The confined cavity of a coordination cage suppresses the photocleavage of α-diketones to give cyclization products through kinetically unfavorable pathways

Article abstract of DOI:10.1002/anie.200701250

(Figure Presented) It's a trap: The photochemical homolytic cleavage of an α-diketone leading to degradation products was suppressed through the encapsulation of the diketone in a self-assembled cage. Instead, intramolecular cyclization products were formed through otherwise unfavorable (kinetically hidden) reaction pathways. This provides an approach to find new reactions of photolabile compounds that had been abandoned because of predominant cleavage reactions.

Full text of DOI:10.1002/anie.200701250

Angewandte
Chemie
DOI: 10.1002/anie.200701250
Photoreactions
The Confined Cavity of a Coordination Cage Suppresses the
Photocleavage of a-Diketones To Give Cyclization Products through
Kinetically Unfavorable Pathways**
Takahito Furusawa, Masaki Kawano, and Makoto Fujita*
In contrast with the rich photochemistry of ketones,[1] the
photochemical reactions of a-diketones have been largely
unexplored, mainly because the major reaction pathways
from a-diketones are initiated by homolytic cleavage into acyl
radicals that subsequently give a mixture of many degradation
products.[2,3] By analogy with ketones, a-diketones should
potentially have photochemical pathways leading to syntheti-
cally useful species.However, the formation of such com-
pounds is normally dominated by homolytic cleavage.If a-
diketones are confined in a restricted cavity of cages, the acyl
radicals formed by the homolytic cleavage are immediately
recombined to give the starting a-diketones.[4] As a result, the
cleavage pathway is negligible and otherwise unfavorable
reaction pathways can be major reaction courses.Expecting
the formation of kinetically unfavorable photochemical
Scheme 1. The photoreaction of 2 in the cavity of 1.
products from a-diketones, we examined the enclathration
of an a-diketone by a cage compound and studied subsequent
photochemical reactions in the cage.We employed the self-
assembled M6L4 cage (1), which has a well-established
binding ability for neutral organic molecules.[5] We found
that the unprecedented intramolecular photocyclization of
the a-diketone (2) can lead to cyclized products without
cleavage of the a-diketone framework (Scheme 1).
Diphenylethanedione (2) was employed as a guest
molecule.When an excess amount (approximately 5 equiv-
alents) of 2 was suspended in an aqueous solution of 1 (8 mm)
at 1008C for 1 h, water-insoluble 2 was partially dissolved and
the colorless solution turned pale yellow.After the filtration
1
of excess 2, H NMR spectroscopy indicated that the guest
signals were significantly shifted upfield (Dd ꢀ À2.1–À3.5),
which was diagnostic of the formation of an inclusion complex
(Figure 1).From the integral ratio, we estimated that
Figure 1. 1H NMR spectra (500 MHz, RT, TMS as the internal stan-
dard) of a) 2 in CDCl3 and b) the 1ꢁ(2)2 complex in D2O. Pya and Pyb
represent the pyridine a and b protons of the ligand.
[*] T. Furusawa, Dr. M. Kawano, Prof. Dr. M. Fujita
Department of Applied Chemistry
School of Engineering
approximately two guest molecules were encapsulated per
cage, giving the complex 1ꢁ(2)2.Single crystals suitable for X-
ray crystal structure analysis were obtained from water by the
slow evaporation of water over a week.The crystallographic
analysis confirmed the structure of the 1ꢁ(2)2 complex.The
single-crystal X-ray diffraction analysis revealed that the two
guest molecules were orthogonally packed in the cavity of 1,
wherein each of them adopted a twisted conformation with a
dihedral angle of 828 between the two carbonyl groups
(Figure 2).
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax: (+81)3-5841-7257
E-mail: mfujita@appchem.t.u-tokyo.ac.jp
[**] This research was supported by the CREST project of the Japan
Science and Technology Agency (JST) for which M.F. is the principal
investigator. This research was partially supported by the Ministry of
Education, Culture, Sports, Science and Technology of Japan.
Supporting information (including full experimental procedures,
physical data of the photoreaction products, 1D and 2D NMR
spectra, and the X-ray structure analysis data) for this article is
available on the WWW under http://www.angewandte.org or from
the author.
Upon photoirradiation, we obtained rather unusual
products from 2 accommodated in the cage.An aqueous
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assigned as a benzylic proton (Figure 3b).For the two other
products, hydroxy protons observed at d = 8.79 ppm and
11.39 ppm were seen to be characteristic (Figure 3c,d). All
the products were shown to incorporate aromatic rings: a
monosubstituted as well as an o-disubstituted benzene ring.
From the information given above, coupled with the detailed
analysis of the 2D NMR data, we assigned the structures of
three main products (3–5) as shown in Figure 3b–d.The yields
of 3–5 were estimated to be 31, 7, and 14%, respectively, by
1
integration of the H NMR spectra.
Single crystals of 3–5 that were suitable for X-ray
diffraction were obtained by recrystallization from appropri-
ate solvents.This confirmed our proposed structure for the
products 3–5 (Figure 4).For 3, the intramolecularly cyclized
Figure 2. Crystal structure of the 1ꢁ(2)2 complex.
solution of the clathrate 1ꢁ(2)2 was irradiated for 6 h by using
a high-pressure mercury lamp.The
1H NMR spectrum
recorded after irradiation showed that the signals that were
assigned to guest 2 completely disappeared along with the
apparition of new signals.Although the 1H NMR spectrum
after extraction with chloroform was very complex (Fig-
ure 3a), we were able to isolate three major products by using
silica-gel column chromatography and gel-permeation chro-
matography.For the major product, we noticed a singlet
signal appearing at d = 5.02 ppm, which was tentatively
Figure 4. Thermal-ellipsoid plots (50% probability level) of the molec-
ular structures of a) 3, b) 4, and c) 5.
structure with a magnetically isolated benzylic proton was
confirmed (Figure 4a).Product 4 has an analogous structure
with a HOO group at the benzylic position (Figure 4b).
Product 5 was shown to have the same diketone framework as
the starting material 2 and a hydroxy group was introduced at
the ortho position of the benzene ring (Figure 4c).
The proposed reaction mechanisms for the formation of
these three products are shown in Scheme 2.First, the
biradical 6 was generated by the photoexcitation of the
carbonyl n–p* transition.Subsequently, the nucleophilic
radical center on the oxygen atom attacked the terminal of
the a,b-unsaturated carbonyl moiety of the adjacent benzoyl
moiety to give cyclized structure 7 through a radical addition–
elimination reaction.The resulting carbon radical abstracted
the hydrogen radical either directly or after being trapped by
molecular oxygen to give the cyclized products 3 and 4,
respectively.Even under the anaerobic conditions used, it is
likely that a trace amount of oxygen remained and the
formation of 4 could not be completely avoided.The product
5 was presumably formed through the direct conjugate
addition of a hydroxyl radical to the benzene ring while the
diketone framework remained intact.The hydroxyl radical
Figure 3. 1H NMR spectra (500 MHz, CDCl3, RT, TMS as the internal
standard) of a) reaction mixture after extraction, b) 3 (in C6D6), c) 4,
and d) 5.
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Angewandte
Chemie
was found in less than 5% yield by 1H NMR spectroscopy and
were not further analyzed.The presence of traces of 3 in the
resulting aqueous solution indicates that the reaction pathway
leading to this product is possible under these conditions, but
is overwhelmingly dominated by the competing diketone
cleavage pathway.We emphasize herein that the diketone
homolytic cleavage is completely suppressed within cage 1
and that kinetically unfavorable pathways without homolytic
cleavage became major pathways thanks to the remarkable
cage effect of 1.
Received: March 21, 2007
Published online: June 25, 2007
Keywords: a-diketones · cage compounds · cyclization ·
photochemistry · self-assembly
.
Scheme 2. Proposed reaction mechanisms for the formation of 3, 4,
and 5.
[1] a) N.J. Turro, Modern Molecular Photochemistry, 1st ed., The
Benjamin/Cummings Publishing Co., Menlo Park, 1978.
can be formed from water through hydrogen radical abstrac-
tion.Several products (such as, for example, more oxidation
products of 3–5) were probably involved in the complex
reaction mixture, however, none have been isolated thus far.
To study how cage 1 affected the photoreaction of 2, a
control experiment without cage 1 under anaerobic condi-
tions was examined.The degassed cyclohexane solution of 2
was irradiated for 3 h to give benzaldehyde (5%) and
cyclohexyl phenyl ketone (10%) as major products.These
were formed through the benzoyl radical route as a result of
the homolytic cleavage of the a-diketone unit (Scheme 3).
[2] For the cleavage reactions of a-diketones, see: a) I.Tabushi, S.
Kojo, Z.Yoshida, Tetrahedron Lett. 1973, 14, 2329 – 2332; b) P.
Kaszynski, J.Michl, J. Org. Chem. 1988, 53, 4593 – 4594; c) Y.
Sawaki, C.S. Foote, J. Org. Chem. 1983, 48, 4934 – 4940; d) Y.
Sawaki, Bull. Chem. Soc. Jpn. 1983, 56, 3464 – 3470.
[3] For the photoreactions of a-diketones except for cleavage
reaction, see: a) K.Nakatani, K.Tanabe, I.Saito,
Tetrahedron
Lett. 1997, 38, 1207 – 1210; b) A.Takuwa, Y.Nishigaichi, K.
Yamashita, H.Iwamono, Chem. Lett. 1990, 639 – 642; c) A.
Thomas, G.Anikumar, V.Nair,
Tetrahedron 1996, 52, 2481 –
2488; d) W.H.Urry, D.J.Trecker, J. Am. Chem. Soc. 1962, 84,
118 – 120; e) M.B.Rubin, P.Zwitkowits, J. Org. Chem. 1964, 29,
2362 – 2368; f) J.Mattay, J.Gersdorf, U.Freudenberg,
Tetrahe-
dron Lett. 1984, 25, 817 – 820.
[4] For cage effects in photoreactions, see: a) J.Franck, E.Rabino-
witsch, Trans. Faraday Soc. 1934, 30, 120 – 131; b) N.J. Turro,
Chem. Commun. 2002, 2279 – 2292; c) V.F.Tarasov, N.D.Ghat-
lia, A.L.Buchachenko, N.J.Turro, J. Am. Chem. Soc. 1992, 114,
9517 – 9526; d) L.S.Kaanumalle, J.Nithyanandhan, M.Pattabira-
man, N.Jayaraman, V.Ramamurthy, J. Am. Chem. Soc. 2004, 126,
8999; e) V.Ramamurthy, D.F.Eaton, Acc. Chem. Res. 1988, 21,
300 – 306; f) L.S. Kaanumalle, C.L.D. Gibb, B.C. Gibb, V.
Ramamurthy, J. Am. Chem. Soc. 2004, 126, 14366 – 14367; g) D.J.
Cram, M.E.Tanner, R.Thomas, Angew. Chem. 1991, 103, 1048 –
1051; Angew. Chem. Int. Ed. Engl. 1991, 30, 1024 – 1027.
[5] a) M.Fujita, D.Oguro, M.Miyazawa, H.Oka, K.Yamaguchi, K.
Ogura, Nature 1995, 378, 469 – 471; b) T.Kusukawa, M.Fujita,
Angew. Chem. 1998, 110, 3327 – 3329; Angew. Chem. Int. Ed.
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Scheme 3. Photoreaction of 2 in cyclohexane.
Benzoic acid was also formed (10%), although we could not
determine the reaction pathway.More importantly, we could
not detect any trace amounts of 3–5, which form in the
absence of homolytic cleavage.When this reaction was
examined under aqueous conditions (H2O/methanol = 6:4),
only a trace amount (< 1%) of the product 3 was detected in
the reaction mixture.Each of the additional products formed
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