Photochemical formation and decomposition of 8-[β-arylethenyl]-2,2,6- trimethyl-7,9,10-trioxa-tricyclo[6.2.2.01,6]dodec-11-ene to novel 6-hydroxy-1,7,7-trimethyl-2-oxa-bicyclo[4.4.0]dec-4-en-3-one in the presence of oxygen

Article abstract of DOI:10.1016/j.tetlet.2012.08.028

Irradiation of (E,E)-arylidene-β-ionones in the presence of oxygen leads to the formation of 8-[β-arylethenyl]-2,2,6-trimethyl-7,9,10-trioxa- tricyclo[6.2.2.0^1,6]dodec-11-enes (3). However, prolonged irradiation in the presence of oxygen leads to their conversion to 6-hydroxy-1,7,7- trimethyl-2-oxa-bicyclo[4.4.0]dec-4-en-3-one (4), apparently proceeding through addition of oxygen to the side chain π-bond in 3.

Full text of DOI:10.1016/j.tetlet.2012.08.028

Tetrahedron Letters 53 (2012) 5649–5651
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Photochemical formation and decomposition of 8-[b-arylethenyl]-2,2,6-tri-
1,6
methyl-7,9,10-trioxa-tricyclo[6.2.2.0 ]dodec-11-ene to novel 6-hydroxy-1,7,7-
trimethyl-2-oxa-bicyclo[4.4.0]dec-4-en-3-one in the presence of oxygen
a
b
b
c
a,
⇑
Vishal Sharma , Vivek Gupta , Sumati Anthal , Ajit K. Saxena , Mohan Paul S. Ishar
a
Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India
Post-Graduate Department of Physics, University of Jammu, Jammu Tawi 180 006, India
Indian Institute of Integrative Medicine, Jammu Tawi 180 006, India
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Irradiation of (E,E)-arylidene-b-ionones in the presence of oxygen leads to the formation of 8-[b-arylethe-
nyl]-2,2,6-trimethyl-7,9,10-trioxa-tricyclo[6.2.2.0 ]dodec-11-enes (3). However, prolonged irradiation
in the presence of oxygen leads to their conversion to 6-hydroxy-1,7,7-trimethyl-2-oxa-bicyclo
Received 10 June 2012
Revised 6 August 2012
Accepted 8 August 2012
Available online 15 August 2012
1,6
[4.4.0]dec-4-en-3-one (4), apparently proceeding through addition of oxygen to the side chain
p-bond
in 3.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
(E,E)-Arylidene-b-ionones
Photocycloaddition
Endoperoxides
Photodecomposition
Endoperoxides include 1,2-dioxanes, 1,2,4-trioxanes, and
,2,4,5-tetraoxanes, all of which possess the critical peroxide link-
Attention has also been focused on the preparation of stable
endoperoxides photochemically. Earlier we had reported that on
irradiation of (E,E)-arylidine-b-ionones in the presence of oxygen,
the in situ generated diene (tetrahydrobenzopyran, 2) undergoes
regioselective photocycloaddition with molecular oxygen to gener-
ate endoperoxide (3) possessing a stable trioxane moiety (Scheme
1
age. These are of significant interest on account of their synthetic
1
applications as well as their valuable biological activities. Among
them, the 1,2,4-trioxane moiety constitutes the pharmacophore
2
responsible for cytotoxic and antimalarial activity. The molecules
1
0
possessing the 1,2,4-trioxane moiety have attracted increasing
attention after a naturally occurring endoperoxide, artemisinin
and its synthetic derivatives, emerged as the first line drug for the
1). These molecules are thermally stable and can be stored even
at ambient temperature for long durations.
Herein, we report the formation of endoperoxides 3a–c through
direct irradiation of (E,E)-arylidine-b-ionones (1a–c) in thiophene-
free dry benzene under constant bubbling of oxygen, using immer-
sion well type Pyrex glass, water-cooled photoreactor with UV light
from a 125-Watt medium pressure Hg arc placed coaxially inside the
reactor. However, when 1d and 1e were directly irradiated under UV
light in the presence of oxygen there is no formation of endoperox-
ides 3d and 3e. Therefore, 1d and 1e were irradiated under nitrogen
atmosphere to obtain pyrans 2d and 2e, which upon further irradi-
ation in the presence of oxygen afforded endoperoxides 3d and 3e.
Endoperoxides 3a–e were characterized by rigorous spectroscopic
3
treatment of uncomplicated Plasmodium falciparum malaria. It
has also been discovered that Fe2 -triggered activation of endoper-
oxide moiety leads to the formation of radical species, which are
implicated in cytotoxicity, DNA damage, oxidative stress, and dam-
age to the electron transport chain with possible anticancer
+
4
applications.
Advancements have been made in the preparation of both semi-
synthetic and synthetic endoperoxides, however, in general, endop-
eroxides are still considered as unstable entities and are difficult to
5
isolate, particularly, in many photooxidation reactions. Various
1
13
methods reported to synthesize stable endoperoxides include cycli-
techniques such as IR, H & C NMR, and mass. It was observed that
another compound (4) was also formed in traces along with
endoperoxides (Scheme 2 and Table 1). Finally, the structure of 3a
6
zation of vicinal hydroxyl-hydroperoxide with ketones, cyclization
7
of hydroperoxyacetals with olefins or epoxides, trapping of
8
11
b-peroxycarbocations with aldehydes or ketones, and autooxida-
was confirmed by X-ray crystallography (Fig. 1).
tion of imines in the presence of aldehydes.9
To investigate the formation of compound 4, endoperoxides
3
a–e were further irradiated in the presence of oxygen when they
⇑
Corresponding author. Tel.: +91 183 2258802x3321; fax: +91 183 2258820.
E-mail address: mpsishar@yahoo.com (M.P.S. Ishar).
were completely transformed into 4 and their respective aldehydes
(5, Scheme 3). Compound 4 and aldehydes were characterized
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.028

5
650
V. Sharma et al. / Tetrahedron Letters 53 (2012) 5649–5651
Scheme 1. Formation of stable endoperoxides.
Scheme 2. Synthesis of endoperoxides 3a–e and compound 4.
Table 1
Reaction time (min) and yield (%) of products (3a–e)
Compound no.
Reaction time (min)
Yield (%) of 3
3
3
3
3
3
a
b
c
d
e
40
40
35
30
30
65
60
65
60
60
2
Scheme 3. Photodecomposition of 3a–e in the presence of O .
Figure 1. X-ray structure of 3a.
spectroscopically (IR, 1H & 13C NMR, mass) and finally, the struc-
ture of 4 was confirmed by X-ray crystallography (Fig. 2).1
As such endoperoxides 3a–e do not decompose when irradiated
in UV light under inert atmosphere (nitrogen atmosphere).
The probable mechanism for the formation of compound 4 may in-
volve the decomposition of 1,2-dioxetane which are formed in situ
2
by 1,2-cycloaddtion of singlet 1
O
at the C
0
-C
2
0
p
bond of the
Figure 2. X-ray structure of 4.
2
1

V. Sharma et al. / Tetrahedron Letters 53 (2012) 5649–5651
5651
Figure 3. Mechanism for the formation of 4.
References and notes
Table 2
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7
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1
of sensitizer wherein several mechanisms for O
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2
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1
1
1
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4
2. The crystal data of
4 had already been submitted to The Cambridge
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2
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Supplementary data associated with this article can be found, in
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1
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