Novel entry into oxepane-diquinane and oxepane-sterpurane hybrids: Synthesis and photochemistry of 3-oxatricyclo[7.2.2.01,7]tridecenones

Article abstract of DOI:10.1016/S0040-4039(02)02611-4

A new synthesis of 3-oxatricyclo[7.2.2.0^1,7]tridecenones via intramolecular π^4s+π^2s cycloaddition in cyclohexa-2,4-dienones is described. Their photochemical reactions leading to oxepane-diquinane and oxepane-sterpurane hybrids are depicted. The crystal structure of a key intermediate is also presented.

Full text of DOI:10.1016/S0040-4039(02)02611-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 475–478
Novel entry into oxepane–diquinane and oxepane–sterpurane
hybrids: synthesis and photochemistry of
3-oxatricyclo[7.2.2.01,7]tridecenones
Vishwakarma Singh,a,* Punitha Vedantham,a Vinayak V. Kaneb,*,† and Kurt Polbornb
aDepartment of Chemistry, Indian Institute of Technology, Bombay 400076, India
bLudwig-Maximilians-Universitat Muenchen, Institut fur Organische Chemie, Butenandtstrasse 5-13, Haus F,
D-81377 Muenchen, Germany
Received 1 October 2002; accepted 15 November 2002
This paper is dedicated to Professor Paul Knochel, scholar and teacher
Abstract—A new synthesis of 3-oxatricyclo[7.2.2.01,7]tridecenones via intramolecular p4s+p2s cycloaddition in cyclohexa-2,4-
dienones is described. Their photochemical reactions leading to oxepane–diquinane and oxepane–sterpurane hybrids are depicted.
The crystal structure of a key intermediate is also presented. © 2002 Elsevier Science Ltd. All rights reserved.
There is considerable interest in the diquinanes fused
with oxygen heterocycles 1 and congeners. They have
shown promising biological activity and have proven to
be useful for the treatment of leukemia, osteosarcoma,
breast and ovarian cancer.1,2 In view of this and the
growing interest in design and synthesis of new
molecules which combine structural features of differ-
ent classes of compounds,3,4 we considered developing a
synthetic route to compounds 2 and 3 (Fig. 1) in which
an oxepane ring is fused to a diquinane and a bicy-
clo[4.2.0]octane ring, respectively. The oxepane ring
was chosen since it is present in many natural products
that display interesting biological profiles.5,6 Compound
3 possesses structural features of sterpuranes, another
class of biologically active sesquiterpenes.7 We antici-
pated that compounds of type 2 and 3 would result
from the endo tricyclic compound 4 in a stereoselective
fashion via photochemical 1,2- and 1,3-acyl shifts,
respectively (Scheme 1). It was expected that the desired
tricyclic compound 4 could be prepared from the aro-
matic precursor 7 via 5 and 6 (Scheme 1).
The aromatic precursor 7 was readily prepared from 8
by O-alkylation with 5-bromo-1-pentene using NaH in
THF and subsequent acid hydrolysis of the acetonide
moiety (Scheme 2).8 Compound 7 was oxidized with
Figure 1.
Keywords: intramolecular cycloaddition; photoreactions; oxa-di-p-methane rearrangement.
* Corresponding authors. E-mail: vks@ether.chem.iitb.ac.in; vkane@hotmail.com
† Present address: Department of Chemistry, Universitat Wurzburg, Am Hubland, D-97074 Wurzburg, Germany.
0040-4039/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02611-4

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V. Singh et al. / Tetrahedron Letters 44 (2003) 475–478
gave 4, while oxidation of 14 followed by decarboxyla-
tion furnished the ketone 15 (Scheme 3).
sodium metaperiodate following a procedure of Adler
which was modified and further developed in our labo-
ratory.9 However it did not give the desired ketoepoxide
5. Instead, the dimer 9 was obtained as a result of
intermolecular cycloaddition. Therefore, 9 was converted
to the bis-chlorohydrin 10 by treatment with dil. HCl in
dioxane which on heating at 160°C in o-dichlorobenzene
gave 12 in 68% (Scheme 2).
Having developed a route to the tricyclic systems 4, 5 and
15, the photochemical reactions of 4 and 5 were investi-
gated. A solution of 4 in acetone (both as a sensitizer and
solvent) was irradiated for 1 h to give compound 2 in 64%
yield as a result of a 1,2-acyl shift.11–13 Irradiation of 4
in benzene for 20 min gave the linearly fused tricyclic
compound 3 (40%), along with unreacted starting mate-
rial. Compound 3 is a product of a 1,3-acyl shift.12,13
Alternative structures 12a and 12b could not be ruled out
unequivocally on the basis of 600 MHz NMR spec-
troscopy, but X-ray crystallographic analysis firmly
established structure 12 and the stereochemistry of the
cycloaddition (Fig. 2).10 The endo adduct 12 was formed
as a result of a retro Diels–Alder reaction of 10 to the
monomer 11 followed by intramolecular cycloaddition.
Next we explored the photochemical behavior of 5 since
it contains an a-keto-oxirane functional group as well as
a constrained b,g-enone system. No appreciable photo-
chemical reaction of the keto-epoxide 5 was observed in
acetone (solvent and sensitizer) over a period of 3 h.
Therefore, a solution of 5 in acetone containing ace-
tophenone as a sensitizer was irradiated which gave in
addition to the starting material, compound 16 in 15%
yield as a result of oxa-di-p-methane rearrangement
(Scheme 4).
Treatment of 12 under basic conditions gave the keto-
epoxide 5 in 92%. Reduction of keto-epoxide 5 with zinc
in dioxane containing ammonium chloride gave the
compounds 13 and 14 in a ratio of 3:1 (63% yield).
Alkylation of 13 with MeI in the presence of NaH–THF
Scheme 1.
Scheme 2. Reagents and conditions: (i) NaH, 5-bromo-1-pentene, THF, D; (ii) HClO4, acetone–H2O; (iii) NaIO4, aq. CH3CN; (iv)
HCl, dioxane; (v) o-dichlorobenzene, sealed tube, 160°C.

V. Singh et al. / Tetrahedron Letters 44 (2003) 475–478
477
Acknowledgements
We thank RSIC I.I.T. Bombay and Ms. Claudia
Dubler LMU for spectral data of our compounds. V.S.
is grateful to CSIR, New Delhi for continuing financial
support.
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478
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