Photochemistry of 2-nitrobenzyl enol ethers: Oxidative C=C bond scission

Article abstract of DOI:10.1021/ol0508072

(Chemical Equation Presented) 2-Nitrobenzyl enol ethers, when photolyzed in the presence of air, result in an oxidative C=C bond scission, forming a ketone as the major product (>60% yield). Enol release leads to the aldehyde as the minor product.

Full text of DOI:10.1021/ol0508072

ORGANIC
LETTERS
2005
Vol. 7, No. 12
2485-2487
Photochemistry of 2-Nitrobenzyl Enol
Ethers: Oxidative C C Bond Scission
d
Promise K. Yong and Anamitro Banerjee*
Department of Chemistry, UniVersity of North Dakota,
Grand Forks, North Dakota 58202-9024
abanerjee@chem.und.edu
Received April 13, 2005
ABSTRACT
2-Nitrobenzyl enol ethers, when photolyzed in the presence of air, result in an oxidative C
d
C bond scission, forming a ketone as the major
product (>60% yield). Enol release leads to the aldehyde as the minor product.
The photochemistry of 2-nitrobenzyl groups has been
extensively studied in the past due to their utility as
photoremovable protecting groups.1 The 2-nitrobenzyl group
has been used to photochemically release acids, alcohols,
amines, phosphates, and ketones.2 While the photochemistry
of 2-nitrobenzyl esters has been studied, their enol ethers
have never been investigated. We expected that photolysis
of the 2-nitrobenzyl enol ethers could lead to (1) the release
of the enol, which will then tautomerize to the keto form in
the absence of an electrophile, and/or (2) a photoinduced
intramolecular electron transfer leading to the oxidation of
the enolic double bond. The photochemistry of benzyl enol
ethers3 and silyl enol ethers4 has been studied in the past,
but enol generation or oxidative cleavage has not been
reported in these cases.5 Enols have been generated photo-
chemically in the past by H atom transfer (Norrish type II
reaction),6 OH insertion of a carbene,7 and addition of water
to ketenes.8 These methods require specific solvents (water)
or could generate specific kinds of enols. Enol release from
a photoremovable group, in our opinion, would be a more
convenient method to access the enols. On the other hand,
oxidation of the enolic double bond could lead to the
“release” of a ketone.
Our study of the photochemistry of 2-nitrobenzyl enol
ethers indicates that the oxidative cleavage of the double
bond is a major pathway in the presence of oxygen when
350 nm light is used.
The synthesis of the 2-nitrobenzyl enol ethers is described
in Scheme 1. The commercially available 2-nitrobenzyl
alcohol was converted to 1-methylsulfanylmethoxymethyl-
2-nitrobenzene 2 in nearly 50% yield. Compound 2 was then
(5) Newcomb and co-workers have previously reported generation of
enol ether radical cations by bond heterolysis of photochemically generated
radicals. See: Horner, J. H.; Taxil, E.; Newcomb, M. J. Am. Chem. Soc.
2002, 124, 5402-5410 and references therein.
(1) (a) Yip, R. W.; Sharma, D. K.; Giasson, R.; Gravel, D. J. Phys. Chem.
1985, 89, 5328-5330. (b) Schupp, H.; Wong, W. K.; Schnabel, W. J.
Photochem. 1987, 36, 85-97. (c) Blanc, A.; Bochet, C. G. J. Am. Chem.
Soc. 2004, 126, 7174-7175. (d) Il’ichev, Y. V.; Schwo¨rer, M. A.; Wirz, J.
J. Am. Chem. Soc. 2004, 126, 4581-4595.
(2) (a) Pillai, V. N. R. Organic Photochemistry; Marcel Dekker: New
York, 1987; Vol. 9. (b) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups
in Organic Synthesis; Wiley: New York, 1991. (c) Blanc, A.; Bochet, C.
G. J. Org. Chem. 2003, 68, 1138-1141.
(3) Pinhey, J. T.; Schaffner, K. Aust. J. Chem. 1968, 21, 2265-2276.
(4) Bockman, T. M.; Shukla, D.; Kochi, J. K. J. Chem. Soc., Perkin
Trans. 2 1996, 1623-1632. (b) Bockman, T. M.; Kochi, J. K. J. Chem.
Soc., Perkin Trans. 2 1996, 1633-1643.
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2607. (c) Henin, F.; Muzart, J.; Pete, J.-P.; M’boungou-M’passi, A.; Rau,
H. Angew. Chem., Int. Ed. Engl. 1991, 30, 416-418. (d) Pelliccioli, A. P.;
Kla´n, P.; Zabadal, M.; Wirz, J. J. Am. Chem. Soc. 2001, 123, 7931-7932.
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Chem. 2004, 69, 6528-6532.
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Y.; Popok, V. V. J. Am. Chem. Soc. 2001, 123, 2681-2682 and references
therein.
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10.1021/ol0508072 CCC: $30.25
© 2005 American Chemical Society
Published on Web 05/12/2005

Scheme 1. Synthesis of 2-Nitrobenzyl Enol Ether
Table 1. Yields of CdC Cleavage Products from Photolysis of
2-Nitrobenzyl Enol Ethers
converted to the chloromethyl ether 3.9 The chloromethyl
ether decomposes during purification by column chroma-
tography or when stored. As a result, we followed its
formation by TLC and converted the crude chloromethyl
ether to 2-(2-nitrobenzyloxymethanesulfanyl)benzothiazole
4, which was then oxidized to 2-{[(2-nitrobenzyloxy)methyl]-
sulfonyl}benzothiazole 5. The compound 5 was converted
to the target 2-nitrobenzyl enol ether 1 by Julia olefination.10
The different enol ethers synthesized are listed in Table 1.
When symmetric ketones were not used (R1 * R2), a mixture
of E and Z isomers was formed. So far, we have not been
able to separate these two isomers. Since the release of the
enol or the CdC oxidation will lead to the same set of
aldehyde or ketone for both the isomers, we did not resolve
the isomers. The enol ether 1f was synthesized as per
published procedures.11
The photolysis of the 2-nitrobenzyl enol ethers was carried
out in a Rayonet photochemical reactor with 350 nm light.
The reaction was followed with TLC, and the irradiation was
stopped after 2 h 45 min. The product mixture was then
analyzed by GC-MS, and the products were identified by
their mass spectra as well as by their retention times. The
yields of the major products (listed in Table 1) were
calculated from the concentration curves obtained using
authentic samples. It was found that for enol ethers 1a-d,
the photolysis led to an oxidative CdC cleavage to produce
a ketone as the major product. The enol ether 1e produced
only 22% cyclohexanone, and a mixture of polymeric adducts
and rearrangement products was detected by GC-MS as
major decomposition products. Only trace amounts of the
a Nearly 23% 2,2-diphenylacetaldehyde was obtained as the minor
product. The yield of the minor product did not change significantly when
the reaction was carried out under O2. b Nearly quantitative yields of 1,3-
cyclohexanedione were obtained when the photolysis was carried out for 6
h (low conversions) or when λ > 320 nm was used.
expected aldehydes were detected for all the enol ethers
(except 1a, in which case 2,2-diphenylacetaldehyde was
obtained in 23% yield). 2-Nitrosobenzaldehyde (along with
other unidentified decomposition byproducts) was detected
as a byproduct (possibly the result of secondary photolysis
of the formic acid ester). Control experiments ruled out the
possibility of secondary photolysis of the released enols in
their keto forms (we assume that the enols will undergo rapid
tautomerism to the keto form prior to absorption of another
photon) as a possible pathway for the oxidative cleavage
products under these conditions.12
The enol ethers 1a and 1b were photolyzed under nitrogen
and under oxygen. The photolysis in the absence of oxygen
(under nitrogen) reduced the yield of benzophenone and
acetophenone to 23 and 32%, respectively. Under oxygen,
however, the yield of the enol release increased marginally
for the enol ethers (69% for 1a and 65% for 1b) when
compared to photolysis under air. The marginal improve-
ments in oxidative cleavage yields in the presence of oxygen,
as well as the decline in the yields when the photolysis was
(9) (a) Benneche, T.; Strande, P.; Undheim, K. Synthesis 1983, 762-
763. (b) Schwartz, M. E.; Breaker, R. R.; Asteriadis, G. T.; deBear, J. S.;
Gough, G. R. Bioorg. Med. Chem. Lett. 1992, 2, 1019-1024.
(10) Surprenant, S.; Chan, W. Y.; Berthelette, C. Org. Lett. 2003, 5,
4851-4854.
(11) Wu, C.-S.; Huang, J.-L.; Sun, Y.-S.; Yang, D.-Y. J. Med. Chem.
2002, 45, 2222-2228.
(12) Clennan, E. L.; Pan, G.-L. Org. Lett. 2003, 5, 4979-4982.
Org. Lett., Vol. 7, No. 12, 2005
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prolonged periods of time, produced only 1,3-cyclohexanedi-
one (no CdC oxidative cleavage products were detected).
The lack of reactivity of 1f under these conditions is
consistent with the proposed electron-transfer mechanism.
The alkene cation radical then reacts with molecular oxygen
to form a dioxetane radical cation 6. On the basis of previous
reports, it is likely that the dioxetane ring formation occurs
via a peroxy radical intermediate.16 The back electron transfer
from the nitrobenzyl ring to the dioxetane ring occurs to form
the compound 6′. The dioxetane ring then decomposes to
form the products.
Scheme 2. Proposed Mechanism of CdC Oxidative Cleavagea
The reduced yield of the oxidative cleavage products under
nitrogen is not negligible and cannot be explained by traces
of dissolved oxygen. This leads us to believe that an alternate
pathway exists for this reaction under these conditions. It is
possible that under nitrogen, traces of dissolved water could
hydrate the radical cation leading to the ketone. Alternatively,
the oxygen of the nitro goup could transfer to form the
ketone. These possible pathways could at best be a minor
pathway in the presence of air or oxygen since the ketone
yields are substantially higher under these conditions even
though the same solvent is used.
Due to the high yields of the products obtained, we believe
that this reaction could be useful to synthetic chemists. In
the future, we will investigate the substitution effects and
the possibility of using an external excited-state electron
acceptor to the alkyl enol ether in order to carry out these
reactions. This will simplify the synthesis of the enol ethers,
maximize the yields of the ketone, reduce the possibility of
rearrangements, and offer flexibility with respect to the use
of the electron acceptor. We also plan to study the possibility
of using vinyl halides for these types of oxidative cleavage
reactions.
a SET: single-electron transfer. BET: back electron transfer.
carried out in the presence of nitrogen, lead us to believe
that molecular oxygen was involved in the reaction. While
singlet oxygen is known to form dioxetane rings with alkene
via [2 + 2] cyclizations,13 it is unlikely to occur in this case,
as there is no known source of singlet oxygen. The triplet
oxygen has been shown to form an adduct with alkene radical
cations, which can then cyclize to form a dioxetane radical
cation ring.14 On the basis of these observations and literature
reports, we propose the following mechanism for the
oxidative cleavage of CdC for the enol ethers (Scheme 2).
Photolysis of 1 leads to its excited singlet state with the
2-nitrobenzyl group acting as the chromophore. Schore and
Turro have shown that excited singlet states of ketones can
be quenched by enol ethers via an electron-transfer pathway
to produce ion radical pairs.15 We believe that in this case,
the enol ether quenches the 2-nitrobenzyl chromophore by
an intramolecular electron transfer to form the zwitterionic
species. The aromatic rings on the double bond help stabilize
the electron-deficient double bond, which is consistent with
our observation that the yield of the oxidative cleavage drops
when no aromatic rings are present (entry 1e). 3-(2-
Nitrobenzyloxy)cyclohex-2-enone, 1f, when photolyzed for
Acknowledgment. The authors thank ND-EPSCoR, the
ND-EPSCoR “Network in Catalysis” program (NSF-EPS-
0132289), and the University of North Dakota for funding
this research. The authors also thank Ms. Ann Cody, Ms.
Judy Miska, and Ms. Yan Liang for their help in the synthesis
of the enol ethers.
Supporting Information Available: Experimental pro-
cedures and spectral data for all the materials. This material
is available free of charge via the Internet at http://pubs.acs.org.
(13) Schank, K.; Weiter, M.; Keasalar, R. HelV. Chim. Acta 2002, 85,
2105-2124.
(14) (a) Nelsen, S. F.; Akaba, R. J. Am. Chem. Soc. 1981, 103, 2096-
2097. (b) Clennan, E. L.; Simmons, W.; Almgren, C. W. J. Am. Chem.
Soc. 1981, 103, 2098-2099.
OL0508072
(15) Schore, N. E.; Turro, N. J. J. Am. Chem. Soc. 1975, 97, 2482-
2488.
(16) ReactiVe Intermediate Chemistry; Moss, R. A., Platz, M. S., Jones,
M., Jr., Eds.; Wiley-Interscience: Hoboken, NJ, 2004.
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