Photocyclization of 2,4,6-triethylbenzophenones in the solid state

Article abstract of DOI:10.1016/j.tet.2008.10.105

Photocyclization of 2,4,6-triethylbenzophenones (TEBPs) into (E)- or (Z)-benzocyclobutenols ((E)- or (Z)-CBs) is E-selective in solution. By contrast, upon solid-state photolysis, TEBP-3,4-diCl and especially TEBP-4-t-Bu gave (Z)-CB relative to (E)-CB wit

Full text of DOI:10.1016/j.tet.2008.10.105

Tetrahedron 65 (2009) 677–689
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Photocyclization of 2,4,6-triethylbenzophenones in the solid state
,
b
a
c
Yoshikatsu Ito a , Hiroki Takahashi , Jun-ya Hasegawa , Nicholas J. Turro
*
a Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Kyoto 615-8510, Japan
b Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan
c Department of Chemistry, Columbia University, New York City, NY 10027, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Photocyclization of 2,4,6-triethylbenzophenones (TEBPs) into (E)- or (Z)-benzocyclobutenols ((E)- or (Z)-
CBs) is E-selective in solution. By contrast, upon solid-state photolysis, TEBP-3,4-diCl and especially
TEBP-4-t-Bu gave (Z)-CB relative to (E)-CB with a much higher proportion than that in solution. For TEBP-
4-t-Bu, the most major product in the solid state is an indanol derivative (Inol) (E/Z/Inol¼1:3.9:10.3 at 9%
conversion). On the basis of the X-ray crystallographic analysis, Inol and (Z)-CB are both topochemical
products. Notably, the relative proportion of (E)-CB increased with increased conversion, namely with
increased disruption of the crystal lattice. The DFT calculation of highly hindered 2,6-diisopropyl-
benzophenone (DIBP) was also conducted. These results in conjunction with the previous results on
2,4,6-triisopropylbenzophenones (TIBPs) indicate that CB is formed either via trans-enol followed by its
conrotatory ring-closure (paths a and d) or through direct cyclization of biradical (BR) (path b) as shown
in Scheme 1. Normally the former route is faster. However, in the crystalline state or in the case of
sterically hindered phenyl ketones, path b tends to be adopted.
Received 10 October 2008
Received in revised form 30 October 2008
Accepted 31 October 2008
Available online 8 November 2008
Keywords:
Photocyclization
Solid-state photochemistry
2,4,6-Triethylbenzophenone
Benzocyclobutenol
2,4,6-Triisopropylbenzophenone
Biradical
Photoenolization
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Wagner strongly insisted that CB should be formed solely through
conrotatory cyclization of trans-enol (paths a and d), not at all di-
There is a long-time controversy in the mechanism of photo-
cyclization for o-alkyl phenyl ketones giving benzocyclobutenols
(CBs) (either paths a and d or path b in Scheme 1).1–4 In the 1990s,
rectly via biradical (BR) (path b), as illustrated in Scheme 2.1 On the
other hand, one of the present authors had proposed in the 1980s
that for 2,4,6-triisopropylbenzophenones (TIBPs), direct cyclization
of BR accompanied by concomitant intersystem crossing (path b)
occurred both in solution and in the solid state (Scheme 3).2,3 The
present investigation on the photocyclization of 2,4,6-triethy-
lbenzophenones (TEBPs) (Eq. 1) was undertaken to make up this
discrepancy.
TIBP is similar in molecular shape to the corresponding CB, but is
very different from trans- or cis-enol,3 as confirmed by the DFT
calculation, which is described later. Therefore, if an intermediate
such as trans-enol exists before cyclization to CB, the photo-
cyclization will be very slow or do not occur in the crystal lattice
because of the mobility constraint due to the rigid confined void-
space, i.e., paths a and d will be unfeasible from the reaction cavity
concept.5,6 However, it has already been reported that several TIBPs
(TIBP-X: X¼p-OMe, p-t-Bu, p-Me, H) give the corresponding CBs
*3
R
R
R
1) hν
isc
(b)
O
OH
OH
2) isc
3) H abstr
Me
CH2
BR
isc (a)
CB
conrotatory
cyclization
(d)
OH
(c)
R
OH
R
+
very efficiently in the solid state, i.e.,
F
(crystal)w
F
(solution)¼0.1–
0.5 (Scheme 4A).3a Furthermore, the solid-state photocyclization of
chiral TIBP (S)-7 (TIBP-X: X¼p-(S)-phenylalaninocarbonyl methyl
ester (p-COAS)) proceeded with high diastereoselectivity (99% de at
34% conversion, Scheme 4B).3b The crystal structure (orthorhombic,
space group P212121) was retained during the transformation up to
100% conversion with small changes in lattice constants (a, b, and c)
(Scheme 5).3e These results support that the solid-state photolysis
cis-enol
trans-enol
Scheme 1. Possible mechanisms for photocyclization of o-alkyl phenyl ketones into
their benzocyclobutenols.
* Corresponding author. Tel./fax: þ81 774 45 1428.
E-mail address: yito@sbchem.kyoto-u.ac.jp (Y. Ito).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.105

678
Y. Ito et al. / Tetrahedron 65 (2009) 677–689
*3
*3
R
R
OH
R
1) hν
O
OH
H
H
2) isc
3) H abstr
lowest energy biradical
R'
R'
3BR
3BR
R'
spin-flip
tautomerization
R
OH
R
conrotatory
cyclization
OH
H
OH
+
R
H
H
R'
R'
cis-enol
R'
trans-enol
dienophile
CB
Diels–Alder adducts
Scheme 2. Wagner’s mechanism.
A In solution2
O
H
hν
T1
H
solution
bond rotation
and H abstr
TIBP
bond rotation
and
OH
OH
spin-flip
cyclization
OH
CB
BR
B In the solid state3
O
H
hν
T1
H
crystal
TIBP
H abstr
OH
H
OH
spin-flip and
cyclization
OH
CB
BR
Scheme 3. Ito’s mechanism for benzocyclobutenol formation.
of TIBPs gave CBs directly via BR, not via intermediacy of trans-enol.
In order to further support this conclusion, we have now in-
vestigated the photocyclization of TEBPs. Since there are two
possible stereoisomers for CB in this case ((E)- and (Z)-CB, Eq. 1),
important information about the cyclization mechanism is expec-
ted to emerge from this investigation.
O
X
X
HO
HO
hν (Pyrex)
+
X
(1)
crystal or
solution
TEBP (1)
(E)-CB (2)
(Z)-CB (3)
X = 4-t-Bu (a), 4-Cl (b), 3,4-diCl (c), 3,5-diCl (d), 2,4-diCl (e), 4-CO2Me (f)

Y. Ito et al. / Tetrahedron 65 (2009) 677–689
679
A
O
OH
X
hν
X
TIBP-X
X
=
p-OMe
0.56
Φ (benzene) = 0.48
p-t-Bu
0.20
p-Me
0.48
0.42
H
p-Cl
0.072 0.011
0.51 0.30
p-CF3
p-CO2Me
~0
Φ (crystal) =
0.13
0.52
0.38
0.13
Φ(crystal) are comparable with Φ(solution).
B
O
OH
COAS
hν
H
S
crystal
4 °C
N
CH2Ph
CO2Me
S
(S,S)-8
O
H
100 % yield
( = COAS
)
(S)-7
irrad time
conversion
34 %
96
de
99 %
87
-
5 h
In benzene solution,100 % yield
5 h
100 %
0 %
The solid-state photocyclization proceeded with high diastereoselectivity.
Scheme 4. Our previous results3a,b which are inconsistent with the Wagner’s mechanism.
2. Results and discussion
2.1. Photolysis
filter) under an argon atmosphere produced the corresponding
(E)-CB (2) with high yield and efficiency. In agreement with the
previous results,2h the other stereoisomer (Z)-CB (3) was yielded
only in a little quantity: E/Z¼18–32. The stereochemistry of (E)-CB
was assigned on the basis of the unusually high-field 1H NMR
It has already been reported that many of TEBPs are oil except 4-
Cl-substituted TEBP.2h Cl substitution is known to be a good method
to steer crystal packing.5 Consulting also the substituted TIBPs
having higher melting points,3a several new TEBPs (TEBP-X: X¼3,4-
diCl, 3,5-diCl, 2,4-diCl, 4-t-Bu, and 4-CO2Me) were now prepared.
Among them, TEBP-3,4-diCl and TEBP-4-t-Bu were found to be
crystalline (Table 1). Therefore, the photochemistry of 4-Cl-, 3,4-
diCl-, and 4-t-Bu-substituted TEBPs was here investigated.
doublet signal of the 2-Me group (
d
w0.83, Jw7.3 Hz),2h,7 whereas
w1.35
the corresponding signal for (Z)-CB resonanced at
d
(Jw7.3 Hz). In addition to (E)- and (Z)-CB, a small amount of an
anthrone derivative (An, 4) was constantly produced, judging from
the presence of a doublet peak at
d w1.5 (Jw7.3 Hz), which is
attributable to the 10-Me group. Retention times on a C18 HPLC
column eluted with MeOH–H2O increased in the order
(E)-CB<(Z)-CB<TEBP<An. Yields and proportions of the products
listed in Tables 2 and 3 were determined by direct 1H NMR and
HPLC analyses of the photolysate.
As summarized in Table 2, irradiation of TEBP-4-t-Bu (1a),
TEBP-4-Cl (1b), and TEBP-3,4-diCl (1c) in benzene or MeCN for 2 h
at 10 or 2 ꢀC with a 400-W high-pressure mercury lamp (Pyrex
Scheme 5. Crystal-to-crystal transformation of TIBP-p-COAS (S)-7: projection of the crystal structure along c.3e

680
Y. Ito et al. / Tetrahedron 65 (2009) 677–689
Table 1
the triisopropylbenzoyl moiety, each TIBP has a very similar con-
formation to the corresponding part of CB.z Hence, the trans-
formation of TIBP into CB may proceed with small distortion of the
reaction cavity and be topochemically feasible,5b if there are no
other obstacles. In fact, in the case of X¼p-OMe, p-t-Bu, p-Me, H,
and p-COAS, the quantum yield in the solid state was comparable to
or even larger than that in solution (see the data in Scheme 4).3a,b
More data for the solid-state photoreactivity of TIBPs3a–c are sum-
marized in Table 4.
Melting points of substituted 2,4,6-triethylbenzophenones (TEBPs)
TEBP-X
Mp (ꢀC)
a
4-OMe
4-t-Bu
4-Me
H
4-Cl
3,4-DiCl
3,5-DiCl
2,4-DiCl
4-CO2Me
4-CF3
Oil
41–42.5
Oil
This work
a
a
a
Oil
43–44
69.5–70.5
Oil
Oil
Oil
This work
This work
This work
Table 4 demonstrates that TIBP-p-CO2Me and TIBP-p-COCl are
photostable, TIBP-X with X¼p-CO2H, m-COCl, p-CO2Et, and p-Cl
react relatively slowly, and TIBP-X with X¼p-OMe, m-OMe, p-t-Bu,
p-Me, H, m-CO2Me, and p-COAS are highly reactive. In order to
understand these reactivity differences, their crystal structures
were inspected again.3a,d,e The inspection has brought clear that, in
the case of the stable or low-reactive TIBPs, the Ph-X groups are
packed closely. The interplanar separations between the nearest
Ph-X planes, which are related by a center of symmetry and are
This work
a
Oil
a
Ref. 2h.
Next, the crystals of these three TEBPs were crushed and were
irradiated in the solid-state apparatus6 at 2–3 ꢀC. While TEBP-4-Cl
resisted to photoreact, TEBP-3,4-diCl reacted with reasonable effi-
ciency to give (E)- and (Z)-CB (Table 3). The E/Z ratio was 3.9 after
1 h of irradiation (conversion 8%) and thus the relative yield of (Z)-
CB is much higher than that in solution. Extended irradiation (10 h,
35% conversion) impaired the reaction stoichiometry, giving con-
siderable amounts of uncharacterized byproducts.
Interestingly, the solid-state photoreaction of TEBP-4-t-Bu was
facile and clean (Table 3). Only after 0.2 h of irradiation, a consid-
erable conversion (9%) was reached, producing (E)-CB (2a), (Z)-CB
(3a), and an indanol derivative (Inol, 5a) (Eq. 2). Inol was stable
under the HPLC conditions and was eluted between (E)-CB and
(Z)-CB. However, it was fairly easily dehydrated in CDCl3 or under
the preparative TLC conditions to furnish an indene derivative
(6a), which also underwent further decomposition during the
interacting through
p–p interactions except the case of TIBP-p-
CO2H, are 3.4–3.6 Å. For example, see Figure 1b for TIBP-p-Cl; for
the cases of p-CO2Me, p-COCl, m-COCl, and p-CO2Et, see Ref. 3d.
With photostable TIBP-p-CO2Me and TIBP-p-COCl, the two Ph-X
planes are especially well overlapped, leading to the narrow re-
action cavity.3c,d The Ph-CO2H plane of TIBP-p-CO2H form a cyclic
hydrogen bond by the CO2H group and the hydrogen-bonded di-
mers are all arrayed in the same way in three dimensions.3d In
contrast to the stable or low-reactive TIBPs, the Ph-X planes of
the highly reactive TIBPs (X¼p-OMe, m-OMe, p-t-Bu, p-Me, H,
m-CO2Me, and p-COAS) are much separated (the interplanar sepa-
ration >7 Å) or are much slipped aside and thus the
p–p over-
lapping interactions do not exist. As aforementioned, the
conformation of the triisopropylbenzoyl moiety is similar to that of
CB. Consequently, it can be viewed that the solid-state photo-
cyclization of TIBPs was controlled by the confined space in crystal
packing around the Ph-X moiety rather than around the triiso-
propylbenzoyl moiety. This is also understandable from molecular
models, because it is the Ph-X moiety that is moved most when the
cyclization to CB occurs. Small or negligible restriction from the
confined space around the triisopropylbenzoyl moiety indicates
that the TIBP crystals undergo photocyclization to CB via BR, not via
trans-enol, since trans-enol is very different from TIBP and CB in
molecular shape.
Figures 2 and 3 show the crystal structures for three TEBPs
(TEBP-X: X¼4-t-Bu, 4-Cl, 3,4-diCl) and one TMBP. Like TIBPs,3a,d,e
the carbonyl plane is almost perpendicular to the trialkyl-
substituted Ph ring (the torsion angles: 88ꢀ, 89ꢀ, 89ꢀ, and 71ꢀ, re-
spectively), and is near coplanar with the other Ph ring (the torsion
angles: 7ꢀ, 12ꢀ, 12ꢀ, and 11ꢀ, respectively). The intramolecular dis-
separation procedure (Eq. 3). Inol is a product of
d-hydrogen
abstraction by the carbonyl group.8 Irradiation for a longer time
(1 h, 35% conversion) resulted in a little melted appearance,
spoiled somewhat the stoichiometry, and led to side formation of
An. It should be noted that the most major product is Inol and that,
at a short irradiation time (0.2 h, 9% conversion) where the reg-
ularity of the crystal lattice is not destroyed much, the yields
of (Z)-CB and Inol overwhelmed that of (E)-CB, i.e., E/Z/
Inol¼1:3.9:10.3. Thus, as hoped, (Z)-CB became a main product in
the solid state for both TEBP-3,4-diCl and TEBP-4-t-Bu. It should
also be mentioned that the proportion of (E)-CB relative to (Z)-CB
(and Inol) increased with the increase in conversion for both
TEBP-3,4-diCl and TEBP-4-t-Bu.
For comparison, irradiation of 2,4,6-trimethylbenzophenone
(TMBP) was carried out. As reported previously,2c,7 a low yield of
CB was produced in solution (Table 2). In the solid state, essentially
no reaction products were observed (Table 3).
tances between the carbonyl O and the nearest o-alkyl a-H (O1/
2.2. Crystal structure
H14) are 3.09, 2.95, 3.13, and 2.47 Å, respectively (Table 5).y The
terminal Me groups of the o-Ets in each TEBP are directed toward
the side of the carbonyl O atom (Fig. 2). As described above for
TIBPs, the neighboring Ph-X planes of photostable TEBP-4-Cl or
TMBP and low-reactive TEBP-3,4-diCl are related by a center of
Crystal structures of 12 TIBPs (TIBP-X: X¼p-OMe, m-OMe, p-t-
Bu, p-Me, H, p-CO2Me, m-CO2Me, p-CO2Et, p-CO2H, p-COCl, m-COCl,
and p-COAS) were already reported.3a–e The crystal structure of
TIBP-p-Cl was successfully solved here (Fig.1). In all these TIBPs, the
carbonyl plane is almost perpendicular to the triisopropylphenyl
ring (the torsion angles 79ꢀ–89ꢀ) and is near coplanar with the X-
substituted phenyl ring (the torsion angles 3ꢀ–15ꢀ). The intra-
molecular distance between the carbonyl oxygen atom and the
nearer o-isopropyl methine H in each TIBP is 2.7–3.0 Å, the distance
to another o-isopropyl methine H being 2.9–3.2 Å.y With respect to
symmetry and are overlapped through
p–p interactions (the
interplanar distances: 3.14, 3.39, 3.66 Å, respectively) (Fig. 3b–d).
On the other hand, the neighboring Ph-X planes of highly reactive
TEBP-4-t-Bu are much slipped aside (Fig. 3a) and thus the
p–p
interactions do not exist. Hence, in the solid-state photocyclization
of TEBPs and TMBP, the Ph-X moiety rather than the trialkylbenzoyl
y
z
These values are almost within the maximum distance for the intramolecular
Since it was difficult to obtain good quality of crystals for CB, only the crystal
hydrogen abstraction process to take place. The optimum distance between the
carbonyl oxygen and the to-be-abstracted hydrogen is 2.72 Å, but the distances as
great as 3.1 Å can be tolerated.9,10
structures of CB-m-OMe and CB-p-COAS were successfully obtained so far.3e How-
ever, the molecular shape of CB can be quite precisely known from molecular
modeling, e.g., the DFT calculation (vide infra).

Y. Ito et al. / Tetrahedron 65 (2009) 677–689
681
O
O
O
Cl
Cl
t-Bu
Cl
Cl
TEBP-4-t-Bu (1a)
TEBP-4-Cl (1b)
Cl
TEBP-3,4-diCl (1c)
O
O
O
Cl
CO2Me
Cl
TEBP-3,5-diCl (1d)
TEBP-2,4-diCl (1e)
TEBP-4-CO2Me (1f)
O
O
X
An (4)
TMBP
Table 2
Photochemistry of 2,4,6-triethylbenzophenones (TEBPs) in solutiona
Inol¼1:3.9:10.3 at 9% conversion). Formation of Inol is also ratio-
nalizable from the topochemical principle, because the carbonyl O
is very close to o-Et
(O1/H14¼3.09 Å) (Table 5). For TEBP-4-Cl and TEBP-3,4-diCl, the
relevant O/ -H distances are 2.88 and 2.81 Å, respectively, and the
b
-H (O1/H19¼2.68 Å) as compared with
a-H
TEBP-X
Solvent
Temp Irrad
(ꢀC)
time (h)
Conv (%) Product yield (%)
E/Z ratio
(E)-CB (Z)-CB An
b
4-t-Bu
4-Cl
3,4-DiCl Benzene 10
Benzene 10
Benzene 10
2
2
2
100
99
99
87
97
92
88
83
86
29
5
3
4
4
3
3
3
5
d
18:1
27:1
20:1
32:1
d
corresponding Inol derivatives were not formed.
MeCN
Benzene 10
2
2
TMBPb
10
2.3. DFT calculation
a
Irradiation was carried out with a 400-W high pressure mercury lamp (Pyrex) at
10 or 2 ꢀC under the Ar atmosphere.
The DFT calculations at the level of B3LYP/6-31G(d) were
performed on 2,6-diisopropylbenzophenone (DIBP) and 2-methyl-
benzophenone (MBP), a typical example of sterically hindered
and unhindered o-alkylbenzophenones, respectively, and on the
possible intermediates and products formed photochemically
thereof. The calculated stable conformations and energies of
these molecules are summarized in Figures 4 and 5. The changes
of energy levels relative to the ketone ground state are shown in
Figure 6. The twisted conformations of DIBP and MBP (Figs. 4 and
5) are consistent with the X-ray structures of TIBPs, TEBPs, and
TMBP described above. As expected from the previous publica-
b
2,4,6-Trimethylbenzophenone.
moiety appears to suffer the confined-space-restriction of the
crystal lattice, like the cases of TIBPs (vide supra).
Reactions in crystals proceed with minimum movement of
atoms and molecules.5a On the basis of this topochemical principle,
the X-ray molecular structures of the three TEBPs (Fig. 2) predict
that a Z isomer rather than an E isomer of CB should be produced by
their solid-state photolysis. We are fortunate to have obtained such
results (Table 3). Thus, upon short-time solid-state photolysis,
TEBP-3,4-diCl and especially TEBP-4-t-Bu gave (Z)-CB relative to
(E)-CB with much higher proportions than in solution, i.e., the E/Z
ratios are 3.9:1 (solid) and 20–32:1 (solution) for TEBP-3,4-diCl and
are 1:3.9 (solid) and 18:1 (solution) for TEBP-4-t-Bu. The E isomers
were probably formed at the imperfect crystal lattice or surface. For
TEBP-4-t-Bu, the most major product in the solid state is Inol (E/Z/
tion,9,11 the conformations of DIBP and MBP are not altered by
x
excitation to their triplet states 3DIBP
*
and 3MBP{
*
.
3DIBP
has
*
a slightly higher energy (0.4 kcal/mol) than 3MBP
*
.
There is one
stable form of BR (or enol triplet) in the case of DIBP and are two
stable forms of BR (or enol triplet) in the case of MBP.k In both
cases, BR converged to nearly the same conformation and energy
as enol triplet, supporting a notion that BR and enol triplet are
different names of the same species.17,18 The conformations of
these stable BRs are essentially equivalent to the conformer
3tw,co in Scheme 6 (vide infra). Calculations of trans- and cis-
enols and CB have disclosed that (a) both enols are considerably
less stable than CB and (b) CB from DIBP is more stable than CB
Table 3
Photochemistry of 2,4,6-triethylbenzophenones (TEBPs) in the solid statea
TEBP-X
Irrad
time (h)
Conv
(%)
Product yield (%)
E/Z/Inol ratio
(E)-CB
(Z)-CB
An
Inol
4-t-Bu
0.2
0.5
1
9
20
35
6
9
15
26
24
18
0
68
67
52
1:3.9:10.3
1:2.6:7.2
1:1.2:3.5
Trace
7
x
Dichotomous observations, i.e., the existence of either one triplet12,19 or two
kinetically distinct triplets,13 were reported for 3MBP
{
(w0.5 kcal/mol) than benzophenone triplet 3BP
*
.
4-Cl
2
w0
No reaction
d
It has been reported previously2h that 3TIBP
*
has a slightly higher triplet energy
, but the triplet energy transfer
3,4-DiCl
1
2
5
10
8
13
19
35
69
62
63
37
18
0
0
0
0
d
d
d
d
3.9:1:-
4.1:1:-
4.3:1:-
5.4:1:-
*
15
16
9
occurs from BP to TIBP. This unusual event was interpreted in terms of the effect of
internal rotational entropy.2h More investigations on the effects of molecular
structure, temperature, and solvation are desirable in order to attribute this out-
come to the entropy effect.14
TMBPb
10
w0
No reaction
d
By means of laser photolysis, one BR was detected for the MBP case18–20 and BR
k
a
was undetectable for the TIBP case because of its short lifetime (ꢁ100 ns).15–17 In
the former case, the syn and anti forms of BR were proposed to interconvert so
rapidly that only one species can be apparently observed.
Irradiation was carried out with a 400-W high pressure mercury lamp (Pyrex) at
2–3 ꢀC under the Ar atmosphere.
b
2,4,6-Trimethylbenzophenone.

682
Y. Ito et al. / Tetrahedron 65 (2009) 677–689
t-Bu
O
HO
hν
crystal
+
(2)
t-Bu
TEBP-4-t-Bu (1a)
Inol (5a)
OH
OH
t-Bu
t-Bu
+
(Z)-CB (3a)
(E)-CB (2a)
NMR time scale, the observed rotational rate being 1.4–68 sꢂ1 2b
,
t-Bu
which is very much slower than the BR decay, since the lifetimes of
photoenol biradicals are generally 100–5000 ns.17 Accordingly, the
situation for BR to reach conformational equilibrium within its
lifetime (a prerequisite for the Wagner’s mechanism1a–d) is unlikely
to happen for TIBP.yy
t-Bu
HO
polymeric material
(3)
A problem concerning the Wagner’s mechanism1a–d is that the
competition between conformational interconversion and in-
tersystem crossing in BR is not properly considered. BR lifetimes are
usually determined by the isc rate.25,26 The same drawback of his
mechanism was indicated also in the case of the Norrish type II
reaction.27 In the photoenolization mechanism of Scheme 2,
the reason for the complete neglect of the direct cyclization of BR to
CB (path b in Scheme 1) is unclear. Eventually, in order to accom-
modate these problems, we wish to propose Scheme 1 as a final
mechanism or Scheme 6 as a detailed explanation of Scheme 1.
In Scheme 6, the radical centers of BR are represented as either
twisted 90ꢀ (tw) or coplanar (co) with the triisopropylphenyl ring.
Although the conformers 3co,tw, 3tw,tw, and 3co,co are not stable
forms of BR, they are shown in this mechanistic scheme for con-
venience, because these geometries correspond to nascent species
of solution (3co,tw) or solid-state (3tw,tw) hydrogen abstraction
and to immediate precursors to products (1co,co to enol and 1tw,tw
to CB). The conformer 3tw,co is the most stable form of BR (see
Section 2.3). It has a favorable orthogonal geometry for efficient
intersystem crossing to occur concomitantly with the reaction
(reaction 5 or reaction 6) and this phenomenon is called a coupled
spin-flip and bond rotation.2e,28 The reaction 5 or 6 involves a hy-
pothetical intermediate 1co,co or 1tw,tw, respectively. In crystals or
Inol (5a)
In (6a)
from MBP, while the opposite is the case for the enols. Relative to
CB, the energies of BR and trans-enol, which are possible im-
mediate precursors to CB, were found to be, respectively, 28 and
16 kcal/mol for DIBP and, respectively, 23 and 10 kcal/mol for
MBP. The larger exothermicity of the cyclization process for DIBP
than for MBP (Fig. 6) is consistent with the experimental fact that
2,6-dialkyl substitution enhances the photocyclization of o-alkyl
phenyl ketones and the thermal stability of the resultant CB.7 As
expected, the shape of DIBP is similar to that of CB, whereas the
shape of trans- or cis-enol is very different from that of DIBP
(Fig. 4). The isopropyl-substituted benzene rings of these enols
are far from planar. Therefore, it is unlikely that trans-enol is
efficiently formed as the intermediate in the perfect crystalline
state of TIBP.
2.4. Final mechanism
As described above, the solid-state photocyclization reactions of
a series of o-alkylbenzophenones (TIBPs, TEBPs, and TMBP) are
interpretable in terms of the reaction cavity concept and the top-
ochemical principle. The findings a–c about the photochemistry of
TEBP-4-t-Bu in crystals, (a) high solid-state photoreactivity, (b)
formation of Inol and (Z)-CB with very minor formation of (E)-CB,
and (c) both Inol and (Z)-CB are topochemically controlled prod-
ucts, are strong evidences that CB can be formed directly via BR
(path b in Scheme 1). However, as seen from Table 3, the relative
yield of (E)-CB-4-t-Bu or (E)-CB-3,4-diCl increased with the in-
crease in conversion, i.e., the increased disruption of the crystal
lattice. This indicates that without restriction due to the confined
space of rigid crystals, TEBP tends to yield (E)-CB through con-
rotatory cyclization of trans-enol as in solution (paths a and d in
Scheme 1). In the case of more sterically hindered TIBP, CB appears
to be produced along path b until 100% conversion, since the
crystal-to-crystal photocyclization of (S)-7 was highly diaster-
eoselective even at high conversion (87% de at 96% conversion).3b,e
Therefore, it is natural to presume that path b is also occurring in
solution to a certain extent in the case of TIBP. We would like to
point out that the rotation around a single bond linking the tri-
isopropylphenyl group and the carbonyl group is hindered on the
in the case of sterically hindered compounds, the paths leading to
or
the congested molecules (1
3co,co and cis- or trans-enol) are
yy
Laser photolysis study of TIBP successfully revealed the existence of the
short-lived transients such as ketone triplet (280 ns), cis-enol (w4 ms), and trans--
enol (>100
m
s), but failed to detect BR due to its short lifetime (ꢁ100 ns).16,17 As
pointed out there,16,17 the BR assignment in our joint work with the laser spec-
troscopists24 was found to be in error. The both enols were shown to be unreactive
toward molecular oxygen.16 This fact indicates that it is not the enol but BR that
reacts with oxygen (Eq. 4), since TIBP easily afforded the cyclic peroxide upon ir-
radiation in the presence of oxygen.2f,7 This piece of conclusion is consistent with
most of the previously published papers2e,f,21–23 (and the references cited in Refs.
2e and 2f). Concerning this point, a part of the discussion in Refs. 1a and 1b needs
reconsideration.
OH
HO Ph
Ph
O
O
(4)
+
O2
BR

Y. Ito et al. / Tetrahedron 65 (2009) 677–689
683
hindrance of the molecule is an important factor as well. Finally, as
exemplified in this and other articles,5,9,10,27 the crystalline state can
be an important approach to elucidate reaction mechanisms.
4. Experimental
4.1. Instruments and materials
1H and 13C NMR spectra were measured on a JEOL AL-300 or EX-
400 spectrometer. Mass and IR spectra were gathered with JEOL
JMS-HX 110A and SHIMADZU FTIR-8400 spectrometers, re-
spectively. LC–MS was recorded on a PE SCIEX API-2000 spec-
trometer. HPLC analyses were performed with a JASCO PU-980
pump and a SHIMADZU SPD-6AV detector (fixed at 217 nm) by
using a Cosmosil 5C18-AR column (4.6 mm i.d.ꢃ150 mm) and were
eluted with a mixture of MeOH–H2O. Preparative HPLC was carried
out by JAI LC-9101 (fixed at 217 nm) by using a Cosmosil 5C18 col-
umn (20 mm i.d.ꢃ250 mm) and was eluted with MeOH.
2,4,6-Triisopropyl-40-chlorobenzophenone (TIBP-p-Cl) and 2,4,6-
trimethylbenzophenone (TMBP) were available from our previous
work.2 These were recrystallized from MeOH and hexane, re-
spectively, priortouse. 2,4,6-Triethylbenzophenones (TEBPs1a–1for
TEBP-X: X¼4-t-Bu (1a), 4-Cl (1b), 3,4-diCl (1c), 3,5-diCl (1d), 2,4-diCl
(1e), and 4-CO2Me (1f)) were prepared from 1,3,5-triethylbenzene
and the corresponding benzoyl chlorides by the Friedel–Crafts re-
action as described previously.2b–d,h
Spectroscopic data for new TEBPs are as follows.
4.1.1. 2,4,6-Triethyl-40-tert-butylbenzophenone or (4-tert-butyl-
phenyl)(2,4,6-triethylphenyl)methanone (TEBP-4-t-Bu, 1a)
Colorless plates, mp 41–42.5 ꢀC (from hexane); 1H NMR
(300 MHz, CDCl3)
d
7.71 (2H, d, J¼8.6 Hz), 7.41 (2H, d, J¼8.6 Hz),
6.94 (2H, s), 2.65 (2H, q, J¼7.7 Hz), 2.38 (4H, q, J¼7.7 Hz), 1.31 (9H,
s), 1.26 (3H, t, J¼7.5 Hz), 1.07 (6H, t, J¼7.5 Hz); 13C NMR (75.5 MHz,
CDCl3)
d 200.43, 157.22, 144.91, 140.43, 136.35, 135.39, 129.46,
125.53, 125.36, 35.16, 31.09, 28.82, 26.34, 15.53, 15.48; IR (neat)
2964, 1667, 1605, 1279, 934 cmꢂ1; MS (EIþ) m/z 322 (Mþ, 14), 265
(100), 250 (16), 236 (14); HRMS (EIþ) calcd for C23H30O 322.2297,
found 322.2291.
Figure 1. (a) The molecular structure of TIBP-p-Cl. (b) The dimeric structure of TIBP-p-
Cl, where weak interactions exist between the adjacent phenyl-Cl planes; sym-
p–p
metry operation 1ꢂx, 1ꢂy, 1ꢂz, the interplanar distance 3.60 Å. Projections in two
4.1.2. 2,4,6-Triethyl-30,40-dichlorobenzophenone or (3,4-dichloro-
phenyl)(2,4,6-triethylphenyl)methanone (TEBP-3,4-diCl, 1c)
Colorless plates, mp 69.5–70.5 ꢀC (from hexane); 1H NMR
directions are shown.
slowed down, and thus a spin-flip leading to 1tw,tw followed by CB
formation (Eq. 6) will be faster than the enol formation (Eq. 5).zz
(300 MHz, CDCl3)
d
7.90 (1H, s),xx 7.57 (1H, d, J¼8.4 Hz),xx 7.49 (1H,
isc
d, J¼8.4 Hz), 6.96 (2H, s), 2.34 (4H, q, J¼7.5 Hz), 1.26 (3H, t,
3tw; co
1co; co/cis- or trans-enol
(5)
ƒ!
J¼7.5 Hz), 1.07 (6H, t, J¼7.5 Hz); 13C NMR (75.5 MHz, CDCl3)
d
198.40, 145.68, 140.53, 138.12, 137.59, 134.78, 133.46, 131.03,
isc
3tw; co
1tw; tw/CB
(6)
ƒ!
130.83, 128.57, 125.71, 28.79, 26.39, 15.54, 15.37; IR (neat) 2966,
1674, 1580, 1464, 1381, 1283, 1236, 1175, 1031, 946 cmꢂ1; MS (EIþ)
m/z 336 (Mþ, 54), 334 (Mþ, 83), 299 (100), 284 (36), 189 (43); HRMS
(EIþ) calcd for C19H20O35Cl37Cl 336.0862, found 336.0862.
3. Conclusion
In conclusion, CB is formed either via trans-enol (paths a and d) or
through direct cyclization of BR (path b) as shown in Scheme 1. Nor-
mally the former route is faster. However, in crystals or in the case of
sterically hindered compounds, path b tends to be adopted. Crystal-
line medium is not a sufficient condition to suppress path a, consid-
ering the results that (a) both TEBP-3,4-diCl and TEBP-4-t-Bu yielded
(E)-CBalongwith(Z)-CB(andInol)evenatalowconversionincrystals
(Table 3) and (b) mesitaldehydes, which are much less crowded than
TIBP, formed trans-enols upon irradiation in crystals.4 Hence, steric
4.1.3. 2,4,6-Triethyl-30,50-dichlorobenzophenone or (3,5-dichloro-
phenyl)(2,4,6-triethylphenyl)methanone (TEBP-3,5-diCl, 1d)
Colorless oil; 1H NMR (300 MHz, CDCl3) 7.63 (2H, s),xx 7.53 (1H,
d
s),xx 6.96 (2H, s), 2.66 (2H, q, J¼7.6 Hz), 2.34 (4H, q, J¼7.6 Hz), 1.27
(3H, t, J¼7.5 Hz), 1.07 (6H, t, J¼7.5 Hz); 13C NMR (75.5 MHz, CDCl3)
d
198.04, 145.84, 140.57, 140.47, 135.75, 134.49, 133.13, 127.63,
125.78, 28.80, 26.42, 15.53, 15.32; IR (neat) 2966, 1679, 1566, 1271,
1243,1178, 873, 806 cmꢂ1; MS (EIþ) m/z 336 (Mþ, 39), 334 (Mþ, 58),
299 (100), 189 (41); HRMS (EIþ) calcd for C19H20O35Cl37Cl 336.0862,
found 336.0856.
zz
As assumed in Ref. 2h, the step BR(¼enol triplet)/CB can even be a symme-
xx
try-allowed disrotatory ring-closure.
Each peak is finely split (J¼1–2 Hz).

684
Y. Ito et al. / Tetrahedron 65 (2009) 677–689
Table 4
Summary for the photoreactivity of TIBPs in the solid state3a–c
TIBP-X
p-OMe
m-OMe
p-t-Bu
p-Me
H
p-Cl
p-CO2Me
m-CO2Me
p-CO2Et
p-CO2H
p-COCl
m-COCl
p-COAS
Irrad time (h)
Conv (%)
2
100
2
100
2
100
2
100
4
100
8
89
10
0
2
100
4
76
4
28
10
0
4
35
5
96
4.1.4. 2,4,6-Triethyl-20,40-dichlorobenzophenone or (2,4-dichloro-
phenyl)(2,4,6-triethylphenyl)methanone (TEBP-2,4-diCl, 1e)
Colorless oil (this contains an impurity in 9%, which is probably
2,4,5-triethyl-20,40-dichlorobenzophenone); 1H NMR (300 MHz,
photolysis vessel6 and was irradiated under the stream of Ar gas at
2–3 ꢀC.
The yields of photoproducts were determined by direct 1H NMR
and HPLC analyses of the photolysate. When necessary for struc-
tural identification of the photoproducts, they were separated by
preparative TLC (Merck silica gel 60-PF254, 2 mm, hexane–AcOEt) or
by preparative TLC and subsequent preparative HPLC. Their spec-
troscopic data are described below.
CDCl3)
d
7.49 (1H, s),xx 7.40 (1H, d, J¼8.4 Hz), 7.21 (1H, d, J¼8.4 Hz),xx
6.93 (2H, s), 2.64 (2H, q, J¼7.6 Hz), 2.41 (4H, q, J¼7.6 Hz), 1.24 (3H, t,
J¼7.6 Hz), 1.08 (6H, t, J¼7.5 Hz); 13C NMR (75.5 MHz, CDCl3)
d
197.84, 146.00, 141.03, 138.53, 136.21, 135.65, 134.55, 133.33,
131.55, 126.98, 125.96, 28.78, 26.51, 15.56, 15.31; IR (neat) 2966,
1682, 1582, 1462, 1373, 1285, 1236, 932, 874 cmꢂ1; MS (EIþ) m/z 336
(Mþ, 9), 334 (Mþ, 14), 299 (100), 284 (19), 270 (17); HRMS (EIþ)
calcd for C19H20O35Cl37Cl 336.0862, found 336.0857.
4.3. Characterization of the photoproducts
4.3.1. Products from TEBP-4-t-Bu (1a)
A photolysate from 3.5 h irradiation of 458 mg of 1a in benzene
(100 mL) was separated with preparative TLC (12:1 hexane–AcOEt)
to afford 298 mg (65% yield) of (E)-1-(4-tert-butylphenyl)-4,6-
diethyl-2-methyl-1,2-dihydrobenzocyclobuten-1-ol ((E)-CB-4-t-Bu,
2a) as a colorless viscous substance.
4.1.5. 2,4,6-Triethyl-40-methoxycarbonylbenzophenone or methyl 4-
(2,4,6-triethylbenzoyl)benzoate (TEBP-4-CO2Me, 1e)
A colorless viscous substance; 1H NMR (300 MHz, CDCl3)
d 8.07
(2H, d, J¼8.8 Hz), 7.84 (2H, d, J¼8.8 Hz), 6.96 (2H, s), 3.92 (3H, s),
2.66 (2H, q, J¼7.6 Hz), 2.35 (4H, q, J¼7.5 Hz), 1.26 (3H, t, J¼7.6 Hz),
1.05 (6H, t, J¼7.5 Hz); 13C NMR (75.5 MHz, CDCl3)
d 200.15, 166.24,
4.3.1.1. Compound 2a. 1H NMR (300 MHz, CDCl3)
d 7.30 (2H, d,
J¼8.8 Hz),xx 7.17 (2H, d, J¼8.8 Hz),xx 6.98 (1H, s), 6.88 (1H, s), 3.61
(1H, q, J¼7.2 Hz), 2.65 (2H, q, J¼7.6 Hz), 2.62–2.43 (2H, m), 1.29
(9H, s), 1.25 (3H, t, J¼7.5 Hz), 1.17 (3H, t, J¼7.5 Hz), 0.82 (3H, d,
145.51, 141.06, 140.57, 135.46, 134.19, 129.88, 129.32, 125.65, 52.44,
28.79, 26.39, 15.52, 15.39; IR (neat) 2966, 1728, 1674, 1276, 1105,
933, 729 cmꢂ1; MS (EIþ) m/z 324 (Mþ, 45), 309 (36), 265 (100);
HRMS (EIþ) calcd for C21H24O3 324.1725, found 324.1722.
J¼7.3 Hz); 13C NMR (75.5 MHz, CDCl3)
d 150.08, 147.37, 146.42,
141.73, 139.57, 138.23, 127.06, 126.37, 124.76, 119.41, 84.58, 54.66,
34.45, 31.36, 29.69, 24.86, 15.99, 15.42, 14.81; IR (neat) 3385, 2961,
1463, 1200, 1056, 1017, 822 cmꢂ1; MS (FABþ) m/z 321 (Mþꢂ1, 80),
305 (100), 265 (45); HRMS (FABþ) calcd for C23H29O 321.2218,
found 321.2212.
4.2. Photolysis of TEBPs and TMBP
Irradiation was carried out with a 400-W high-pressure mer-
cury lamp. A solution of TEBP or TMBP in benzene or MeCN (ca.
0.01 M, 5–100 mL) was placed in a suitable Pyrex tube. After bub-
bling Ar gas for 0.5–0.6 h, the tube was sealed with a rubber septum
and was irradiated at 10 or 2 ꢀC. The temperature controls were
conducted by thermostated circulating water. In the case of the
solid-state photolysis, a crystal sample (10–120 mg) was crushed
and sandwiched between two Pyrex plates, then set in a special
A combined photolysate from the four experiments of the solid-
state photolysis of 1a (irradiation time 0.2–2 h, total weight ca.
130 mg) was separated with preparative TLC (20:1 hexane–AcOEt)
to afford 96 mgof recovered 1a,12 mgof a mixture of (Z)-CB (3a) and
Inol (5a), and 17 mg of a mixture of 5a and (E)-CB (2a). The latter two
fractions were further separated with repeated preparative HPLC to
Figure 2. The molecular structures of (a) TEBP-4-t-Bu, (b) TEBP-4-Cl, (c) TEBP-3,4-diCl, and (d) TMBP.

Y. Ito et al. / Tetrahedron 65 (2009) 677–689
685
Figure 3. The dimeric structures of (b) TEBP-4-Cl, (c) TEBP-3,4-diCl, and (d) TMBP, where p–p interactions exist between the neighboring phenyl-X planes; symmetry operations
1ꢂx, 1ꢂy, 1ꢂz; 1ꢂx, ꢂy, 1ꢂz; and ꢂx, ꢂy, ꢂz, respectively, the interplanar distances 3.14, 3.39, and 3.66 Å, respectively. Projections in two directions are shown. For (a) TEBP-4-t-Bu,
the dimeric interactions do not exist between the neighboring phenyl-X planes (symmetry operation 1ꢂx, 1ꢂy, 1ꢂz), because they are much slipped aside.
isolate 3a and 5a, affording 8 mg of 3a and 10 mg of a mixture of 5a
and 2a (molar ratio 75:25). Both of these isolated samples were
contaminated with a small amount of the fillings of the preparative
HPLC column. Inol (5a) was gradually dehydrated during the sepa-
ration treatments (e.g., in CDCl3 or under the preparative HPLC
conditions), giving an indene derivative In (6a), which was further
decomposed to insoluble white materials in several days.
(1H, m), 2.88–2.80 (1H, m), 2.64 (2H, q, J¼7.5 Hz), 2.52–2.35 (3H,
m), 2.32–2.22 (1H, m), 1.28 (9H, s), 1.24 (3H, t, J¼7.6 Hz), 0.93 (3H, t,
J¼7.5 Hz); 13C NMR (100 MHz, CDCl3)
d 149.28, 145.12, 144.43,
144.20, 141.99, 141.31, 127.22, 124.85, 124.75, 121.58, 86.24, 46.57,
34.37, 31.37, 29.71, 28.78, 24.31, 15.67, 14.79; 1H NMR (400 MHz,
CD3COCD3)
d
7.30 (2H, d, J¼8.8 Hz), 7.21 (2H, d, J¼8.8 Hz), 6.94 (1H,
s), 6.86 (1H, s), 3.01–2.93 (1H, m), 2.85–2.77 (1H, m), 2.61 (2H, q,
J¼7.4 Hz), 2.49–2.35 (3H, m), 2.34–2.24 (1H, m), 1.28 (9H, s), 1.21
(3H, t, J¼7.5 Hz), 0.86 (3H, t, J¼7.5 Hz); 13C NMR (100 MHz,
4.3.1.2. (Z)-1-(4-tert-Butylphenyl)-4,6-diethyl-2-methyl-1,2-dihy-
drobenzocyclobuten-1-ol ((Z)-CB-4-t-Bu, 3a). A colorless sub-
CD3COCD3) d 149.37, 146.62, 145.20, 144.81, 143.96, 142.16, 127.79,
stance; 1H NMR (400 MHz, CDCl3)
d
7.30 (2H, d, J¼8.8 Hz), 7.27 (2H,
125.65,125.27,122.04, 85.98, 47.25, 34.81, 31.69, 30.08, 29.35, 24.82,
16.30, 15.19; MS (FABþ) m/z 321 (Mþꢂ1, 11), 305 (100), 265 (16);
HRMS (FABþ) calcd for C23H30O 322.2297, found 322.2293.
d, J¼8.3 Hz), 6.93 (1H, s), 6.87 (1H, s), 3.58 (1H, q, J¼7.3 Hz), 2.64
(2H, q, J¼7.5 Hz), 2.56–2.40 (2H, m), 2.37 (1H, s, OH), 1.37 (3H, d,
J¼7.3 Hz), 1.28 (9H, s), 1.24 (3H, t, J¼7.6 Hz), 1.10 (3H, t, J¼7.6 Hz);
13C NMR (100 MHz, CDCl3)
d 149.68, 148.38, 146.34, 143.31, 141.53,
Table 5
The intramolecular distances between the carbonyl O and the o-alkyl
a
-Hs or o-Et
139.49, 127.15, 125.03, 124.55, 119.25, 81.89, 53.45, 34.41, 31.36,
29.70, 24.71, 15.95, 14.71, 14.60; IR (neat) 3469, 2962, 2913, 1205,
1179, 1066, 1014, 915, 816 cmꢂ1; MS (FABþ) m/z 321 (Mþꢂ1, 17), 305
(100), 265 (49); HRMS (FABþ) calcd for C23H29O 321.2218, found
321.2220.
b-Hs at both ortho positions for the crystals analyzed here
O/ -H (Å) O/b-H (Å)
a
O1/H14
O1/H18
O1/H15
O1/H19
TEBP-4-t-Bu
TEBP-4-Cl
TEBP-3,4-diCl
TMBP
3.09
2.95
3.13
2.47
2.93
3.23
3.16
3.16
3.37 (O1/H16)
3.03 (O1/H20)
2.84
3.67
2.81
d
2.68
2.88
3.30
d
4.3.1.3. 1-(4-tert-Butylphenyl)-5,7-diethylindan-1-ol (Inol, 5a). A
colorless substance; 1H NMR (400 MHz, CDCl3)
d
7.28 (2H, d,
TIBP-p-Cl
d
d
J¼8.5 Hz), 7.19 (2H, d, J¼8.3 Hz), 6.96 (1H, s), 6.89 (1H, s), 3.04–2.97

686
Y. Ito et al. / Tetrahedron 65 (2009) 677–689
Figure 4. DFT calculations on 2,6-diisopropylbenzophenone (DIBP) and on the possible intermediates and products formed photochemically thereof.
4.3.1.4. 3-(4-tert-Butylphenyl)-4,6-diethylindene (In, 6a). A color-
less substance; 1H NMR (300 MHz, CDCl3)
7.28 (2H, d, J¼8.4 Hz), 7.20 (1H, s), 6.91 (1H, s), 6.26 (1H, t, J¼2.0 Hz),
3.40 (2H, d, J¼2.0 Hz), 2.67 (2H, q, J¼7.5 Hz), 2.38 (2H, q, J¼7.5 Hz),
1.35 (9H, s), 1.26 (3H, t, J¼7.5 Hz), 0.88 (3H, t, J¼7.5 Hz); LC–MS
(Inertsil ODS-3, acetonitrile, ESIþ) m/z 305 (Mþþ1, 100).
4.3.2. Products from TEBP-3,4-diCl (1c)
d
7.37 (2H, d, J¼8.4 Hz),
A photolysate from 3 h irradiation of 329 mg of 1c in benzene
(75 mL) was separated with preparative TLC (15:1 hexane–AcOEt) to
afford 230 mg (70% yield) of (E)-1-(3,4-dichlorophenyl)-4,6-diethyl-
2-methyl-1,2-dihydrobenzocyclobuten-1-ol ((E)-CB-3,4-diCl, 2c) as
a colorless viscous substance. This isolated 2c contained as an
Figure 5. DFT calculations on 2-methylbenzophenone (MBP) and on the possible intermediates and products formed photochemically thereof.

Y. Ito et al. / Tetrahedron 65 (2009) 677–689
687
kcal/mol
60
DIBP and the species
derived thereof
*3
O
only one stable structure
two stable structures
R
OH
Ph
R'
Ph
R'
R
MBP and the species
derived thereof
cis
trans
trans
cis
R'
ketone
triplet
40
20
0
R'
OH
Ph
R'
R
biradical or
enol triplet
R
OH
Ph
R'
R'
enol
O
R
Ph
R'
R'
CB
R'
ketone
Figure 6. Potential energies relative to the ketone ground state.
impurity a tiny amount of (Z)-1-(3,4-dichlorophenyl)-4,6-diethyl-2-
methyl-1,2-dihydrobenzocyclobuten-1-ol ((Z)-CB-3,4-diCl, 3c). The
3c content was increased by repeated preparative TLC to afford
43 mg of a colorless mixture of 3c and 2c (molar ratio 16:84). Further
purification of 3c was not attempted.
140.69, 139.45, 132.19, 131.21, 129.79, 128.67, 127.61, 126.17, 119.61,
83.62, 55.28, 29.68, 24.76, 15.92, 15.25, 14.70; IR (neat) 3385, 2964,
1471, 1378, 1198, 1030, 817 cmꢂ1; MS (FABþ) m/z 335 (45), 333 (66),
317 (100); MS HR(FABþ) calcd for C19H21O35Cl2 335.0969, found
3335.0959.
4.3.2.1. Compound 2c. 1H NMR (300 MHz, CDCl3)
d
7.41 (1H, s),xx
4.3.2.2. Compound 3c. 1H NMR (300 MHz, CDCl3) 7.50 (1H, s),xx
d
7.35 (1H, d, J¼8.1 Hz), 7.03 (1H, d, J¼8.2 Hz),xx 6.99 (1H, s), 6.89 (1H,
s), 3.60 (1H, q, J¼7.2 Hz), 2.655 (2H, q, J¼7.6 Hz), 2.56–2.38 (2H, m),
2.28 (1H, br), 1.255 (3H, t, J¼7.6 Hz), 1.13 (3H, t, J¼7.5 Hz), 0.85 (3H,
7.33 (1H, d, J¼8.1 Hz), 7.12 (1H, d, J¼8.2 Hz),xx 6.95 (1H, s), 6.93
(1H, s), 3.53 (1H, q, J¼7.2 Hz), 2.645 (2H, q, J¼7.6 Hz), ca. 2.55–
2.36 (2H, m), 1.36 (3H, d, J¼7.0 Hz), 1.25 (3H, t, J¼7.6 Hz), 1.07 (3H,
t, J¼7.5 Hz).
d, J¼7.0 Hz); 13C NMR (75.5 MHz, CDCl3)
d
147.14, 147.08, 141.95,
Ph
OH
Ph
OH
OH
Ph
OH
Ph
OH
Ph
3tw,tw
3tw,co
3co,tw
cis-enol
trans-enol
double-twisted enol triplet:
initial biradical in the solid
state
lowest energy biradical
initial biradical
in solution
Ph
OH
OH
Ph
The radical center is twisted 90° (tw) or coplanar (co)
with the isopropyl-substituted benzene ring.
3co,co(cis)
cis-enol
3co,co(trans)
3co,co
(cis or trans)
spin-flip
spin-flip
trans-enol
back-H
shift
conrotatory
cyclization
3tw,co
3co,tw
soln
O
OH
1) hν
H abstr
cryst
spin-flip
3tw,tw
T1
2) isc
conformational equilibrium and
spin-flip associated with BR
CB
TIBP
Hypothetical BR conformers 3tw,tw and 3co,co are taken into consideration, because a spin-
flip to reactive 1BR may be competitive with the conformational interconversions of BR. In
crystals or in the case of the sterically crowded compounds, the spin-flip may be faster than
the conformational equilibrium.
Scheme 6. Detailed photocyclization mechanism proposed for TIBP: idealized conformations of BR and their notations are illustrated.

688
Y. Ito et al. / Tetrahedron 65 (2009) 677–689
Table 6
Crystallographic parameters
TIBP-p-Cl
TEBP-4-t-Bu
C23H30
TEBP-4-Cl
TEBP-3,4-diCl
TMBP
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
C22H27OCl
342.91
Orthorhombic
Pbca (#61)
16.4264(11)
11.5254(7)
20.5096(14)
da
O
C19H21OCl
300.83
Monoclinic
P21/c (#14)
10.4106(4)
15.8700(7)
10.7195(4)
da
C19H20OCl2
335.27
Orthorhombic
Pbca (#61)
17.0159(6)
10.8347(4)
19.1795(9)
da
C16H16O
322.49
Monoclinic
C2/c (#15)
20.977(2)
8.8971(8)
22.7043(19)
da
224.30
Triclinic
P1 (#2)
7.8788(7)
8.2646(7)
10.7054(9)
100.877(2)
91.960(2)
108.996(2)
643.85(9)
2
b (Å)
c (Å)
a
b
g
(ꢀ)
(ꢀ)
(ꢀ)
da
da
110.152(2)
da
110.9680(13)
da
da
da
V (Å3)
3882.9(4)
8
3978.0(6)
4
1653.75(12)
4
3536.0(2)
8
Z
Dcalcd (g/cm3)
No. observations
No. variables
R1
wR2
GOF
1.173
4434
326
0.0647
0.1589
1.077
4564
339
0.0758
0.2761
1.110
1.208
3782
215
0.0588
0.1928
1.115
1.259
4017
220
0.0774
0.2623
1.080
1.157
2557
191
0.0729
0.289
1.038
1.034
a
90ꢀ by definition.
4.3.3. Products from TEBP-4-Cl (1b)
MS (EIþ) m/z 314 (Mþ,100), 299 (51), 279 (60), 203 (82); HRMS (EIþ)
The photocyclization of 1b in benzene into (E)-1-(4-chloro-
phenyl)-4,6-diethyl-2-methyl-1,2-dihydrobenzocyclobuten-1-ol
((E)-CB-4-Cl, 2b) was previously studied.2h The isolated 2b con-
tained a tiny amount of (Z)-CB-4-Cl (3b), characteristic peaks of
calcd for C19H19O325Cl 314.1073, found 314.1073.
4.4. X-ray crystal structure analysis
which were clearly visible at
d
1.35 (3H, d, J¼7.3 Hz) and other re-
The diffraction data were collected at ꢂ100ꢄ1 ꢀC on a Rigaku
gions (
d
6.94 (1H, s), 6.92 (1H, s), 3.53 (1H, q, J¼7.2 Hz)).
RAXIS-RAPID Imaging Plate diffractometer with graphite mono-
chromated Mo Ka radiation to a maximum 2q
value of 54.9ꢀ. The
4.3.3.1. Compound 2b. 1H NMR (300 MHz, CDCl3)
7.27 (2H, d,
d
data were corrected for Lorentz and polarization effects. The
structure was solved by direct methods29 and expanded using
Fourier techniques.30 Non-hydrogen atoms were refined aniso-
tropically. Hydrogen atoms were refined isotropically. Some hy-
drogen atoms were refined using the riding model. All calculations
were performed using the CrystalStructure31 crystallographic
software package except for refinement, which was performed
using SHELXL-97.32 The crystal structure parameters for TIBP-p-Cl,
TEBP-4-t-Bu, TEBP-4-Cl, TEBP-3,4-diCl, and TMBP are summarized
in Table 6. Crystallographic data (excluding structure factors) for
the structures in this paper have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication
nos. CCDC 704821–704825, respectively. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: þ44 (0) 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
J¼8.8 Hz), 7.18 (2H, d, J¼8.8 Hz), 6.98 (1H, s), 6.89 (1H, s), 3.60 (1H,
q, J¼7.2 Hz), 2.65 (2H, q, J¼7.6 Hz), 2.53–2.41 (2H, m), 1.24 (3H, t,
J¼7.7 Hz), 1.13 (3H, t, J¼7.7 Hz), 0.82 (3H, d, J¼7.0 Hz).
When the photolysis was carried out under bubbling of Ar (not
in the closed system as above), a considerable amount of 2-(4-
chlorobenzoyl)-3,5-diethylacetophenone (9) was produced. Re-
sidual oxygen in Ar is probably responsible for the formation of 9.
Thus, a photolysate from 2 h irradiation of 302 mg of 1b in benzene
(75 mL) was separated with repeated preparative TLC (15–10:1
hexane–AcOEt) to afford 194 mg (64%) of 2b, 24 mg (8%) of 6-
chloro-1,3-diethyl-10-methylanthrone (4b) containing 13 mg (4%)
of recovered 1b, and 25 mg (8%) of 9. Unlike the related anthrones,
which were previously reported,2d,e,g,h anthrone 4b was not very
stable on silica gel. Therefore, the above mixture of 4b and 1b
(molar ratio 63:37) could not be further separated by preparative
TLC.
4.5. Computational methods
O
O
The B3LYP functional was used for the DFT calculation of 2,6-
diisopropylbenzophenone (DIBP) and 2-methylbenzophenone
(MBP), and of the possible intermediates and products formed
photochemically thereof (i.e., ketone triplet, biradical, enol triplet,
trans- and cis-enols, and benzocyclobutenol). All of the possible
conformations in the biradical triplet state (3co,tw, 3tw,co, and
3tw,tw) were considered as the initial guess of the geometry opti-
mization. In DIBP, the three starting structures converged a 3tw,co
structure (see Fig. 4). In MBP, two 3tw,co structures having cis-like
and trans-like conformations (see Fig. 5) were obtained, although
the potential energies of the cis- and trans-like structures are very
similar to each other (see Fig. 5). The 6-31G(d) basis set was used
for the optimization of the geometry. Computations were per-
formed using Gaussian03 package.33–35
Cl
9
4.3.3.2. Compound 4b. 1H NMR (300 MHz, CDCl3)
d 8.10 (1H, d,
J¼8.4 Hz), 7.40 (1H, s),xx 7.35 (1H, d, J¼8.4 Hz),xx 7.11 (1H, s), 7.06
(1H, s), 4.16 (1H, q, J¼7.2 Hz), 3.19 (2H, q, J¼7.2 Hz), 2.69 (2H, q,
Jw7.2 Hz), 1.52 (3H, d, J¼7.3 Hz), 1.31–1.24 (6H, m).
4.3.3.3. Compound 9. A pale yellow substance; 1H NMR (300 MHz,
CDCl3)
d
7.64 (2H, d, J¼8.6 Hz), 7.59 (1H, s), 7.34 (2H, d, J¼8.6 Hz),
7.34 (1H, s), 2.75 (2H, q, J¼7.6 Hz), 2.49 (3H, s), 2.41 (2H, q,
J¼7.6 Hz), 1.31 (3H, t, J¼7.7 Hz), 1.07 (3H, t, J¼7.5 Hz); 13C NMR
Acknowledgements
(75.5 MHz, CDCl3)
d 197.98, 197.75, 145.45, 142.22, 138.98, 136.99,
136.52, 136.12, 133.23, 129.79, 128.81, 127.32, 28.63, 26.96, 25.88,
The authors thank Ms. Keiko Kuwata for measuring MS and LC–
MS spectra for us.
15.51, 15.41; IR (neat) 2967, 1680, 1586, 1284, 1256, 1089, 932 cmꢂ1
;

Y. Ito et al. / Tetrahedron 65 (2009) 677–689
689
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