Ozonolysis of highly methylated 1,2-bis(methylene)cycloalkanes. Influence of the methyl substituents on the course of the reaction

Article abstract of DOI:10.1021/jo960397i

In the ozonolyses of highly methylated 3,3,4,4,5,5-hexamethyl-1,2-bis(methylene)cyclopentane (1a) and 3,3,6,6-tetramethyl-1,2-bis(methylene)cyclohexane (1b), the epoxidation competed with the cleavage of the C-C double bond, whereas only the latter proces

Full text of DOI:10.1021/jo960397i

J . Org. Chem. 1996, 61, 5939-5943
5939
Ozon olysis of High ly Meth yla ted 1,2-Bis(m eth ylen e)cycloa lk a n es.
In flu en ce of th e Meth yl Su bstitu en ts on th e Cou r se of th e
Rea ction
Hideyuki Yamakoshi,† Shin-ichi Kawamura,† Masatomo Nojima,*,† Herbert Mayr,*,‡ and
J anusz Baran‡,§
Department of Material Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565, J apan,
and Institut fur Organische Chemie, Technische Hochschule Darmstadt, 64287 Darmstadt, Germany
Received February 27, 1996X
In the ozonolyses of highly methylated 3,3,4,4,5,5-hexamethyl-1,2-bis(methylene)cyclopentane (1a )
and 3,3,6,6-tetramethyl-1,2-bis(methylene)cyclohexane (1b), the epoxidation competed with the
cleavage of the C-C double bond, whereas only the latter process was observed in the case of the
nonmethylated 1,2-bis(methylene)cycloalkanes 1c,d . Competition experiments revealed that the
reactivity of the highly methylated 1,2-bis(methylene)cycloalkanes 1a ,b is significantly smaller
than that of the nonmethylated ones (1c,d ), suggesting that the formation of the primary ozonides
2c,d occurs by a concerted 1,3-dipolar cycloaddition process.
Sch em e 1
3,3,4,4,5,5-Hexamethyl-1,2-bis(methylene)cyclopen-
tane (1a ) incorporates a planar s-cis-fixed 1,3-diene
system in which the nonterminal positions are sterically
shielded. As a consequence, compound 1a has been found
to show a relatively great tendency to undergo 1,4-
additions instead of 1,2-additions with dihalocarbenes,
diphenylketene, (1,3-diphenylazaallyl)lithium, and C,N-
diphenylnitrone.1 We considered that the reaction of the
diene 1a with ozone would provide further insight into
the mechanism of the ozonization reaction, e.g., the
competition between cleavage of the C-C double bond
vs epoxidation,2 the concertedness of the 1,3-dipolar
cycloaddition yielding the primary ozonide, and the
direction of cleavage of the primary ozonide.3 For this
purpose, ozonolyses of the diene 1a were conducted under
several conditions, and the results were compared with
those of 3,3,6,6-tetramethyl-1,2-bis(methylene)cyclohex-
ane (1b) and the nonmethylated 1,2-bis(methylene)-
cycloalkanes 1c,d .
Resu lts a n d Discu ssion
Rea ction P r od u cts. The reaction of diene 1a with
2.5 equiv of ozone in ether led to the formation of epoxy
ketone 8a (42%) and normal ozonide 10a (16%) (Scheme
1 and Table 1). From the reaction with 1 equiv of ozone,
ozonide 10a , vinyl epoxide 3a , and epoxy ketone 8a were
obtained in yields of 20%, 20%, and 16%, respectively.
Vinyl epoxide 3a was labile, and during column chroma-
tography on silica gel, it sometimes rearranged to vinyl
aldehyde 12a (Scheme 2). Pure vinyl epoxide 3a was
prepared by the reaction of diene 1a with 3,3-dimethyl-
1,2-dioxirane,4 followed by distillation under reduced
pressure (Scheme 2). Treatment of 3a with ozone gave
epoxy ketone 8a , which was reduced by lithium alumi-
num hydride to give diol 13a as a 9:1 mixture of two
Ta ble 1. Ozon olysis of 1,2-Bis(m eth ylen e)cycloa lk a n es
1a -ea
substr
solvent
additivec
products (% yield)
1a b
1a
1a
1a
1b
1b
1b
1c
1c
1d
1d
1e
a
ether
ether
MeOH-ether (1:2)
ether
ether
3a (20), 8a (16), 10a (20)
8a (42), 10a (16)
8a (24), 12a (15)
PhCOCF3 8a (42), 9a (11), 11 (23)
3b (19), 10b (33)
MeOH-ether (1:2)
3b (26), 14b (53)
ether
ether
ether
ether
ether
ether
PhCOCF3 3b (41), 9b (45), 11 (11)
10c (13)d
PhCOCF3 9c (71)
10d (14)d
PhCOCF3 9d (86)
PhCOCF3 9e (71)
† Osaka University.
‡ Technische Hochschule Darmstadt.
Unless otherwise noted, substrate 1 was treated with 2.5 equiv
§ Present address: Institute of Fundamental Chemistry, Technical
University of Szczecin, Al. Piastow 42, PL-71065, Szczecin, Poland.
X Abstract published in Advance ACS Abstracts, J uly 1, 1996.
(1) Mayr, H.; Baran, J .; Heigl, U. W. Gazz. Chim. Ital. 1991, 121,
373.
of ozone at -70 °C. Reaction with 1 equiv of ozone. c Reaction in
b
the presence of 1 equiv of trifluoroacetophenone. The 1H NMR
d
spectrum of the crude reaction mixture showed that the ozonide
was produced almost quantitatively. However, during isolation
by column chromatography on silica gel, it decomposed signifi-
cantly.
(2) Bailey, P. S.; Hwang, H. H.; Chiang, C. -Y. J . Org. Chem. 1985,
50, 231.
(3) (a) Mayr, H.; Baran, J .; Will, E.; Yamakoshi, H.; Teshima, K.;
Nojima, M. J . Org. Chem. 1994, 59, 5055. (b) Criegee, R. Chem. Ber.
1975, 108, 743. (c) Griesbaum, K.; Volpp, W. Chem. Ber. 1988, 121,
1795. (d) Teshima, K.; Kawamura, S.; Ushigoe, Y.; Nojima, M.;
McCullough, K. J . J . Org. Chem. 1995, 60, 4755.
diastereoisomers. In contrast to the high reactivity of
vinyl epoxide 3a toward ozone, vinyl ozonide 10a did not
react with this reactive 1,3-dipole.
S0022-3263(96)00397-0 CCC: $12.00 © 1996 American Chemical Society

5940 J . Org. Chem., Vol. 61, No. 17, 1996
Yamakoshi et al.
Sch em e 2
Sch em e 3
The structures of the products imply that two alterna-
tive pathways participate in the ozonization of diene 1a :
the cleavage process leading to the formation of normal
ozonide 10a and the epoxidation leading to the formation
of vinyl epoxide 3a and products 8a and 12a derived from
it.5 Cleavage of the double bond in 1a proceeds via
primary ozonide 2a (Scheme 1). To confirm the direction
of cleavage of 2a , we first studied the reaction of diene
1a in MeOH-ether. However, only 12a and 8a , derived
from epoxidation, were isolated (Scheme 2). In order to
capture the expected carbonyl oxides, 4a and 7, derived
from the cycloreversion of 2a , we conducted the reaction
in ether in the presence of trifluoroacetophenone.6 To-
gether with epoxy ketone 8a (42% yield), two cross-
ozonides, 9a and 11, were obtained in yields of 11% and
23%, respectively. Though a part of the material could
not be detected, the product composition 8a /(9a + 11)
indicates that epoxidation and cleavage occur to a similar
extent. The ratio of 9a /11 led us to deduce that both of
the possible modes of cleavage of 2a (paths a and b in
Scheme 1) participate, the ratio being around 1:2. In
other words, the formation of the less hindered formal-
dehyde oxide 7 predominates.
Sch em e 4
The behavior of 3,3,6,6-tetramethyl-1,2-bis(methylene)-
cyclohexane (1b) toward ozone in ether was similar to
that of 1a (Scheme 3 and Table 1). Treatment of the
diene 1b with ozone in ether gave vinyl ozonide 10b
(33%) and vinyl epoxide 3b (19%). When the same
reaction was repeated in MeOH-ether, however, meth-
oxyalkyl hydroperoxide 14b, derived from capture of
ketone oxide 4b, was isolated in 53% yield, together with
vinyl epoxide 3b (26%). The reaction of 1b in ether in
the presence of trifluoroacetophenone gave a mixture of
vinyl epoxide 3b (41%) and two cross-ozonides, 9b and
11. It is interesting to note that the yield of 9b (45%)
was significantly higher than that of 11 (11%). The latest
reaction suggested that (i) the ratio of epoxidation vs
cleavage is ca. 2:3 and (ii) for the cleavage of 2b, path a
affording the more-hindered ketone O-oxide 4b is favored.
It should be noticed that in the case of 2a the alternative
path b predominated.
presence or absence of trifluoroacetophenone (Table 1 and
Scheme 4). The reaction of 1,2-bis(methylene)cyclopen-
tane (1c) in ether gave quantitatively the expected vinyl
ozonide 10c, which was however very labile on silica gel.7
Therefore, the ozonide 10c could only be isolated in a
yield of 13%. Analogously, 14% of 10d was isolated from
the ozonolysis of 1,2-bis(methylene)cyclohexane (1d ).
When the reaction of the diene 1c was conducted in the
presence of trifluoroacetophenone, ketone O-oxide 4c was
intercepted by the additive and vinyl ozonide 9c was
isolated in 71% yield. The analogous ozonide 9d was
even obtained in 86% yield by ozonolysis of diene 1d
under the same conditions (Table 1). These results
suggest that in the ozonolyses of 1c,d 1,3-dipolar cy-
cloaddition is the initial reaction and, moreover, the
directions of cleavage of the primary ozonides 2c,d are
highly selective, yielding exclusively the corresponding
ketone O-oxides 4c,d . This is in harmony with the fact
that ozonolysis of 2,3-dimethyl-1,3-butadiene (1e) in the
presence of trifluoroacetophenone gave only the corre-
sponding ozonide 9e in 71% yield (eq 1). In this connec-
tion, Griesbaum and Volpp3c have found that ozonolysis
of 2,3-di-tert-butyl-1,3-butadiene, a sterically more con-
gested diene, in methanol proceeds by an alternative
To understand the methyl-substituent effects on the
course of the reactions of 1a ,b, the ozonolyses of the
nonmethylated dienes 1c,d were carried out in the
(4) Curci, R.; Fiorentino, M.; Troisi, L.; Edwards, J . O.; Pater, R. H.
J . Org. Chem. 1980, 45, 4758.
(5) (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.
(6) Fukagawa, R.; Nojima, M. J . Chem. Soc., Perkin Trans. 1 1994,
2449.
(7) Small vinyl ozonides are well-known to be labile thermally and
on silica gel: Griesbaum, K.; Volpp, W.; Greinert, R.; Greunig, H.-J .;
Schmid, J .; Henke, H. J . Org. Chem. 1989, 54, 383 and references
therein.

Methylated 1,2-Bis(methylene)cycloalkane Ozonolysis
J . Org. Chem., Vol. 61, No. 17, 1996 5941
Ta ble 2. Com p etitive Rea ction of Tw o Su bstr a tes w ith
Ozon e in th e P r esen ce of Tr iflu or oa cetop h en on ea
Sch em e 5
entry
substr
products (% yield)
recovered diene (%)
1
2
3
4
5
6
7
1a , 1c
1a , 15
1c, 15
1b, 1d
1b, 15
1d , 15
1c, 1d b
9c (68)
16 (65)
9c (53), 16 (35)
9d (80)
16 (51)
1a (56)
1a (58)
1b (59)
1b (59)
9d (64), 16 (33)
10c (43), 10d (46)c
reactive than its nonmethylated analogue 1c (8.73 eV)
as previously reported for the relative reactivities of these
two dienes toward the electrophilic diethyl acetylenedi-
carboxylate (k1a /k1c ) 6.9).9
a
Ozonolysis of a 1:1 mixture of two substrates (1 mmol of each)
with ozone (1 mmol) in the presence of trifluoroacetophenone (1
b
mmol) in ether at -70 °C. Ozonolysis in the absence of trifluo-
roacetophenone. c Yield determined by the 1H NMR spectrum of
the crude reaction mixture.
The low reactivity of 1a (and 1b) toward ozone,
therefore, indicates that the accelerating electronic effect
of the methyl groups is overcompensated by their retard-
ing steric effect, which may be operative in the transition
state of a concerted cycloaddition reaction (17, Scheme
5). The observed relative reactivities of the methylated
and nonmethylated dienes 1 exclude a stepwise cycload-
dition mechanism to account for the formation of 2: If
rate-determining attack of ozone at one of the freely
accessible terminal H2C groups of 1a and 1c would occur
to lead to the formation of the dipolar or diradical
intermediate 18 (Scheme 5), 1a would be expected to
react faster than 1c for the electronic reasons discussed
above. Reversible formation of 18 with rate-determining
cyclization cannot account for the >100 fold difference
in reactivity either, since all eventual intermediates 18
(R ) H or CH3) would undergo rapid cyclizations. The
steric blocking which might retard the formation of
primary ozonide 2a or epoxide 3a from 18 could be
circumvented by cyclization to a seven-membered ring
compound, as previously observed with other 1,3-dipoles.1
We, therefore, have to conclude that the high rate of
formation of primary ozonide 2c compared to 2a excludes
the formation of the “ordinary” vinyl ozonide 2c by a
stepwise cycloaddition pathway. The data are consistent,
however, with the formation of 2c by a concerted 1,3-
dipolar cycloaddition mechanism. Since it cannot be
decided whether case c or d (Scheme 27 in ref 1) is
encountered, the mechanism responsible for the forma-
tion of sterically shielded ozonides 2a and 2b remains
open for discussion.
scission pathway, yielding formaldehyde oxide and tert-
butyl 1-tert-butylvinyl ketone, together with an epoxide.
Rela tive Rea ctivities. Thus, it is clear that in the
ozonolyses of bis(methylene)cycloalkanes the allylic me-
thyls exert a significant influence on the mode of addition
of ozone to the olefinic double bond and also on the
direction of cleavage of the primary ozonide. To obtain
information on the effect of the allylic methyls on the
relative reactivity of the dienes toward ozone, we con-
ducted a series of competitive reactions. When an
equimolar mixture of the dienes 1a and 1c was treated
with 0.5 equiv of ozone (i.e., 1a :1c:O3 ) 1:1:1) in the
presence of trifluoroacetophenone, the crossed-ozonide 9c
(68%) derived from capture of carbonyl oxide 4c by
trifluoroacetophenone was the sole isolable product.
While 56% of unreacted diene 1a was recovered, no
evidence for the reaction of 1a with ozone was obtained
(Table 2, entry 1). The analogous experiment with a 1:1
mixture of 1b and 1d showed the exclusive ozonization
of 1d (Table 2, entry 4). Competition experiments with
the pairs 1c/15 and 1d /15 (eq 2, Table 2, entries 3 and
6) indicated monoene 15 to be approximately half as
reactive as nonmethylated dienes 1c and 1d . In ac-
Exp er im en ta l Section
Gen er a l. 1H and 13C NMR spectra were taken on J EOL
J NM-EX 270 MHz or J NM-PS 100 MHz spectrometer in CDCl3
(unless otherwise noted) with SiMe4 as standard. Dienes 1a ,10
1b,11 1c,12 and 1d 12 were prepared by the reported methods.
Ozonolyses were carried out with a Nippon Ozone Model ON-
1-2 ozonator; dry oxygen containing about 2% of ozone was
introduced at a speed of 50 L/h in the solution of the substrate.
Rea ction of 3,3,4,4,5,5-Hexa m eth yl-1,2-bis(m eth ylen e)-
cyclop en ta n e (1a ) w ith 2.5 Equ iv of Ozon e in Eth er . A
solution of diene 1a (534 mg, 3.00 mmol) in ether (15 mL) was
treated with 2.5 equiv of ozone at -70 °C. After evaporation
of the solvent, the residue was separated by column chroma-
tography on silica gel (column 2.0 × 60 cm; 40 g of silica gel).
cordance with this, the 1H NMR spectrum of the reaction
mixture obtained from the reaction of a 1:1 mixture of
1c and 1d with 0.5 equiv of ozone in ether provided a ca.
1:1 mixture of vinyl ozonides 10c and 10d . Yet, when
equimolar mixtures of 1a and 15 or 1b and 15 were
treated with 0.5 equiv of ozone in the presence of
trifluoroacetophenone, again no evidence for the reaction
of methylated dienes 1a and 1b was found (Table 2,
entries 2 and 5). Assuming an NMR detection limit of
3%, one can derive from these experiments that methyl-
ated dienes 1a and 1b are at least 2 orders of magnitude
less reactive than their nonmethylated counterparts 1c
and 1d , respectively.
(8) (a) Sustmann, R. Pure Appl. Chem. 1974, 40, 569. (b) Houk, K.
N.; Yamaguchi, K. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A.,
Ed.; Wiley: New York, 1984; Vol. II, Chapter 13.
(9) Baran, J .; Mayr, H. Tetrahedron 1989, 45, 3347.
(10) Baran, J .; Klein, H.; Schade, C.; Will, E.; Koschinsky, R.; Ba¨uml,
E.; Mayr, H. Tetrahedron 1988, 44, 2181.
(11) (a) Mayr, H.; Klein, H.; Sippel, E. Chem. Ber. 1983, 116, 3624.
(b) Mayr, H.; Heigl, U. W.; Baran, J . Chem. Ber. 1993, 126, 1913.
(12) van Straten, J . W.; van Norden, J . J .; van Schaik, T. A. M.;
Franke, G. T.; de Wolf, W. H.; Bickelhaupt, F. Recl. Trav. Chim. Pays-
Bas 1978, 97, 105.
Ozone is by far the most electrophilic of the common
1,3-dipoles, i.e., its reactions with C-C double bonds are
controlled by the HOMO (olefin)/LUMO (O3) interaction.8
For electronic reasons, methylated diene 1a (vertical
ionization potential ) 8.4 eV)1 should therefore be more

5942 J . Org. Chem., Vol. 61, No. 17, 1996
Yamakoshi et al.
Elution with ether-hexane (3:97) gave vinyl ozonide 10a (108
mg, 16%). Subsequent elution with ether-hexane gave keto
epoxide 8a (245 mg, 42%). Treatment of isolated ozonide 10a
(60 mg) with 1.2 equiv of ozone in ether at -70 °C, followed
by column chromatography on silica gel, resulted in quantita-
tive recovery of the ozonide 10a (58 mg).
7,7,8,8,9,9-Hexa m eth yl-6-m eth ylen e-1,2,4-tr ioxa sp ir o-
[4.4]n on a n e (10a ): oil; 1H NMR (CCl4) δ 0.88 (br s, 12 H),
1.08 (s, 3 H), 1.12 (s, 3 H), 5.07 (s, 1 H), 5.10 (s, 1 H), 5.18 (s,
1 H), 5.38 (s, 1 H); 13C NMR δ 18.86, 21.03, 22.23, 23.19, 29.22,
29.69, 42.90, 44.34, 47.78, 94.09, 110.89, 115.11, 158.73. Anal.
Calcd for C13H22O3: C, 68.99; H, 9.80. Found: C, 69.17; H,
9.78.
47.43, 47.76, 64.94, 108.28, 158.38, 204.32; IR 2900-3000,
1715, 1450, 1380, 1140, 1070, 880 cm-1
.
Ozon olysis of Dien e 1a in th e P r esen ce of Tr iflu or o-
a cetop h en on e in Eth er . Ozonolysis of 1a (214 mg, 1.20
mmol) was conducted in the presence of 1 equiv of trifluoro-
acetophenone (209 mg, 1.20 mmol) in ether (15 mL). After
evaporation of the solvent, the residue was separated by
column chromatography on silica gel. The first fraction
(elution with ether-hexane, 2:98) gave ozonide 9a (50 mg,
11%) as a 9:1 mixture of two stereoisomers (major isomer, δ
4.68, 4.78; minor isomer, δ 5.35, 5.87) (vinyl protons). By
repeated column chromatography on silica gel, the major
isomer of 9a was isolated in a pure state. From the second
fraction, ozonide 11 (60 mg, 23%) was obtained. The third
fraction (elution with ether-hexane, 8:92) contained epoxy
ketone 8a (100 mg, 42%).
3-P h en yl-3-(t r iflu or om et h yl)-6-m et h ylen e-7,7,8,8,9,9-
h exam eth yl-1,2,4-tr ioxaspir o[4.4]n on an e (9a): oil; 1H NMR
(CCl4) δ 0.93 (s, 6 H), 1.03 (s, 6 H), 1.07 (s, 3 H), 1.15 (s, 3 H),
4.68 (s, 1 H), 4.78 (s, 1 H), 7.3-7.7 (m, 5 H); 13C NMR δ 18.34,
21.51, 22.52, 23.47, 29.16, 29.71, 42.81, 44.43, 47.70, 102.63
(q, J ) 33 Hz), 111.58, 119.00, 121.61 (q, J ) 288 Hz), 126.90,
128.14, 128.18, 130.13, 157.52; Anal. Calcd for C20H25F3O3:
C, 64.85; H, 6.80. Found: C, 64.58; H, 6.94.
4-Oxo-5,5,6,6,7,7-h exa m et h yl-1-oxa sp ir o[2.4]h ep t a n e
(8a ): oil; 1H NMR (CCl4) δ 0.90 (br s, 12 H), 1.08 (s, 3 H), 1.27
(s, 3 H), 2.74 (d, J ) 7 Hz, 1 H), 2.90 (d, J ) 7 Hz, 1 H); 13C
NMR δ 20.13, 21.32, 21.79, 23.20, 23.68, 24.75, 39.56, 42.87,
49.32, 51.87, 66.22, 220.66; IR 2900-3000, 1740, 1380 cm-1
.
Reduction of 8a with lithium aluminum hydride in ether led
to the quantitative formation of 2,3,3,4,4,5,5-heptamethyl-1,2-
cyclopentanediol (13a ) as a 9:1 mixture of two stereoisomers,
from which only the major isomer was isolated in a pure state
1
by crystallization from hexane: mp 123-128 °C; H NMR δ
0.80 (s, 3 H), 0.84 (s, 3 H), 0.90 (s, 3 H), 0.91 (s, 3 H), 0.98 (s,
3 H), 1.00 (s, 3 H), 1.18 (s, 3 H), 3.56 (s, 1 H); IR 3500-3100,
3-P h en yl-3-(tr iflu or om eth yl)-1,2,4-tr ioxola n e (11): oil;
1H NMR (CCl4) δ 5.13 (s, 1 H), 5.45 (s, 1 H), 7.3-7.7 (m, 5 H);
13C NMR δ 95.56, 103.03 (q, J ) 34 Hz), 121.49 (q, J ) 289
Hz), 126.77, 128.73, 130.58, further signals not detectable.
Anal. Calcd for C9H7F3O3: C, 49.10; H, 3.21. Found: C, 49.00;
H, 3.03.
Ozon olysis of 3,3,6,6-Tetr a m eth yl-1,2-bis(m eth ylen e)-
cycloh exa n e (1b) in Eth er . A slow stream of ozone (2.5
equiv) was passed into an ether solution (15 mL) of 1b (197
mg, 1.20 mmol) at -70 °C. After evaporation of the solvent,
the residue was separated by column chromatography on silica
gel. Elution with ether-hexane (2:98) gave first ozonide 10b
(84 mg, 33%) and then epoxide 3b (40 mg, 19%).
3000-2900, 1460, 1380, 1100, 1050 cm-1
. Anal. Calcd for
C12H24O2: C, 71.95; H, 12.08. Found: C, 71.77; H, 12.18.
Rea ction of Dien e 1a w ith 1 Equ iv of Ozon e in Eth er .
A solution of diene 1a (303 mg, 1.70 mmol) in ether (15 mL)
was treated with 1 equiv of ozone at -70 °C. After evaporation
of the solvent, the residue was separated by column chroma-
tography on silica gel. Elution with ether-hexane (3:97) gave
a mixture of vinyl ozonide 10a and 4-methylene-5,5,6,6,7,7-
hexamethyl-1-oxaspiro[2.4]heptane (3a ) (the 10a /3a ratio )
1:1; 143 mg, 40%), which could not be separated. Subsequent
elution with ether-hexane (8:92) gave keto epoxide 8a (53 mg,
16%).
Tr ea tm en t of 1a w ith 3,3-Dim eth yl-1,2-d ioxir a n e. To
a solution of diene 1a (615 mg, 3.45 mmol) in benzene was
added a solution of 2KHSO5-KHSO4-K2SO4 (Oxone) (2.9 g),
NaHCO3 (2.0 g), and 18-crown-6 (123 mg) in acetone (2.3 mL)/
H2O (25 mL), and the mixture was kept at room temperature
for 4 h. After ether (50 mL) was added, the organic layer was
washed with aqueous NaHCO3 and then with saturated brine,
and the solvent was evaporated (room temperature, 15 mmHg).
Then the residue was distilled under reduced pressure to give
epoxide 3a (400 mg, 60%).
4-Met h ylen e-5,5,6,6,7,7-h exa m et h yl-1-oxa sp ir o[2.4]-
h ep ta n e (3a ): bp 80 °C/3 mmHg; 1H NMR (CCl4) δ 0.88 (br s,
12 H), 1.07 (s, 3 H), 1.17 (s, 3 H), 2.58 (d, J ) 6 Hz, 1 H), 2.88
(d, J ) 6 Hz, 1 H), 4.85 (s, 1 H), 4.88 (s, 1 H); 13C NMR δ
20.58, 21.58, 21.91, 22.54, 28.72, 29.08, 42.66, 44.37, 45.16,
54.49, 67.80, 104.89, 159.84.
Rea ction of Vin yl Ep oxid e 3a w ith Ozon e. A slow
stream of ozone (1 equiv) was passed into an ether solution
(15 mL) of 3a (270 mg, 1.39 mmol) at -70 °C. After evapora-
tion of the solvent, the residue was separated by column
chromatography on silica gel. Elution with ether-hexane (8:
92) gave epoxy ketone 8a (192 mg, 70%).
Ozon olysis of Dien e 1a in MeOH-Eth er . A MeOH-
ether solution (15 mL, 1:2 v/v) of compound 1a (250 mg, 1.40
mmol) was treated with ozone (3.50 mmol, 2.5 equiv) at -70
°C. After ether (50 mL) was added, the organic layer was
washed with aqueous NaHCO3 and then with saturated brine,
and the solvent was evaporated (room temperature, 15 mmHg).
The 1H NMR spectra of the crude products showed the
formation of vinyl epoxide 3a and epoxy ketone 8a . Column
chromatography of the residue on silica gel (ether-hexane,
5:95) resulted in the elution of vinyl aldehyde 12a (41 mg, 15%)
and then epoxy ketone 8a (66 mg, 24%).
6-Met h ylen e-7,7,10,10-t et r a m et h yl-1,2,4-t r ioxa sp ir o-
[4.5]d eca n e (10b): oil; 1H NMR (CCl4) δ 0.93 (s, 6 H), 1.13 (s,
6 H), 1.3-1.6 (m, 4 H), 5.00 (s, 1 H), 5.02 (d, J ) 2 Hz, 1 H),
5.10 (s, 1 H), 5.28 (d, J ) 2 Hz, 1 H); 13C NMR δ 23.10, 28.66,
29.78, 34.13, 35.68, 37.26, 38.23, 94.25, 110.70, 111.83, 150.42.
Anal. Calcd for C12H20O3: C, 67.89; H, 9.50. Found: C, 67.78;
H, 9.75.
4-Me t h yle n e -5,5,8,8-t e t r a m e t h yl-1-oxa sp ir o[2.5]oc-
ta n e (3b): oil; 1H NMR (CCl4) δ 0.78 (s, 3 H), 0.88 (s, 3 H)
1.05 (s, 3 H), 1.13 (s, 3 H), 1.2-1.8 (m, 4 H), 2.22 (d, J ) 6 Hz,
1 H), 2.87 (d, J ) 6 Hz, 1 H), 4.74 (d, J ) 2 Hz, 1 H), 4.98 (d,
J ) 2 Hz, 1 H); 13C NMR δ 22.54, 24.43, 26.99, 28.60, 34.63,
35.39, 36.14, 37.97, 53.59, 63.87, 104.97, 153.80.
Ozon olysis of 1b in th e P r esen ce of Tr iflu or oa c-
etop h en on e in Eth er . A slow stream of ozone (2.5 equiv)
was passed into an ether solution (15 mL) of 1b (246 mg, 1.50
mmol) and trifluoroacetophenone (251 mg, 1.50 mmol) at -70
°C. After evaporation of the solvent, the residue was separated
by column chromatography on silica gel. Elution with ether-
hexane (2:98) gave ozonide 9b (240 mg, 45%) as a 4:1 mixture
of two isomers (on the basis of the signals of the vinyl protons
in the 1H NMR spectrum). Subsequent elution with ether-
hexane (5:95) gave ozonide 11 (37 mg, 11%) and then vinyl
epoxide 3b (110 mg, 41%). Repeated column chromatography
of a 4:1 mixture of two isomeric ozonides of 9b resulted in the
isolation of the major isomer in a pure state.
3-P h en yl-3-(t r iflu or om et h yl)-6-m et h ylen e-7,7,10,10-
tetr a m eth yl-1,2,4-tr ioxa sp ir o[4.5]d eca n e (9b) (major iso-
1
mer): oil; H NMR (CCl4) δ 0.7-2.0 (m, 16 H), 4.81 (s, 1 H),
5.00 (s, 1 H), 7.3-7.7 (m, 5 H); 13C NMR δ 22.85, 23.68, 28.64,
29.49, 34.73, 35.81, 37.45, 38.11, 103.35 (q, J ) 33 Hz), 112.86,
116.04, 121.58 (q, J ) 290 Hz), 126.65, 127.90, 129.72, 131.88,
148.35. Anal. Calcd for C19H23F3O3: C, 64.03; H, 6.51.
Found: C, 64.12; H, 6.55. The minor isomer was obtained as
an admixture with 75% of the major one; oil, the following
additional signals were assigned to this isomer: 1H NMR
(CCl4) δ 0.7-2.0 (m, 16 H), 5.16 (s, 1 H), 5.53 (s, 1 H), 7.3-7.7
(m, 5 H); 13C NMR δ 23.42, 23.70, 27.64, 28.18, 34.43, 34.86,
2-F or m yl-3,3,4,4,5,5-h exa m eth yl-1-m eth ylen ecyclop en -
1
ta n e (12a ): oil; H NMR (CCl4) δ 0.88 (s, 6 H), 1.05 (s, 6 H),
1.08 (s, 3 H), 1.20 (s, 3 H), 3.05 (q, J ) 3 Hz, 1 H), 4.88 (d, J
) 3 Hz, 1 H), 5.10 (d, J ) 3 Hz, 1 H), 9.60 (d, J ) 3 Hz, 1 H);
13C NMR δ 19.39, 21.95, 23.24, 26.01, 28.42, 29.59, 47.40,

Methylated 1,2-Bis(methylene)cycloalkane Ozonolysis
J . Org. Chem., Vol. 61, No. 17, 1996 5943
35.87, 37.58, 103.40 (q, J ) 33 Hz), 111.61, 117.29, 121.64 (q,
J ) 290 Hz), 126.95, 127.92, 128.14, 129.94, 147.57.
(CCl4) δ 1.43 (s, 3 H), 1.90 (d, J ) 0.6 Hz, 3 H), 5.10 (q, J )
0.6 Hz, 1 H), 5.38 (s, 1 H), 7.2-7.8 (m, 5 H). Anal. Calcd for
Ozon olysis of Dien e 1b in MeOH-Eth er . A MeOH-
ether solution (15 mL, 1:2 v/v) of compound 1b (197 mg, 1.20
mmol) was treated with ozone (3.00 mmol, 2.5 equiv) at -70
°C. After ether (50 mL) was added, the organic layer was
washed with aqueous NaHCO3 and then with saturated brine,
and the solvent was evaporated (room temperature, 15 mmHg).
Column chromatography of the residue on silica gel (ether-
hexane, 2:98) resulted in the elution of vinyl epoxide 3b (56
mg, 26%). Elution with ether-hexane (8:92) gave methoxy-
alkyl hydroperoxide 14b (137 mg, 53%).
C
13H13F3O3: C, 56.93; H, 4.79. Found: C, 56.59; H, 4.68.
Com p etitive Ozon olysis of Dien es 1a a n d 1c in th e
P r esen ce of Tr iflu or oa cetop h en on e. A mixture of 1a (178
mg, 1.00 mmol), 1c (94 mg, 1.00 mmol), and trifluoroacetophe-
none (174 mg, 1.00 mmol) in ether (15 mL) was treated with
ozone (1.00 mmol) at -70 °C. After evaporation of the solvent,
the residue was separated by column chromatography on silica
gel. The first fraction (elution with hexane) contained starting
diene 1a (99 mg, 56%). The second fraction (elution with
ether-hexane, 2:98) gave ozonide 9c (195 mg, 68%).
Com p etitive Ozon olysis of Dien e 1a a n d 3-Hexen e (15)
in th e P r esen ce of Tr iflu or oa cetop h en on e. A mixture of
diene 1a (178 mg, 1.00 mmol), 3-hexene (15) (84 mg, 1.00
mmol), and trifluoroacetophenone (174 mg, 1.00 mmol) in ether
(15 mL) was treated with ozone (1.00 mmol) at -70 °C. After
evaporation of the solvent, the residue was separated by
column chromatography on silica gel. The first fraction
(elution with hexane) contained starting diene 1a (103 mg,
58%). The second fraction (elution with ether-hexane, 2:98)
gave 3-ethyl-5-phenyl-5-(trifluoromethyl)-1,2,4-trioxolane (16)
(161 mg, 65%) as a 2:1 mixture of two stereoisomers.
1-Met h oxy-2-m et h ylen e-3,3,6,6-t et r a m et h ylcycloh ex-
yl h yd r op er oxid e (14b): oil; 1H NMR δ 1.01 (s, 3 H), 1.15 (s,
9 H), 1.2-1.7 (m, 4 H), 3.33 (s, 3 H), 5.33 (d, J ) 2 Hz, 1 H),
5.43 (d, J ) 2 Hz, 1 H), 7.20 (br s, 1 H); 13C NMR δ 22.83,
23.40, 29.89, 35.33, 36.18, 37.08, 40.66, 50.72, 106.91, 114.81,
148.66. Anal. Calcd for C12H22O3: C, 67.29; H, 10.28.
Found: C, 67.40; H, 10.25.
Ozon olysis of 1,2-Bis(m eth ylen e)cycloa lk a n es 1c,d in
Eth er . Ozonolysis of 1c is representative. A solution of diene
1c (198 mg, 2.10 mmol) in ether (15 mL) was treated with 1
equiv of ozone at -70 °C. After evaporation of the solvent,
the 1H NMR spectrum of the crude product mixture was
measured, which indicated exclusive formation of vinyl ozonide
10c. Column chromatography on silica gel (elution with
ether-hexane, 3:97) gave vinyl ozonide 10c (40 mg, 13%).
Subsequent elution with ether-hexane (1:1) gave a complex
mixture of unidentified products (180 mg).
3-E t h yl-5-p h en yl-5-(t r iflu or om et h yl)-1,2,4-t r ioxola n e
(16): oil; 1H NMR δ 0.97 (t, J ) 8 Hz, 2.1 H), 1.10 (t, J ) 8 Hz,
0.9 H), 1.7-1.8 (m, 2 H), 5.23 (t, J ) 5 Hz, 0.33 H), 5.56 (t, J
) 5 Hz, 0.67 H), 7.4-7.6 (m, 5 H); 13C NMR (major isomer) δ
7.71, 23.97, 103.69 (q, J ) 33 Hz), 107.91, 121.68 (q, J ) 287
Hz), 126.79, 128.27, 130.26, 132.51; the following additional
signals were assigned to the minor isomer in the 13C NMR
spectrum; δ 7.74, 22.36, 103.30 (q, J ) 33 Hz), 106.74, 121.67
(q, J ) 287 Hz), 126.67, 128.39, 130.56. Anal. Calcd for
6-Meth ylen e-1,2,4-tr ioxa sp ir o[4.4]n on a n e (10c): oil; 1H
NMR δ 1.5-2.1 (m, 4 H), 2.2-2.7 (m, 2 H), 5.10 (s, 1 H), 5.18
(s, 1 H), 5.20 (t, J ) 2 Hz, 1 H), 5.38 (t, J ) 2 Hz, 1 H); 13C
NMR δ 21.12, 30.06, 35.90, 94.61, 112.57, 115.64, 146.28.
6-Meth ylen e-1,2,4-tr ioxa sp ir o[4.5]d eca n e (10d ): oil; 1H
NMR δ 1.4-2.4 (m, 8 H), 4.91 (t, J ) 1 Hz, 1 H), 5.15 (s, 1 H),
5.20 (t, J ) 1 Hz, 1 H), 5.21 (s, 1 H); 13C NMR δ 24.01, 26.76,
33.68, 35.31, 94.09, 107.71, 109.67, 144.85.
C
11H11F3O3: C, 53.23; H, 4.47. Found: C, 53.29; H, 4.66.
Com p etitive Ozon olysis of Dien e 1c a n d 3-Hexen e (15)
in th e P r esen ce of Tr iflu or oa cetop h en on e. A mixture of
diene 1c (94 mg, 1.00 mmol), 3-hexene (15) (84 mg, 1.00 mmol)
and trifluoroacetophenone (174 mg, 1.00 mmol) in ether (15
mL) was treated with ozone (1.00 mmol) at -70 °C. After
evaporation of the solvent, the residue was separated by
column chromatography on silica gel. Elution with ether-
hexane (2:98) gave a mixture of ozonide 9c and 3-ethyl-5-
phenyl-5-(trifluoromethyl)-1,2,4-trioxolane (16) (239 mg). On
the basis of the characteristic signals of ozonide 9c (δ 5.83)
and ozonide 16 (δ 5.23, 5.56) in the 1H NMR spectrum, the
ratio was determined to be ca. 3:2.
Ozon olysis of 1,2-Bis(m et h ylen e)cycloa lk a n es 1c,d
a n d 2,3-Dim eth yl-1,3-bu ta d ien e (1e) in th e P r esen ce of
Tr iflu or oa cet op h en on e in E t h er . Ozonolysis of 1,2-di-
methylenecyclohexane (1d ) is representative. Ozonolysis of
1d (203 mg, 1.88 mmol) was conducted in the presence of 1
equiv of trifluoroacetophenone (327 mg, 1.88 mmol) in ether
(15 mL). After evaporation of the solvent, the residue was
separated by column chromatography on silica gel. Elution
with ether-hexane (3:97) gave ozonide 9d (484 mg, 86%).
3-P h e n yl-3-(t r iflu or om e t h yl)-6-m e t h yle n e -1,2,4-t r i-
Com p et it ive Ozon olysis of Dien es 1b a n d 1d in t h e
P r esen ce of Tr iflu or oa cetop h en on e. A mixture of 1b (164
mg, 1.00 mmol), 1d (108 mg, 1.00 mmol), and trifluoroac-
etophenone (174 mg, 1.00 mmol) in ether (15 mL) was treated
with ozone (1.00 mmol) at -70 °C. After evaporation of the
solvent, the residue was separated by column chromatography
on silica gel. The first fraction (elution with hexane) contained
starting diene 1b (96 mg, 59%). The second fraction (elution
with ether-hexane, 2:98) gave ozonide 9d (240 mg, 80%).
Com p etitive Ozon olysis of Dien es 1c a n d 1d in Eth er .
A mixture of 1c (94 mg, 1 mmol) and 1d (108 mg, 1 mmol) in
ether (15 mL) was treated with ozone (1 mmol) at -70 °C. After
evaporation of the solvent, the 1H NMR spectrum of the
residue indicated the formation of a ca. 1:1 mixture of the
ozonides 10c (40%, δ 5.38) and 10d (43%, δ 4.91). By column
chromatography on silica gel (elution with hexane), a 1:1
mixture of two ozonides, 10c and 10d (16 mg), was obtained.
1
oxa sp ir o[4.4]n on a n e (9c): oil (one stereoisomer); H NMR
δ (CCl4) 1.5-2.2 (m, 4 H), 2.2-2.7 (m, 2 H), 5.45 (t, J ) 2 Hz,
1 H), 5.83 (t, J ) 2 Hz, 1 H), 7.3-7.7(m, 5 H); 13C NMR δ
21.50, 30.18, 36.88, 103.51 (q, J ) 33 Hz), 116.13, 116.24,
121.81 (q, J ) 289 Hz), 126.54, 128.27, 128.31, 130.30, 141.56;
IR 3000-2900, 1460, 1310, 1190, 1080, 1060, 715 cm-1. Anal.
Calcd for C14H13F3O3: C, 58.73; H, 4.59. Found: C, 58.43; H,
4.66.
3-P h e n yl-3-(t r iflu or om e t h yl)-7-m e t h yle n e -1,2,4-t r i-
oxa sp ir o[4.5]n on a n e (9d ): oil (a 85:15 mixture of two
isomers); 1H NMR δ 1.3-2.6 (m, 8 H), 4.73 (s, 0.15 H), 4.89 (s,
0.15 H), 5.02 (t, J ) 1 Hz, 0.85 H), 5.47 (t, J ) 1 Hz, 0.85 H),
7.3-7.8 (m, 5 H); 13C NMR (major isomer) δ 23.56, 26.62, 34.32,
35.82, 103.67 (q, J ) 34 Hz), 111.34, 111.97, 121.61 (q, J )
289 Hz), 126.63, 128.23, 128.28, 130.28, 140.99; the following
additional signals were assigned to the minor isomer in the
13C NMR spectrum; δ 24.08, 26.92, 33.48, 33.98, 103.97 (q, J
) 34 Hz), 110.85, 111.90, 130.15, 144.17; IR 2950, 1460, 1310,
1190, 1090, 960, 720 cm-1. Anal. Calcd for C15H15F3O3: C,
60.00: H, 5.04. Found: C, 59.80: H, 4.99.
Ack n ow led gm en t. J .B. thanks the Deutsche Aka-
demische Austauschdienst for a stipend.
3-Meth yl-3-(1-m eth yleth en yl)-5-p h en yl-5-(tr iflu or om -
eth yl)-1,2,4-tr ioxola n e (9e): oil (one stereoisomer); 1H NMR
J O960397I