Novel photo-rearrangement of 1,5-di(p-methoxyphenyl)-6,7-dioxabicyclo[3.2.2]nonane through an O-neophyl-type 1,2-aryl shift: Evidence for a 1,6-dioxyl diradical intermediate

Article abstract of DOI:10.1016/S0040-4039(01)01973-6

Photolysis and thermolysis of 1,5-diaryl-6,7-dioxabicyclo[3.2.2]nonane 1a-c (a: Ar=p-MeOC₆H₄, b: Ar=p-MeC₆H₄, c: Ar=Ph) were investigated. (p-Methoxyphenyl)-substituted 1a underwent a novel photo-initiated O-neophyl-type 1,2-aryl shift to afford 1-(p-methoxyphenyl)oxy-5-(p-methoxyphenyl)-8-oxabicyclo[3.2.1]octane 7a along with a small amount of 1-(p-methoxyphenyl)-3-(2-(4′-methoxyphenyl)tetrahydrofuran-2-yl) propan-1-one 4a through an 1,6-dioxyl diradical intermediate, while the thermolysis mainly afforded the 1,5-di(p-methoxyphenyl)pentan-1,5-dione 5a and 1,4-di(p-methoxyphenyl)butan-1,4-dione 8a.

Full text of DOI:10.1016/S0040-4039(01)01973-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9027–9030
Novel photo-rearrangement of
1,5-di(p-methoxyphenyl)-6,7-dioxabicyclo[3.2.2]nonane through an
O-neophyl-type 1,2-aryl shift: evidence for a 1,6-dioxyl
diradical intermediate
Masaki Kamata* and Ken-ichi Komatsu
Department of Chemistry, Faculty of Education and Human Science, Niigata University, Ikarashi, Niigata 950-2181, Japan
Received 19 September 2001; revised 15 October 2001; accepted 19 October 2001
Abstract—Photolysis and thermolysis of 1,5-diaryl-6,7-dioxabicyclo[3.2.2]nonane 1a–c (a: Ar=p-MeOC6H4, b: Ar=p-MeC6H4, c:
Ar=Ph) were investigated. (p-Methoxyphenyl)-substituted 1a underwent a novel photo-initiated O-neophyl-type 1,2-aryl shift to
afford 1-(p-methoxyphenyl)oxy-5-(p-methoxyphenyl)-8-oxabicyclo[3.2.1]octane 7a along with
a small amount of 1-(p-
methoxyphenyl)-3-(2-(4%-methoxyphenyl)tetrahydrofuran-2-yl)propan-1-one 4a through an 1,6-dioxyl diradical intermediate, while
the thermolysis mainly afforded the 1,5-di(p-methoxyphenyl)pentan-1,5-dione 5a and 1,4-di(p-methoxyphenyl)butan-1,4-dione 8a.
© 2001 Elsevier Science Ltd. All rights reserved.
Cyclic peroxides have attracted much attention from
synthetic and mechanistic viewpoints.1–7 In particular,
the fragmentation mechanisms for 1,2-dioxolanes and
1,2-dioxanes have been intensively investigated to
explore the reactivities of oxyl radical species8–10 and to
clarify potent antimalarial intermediates.11–15 Posner
and co-workers reported that structurally simple and
On the other hand, photolysis and thermolysis are the
more common methods to induce OꢀO bond cleavage
of peroxy compounds.18–20 Bloodworth and co-workers
reported that structurally simple 6,7-dioxabicy-
clo[3.2.2]nonane 1d photochemically and thermally
underwent the fragmentation through an OꢀO bond
cleaved 1,6-dioxyl diradical (Scheme 2).21 In this
respect, we reported that photochemical and thermal
behaviors of arylated monocyclic peroxides, such as
3,3,5,5-tetraary-1,2-dioxolanes22 and 3,3,6,6-tetraary-
1,2-dioxanes23 are significantly different from that of
the related aliphatic peroxides.8–10 These contrastive
results have strongly prompted us to study the reactivi-
ties of 1,6-dioxyl diradical species generated from the
1,5-diaryl-6,7-dioxabicyclo[3.2.2]nonanes 1. Herein, we
easily
prepared
1,5-diaryl-6,7-dioxabicyclo[3.2.2]-
nonanes 1a and 1c are potent antimalarials.16,17 They
also demonstrated that the reaction of 1,5-diphenyl
derivative 1c with FeBr2, in which the reductive OꢀO
bond cleavage is a key step to promote a mono-oxyl
radical rearrangement involving 1,5-hydrogen atom
transfer, afforded various rearrangement products and
fragmentation products 2c–6c (Scheme 1).16,17
HO
FeBr2
Ph
Ph
O
Ph
Ph
Ph
Ph
O
+
Ph
Ph
THF
O
O
OH
HO
O
Fe(III)O
1c
3c(9%)
2c(42%)
Ph
Ph
+
Ph
Ph
O
+
+ Ph
Ph
O
O
O
6c(17%)
5c(13%)
4c(16%)
Scheme 1.
* Corresponding author. Tel./fax: +81-25-262-7150; e-mail: kamata@ed.niigata-u.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01973-6

9028
M. Kamata, K. Komatsu / Tetrahedron Letters 42 (2001) 9027–9030
hν
H
H
H
+
other products
O
O
H2
+
C6H6
O
1d
O
H
H
∆
H
+
O
O
H2
+
+ CH2=CH2
O
O
O
O
(85%)
(10%)
1d
Scheme 2.
wish to report our preliminary but novel results that the
1,6-dioxyl diradical intermediate generated by photoly-
sis of (p-methoxyphenyl)-substituted 1a underwent
rearrangement to afford 1-(p-methoxyphenyl)oxy-5-(p-
methoxyphenyl)-8-oxabicyclo[3.2.1]octane 7a through a
novel O-neophyl type 1,2-aryl shift.24†
lamp in a Pyrex tube for 5 h, novel cyclic acetal 7a
(80%) and 1-(p-methoxyphenyl)-3-(2-(4%-methoxy-
phenyl)tetrahydrofuran-2-yl)propan-1-one 4 (2%) were
obtained as rearrangement products along with small
amounts of expected fragmentation products, such as
1,5-di(p-methoxyphenyl)pentan-1,5-dione 5a (5%) and
1,4-di(p-methoxyphenyl)butan-1,4-dione
8a
(2%,
When a nitrogen-purged CH2Cl2 solution of 1a25‡ (0.20
mmol) was irradiated by a 400 W high-pressure Hg
Scheme 3; entry 1 in Table 1).§ On the other hand,
when p-methylphenyl derivative 1b was subjected
hν/N2/CH2Cl2
Ar
Ar
Ar
O
O
or ∆/200°C/neat
Ar
Ar
+
+
O
O
O
O
O
Ar
Ar
Ar
5
8
4
1
1a: Ar = p-MeOC6H4(p-An)
1b: Ar = p-MeC6H4(p-Tol)
1c: Ar = Ph
Ar
O
ArO
+
O
7
Scheme 3.
Table 1. Photolysis of 1,5-diaryl-6,7-dioxabicyclo[3.2.2]nonanes 1a
Entry
1
Additive
Time (h)
Conv. (%)
Yield (%)b
4
5
7
8
1
2
1a
1a
1a
1a
1b
1c
None
O2
5
5
5
5
10
10
100
100
100
67
68
74
2
B1
18
B1
6
19
5
80
82
32
51
B1
0
2
2
4
2
5
4
B1
22
3
13
13
3c
4c
5
Ph2CꢁOd (u\340 nm)
None (u\280 nm)
None
6
None
a 400 W high-pressure mercury lamp; Pyrex cut (u>280 nm); 20–24°C; 1=0.2 mmol; CH2Cl2=10 ml.
b Isolated yields by silica gel TLC.
c 2 kW Xe lamp.
d 0.2 mmol; ET=69.2 kcal mol−1
.
† The first example of an O-neophyl-type 1,2-aryl shift has been reported by Workentin who conducted the electrochemical reduction of
9,10-diphenyl-9,10-epidioxyanthracene.
‡ The UV absorption maxima of 1a–c in CH3CN are 274.5 nm (m 3500), 270 nm (m 900), and 257 nm (m 510), respectively. For each compound
the absorption at wavelength greater than 300 nm is decreased significantly. Their extinction coefficients at 313 nm are 64 for 1a, 23 for 1b, and
11 M−1 cm−1 for 1c, respectively.
§
All products were isolated by silica gel TLC and characterized by their spectral data. The structures 5 and 8 were determined by their authentic
spectral data. Selected data for 7a: mp 109–110°C; IR (KBr, cm−1) 3050, 3020, 2980, 2960, 2890, 2860, 1618, 1590, 1521, 1510. 1H NMR (200
MHz, CDCl3): l 1.52–2.28 (m, 10H), 3.76 (s, 3H), 3.80 (s, 3H), 6.75–6.92 (m, 4H), 7.13–7.24 (m, 2H), 7.28–7.38 (m, 2H). 13C NMR (50 MHz,
CDCl3): l 19.60 (t, 1C), 32.44 (t, 1C), 34.07 (t, 1C), 34.90 (t, 1C), 37.53 (t, 1C), 55.22 (q, 1C), 55.46 (q, 1C), 84.19 (s, 1C), 109.51 (s, 1C), 113.40
(d, 2C), 113.92 (d, 2C), 123.31 (d, 2C), 125.37 (d, 2C), 138.96 (s, 1C), 147.95 (s, 1C), 155.64 (s, 1C), 158.21 (s, 1C). Anal. C, 74.01; H, 7.11,
requires C, 74.09; H, 7.11; MS (EI) 340 (M+, 21), 217 (100), 135 (19), 121 (15). Selected data for 4a: colorless oil; IR (CHCl3, cm−1) 3050, 3020,
1
2970, 2950, 2890, 2850, 1675 (CꢁO), 1603, 1580, 1512; H NMR (200 MHz, CDCl3): l 1.71–2.06 (m, 2H), 2.08–2.35 (m, 4H), 2.48–2.67 (m, 1H),
2.95–3.13 (m, 1H), 3.79 (s, 3H), 3.82 (s, 3H), 3.88–4.02 (m, 2H), 6.82–6.92 (m, 4H), 7.28–7.35 (m, 2H), 7.78–7.88 (m, 2H). 13C NMR (50 MHz,
CDCl3): l 25.53 (t, 1C), 33.59 (t, 1C), 36.38 (t, 1C), 39.32 (t, 1C), 55.14 (q, 1C), 55.32 (q, 1C), 67.57 (t, 1C), 85.81 (s, 1C), 113.42 (d, 4C), 126.26
(d, 2C), 129.97 (s, 1C), 130.17 (d, 2C), 138.04 (s, 1C), 158.07 (s, 1C), 163.12 (s, 1C), 198.99 (s, 1C). Anal. C, 73.81; H, 7.26, requires C, 74.09;
H, 7.11; MS (CI) 341 (M++1, 100).

M. Kamata, K. Komatsu / Tetrahedron Letters 42 (2001) 9027–9030
9029
On the basis of the above results, we propose a plausi-
ble mechanism as shown in Scheme 4. From the results
of the triplet quenching and the triplet sensitization
experiments, acetal 7 and 1,4-diketone 8 are considered
to be generated from the singlet 1,6-dioxyl diradical
S-1. Ketofuran 4 and 1,5-diketone 5 are considered to
be generated from the triplet 1,6-dioxyl diradical T-1.
Two different pathways are plausible for the product
formation from S-1. One is the formation of the inter-
mediate 9 through an O-neophyl type 1,2-aryl shift in
S-1 followed by cyclization to afford actal 7 (path a).
The 1,2-aryl shift would be promoted by electron-
donating aromatic substituents (p-An>p-Tol>Ph). The
other is the formation of 1,4-diketone 8 through simul-
taneous C1ꢀC2 and C4ꢀC5 bond cleavages in S-1 fol-
lowed by elimination of propene or cyclopropane (path
b). On the other hand, two different pathways are also
plausible for the product formation from T-1. One is
the formation of the intermediate 10 through the C1ꢀC2
bond cleavage in T-1 followed by cyclization to afford
ketofuran 4 (path c). The other is the formation of
1,5-diketone 5 through stepwise C1ꢀC9 and C5ꢀC8 bond
cleavages in T-1 followed by elimination of ethylene
(path d).
to the photolysis, only a trace amount of 7b (<1%) was
produced along with 4b (6%), 5b (13%), and 8b (5%) at
68% conversion (entry 5). Likewise, the photolysis of 1c
afforded 4c (19%), 5c (13%), and 8c (4%) at 74%
conversion, but 7c was not produced (entry 6). Diol 2,
hydroxyfuran 3, and furan 6 were not produced in this
study, which is significantly different from the results of
the Fe(II)-mediated fragmentation of 1c (Scheme 1).16,17
In order to determine the multiplicity of the responsible
excited states, a quenching experiment was carried out
by using oxygen as a triplet quencher. The yields of 4a
and 5a were decreased by the addition of oxygen while
those of 7a and 8a were not significantly affected (entry
2). A triplet sensitization experiment of 1a was also
carried out by using benzophenone (u>340 nm). While
the yields of 4a and 5a were increased, those of 7a and
8a were not increased (entry 3, 4). In contrast to the
photoreactions, 5a (58%) and 8a (13%) were obtained
as major products along with small amounts of 4a (4%)
and 7a (3%) when 1a was heated at 200°C for 1 h under
nitrogen atmosphere (entry 1 in Table 2). Likewise, the
thermolysis of 1b and 1c afforded similar product dis-
tributions (entry 2, 3 in Table 2). No acetals 7b–c were
obtained in either case.
On the contrary, thermolysis of 1 mainly generates the
activated complex 11 (partly including an 1,6-dioxyl
diradical intermediate).9,10 The complex 11 affords 1,5-
diketone 5 and ethylene (not isolated) through simulta-
neous OꢀO, C1ꢀC9, and C5ꢀC8 bond cleavages, and
affords 1,4-diketone 8 and propene (or cyclopropane)
via simultaneous OꢀO, C1ꢀC2, and C4ꢀC5 bond cleav-
ages. The isolation of acetal 7a and ketofuran 4 would
indicate the intervention of a 1,6-dioxyl diradical
species.
Table 2. Thermolysis of 1,5-diaryl-6,7-dioxabicyclo-
[3.2.2]nonanes 1a
Entry
1
Temp. (°C)
Conv. (%)
Yield (%)b
4
5
7
8
1
2
3
1a 200
1b 200
1c 200
100
87
93
4
6
5
58
57
53
3
0
0
13
12
10
a Heated under nitrogen atmosphere; 1=0.2 mmol.
In summary, we have found that the photolysis of the
p-methoxyphenyl substituted [3.2.2]cyclic peroxide 1a
b Isolated yields by silica gel TLC.
3
4
2
hν
9
isc
11*
31*
1
5
8
Ar
Ar
O
O
1
∆
Ar
Ar
Ar
Ar
O
O
O
O
T-1
S-1
C1-C9 & C5-C8
cleavage (path d)
C1-C2 & C4-C5
C1-C2 cleavage
(path c)
1,2-aryl shift
(path a)
cleavage (path b)
Ar
Ar
O
O
-C2H4
-C3H6
11
activated complex
Ar
Ar
Ar
ArO
O
O
O
O
9
10
cyclization
cyclization
Ar
Ar
Ar
O
Ar
O
5(major) + 8
ArO
Ar
O
O
O
O
Ar
Ar
8
5
7
4
Scheme 4.

9030
M. Kamata, K. Komatsu / Tetrahedron Letters 42 (2001) 9027–9030
undergoes
a
novel O-neophyl-type 1,2-aryl shift
8. Baumstark, A. L.; Vasquex, P. C.; Chen, Y.-X. J. Org.
Chem. 1994, 59, 6692.
9. Adam, W.; Duran, N. J. Am. Chem. Soc. 1977, 99, 2729.
10. Adam, W.; Sanabia, J. J. Am. Chem. Soc. 1977, 99, 2735.
11. Bloodworth, A. J.; Shah, A. Tetrahedron Lett. 1995, 36,
7551.
through the OꢀO bond cleaved 1,6-dioxyl diradical
intermediate. We are conducting further studies on the
fragmentation of other cyclic peroxides to elucidate the
generality of this novel reaction.
12. Posner, G. H.; Cumming, J. N.; Ploypradith, P.; Oh, C.
Acknowledgements
H. J. Am. Chem. Soc. 1995, 117, 5885.
13. Posner, G. H.; Tao, X.; Cumming, J. N.; Klinedinst, D.;
Shapiro, T. A. Tetrahedron Lett. 1996, 37, 7225.
14. O’Neill, P. M.; Bishop, L. P. D.; Searle, N. L.; Maggs, J.
L.; Storr, R. C.; Ward, S. A.; Park, B. K.; Mabbs, F. J.
Org. Chem. 2000, 65, 1578.
We are grateful to Professor Eietsu Hasegawa (Faculty
of Science, Niigata University), Professor Tsutomu
Miyashi and Dr. Hiroshi Ikeda (Faculty of Science,
Tohoku University), Professor Yasutake Takahashi
(Faculty of Engineering, Mie University), and Professor
Akinori Kon-no (Faculty of Engineering, Shizuoka
University) for their helpful comments and assistance.
15. Jefford, C. W.; Rossier, J.-C.; Milhous, W. K. Heterocy-
cles 2000, 52, 1345.
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