction mixture was stirred at -40 °C for 30
min. The mixture was quenched by addition of a saturated
NaHCO3 aqueous solution. Extractive workup with dichlo-
romethane followed by an ice-water wash, drying over K2-
CO3, and evaporation of the solvent at 0 °C afforded the crude
product 3. To the crude product 3 in dichloromethane (25 mL)
was added maleic anhydride (0.40 g, 4.1 mmol) at 0 °C. The
reaction mixture was stirred at 0 °C for 18 h. The solvent was
evaporated, and the crude product was purified by column
chromatography to give the endo adduct 22 (0.64 g) in 73%
overall yield.
Sp ectr a l d a ta for 23: white solid; mp 112-114 °C; IR
(CHCl3) 3600-3300, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ
5.98 (brs, 2H), 4.22 (d, J ) 8.4 Hz, 1H), 4.13 (brs, 2H), 3.62-
3.56 (m, 2H), 3.43-3.35 (m, 2H), 3.31 (s, 6H), 2.80 (brs, 2H),
2.60-2.56 (m, 2H), 2.08-2.05 (m, 1H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 132.39 (2CH), 102.73 (CH), 63.48 (CH), 62.55
(2CH2), 53.17 (2CH3), 47.75 (2CH), 45.56 (2CH); LRMS m/z
(rel int) 228 (M+, 1), 210 (100); HRMS (EI) calcd for C12H20O4
228.1362, found 228.1368.
Sw er n Oxid a tion of Com p ou n d 23. A mixture of DMSO
(2.5 mL, 35 mmol) and CH2Cl2 (6 mL) was added to a solution
of oxalyl chloride (2.6 g, 20 mmol) in CH2Cl2 (20 mL) at -55
°C. After the mixture was stirred for 30 min, a solution of 23
(0.68 g, 3.0 mmol) in CH2Cl2 (13 mL) and DMSO (12 mL) was
added at -55 °C. The solution was stirred at -55 °C for 2 h.
Triethylamine (9.3 mL, 49 mmol) was then added, and the
reaction mixture was allowed to warm to 25 °C for 30 min.
Water (25 mL) was then added, and the CH2Cl2 layer was
separated. Concentrated HCl was added to the aqueous part,
followed by extraction of the aqueous solution with CH2Cl2.
The combined organic solutions were washed once with 1 N
HCl and once with a saturated NaCl solution. The organic
layer was dried over MgSO4 and evaporated to give the
dihemiacetal 24 (0.58 g) (80%), which is a mixture of stereo-
isomers. The crude product 24 was run for the next ozonolysis
reaction without purification.
Ozon olysis of 24. For m ation of P en taoxa[5]per istylan e
25. A solution of 24 (0.48 g, 2.00 mmol) in dichloromethane
(40 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 (0.25 g, 4.00 mmol) at -78
°C. The reaction mixture was stirred at room temperature for
6 h. The solvent was evaporated, and the crude product was
purified by column chromatography to give the parent pentaoxa-
[5]peristylane 25 (0.084 g) in 20% yield with unidentified
compounds.
2,4,6,8,15-P en ta oxa h exa cyclo[7.5.1.03,13.05,12.07,11.010,14]-
p en ta d eca n e 25: white solid; mp >230 °C (dec); IR (CHCl3)
1
1070 cm-1; H NMR (300 MHz, CD3SOCD3) δ 4.90 (brs, 5H),
2.76 (brs, 5H); 13C NMR (75 MHz, CD3SOCD3, DEPT) δ 113.33
(5CH), 57.45 (5CH); LRMS m/z (rel int) 210 (M+, 1), 182 (22),
79 (100); HRMS (EI) calcd for C10H10O5 210.0528, found
210.0536. Anal. Calcd for C10H10O5: C, 57.13; H, 4.80. Found:
C, 57.02; H, 4.70.
Ozon olysis of 24 F ollow ed by Tr ea tm en t w ith Am -
ber lyst-15. Efficien t Syn th esis of P en ta oxa [5]p er istyla n e
25. A solution of 24 (0.48 g, 2.00 mmol) in dichloromethane
(40 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 (0.25 g, 4.00 mmol) at -78
°C. After 5 min of stirring, Amberlyst-15 (1.00 g) was added
to the solution. Then, the reaction mixture was stirred at room
temperature for 24 h. After filtration of Amberlyst-15, the
solvent was evaporated, and the crude product was purified
by column chromatography to give pentaoxa[5]peristylane 25
(0.36 g) in 85% yield.
Ozon olysis of 23 F ollow ed by Tr ea tm en t w ith Am -
ber lyst-15. Syn th esis of New Tetr a oxa Ca ge Com p ou n d
26. The same reaction conditions and procedure as for the
efficient synthesis of pentaoxa[5]peristylane 25 were applied
for the synthesis of the new-type tetraoxa cage 26 in 85%
yield: white solid; mp 151-153 °C; IR (CHCl3) 1070 cm-1; 1H
NMR (300 MHz, CDCl3) δ 5.84 (d, J ) 6.0 Hz, 2H), 5.70 (d, J
) 6.0 Hz, 1H), 4.29 (dd, J ) 9.0, 4.8 Hz, 2H), 4.02 (dd, J )
9.0, 7.5 Hz, 2H), 3.56-3.47 (m, 2H), 3.30-3.20 (m,1H), 3.10-
3.00 (m, 2H); 13C NMR (75 MHz, CDCl3, DEPT) δ 112.18
(2CH), 111.50 (CH), 70.53 (2CH2), 59.34 (2CH), 52.93 (CH),
47.37 (2CH); LRMS m/z (rel int) 196 (M+, 8), 150 (62), 111
(100); HRMS (EI) calcd for C10H12O4 196.0736, found 196.0748.
Anal. Calcd for C10H12O4: C, 61.20; H, 6.17. Found: C, 61.33;
H, 6.23.
Sp ectr a l d a ta for 22: white solid; mp 93-94 °C; IR (CHCl3)
1865, 1780, 1100 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.35 (brs,
2H), 4.26 (d, J ) 7.8 Hz, 1H), 3.70-3.67 (m, 2H), 3.55-3.52
(m, 2H), 3.38 (s, 6H), 2.30-2.27 (m, 1H); 13C NMR (75 MHz,
CDCl3, DEPT) δ 170.67 (2CO), 133.23 (2CH), 102.03 (CH),
66.89 (2CH), 53.81 (2CH3), 47.16 (CH), 46.76 (2CH); LRMS
m/z (rel int) 238 (M+, 11), 207 (100); HRMS (EI) calcd for
C
12H14O5 238.0841, found 238.0828.
Red u ction of 22 w ith LiAlH4. To a solution of compound
22 (0.50 g, 2.10 mmol) in dry THF (30 mL) was added LiAlH4
(0.21 g, 6.30 mmol) at 25 °C. The reaction mixture was refluxed
for 12 h. After cooling, solid potassium sodium tartrate (3.0 g)
was added. To this reaction mixture was then dropwise added
saturated potassium sodium tartrate (20 mL) at 0 °C. The
reaction mixture was filtered through Celite. The filtrate was
extracted with ether. The combined organic layer was washed
with brine, dried over MgSO4, and evaporated, and the residue
was purified by column chromatography to give the diol 23
(0.335 g) in 70% yield.
P r ep a r a tion of Com p ou n d 28. The same reaction condi-
tions and procedure as for the preparation of compounds 5a -d
were applied for the preparation of compound 28. In this case,

1584 J . Org. Chem., Vol. 64, No. 5, 1999
Wu and Wu
a Diels-Alder reaction of crude compound 3 with (3E)-3-
hexene-2,5-dione 27 in dichloromethane was applied.
Sp ectr a l d a ta for 28: pale yellow oil; IR (neat) 1710, 1380,
1050 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.13 (dd, J ) 6.0, 3.0
Hz, 1H), 5.85 (dd, J ) 6.0, 3.0 Hz, 1H), 4.16 (d, J ) 8.1 Hz,
1H), 3.40-3.37 (m, 1H), 3.24 (brs, 1H), 3.22 (s, 3H), 3.14 (s,
3H), 2.95 (brs, 1H), 2.86 (d, J ) 4.5 Hz, 1H), 2.21-2.18 (m,
1H), 2.17 (s, 3H), 2.08 (s, 3H); 13C NMR (75 MHz, CDCl3,
DEPT) δ 208.02 (CO), 206.30 (CO), 135.29 (CH), 131.27 (CH),
101.73 (CH), 60.30 (CH), 55.14 (CH), 53.30 (CH3), 53.16 (CH3),
51.64 (CH), 47.59 (CH), 46.95 (CH), 29.44 (CH3), 28.51 (CH3);
LRMS m/z (rel int) 252 (M+, 8), 224 (100); HRMS (EI) calcd
for C14H20O4 252.1362, found 252.1371.
m/z (rel int) 238 (M+, 13), 190 (100); HRMS (EI) calcd for
C
12H14O5 238.0841, found 238.0833. Anal. Calcd for C12H14O5:
C, 60.48; H, 5.93. Found: C, 60.61; H, 9.99.
Sw er n Oxid a tion of Com p ou n d 31. The same reaction
conditions and procedure as for the Swern oxidation of
compound 23 were applied for the oxidation of 31 to give the
dihemiacetal 32 as the major product and the other two
stereoisomers as the minor products. The stereochemistry of
the hydroxy groups of 32 was determined on the basis of NOE
experiments.
3â,5â-Dih yd r oxy-4-oxa t r icyclo[5.2.1.02,6]-8-d ecen e 32:
pale yellow oil liquid: IR (neat) 3500-3300, 1050 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 6.10 (brs, 2H), 4.97 (brs, 2H), 3.96
(brs, 2H), 3.05 (brs, 2H), 2.99 (brs, 2H), 1.45-1.33 (m, 2H);
13C NMR (75 MHz, CDCl3, DEPT) δ 134.40 (2CH), 102.20
(2CH), 54.83 (2CH), 51.30 (CH2), 44.80 (2CH); LRMS m/z (rel
int) 168 (M+, 3), 151 (100).
P r ep a r a tion of Com p ou n d 29. The same reaction condi-
tions and procedure as for the preparation of compounds 6a -d
were applied for the preparation of 29.
Sp ectr a l d a ta for 29: pale yellow oil; IR (neat) 2820, 2720,
1
1720, 1710 cm-1; H NMR (300 MHz, CDCl3) δ 9.56 (d, J )
Ozon olysis of 32 F ollow ed by Tr ea tm en t w ith Am -
ber lyst-15. A New En tr y for th e Syn th esis of Tetr a oxa
Ca ge 33. The same reaction conditions and prodecure as for
the ozonolysis of 24 followed by treatment with Amberlyst-15
were applied for the ozonolysis of 32 to give the parent tetraoxa
cage 33 in 85% yield. The parent tetraoxa cage 33 was also
synthesized by ozonolysis of 2-endo-7-anti-diformylnorbornene
34.23d
1.5 Hz, 1H), 6.28 (dd, J ) 6.0, 3.0 Hz, 1H), 6.03 (dd, J ) 6.0,
3.0 Hz, 1H), 3.67 (brs, 1H), 3.48-3.44 (m, 1H), 3.42 (brs, 1H),
3.06-3.04 (m, 1H), 2.67 (d, J ) 1.5 Hz, 1H), 2.26 (s, 3H), 2.17
(s, 3H); 13C NMR (75 MHz, CDCl3, DEPT) δ 207.97 (CO),
205.70 (CO), 202.17 (CHO), 135.86 (CH), 132.45 (CH), 68.04
(CH), 54.80 (CH), 53.02 (CH), 47.43 (CH), 46.47 (CH), 29.71
(CH3), 28.66 (CH3); LRMS m/z (rel int) 206 (M+, 5), 175 (100);
HRMS (EI) calcd for C12H14O3 206.0943, found 206.0950.
Ozon olysis of 29. F or m a tion of Tetr a oxa Ca ge 30. The
same reaction conditions and procedure as for the ozonolysis
of 6a -d were applied for the ozonolysis of 29 to give tetraoxa
cage 30 in 90% yield.
Ack n ow led gm en t. We thank the National Science
Council of the Republic of China for financial support
(Grant NSC86-2113-M009-001). We also thank Dr. S.
L. Wang and Ms. F. L. Liao (at the Department of
Chemistry, National Tsing Hua University) for their
help in carring out the X-ray crystallographic analyses.
3-Met h yl-10-a n ti-a cet yl-2,4,6,13-t et r a oxa p en t a cyclo-
[5.5.1.03,11.05,9.08,12]tr id eca n e 30: white solid; mp 183-184
°C; IR (CHCl3) 1710, 1050 cm-1; 1H NMR (300 MHz, CDCl3) δ
5.80 (d, J ) 5.4 Hz, 1H), 5.76 (d, J ) 5.4 Hz, 1H), 5.56 (d, J )
6.3 Hz, 1H), 3.51-3.42 (m, 2H), 3.13 (brs, 1H), 3.04-2.99 (m,
1H), 2.83-2.80 (m, 1H), 2.30 (s, 3H), 1.48 (s, 3H); 13C NMR
(75 MHz, CDCl3, DEPT) δ 206.94 (CO), 109.77 (C), 109.36
(CH), 108.69 (CH), 102.78 (CH), 56.22 (CH), 53.30 (CH), 52.02
(CH), 51.53 (CH), 47.08 (CH), 27.95 (CH3), 25.94 (CH3); LRMS
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectral data of compounds 5a -c, 6b,c, and 7b,c and the X-ray
data for compounds 25. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O982049H