Intramolecular photocyclization of 2-acylphenyl methacrylates: A convenient access to 4,5-dihydro-1,4-epoxy-2-benzoxepin-3(1H)-ones =benzo[c]-6,8- dioxabicyclo [3.2.1]octan-7-ones

Article abstract of DOI:10.1002/hlca.200590200

The photochemical reactions of 2-acylphenyl methacrylates (=2-acylphenyl 2-methylprop-2-enoates) 1 were investigated. Irradiation of 2-acylphenyl methacrylates 1a-d in MeCN gave the tricyclic lactones 2a-d in good yields, together with a small amount of O-C=O bond cleavage product, the 2-acylphenols 3a-d (Scheme 2, Table). The formation of the tricyclic lactones 2 probably follows a mechanism involving a 1,7-diradical through ζ-H abstraction (1,8-H transfer) by the excited carbonyl O-atom (Scheme 3). Irradiation of 2-acylphenyl tiglate (=2-acylphenyl (2E)-2-methylbut-2-enoate) 1e and 2-acylphenyl methacrylates 1g-i, substituted by a MeO group (δ-H) at the 3,5-positions of the phenylgroup, also gave the tricyclic lactones 2e and 2g-i, but in low yields. On the other hand, no H-abstraction products were observed on irridation of 2-(ethoxycarbonyl)phenyl methacrylate 1f, of 2-acylphenyl methacrylate 1j which is substituted by a Me group (γ-H) at the 3,5-positions of the phenyl group, and of 1k with an OH group at the 3-position of the phenyl group.

Full text of DOI:10.1002/hlca.200590200

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Intramolecular Photocyclization of 2-Acylphenyl Methacrylates:
a Convenient Access to 4,5-Dihydro-1,4-epoxy-2-benzoxepin-3(1H)-ones
=Benzo[c]-6,8-dioxabicyclo[3.2.1]octan-7-ones
(
a
a
a
b
c
by Takehiko Nishio* ), Nobuharu Sakurai ), Kaoru Iba ), Yo-ichi Hamano ), and Masami Sakamoto )
a) Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba-
shi, Ibaraki, 305-8571 Japan
b
)
Graduate School of Environmental Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki, 305-8571, Japan
c) Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Chiba University, Yayoi-cho,
Inage-ku, Chiba, 263-8522, Japan
The photochemical reactions of 2-acylphenyl methacrylates (=2-acylphenyl 2-methylprop-2-enoates) 1
were investigated. Irradiation of 2-acylphenyl methacrylates 1a–d in MeCN gave the tricyclic lactones 2a–d
in good yields, together with a small amount of OꢀC=O bond cleavage product, the 2-acylphenols 3a–d
(Scheme 2, Table). The formation of the tricyclic lactones 2 probably follows a mechanism involving a 1,7-di-
radical through z-H abstraction (1,8-H transfer) by the excited carbonyl O-atom (Scheme 3). Irradiation of 2-
acylphenyl tiglate (=2-acylphenyl (2E)-2-methylbut-2-enoate) 1e and 2-acylphenyl methacrylates 1g–i, substi-
tuted by a MeO group (d-H) at the 3,5-positions of the phenyl group, also gave the tricyclic lactones 2e and 2g–i,
but in low yields. On the other hand, no H-abstraction products were observed on irridation of 2-(ethoxycarbo-
nyl)phenyl methacrylate 1f, of 2-acylphenyl methacrylate 1j which is substituted by a Me group (g-H) at the 3,5-
positions of the phenyl group, and of 1k with an OH group at the 3-position of the phenyl group.
1
. Introduction. – Intramolecular H-abstraction reactions by the excited carbonyl
group have been extensively investigated from synthetic and mechanistic viewpoints
1–3]. Generally, g-H-atoms are abstracted most rapidly through six-membered cyclic
[
transition states (1,5-H-transfer), as in the Norrish-Type-II reaction. This g-H abstrac-
tion is greatly facilitated by favorable stereoelectronic or geometric requirements [2].
Abstraction from remote positions involving 1,6- and greater H-transfers is one of the
most attractive subjects in the photochemistry of carbonyl groups [3–9], while these
reactions are disfavored for medium and large cyclic transition states both statistically
and energetically. Abstraction from such long-range positions has been observed in the
photochemistry of imides [10], amino ketones [11], and S-containing glyoxylates [12]
associated with electron-transfer character. In the course of our studies on the photo-
chemistry of amide derivatives [13], we have reported that the long-range H-abstrac-
tion was observed in the photochemistry of N-(2-acylphenyl)prop-2-enamides and N-
(
2-acylphenyl)propanamides [13c,d]. For example, irradiation of N-(2-acylphenyl)-2-
methylprop-2-enamides (A) [13c] and N-(2-acylphenyl)-2-bromo-2-methylpropana-
mides (B) [13d] afforded the open-chain amides C and the tricyclic lactams D, respec-
tively, via z-H abstraction (1,8-H transfer) by the excited carbonyl O-atom through a
nine-membered transition state (Scheme 1). We now report a new example of a z-H
abstraction reaction in the photochemistry of 2-acylphenyl methacrylates 1, whereby
©
2005 Verlag Helvetica Chimica Acta AG, Zürich

2
604
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Scheme 1
cyclization, followed by rearrangement of the resulting 1,7-biradicals, leads to the for-
mation of the unexpected tricyclic lactones 3.
2
. Results and Discussion. – Irradiation of 2-acylphenyl methacrylates 1a–d in
MeCN with a high-pressure Hg lamp under Ar atmosphere (Pyrex filter, room temper-
ature) gave tricyclic lactones, i.e., 4,5-dihydro-1,4-epoxy-2-benzoxepin-3(1H)-ones
(=benzo[c]-6,8-dioxobicyclo[3.2.1]octan-7-ones) 2a–d in high yields (74–98%),
along with a small amount of 2-acylphenols 3a–d, produced by cleavage of the
OꢀC(=O) bond (Scheme 2, Table). The tricyclic lactone 2a was also obtained when
1a was irradiated in benzene or MeOH, but in low yield. Irradiation of 2-benzoylphenyl
tiglate (=2-benzoylphenyl (2E)-2-methylbut-2-enoate; 1e) afforded the tricyclic lac-
tone 2e, and the possible isomeric lactone 2e’ (see below, Scheme 3) was not detected.
Irradiation of 2-(ethoxycarbonyl)phenyl methacrylate 1f gave no H-abstraction prod-
uct. The formation of the tricyclic lactone 2a was completely quenched by the addition
of triplet quenchers such as 2,5-dimethylhexa-2,4-diene, cyclohexa-1,3-diene, and O2,
suggesting that this reaction proceeds via an n-p* triplet state.
a
Scheme 2 )
a
1
2
)
For R , R , X, and Y, see Table.
The structures of the photoproducts 2 described above were assigned on the basis of
spectral and analytical evidence. In the case of the tricyclic lactone 2a, assignment was
further confirmed by an X-ray crystal structure analysis (Fig.).

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Table 1. Photochemical Reactions of the 2-Acylphenyl Methacrylates 1 in MeCN
Entry
Starting material
Substituents
Isolated yield [%] of products
1
2
R
R
X
Y
2
3
1
1a
1a
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
Ph
Ph
Ph
Me
Et
Ph
EtO
Ph
Me
Et
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
MeO
MeO
MeO
Me
OH
H
H
H
MeO
H
H
H
H
MeO
MeO
MeO
Me
H
98
42
12
84
70
74
1
14
43
12
1
5
2
6
a
2
3
4
5
6
7
8
9
0
1
2
3
)
)
b
c
14 )
d
– )
trace
44
13
23
25
11
1
1
1
1
20
d
1j
1k
Ph
Me
– )
d
d
– )
– )
a) Solvent: benzene. ) Solvent: MeOH. ) 2 :1 Mixture of two diastereoisomers. d) Not detected.
b
c
Figure. X-Ray crystal structure of com-
pound 2a. ORTEP view.
A plausible mechanism for the formation of the tricyclic lactones 2 is depicted in
Scheme 2. z-H (Allylic-H) abstraction by the excited carbonyl O-atom via a nine-mem-
bered transition state would result in the 1,7-biradical E. Subsequent ring closure yields
the spirolactone F, which may undergo ring opening to the oxo-carboxylic acid G, and
then ring closure yields the tricyclic lactone 2. The intramolecular ortho photocycliza-

2
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tion mechanism was reported in the photochemistry of 4-phenoxybut-1-enes [14]. A
similar mechanistic sequence could also be considered, i.e., ipso-cyclization of the ole-
finic C(b)-atom at the phenolic C-atom of the aromatic ring, followed by 1,6-cyclization
of the formed biradical, and then 3,3-sigmatropic rearrangement yielding the final tri-
1
cyclic products (Scheme 4) ). However, no cyclization product could be formed from 2-
(
ethoxycarbonyl)phenyl methacrylate 1f as mentioned above, and irradiation of the
parent phenyl methacrylate and 2-methoxyphenyl methacrylate resulted in the recov-
ery of unchanged starting materials. Further, we recently proposed the analogous H-
abstraction reaction of N-analogues, i.e., of N-(2-acylphenyl)-2-methylprop-2-enam-
ides [13c]. From these facts, we propose the long-range H-abstraction mechanism.
Scheme 4
Subsequently, to examine the intramolecular competition between d-H (1,6-H
transfer) and z-H abstraction (1,8-H transfer), and g-H (1,5 H transfer) and z-H
abstraction, we carried out the photoreaction of 1g–i having MeO substituents (d-
hydrogen) at the m-positions of the phenyl group and 1j having Me substituents (g-
hydrogen) at the m-positions of the phenyl group. Irradiation of 1g–i in MeCN
under the same conditions gave the tricyclic lactones 2g–i (trace-44%), accompanied
by the corresponding 2-acylphenols 3g–i (13–25%), and benzofuran derivatives,
which are expected to be produced via d-H abstraction [2a][15], could not be observed.
When 1j was irradiated, no H-abstraction product was formed, only a small amount of
the corresponding phenol 3j was isolated. This is probably due to the lack of favorable
stereoelectronic or geometric requirements [2]. Irradiation of 2-acyl-3-hydroxyphenyl
methacrylate 1k resulted in the recovery of unchanged starting material, probably due
to intramolecular H-bonding between OH and the acetyl C=O of 1k.
The H-abstraction reaction by the excited carbonyl O-atom is generally facilitated
by favorable stereoelectronic and geometric requirements [2]. Long-range H-atom
abstraction reactions are rare [3]. Our results herein establish the potential of long-
range H-abstraction reactions in case of favorable conformation.
Experimental Part
General. Flash chromatography (FC): Wakogel-C-300 silica gel. M.p.: Yanaco-MP-J3 micro-melting point
apparatus; uncorrected. B.p.: Shibata-GTO-350-RD glass-tube-oven distillation apparatus. IR Spectra: Jasco-
ꢀ
1
1
13
FT/IR-300 spectrophotometer; in cm . H- and C-NMR Spectra: Jeol-JNM-EX-270 (270 MHz) or Varian-
Gemini-200 (200 MHz) spectrometer; in CDCl , with Me Si as internal standard; d in ppm, J in Hz.
3
4
Irradiation of 2-Acylphenyl Methacrylates 1: General Procedure. A soln. of the 1 (1 mmol) in MeCN
70 ml), unless otherwise noted, was irradiated in a Pyrex tube with a high-pressure Hg lamp (Halos EHP
(
1)
We thank a referee for suggesting this mechanism.

2
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HELVETICA CHIMICA ACTA – Vol. 88 (2005)
5
00 W; Eikosha) under Ar for 5–15 h at r.t. After removal of the solvent, the residue was subjected to FC (SiO ,
2
toluene/AcOEt 50 :1 ! 19 :1) to give the photoproducts 2 and 3 (see Table). The structures of the 2-acylphenols
were confirmed by direct comparison of their spectral properties with those of commercially available mate-
rials.
3
4
,5-Dihydro-4-methyl-1-phenyl-1,4-epoxy-2-benzoxepin-3(1H)-one (2a): M.p. 141–1428. IR (KBr): 1795.
1
H-NMR: 1.73 (s, 3 H); 3.13 (d, J=17.5, 1 H); 3.28 (d, J=17.5, 1 H); 6.70 (d, J=7.9, 1 H); 7.06 (t, J=7.6, 1
H); 7.18 (d, J=7.3, 1 H); 7.24–7.34 (m, 1 H); 7.54–7.58 (m, 3 H); 7.62–7.66 (m, 2 H). C-NMR: 21.2; 35.4;
1
3
7
7
9.7; 108.6; 126.1; 126.3; 126,4; 128.4; 128.9; 129.6; 131.7; 134.7; 136.4; 175.0. Anal. calc. for C17
6.67, H 5.30; found: C 76.37, H 5.32.
14 3
H O : C
4
,5-Dihydro-4-methyl-1-phenyl-7-methoxy-1,4-epoxy-2-benzoxepin-3(1H)-7-one (2b): M.p. 130–1318. IR
1
(
(
KBr): 1794. H-NMR: 1.71 (s, 3 H); 3.09 (d, J=17.4, 1 H); 3.27 (d, J=17.4, 1 H); 3.77 (s, 3 H); 6.58–6.72
m, 2 H); 7.36 (s, 1 H); 7.46–7.52 (m, 3 H); 7.60–7.66 (m, 2 H). C-NMR: 20.6; 35.3; 54.7; 79.0; 108.2; 110.9;
1
3
1
13.7; 125.7; 127.0; 127.8; 129.0; 132.9; 134.4; 159.9; 174.7. Anal. calc. for C18
H
16
O
3
: C 72.96, H 5.44; found:
C 73.16, H 5.44.
1
4.5-Dihydro-1,4-dimethyl-1,4-epoxy-2-benzoxein-3(1H)-7-one (2c): M.p. 67–688. IR (KBr): 1783. H-NMR:
1
3
1
3
.67 (s, 3 H); 2.05 (s, 3 H); 3.01 (d, J=17.5, 1 H); 3.13 (d, J=17.5, 1 H); 7.12–7.36 (m, 4 H). C-NMR: 20.1; 21.2;
5.3; 79.4; 107.4; 123.2; 126.6: 129.1; 129.7; 131.4; 135.4; 175.5. Anal. calc. for C12
H
12
O
3
: C 70.57, H 5.96; found:
C 70.67, H 5.97.
1
1
-Ethyl-4,5-dihydro-4-methyl-1,4-epoxy-2-benzoxepin-3(1H)-one (2d): M.p. 62–638. IR (KBr): 1790. H-
NMR: 1.13 (t, J=7.4, 3 H); 1.67 (s, 3H); 2.35–2.49 (m, 2 H): 3.00 (d, J=17.4, 1 H); 3.14 (d, J=17.4, 1 H);
1
3
7
.12–7.36 (m, 4 H). C-NMR: 6.1; 20.6; 24.9; 35.1; 78.7; 108.5; 122.9; 126.2; 127.9; 129.2; 131.6; 134.3; 175.3.
Anal. calc. for C13 : C 71.54, H 6.47; found: C 71.30, H 6.47.
,5-Dihydro-4,5-dimethyl-1-phenyl-1,4-epoxy-2-benzoxepin-3(1H)-one (2e; 2 :1 diastereoisomer mixture):
14 3
H O
4
1
B.p. 185–1878/3 Torr. IR (film): 1797. H-NMR: 1.46 (d, J=7.3, 2 H); 1.47 (d, J=7.3, 1 H); 1.63 (s, 1 H); 1.71
s, 2 H); 3.05 (q, J=7.3, 1=3 H); 3.42 (q, J=7.3, 2= H); 6.66 (d, J=7.9, 1 H); 6.99–7.06 (m, 1 H); 7.22–7.35
m, 2 H); 7.46–7.50 (m, 3 H), 7.59–7.67 (m, 2 H). C-NMR (nonarom. signals): 15.3; 17.8; 19.0; 19.9; 36.9;
9.5; 82.0; 82.6; 108.2; 108.9; 173.1; 175.9. MS: 280 (M ).
,5-Dihydro-7,9-dimethoxy-1,4-dimethyl-1,4-epoxy-2-benzoxepin-3(1H)-one (2h): M.p. 32–338. IR(KBr):
(
(
3
3
1
3
+
4
1
1
3
1
790. H-NMR: 1.63 (s, 3 H); 2.14 (s, 3 H); 2.91 (d, J=17.3, 1 H); 3.08 (d, J=17.3, 1 H); 3.78 (s, 3 H); 3.79 (s,
1
3
H); 6.23 (d, J=2.3, 1 H); 6.29 (d, J=2.3, 1 H). C-NMR: 21.3; 24.1; 36.2; 55.3; 55.4; 78.8; 97.3; 105.2;
08.1; 116.9; 157.7; 160.9; 176.0. Anal. calc. for C14 : C 63.38, H 6.01; found: C 63.62, H 6. 01.
-Ethyl-4,5-dihydro-7,9-dimethoxy-4-methyl-1,4-epoxy-2-benzoxepin-3(1H)-one (2i): M.p. 43–448. IR
16 5
H O
1
1
(
KBr): 1787. H-NMR: 1.03 (t, J=7.3, 3 H); 1.62 (s, 3 H); 2.31–2.42 (m, 1 H); 2.69–2.79 (m, 1 H); 2.90 (d,
J=17.3, 1 H); 3.10 (d, J=17.3, 1 H): 3.77 (s, 3 H); 3.79 (s, 3 H); 6.24 (d, J=2.3, 1 H); 6.29 (d, J=2.3, 1 H).
+
MS: 278 (M ).
2
X-Ray Crystal-Structure Determination ). A crystal of 2a was grown from CH
2
Cl
2
/hexane. The intensity
radiation
l=1.54178 Å), in the w-2q scan mode (2q<69.998). Out of 2844 total reflections, 2204 reflections with inten-
data were collected on a Mac-Science-MXC-18 diffractometer, with graphite-monochromated CuK
(
a
sities greater than 3s(I) were used. No absorption correction was made. The structure was solved by direct meth-
ods with the maXus program. Least-square refinements were performed, including anisotropic thermal param-
eters for non-H-atoms and isotropic refinement of H-atoms located in difference Fourier synthesis.
ꢀ
3
Crystal data for 2a: C18
14 3 x
H O ; M 266.296; V=1353.4 (10) Å, Z=4, D =1.307 Mg cm ; monoclinic, space
group P21/c, a=10.295 (3) Å, b=8.355 (3) Å, c=17.400 (10) Å, a=90.008, b=115.278, g=90.008; R=0.071,
Rw2=0.066.
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[
Received April 28, 2005