Photooxygenation of the C=N bond: A mild new method for oxidative C-C cleavage

Article abstract of DOI:10.1016/S0040-4039(03)01639-3

Upon photooxygenation in the presence of base, α-oximinocarbonyl compounds undergo clean oxidative C-C cleavage giving rise to mixtures of esters and acids. The mechanism of these reactions involves some unusual peroxidic intermediates, including a 2,3,5-trioxapentanes.

Full text of DOI:10.1016/S0040-4039(03)01639-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6947–6949
Photooxygenation of the CꢀN bond: a mild new method for
oxidative CꢁC cleavageꢀ
†
8
Nu¨ket Ocal, Lovelle M. Yano and Ihsan Erden*
San Francisco State University, Department of Chemistry and Biochemistry, 1600 Holloway Avenue, San Francisco, CA, USA
Received 18 June 2003; revised 28 June 2003; accepted 2 July 2003
Abstract—Upon photooxygenation in the presence of base, a-oximinocarbonyl compounds undergo clean oxidative CꢁC cleavage
giving rise to mixtures of esters and acids. The mechanism of these reactions involves some unusual peroxidic intermediates,
including a 2,3,5-trioxapentanes.
© 2003 Elsevier Ltd. All rights reserved.
Oxidative CꢁC cleavage reactions are important func-
tional group transformations in organic chemistry.1
Whereas oxidative CꢀC cleavage is a simple task by
way of ozonolysis, carbonyl compounds are relatively
difficult, direct routes to oxidative CꢁC cleavage are
scarce. The best known example is the haloform reac-
tion that is only applicable to compounds containing
the CH3C(O) moiety.2 One obvious solution to the
problem is ozonolytic cleavage of the enol ether derived
from an aldehyde or a ketone, though regioselectivity in
the enol ether formation may be problematic, and esters
do not lend themselves well for this purpose.3 Alterna-
tively, carbonyl a-oxidation (e.g. Rubottom oxidation),
followed by oxidative cleavage with a variety reagents
has also been employed.4 Direct oxidative cleavage can
be accomplished with dioxygen (or H2O2) and heavy
metal catalysts such as vanadium(V) or copper(II) com-
plexes.5 Multistep oxidative cleavage protocols have
been developed by various groups.6 Herein we report
an exceptionally mild and environmentally benign
methodology for oxidative cleavage of carbonyl
compounds.
Previously we published a survey on dye-sensitized
photooxidation of CꢀN containing compounds and
reported that oximes are unreactive toward singlet oxy-
gen, however, oximate anions rapidly combine with
1O2;7,8 while ketoximates undergo oxidative CꢀN cleav-
age, aldoximates give rise to mixtures of acids, esters
and aldehydes. Carbonyl oxide intermediates have been
postulated as intermediates in these reactions. Recently
we reported on the photooxygenation of amidoximate
anions and found that these compounds undergo oxida-
tive cleavage to nitriles and amides via carbonyl oxide
intermediates.9 In the present study we examined the
photooxygenation of a-oximino carbonyl compounds
these compounds readily react with singlet oxygen
undergoing oxidative CꢁC cleavage to yield esters and
carboxylic acids in high yields (Eq. (1)).10
(1)
The a-oximino (also isonitroso) carbonyl compounds
are readily available by nitrosation (under basic or
acidic conditions) of the respective carbonyl com-
pound.11 The results from these reactions are shown in
Table 1. The formation of both esters and acids (entries
1–4) suggests that during the photooxygenations anhy-
drides are likely intermediates that are cleaved by
methanol. One possible mechanism consistent with the
results is shown in Scheme 1.
ꢀ This work was presented at the 12th European Symposium on
Organic Chemistry (ESOC-12), July 14, 2001, in Groningen, the
Netherlands.
* Corresponding author. Fax: (415) 338 2384; e-mail:
ierden@sfsu.edu
† Present address: Yildiz Technical University, Department of Chem-
istry, Faculty of Arts and Sciences, Davutpasa Campus, 34010
Merter-Istanbul, Turkey.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01639-3

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N. Ocal et al. / Tetrahedron Letters 44 (2003) 6947–6949
6948
Table 1. Photooxygenation of a-oximino carbonyl compounds in the presence of base
Scheme 1.
In analogy to amidoximate photooxygenations the oxi-
mate anion attacks singlet oxygen, the resulting peroxo
anion extrudes NO− giving rise to a carbonyl oxide.
The latter species is adjacent to a carbonyl group that
diazoketones and seems to be the most likely source of
the anhydrides that have been reported to form in these
reactions.12 In support of the anhydride intermediate is
the fact that when acetic benzoic anhydride was inde-
pendently prepared and subjected to methanolysis, the
ratio of benzoic acid and methyl benzoate was essen-
tially the same as that observed in the photooxygena-
tion experiment (entry 1).13 However, another
mechanism involving attack of methanol at the car-
bonyl oxide stage followed by a Baeyer–Villiger rear-
rangement of the resulting hydroperoxide would also
lead to the observed cleavage products via anhydride
participates in the formation of
a tiroxabicylo-
[2.1.0]pentane. This intermediate then undergoes a 1,2-
dioxetane cleavage to give the anhydride that suffers
methanolysis leading to the observed products.
Several aspects of the proposed mechanism deserve
comment. Intermediate 19 has been shown to form as a
reactive intermediate in the photooxygenations of a-

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N. Ocal et al. / Tetrahedron Letters 44 (2003) 6947–6949
6949
and/or anhydride hemiacetal intermediates. This latter
mechanism had been advanced for oxidative CꢁC cleav-
age reactions of unsymmetrical acetylenes with ozone in
alcohol solvents.14
5. Bre´geault, J.-M.; Launay, F.; Atlamsani, A. C.R. Acad.
Sci. Paris, Se´rie IIc, Chimie/Chemistry 2001, 4, 11–26.
6. Ashford, S. W.; Grega, K. C. J. Org. Chem. 2001, 66,
1523 and references cited therein.
7. Castro, C.; Dixon, M.; Erden, I.; Ergo¨nenc¸, P.; Keeffe, J.
R.; Sukhovitsky, A. J. Org. Chem. 1989, 54, 3732–3738.
8. Erden, I.; Griffin, A.; Keeffe, J. R.; Brinck-Kohn, V.
Tetrahedron Lett. 1993, 34, 793.
The methodology described in this paper lends itself
well to oxidative cleavage of a variety of carbonyl
compounds, including aldehydes, ketones, esters,
amides. The a-oximino derivatives are readily available,
and the photooxidations are carried out under mild
conditions, and the use of singlet oxygen in these
reactions, as well as lack of by-products renders this
method environmentally friendly.
8
9. Ocal, N.; Erden, I. Tetrahedron Lett. 2001, 42, 4765–
4767.
10. In a typical experiment, 2–3 mmol of a-oximino carbonyl
compound was treated with 1.2 equiv. of NaOMe in 20
mL of methanol, and irradiated at room temperature
under a positive pressure of oxygen, using a 250 W
high-pressure sodium vapor lamp and rose bengal as
sensitizer. After completion of reaction (ca. 2–3 h) the
mixture was acidified with HCl, and the mixture concen-
trated in vacuo, and the residue extracted with CH2Cl2.
In all cases a crude 1H NMR was obtained in order to
determine the product ratios. The mixtures were chro-
matographed on SiO2, eluting with CH2Cl2 in most cases
(ether/ethyl acetate 3:1, entry 4).
Acknowledgements
We are grateful for financial support from the National
Science Foundation Grant (Grant CHE-9729001) and a
NATO post-doctoral fellowship, administered by
8
Tubitak of Turkey, to Dr. Ocal.
11. (a) Hartung, W. H.; Crossley, F. Org. Syn. Coll. Vol. II
1943, 363; (b) Ferris, A. F. J. Org. Chem. 1959, 24, 1726;
(c) Ferris, A. F. J. Org. Chem. 1960, 25, 12; (d) Ferris, A.
F.; Johnson, G. S.; Gould, F. E. J. Org. Chem. 1960, 25,
496.
12. Ando, W.; Miyazaki, H.; Ito, K.; Auchi, D. Tetrahedron
Lett. 1982, 23, 555–556.
13. Bailey, P. S.; Chang, Y.-G. J. Org. Chem. 1962, 27,
1192–1197.
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