Novel oxa-di-π-methane and Norrish type I reactions in the S2 (π,π*) excited state of a series of β,γ-unsaturated ketones

Article abstract of DOI:10.1021/ol050846d

(Chemical Equation Presented) β,γ-Unsaturated methyl ketones with electron-withdrawing groups at the γ-position of the ene moiety undergo ODPM rearrangements and Norrish type I reactions on direct irradiation at 254 nm. The results are consistent with the

Full text of DOI:10.1021/ol050846d

ORGANIC
LETTERS
2005
Vol. 7, No. 13
2687-2690
Novel Oxa-di-π-methane and Norrish
Type I Reactions in the S2 (
π,π*)
Excited State of a Series of
â,γ-Unsaturated Ketones
Diego Armesto,* Maria J. Ortiz,* Antonia R. Agarrabeitia, and
Mar Mart´ın-Fontecha
Departamento de Qu´ımica Orga´nica I, Facultad de Ciencias Qu´ımicas,
UniVersidad Complutense, 28040 Madrid, Spain
darmesto@quim.ucm.es; mjortiz@quim.ucm.es
Received April 18, 2005
ABSTRACT
â,γ-Unsaturated methyl ketones with electron-withdrawing groups at the γ-position of the ene moiety undergo ODPM rearrangements and
Norrish type I reactions on direct irradiation at 254 nm. The results are consistent with the involvement of alkene S2
(π,π*) as reactive excited
states in these processes.
The oxa-di-π-methane (ODPM) photochemical rearrange-
ment reaction has been the subject of numerous studies
carried out for more than 35 years. The results of these efforts
show that this process usually occurs from the lowest excited
triplet state T1 (π,π*) of the ketone moiety.1 There are very
few exceptions to this general rule. Rogers et al. reported in
1984 that enones 1a, 1b, and 2 undergo ODPM rearrange-
ments to yield 3a, 3b, and 4, respectively, on triplet sensitized
irradiation from the T1 (π,π*) excited states and also on direct
irradiation from the T2 (n,π*) state or, less likely, from S1
(n,π*) states.2 Four years later Cerfontain and Koppes
described the direct irradiation reactions of enones 5a and
5b. They showed that direct irradiation of these substances
using Pyrex-filtered light leads to formation of the respective
ODPM products 6a and 6b. They suggested that these
reactions occur via the alkene S2 (π,π*) excited state.3
However, the conclusions drawn by Cerfontain and Koppes
deserve reevaluation since it is difficult to explain how the
S2 (π,π*) excited state of compounds 5 could be populated
under these photochemical reaction conditions. Another
example of T2 (n,π*) or S1 (n,π*) ODPM reactivity,
uncovered by Dalton, is referred to as unpublished results
in Roger’s and Cerfontain’s papers but apparently has never
been published. As far as we are aware, these are the only
exceptions to the rule mentioned above. In this publication
we report the results of studies that demonstrate that electron-
withdrawing groups at the γ-position of â,γ-unsaturated
ketones promote ODPM rearrangements and Norrish type I
reactions via the S2 (π,π*) excited state of the ene moieties.
As part of our studies exploring the photoreactivity of 1,4-
unsaturated compounds promoted by electron-donor sensitiz-
(1) For reviews, see: (a) Hixson, S. S.; Mariano, P. S.; Zimmerman, H.
E. Chem. ReV. 1973, 73, 531-551. (b) Dauben, G. W.; Lodder, G.;
Ipaktschi, J. Top. Curr. Chem. 1975, 54, 73-114. (c) Houk, K. N. Chem.
ReV. 1976, 76, 1-74. (d) Schuster, D. I. In Rearrangements in Ground
and Excited States; DeMayo, P., Ed.; Academic Press: New York, 1980;
Vol. 3, pp 167-279. (e) Demuth, M. In Organic Photochemistry; Padwa,
A., Ed.; Marcel Dekker: New York, 1991; Vol. 11, pp 37-109. (f) Demuth,
M. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming. I., Paquette,
L. A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, pp 215-237. (g)
Zimmerman, H. E.; Armesto, D. Chem. ReV. 1996, 96, 3065-3112.
(2) Eckersley, E. J.; Parker, S. D.; Rogers, N. A. J. Tetrahedron 1984,
40, 3749-3758.
(3) Koppes, M. J. C. M.; Cerfontain, H. Recl. TraV. Chim. Pays-Bas
1988, 107, 549-562.
10.1021/ol050846d CCC: $30.25
© 2005 American Chemical Society
Published on Web 05/21/2005

The formation of the ODPM product 10a under the above
conditions is surprising. The fact that the ODPM rearrange-
ment of 7a does not proceed upon triplet photosensitization
rules out a reactive T1 (π,π*) triplet state as responsible for
the reaction. On the other hand, the lack of reactivity of 7a
on direct irradiation using Pyrex filtered light discounts the
involvement in the rearrangement of S1 (n,π*) and T2 (n,π*)
excited states of the ketone moiety. The formation of 10a in
the direct irradiation reaction of 7a, using 254 nm light,
suggests that the ODPM rearrangement of 7a proceeds from
the higher energy singlet excited state S2 (π,π*) of the alkene.
As mentioned above, an ODPM reaction of a â,γ-unsaturated
enone that occurs from a state other than T1 (π,π*) is very
uncommon and rarely found in the literature.
Figure 1.
Another interesting observation is that the diene 11,
resulting from decarbonylation (a typical Norrish type I
reaction) is formed when 7a is irradiated at 254 nm. This
compound is not obtained on direct irradiation using Pyrex-
filtered light. Previous studies of Norrish type I reactions of
â,γ-unsaturated enones have established that these reactions
occur from S1 (n,π*) or T2 (n,π*) excited states. In addition,
we have recently reported the first examples of decarbony-
lation and 1,3-formyl migration processes in excited-state
reactions of â,γ-unsaturated aldehydes that take place via
the T1 (π,π*).4 Thus, the formation of Norrish type I products
on 254 nm direct irradiation of 7a represents the first example
of Norrish type I reactions that occurs in an S2 (π,π*) excited
state. The reason for this unusual reactivity might derive from
the fact that the S2 (π,π*) excited state of 7a possesses
sufficient energy to promote homolytic bond fission at the
allylic position. As a result decarbonylation competes with
the ODPM rearrangement.
ers, we investigated the reactivity of radical anions derived
from â,γ-unsaturated ketones that contain electron-withdraw-
ing groups on the alkene unit. Our goal was to determine
whether radical anions centered on the C-C double bond
could be generated selectively on irradiation using N,N-
dimethylaniline (DMA) as electron-donor sensitizer. For this
purpose, methyl ketone 7a was synthesized and irradiated
in an acetonitrile solution containg N,N-dimethylaniline. As
anticipated, this reaction resulted in exclusive formation of
the reduced product 8, arising from the alkene-centered
radical anion 9. However, since the excited-state reactivity
To determine if other â,γ-unsaturated ketones related to
7a also display this unusual reactivity profile, the photo-
chemistry of enones 7b and 7c was explored. Acetone-
sensitized irradiation of (E)-7b affords recovered starting
material as a 2:3 mixture of E/Z diastereoisomers. However,
direct irradiation using Pyrex-filtered light yielded the 1,3-
acyl shift product 12 and dienes 13 and (E)-14, resulting
from decarbonylation of 7b (Scheme 2).
Thus, the replacement of a cyano group in 7a by a methyl
group restores the normal Norrish type I reactivity of the
carbonyl. Irradiation of (E)-7b at 254 nm affords the Norrish
type I photoproducts 12, 13, 14, and cyclopropane 10b
resulting from ODPM rearrangement (Scheme 2). The
formation of 10b under these conditions shows that mono-
cyano substitution at the γ-position of the enone also allows
ODPM rearrangement to take place via the S2 (π,π*) excited
state. In this instance the Norrish type I photoproducts 12,
13, and 14 are formed by excitation of both the carbonyl
and the alkene units.
Figure 2.
profile of 7a was unknown, it was necessary to evaluate its
photobehavior under direct and triplet-sensitized irradiation
conditions. Prolonged direct or acetophenone-sensitized
irradiations of 7a, using a Pyrex filtered light, led to complete
recovery of starting material. However, direct irradiation of
7a through quartz produces the ODPM product 10a (16%)
and the 1,5-diene 11 (12%) (Scheme 1).
Scheme 1 a
Compound 7c does not undergo the ODPM rearrangement
on acetone-sensitized irradiation; only recovered starting
material is obtained as a 2:1 mixture of E/Z diastereoisomers.
Surprisingly, direct irradiation of 7c using Pyrex-filtered light
yields the ODPM product (Z)-10c and the diene 15 (Scheme
a Conditions: (i) acetophenone, 14 h; (ii) direct, Pyrex, 24 h;
(iii) direct, quartz, 254 nm.
(4) Armesto, D.; Ortiz, M. J.; Agarrabeitia A. R.; Aparicio-Lara, S.
Synthesis 2001, 1149-1158.
2688
Org. Lett., Vol. 7, No. 13, 2005

Scheme 2 a
Scheme 4 a
a Conditions: (i) acetophenone, 14 h; (ii) direct, Pyrex, 14 h;
(iii) direct, quartz, 254 nm.
a Conditions: (i) acetone, 7 h; (ii) direct, Pyrex, 6 h; (iii) direct,
quartz, 254 nm.
compound 18, and diene 19. These results demonstrate that
the ODPM and Norrish type I reactions take place via the
S2 (π,π*) state in photoreactions of â,γ-unsaturated ketones
possessing electron-withdrawing γ-substituents other than
cyano.
3). Compounds 10c and 15 should arise from the S1 (n,π*)
or the T2 (n,π*) excited states. As mentioned before there is
only one report in the literature of ODPM reactions via the
S1 or T2 states.2 These two products are also obtained on
irradiation at 254 nm. Under these conditions the excited
state involved in the ODPM and Norrish type I reactions
could be the S2 (π,π*) or, alternatively, the S1 arising from
internal conversion.
The substitution effects observed for compounds 7 and
16 are both surprising and difficult to explain at this point.
The short wavelength promoted reactivity of these com-
pounds could be due to either the electron-withdrawing
properties of the cyano and ester groups or their ability to
conjugatively stabilize biradical intermediates. If the latter
effect predominates, it should operate control on the excited
reactivity profiles of other â,γ-unsaturated ketones that
contain substituents that alter the energies of radical inter-
mediates involved in the OPM process. This possibility can
be probed by using the enone (E)-20, which has monophenyl
substitution at the γ-position that should provide stabilized
radical intermediates. Acetophenone triplet-sensitized ir-
radiation of (E)-205gives recovered starting material only,
as a 1:1 mixture of E/Z diastereoisomers, whereas direct
irradiation, through Pyrex, affords ketone 21, resulting from
1,3-acyl shift and diene 22 arising from decarbonylation and
dimerization of the resulting radicals. Compounds 21 and
22 are also formed on direct irradiation at 254 nm. However,
under these conditions the corresponding ODPM product (E)-
23 is obtained in very low yield (ca. 1%) (Scheme 5). These
results demonstrate that when electron-withdrawing groups
Scheme 3 a
a Conditions: (i) acetone, 8 h; (ii) direct, Pyrex, 6 h; (iii) direct,
quartz, 254 nm.
The unusual reactivity observed for compounds 7 raises
the question whether these reactions only occur when cyano
groups are present at the γ-position of the enone. To clarify
this point, we have investigated the photochemical reactivity
of enone 16 in which cyano groups are replaced by
methoxycarbonyl groups.
Scheme 5 a
Acetophenone-sensitized irradiation of 16 leads to forma-
tion of the ODPM product 17 (15%) arising from the T1
(π,π*) excited state. Thus, replacing the cyano groups in 7a
by methoxycarbonyls restores the normal ODPM reactivity
pattern. Direct irradiation of 16, through Pyrex, also affords
17 (8%), compound 18, resulting from 1,3-acyl shift, and
19, obtained by decarbonylation and dimerization of the
resulting radical (Scheme 4). The formation of 17 under these
conditions could be a result of intramolecular triplet energy
transfer from the carbonyl to the alkene grouping. Finally,
irradiation of 16 through quartz, at 254 nm, using a low-
pressure Hg arc lamp, affords the ODPM product 17,
a Conditions: (i) acetophenone, 5 h; (ii) direct, Pyrex, 1 h; (iii)
direct, quartz, 254 nm.
Org. Lett., Vol. 7, No. 13, 2005
2689

are not present at the γ-position of â,γ-unsaturated ketones,
the efficiency of the ODPM rearrangement taking place via
a S2 (π,π*) excited state decreases considerably.
We have studied the 4-cyano- and 3-cyano-substituted
enones 24 and 25 in order to obtain additional information
on the influence of electron-withdrawing groups on singlet
excited-state ODPM rearrangement reactions of â,γ-unsatur-
ated ketones. The results of this investigation are summarized
in Scheme 6. Triplet-sensitized irradiation of 24 using
usually undergo ODPM rearrangements on triplet-sensitized
irradiation via the T1 (π,π*) excited state. In contrast, direct
irradiation of â,γ-unsaturated ketones promotes 1,3-acyl
migration and decarbonylation reactions that occur in S1
(n,π*) or T2 (n,π*) excited states.1 The results obtained in
the current study show that â,γ-unsaturated methyl ketones
with electron-withdrawing groups at γ-position undergo
ODPM rearrangements and Norrish type I reactions on direct
irradiation at 254 nm. The findings are consistent with the
involvement of a S2 (π,π*) excited state in these reactions.
Under these conditions bond formation and bond cleavage
must be extremely fast to compete with internal conversion.
In some instances ODPM reactions occur on direct irradiation
using Pyrex-filtered light, probably via the S1 (n,π*) or the
T2 (n,π*) states. The reasons for the unusual ODPM
reactivity in the S2 state are unclear at this point. In this
regard it is worth noting that Zimmerman et al.6 have reported
that the multiplicity and regiochemistry of the DPM reaction
are affected by cyano and methoxycarbonyl substitution at
1- and 3-positions of the 1,4-diene. Norrish type I reactivity
of S2 (π,π*) excited states of these substrates might be due
to the high energy content of this excited state that promotes
homolytic bond fission at the allylic position. Further studies
will be necessary to determine the scope and the structural
factors that control these novel reactions. In our opinion, the
results obtained in this study open new lines of research on
the photoreactivity of â,γ-unsaturated carbonyl compounds.
Scheme 6 a
a Conditions: (i) 3-methoxyacetophenone, 8 h; (ii) direct, Pyrex,
1 h; (iii) direct, quartz, 254 nm.
Acknowledgment. M.M.-F. thanks the Ministerio de
Educacion y Ciencia for a postgraduate fellowship. We thank
the Ministerio de Ciencia y Tecnologia (grant no. BQU2001-
1282) and Universidad Complutense of Madrid (grant no.
PR1/05-13271) for financial support. We acknowledge the
support provided by the Centro de Resonancia Magnetica,
the Centro de Microanalisis, and the Servicio de Espec-
trometria de Masas of the Universidad Complutense.
3-methoxyacetophenone gives recovered starting material
only as a 2:3 mixture of E/Z diastereoisomers. In contrast,
direct irradiation of 24 through Pyrex for 1 h affords the
ODPM product (E)-26, the ketone 27 resulting from 1,3-
acyl shift, and the diene 28 arising from decarbonylation and
dimerization of the resulting radicals. The three products are
also formed on direct irradiation at 254 nm, showing that
4-cyano substitution does help to promote ODPM rearrange-
ments and Norrish type I reactions in the S2 (π,π*) excited
state and also by excitation of the carbonyl to the S1 or T2
states (Scheme 6). However, when the cyano group is at
meta-position ((E)-25), only Norrish type I products, 29 and
30, are observed (Scheme 6). This result suggests that
conjugation of the biradical intermediates with cyano groups
is important for the success of the rearrangement.
Supporting Information Available: Experimental pro-
cedures for the preparation of enones 7a-c, 16, 24, and 25;
experimental details for the photolysis; analytical and
spectroscopic data for all photoproducts; and 1H NMR
spectra for all compounds lacking analyses. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL050846D
In summary, earlier studies of the photoreactivity of â,γ-
unsaturated ketones have established that these compounds
(6) (a) Zimmerman, H. E.; Armesto, D.; Amezua, M. G.; Gannett, T.
P.; Johnson, R. P. J. Am. Chem. Soc. 1979, 101, 6367-6383. (b)
Zimmerman, H. E.; Factor, R. E. Tetrahedron 1981, 37, Supplement 1,
125-141. (c) Zimmerman, H. E.; Chen, W. Org. Lett. 2002, 4, 1155-
1158.
(5) van der Weerdt, A. J. A.; Cerfontain, H. Recl. TraV. Chim. Pays-
Bas 1977, 96, 247-248.
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