Photolysis dynamics of diastereoselectivity in the photocyclization of o-ethoxybenzophenone and o-2,2,2-trifluoroethoxybenzophenone

Article abstract of DOI:10.1016/j.jphotochem.2010.12.020

The photochemical reactions of o-ethoxybenzophenone (R-1) and o-2,2,2-trifluoroethoxybenzophenone (R-2) in cyclohexane solutions of 0.7 M pyridine have been investigated using time-resolved laser flash photolysis to understand diastereoselectivity in the photocyclization of the two compounds. Whereas the formation times of biradical intermediates (7 ns) are the same for the two compounds, the lifetime of the biradical intermediate of R-2 (200 ns) is eight times larger than that of R-1 (25 ns), explaining why diastereoselectivity is much lower in the photocyclization of R-2.

Full text of DOI:10.1016/j.jphotochem.2010.12.020

Journal of Photochemistry and Photobiology A: Chemistry 218 (2011) 174–177
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Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
Photolysis dynamics of diastereoselectivity in the photocyclization of
o-ethoxybenzophenone and o-2,2,2-trifluoroethoxybenzophenone
Hahkjoon Kima,∗, Bong Ser Parkb, Du-Jeon Jangc,∗∗
a Department of Chemistry, Duksung Women’s University, Seoul 132-714, Republic of Korea
b Department of Chemistry, Dongguk University, Seoul 100-715, Republic of Korea
c School of Chemistry, Seoul National University, Seoul 151-742, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The photochemical reactions of o-ethoxybenzophenone (R-1) and o-2,2,2-trifluoroethoxybenzophenone
(R-2) in cyclohexane solutions of 0.7 M pyridine have been investigated using time-resolved laser flash
photolysis to understand diastereoselectivity in the photocyclization of the two compounds. Whereas
the formation times of biradical intermediates (7 ns) are the same for the two compounds, the lifetime
of the biradical intermediate of R-2 (200 ns) is eight times larger than that of R-1 (25 ns), explaining why
diastereoselectivity is much lower in the photocyclization of R-2.
Received 8 October 2010
Received in revised form
20 December 2010
Accepted 31 December 2010
Available online 4 January 2011
© 2011 Elsevier B.V. All rights reserved.
Keywords:
Diastereoselectivity
Biradical
Laser photolysis
Time-resolved spectroscopy
Fluorescence decay
Transient absorption
1. Introduction
Kim and Park have reported that o-ethoxybenzophenone (R-1)
undergoes
gen abstraction to produce diastereomeric dihydrobenzofuranols
(P-1) with Z/E ratio of 11:1 in benzene. On the other
a photochemical reaction in benzene via hydro-
Photocyclization reactions via intramolecular hydrogen abstrac-
tion have been studied extensively for decades [1–3]. In the course
of photocyclization reactions, the formation of unwanted diastere-
omers by the bond rotation of a biradical intermediate before or
during cyclization is unavoidable if the two radical centers of the
intermediate are prostereogenic. Thus, it is well known that the
diastereoselectivity of solids is high owing to the restricted rota-
tional motions of reaction intermediates, whereas that of solutions
is low owing to the high rotational flexibility of reaction interme-
diates [4,5]. However, high diastereoselectivity in solutions can be
achieved under certain conditions such as high strain energy asso-
ciated with hydrogen abstraction, large steric hindrance between
two radical moieties, and restricted rotational motion of C–C bonds
in reaction intermediates [6–9]. In the field of pharmaceuticals, the
synthesis of diastereomerically pure compounds is very important
because the biological activities of synthetic drugs are stereoselec-
tive in many cases [10–12].
a
hand, o-2,2,2-trifluoroethoxybenzophenone (R-2) produces 2-
trifluoromethyl-3-phenyldihydrobenzofuran-3-ols (P-2) with a Z/E
ratio of 2:1, as shown in Fig. 1 [15]. They have proposed that a suf-
ficiently long lifetime of the biradical intermediate of R-2 (BR-2)
allows its C–C single bonds to rotate, yielding thermally equili-
brated diastereomers before cyclization. They have attributed the
long lifetime of the biradical intermediate of BR-2 to a combination
of hyperconjugation and captodative effects arising from alkoxy
and trifluoromethyl substituents.
In this paper, we have studied the photolysis dynamics of R-1
and R-2 to report their time-resolved transient-absorption spec-
tra as well as kinetic profiles. We have found that the different
lifetimes of two biradical reaction intermediates appearing dur-
ing their photolysis reactions explain the reason for the difference
in the diastereoselectivities of the photoproducts of the two com-
pounds.
Substituent groups attached to radical centers greatly influ-
ence the diastereoselectivity of a cyclization reaction [13,14].
2. Materials and methods
∗
Corresponding author. Tel.: +82 2 901 8359; fax: +82 2 901 8351.
Corresponding author. Tel.: +82 2 880 4368; fax: +82 2 875 6624.
E-mail addresses: khj730516@duksung.ac.kr (H. Kim), djjang@snu.ac.kr
R-1 and R-2 were synthesized, purified and confirmed by
1H NMR, as described in Ref. [15]. An actively/passively mode-
locked Nd:YAG laser (Quantel, YG 701) with the pulse duration
∗∗
(D.-J. Jang).
1010-6030/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jphotochem.2010.12.020

H. Kim et al. / Journal of Photochemistry and Photobiology A: Chemistry 218 (2011) 174–177
175
Fig. 1. Photochemical reaction scheme of o-ethoxybenzophenone (R-1) and o-2,2,2-trifluoroethoxybenzophenone (R-1) in cyclohexane solutions of 0.7 M of pyridine.
of 25 ps was employed for picosecond fluorescence and transient-
absorption kinetic measurements. Samples were excited with
355 nm laser pulses. Fluorescence was collected from the front sur-
face of the sample excitation. Fluorescence kinetic profiles were
obtained with a 10 ps streak camera (Hamamatsu, C2830) attached
with a CCD (Princeton Instruments, RTE-128-H). The transient
absorption of a sample was probed using fluorescence from an
organic dye excited with the pulses split from sample-excitation
pulses. The comparison of dye-emission kinetic profiles measured
with streak camera without and with sample excitation yields
transient-absorption kinetic profiles. Fluorescence and transient-
absorption kinetic constants were extracted by fitting measured
kinetic profiles to computer-simulated kinetic curves convoluted
with temporal response functions. Transient-absorption spectra
were obtained by monitoring the transmittance changes of samples
excited made with 355 nm pulses from a 6 ns Q-switched Nd:YAG
laser (Quanta System, HYL-101). Probe pulses emitted from an
organic dye excited by pulses split from sample excitation pulses
were detected with a CCD (Princeton Instruments, ICCD-576-G)
attached to a 0.5 m spectrometer (Acton Research, SpectroPro-500).
separated species, while the slower component is attributed to the
S1 decay of the charge-separated species that leads to the formation
of its T1 state.
Fig. 3 shows time-resolved transient-absorption spectra of the
two reactants in cyclohexane solutions of 0.7 M pyridine, mea-
sured at two different time delays after excitation at 355 nm. The
absorption band at 550 nm in Fig. 3a is ascribed to the biradical
intermediate (BR-1) because o-(benzyloxy)benzophenone, which
is structurally analogous to R-1, exhibits absorption bands at
540 and 550 nm resulting from the triplet-state charge-separated
species and the subsequent formation of the biradical intermedi-
3. Results and discussion
Fig. 2 shows the fluorescence kinetic profiles of R-1 and R-2 in
cyclohexane solutions of 0.7 M pyridine, measured at 550 nm after
excitation at 355 nm. We have added pyridine to the cyclohexane
solutions in order to impede the disproportionation reaction of the
biradical intermediates (BR-1 and BR-2) back to the reactant com-
pounds (R-1 and R-2) and to enhance the quantum efficiency of
cyclization [16]. It should be noted that pyridine should be care-
fully used since biradical intermediates might be trapped when the
concentration of pyridine is high. As compared to the best-fit curve,
the kinetic profile of R-1, as shown in Fig. 2a, exhibits biexponen-
tial decays of 50 ps (60%) and 800 ps (40%), while the kinetic profile
of R-2 in Fig. 2b exhibits biexponential decays of 50 ps (88%) and
800 ps (12%). The faster decay component is attributed to the S1
decay of the two reactants that leads to the S1 state of the charge-
Fig. 2. Fluorescence kinetic profiles, excited at 355 nm and monitored at 550 nm, of
5 mM o-ethoxybenzophenone (a) and o-2,2,2-trifluoroethoxybenzophenone (b) in
cyclohexane solutions of 0.7 M pyridine.

176
H. Kim et al. / Journal of Photochemistry and Photobiology A: Chemistry 218 (2011) 174–177
exhibits biexponential decays (7 ns and 200 ns). It is well estab-
lished that the lifetime of a biradical intermediate depends on
the spin–orbit coupling that, in turn, strongly depends on orien-
tation and distance between two radical moieties [19–21]. We
have reported that the lifetime of the biradical intermediate of
1-(o-tolyl)-1-benzoylcyclopropane, which transforms into a five-
membered ring, is 20 ns [22,23]. This indicates that the kinetic
profile in Fig. 4a arises from a biradical intermediate because
distance and orientation between the radical centers of R-1 are
quite similar to respective ones between the radial centers of 1-
(o-tolyl)-1-benzoylcyclopropane. In addition, these radicals do not
have a strong electron-withdrawing or donating group that might
increase or decrease the lifetime of the biradical intermediate by
the synergistic effect discussed later in this paper. Therefore, the
single decay of 25 ns, as shown in Fig. 4a, should be ascribed to
the decay time of BR-1. The 7 ns rise time of the kinetic profile
in Fig. 4a corresponds to the decay time of the triplet-state charge-
separated species leading to the subsequent formation of BR-1. The
formation rates of BR-1 and BR-2 are faster than those of acyclic
analogues because the phenyl group between carbonyl and CH2
increases the conformational rigidity, thus reducing unfavorable
rotational conformations in the transition state [24]. The faster
decay time of the kinetic profile in Fig. 4b is ascribed to the triplet-
state charge-separated species because its decay time of 7 ns is in
good agreement with the decay time of the triplet decay time of
the charge separated species of R-1. It is not surprising that the
formation times of the biradical intermediates of two structurally
analogous compounds are the same because hydrogen abstrac-
tion from CH2 depends strongly on the distance and orientation
between oxygen and hydrogen atoms in a triplet state [25,26]. The
slow decaying component in Fig. 4b is ascribed to the decay time of
BR-2. The decay times of the two distinct components are consis-
tent with the time-resolved transient absorption spectra shown in
Fig. 3b. The photolysis mechanisms of R-1 and R-2 are summarized
in Fig. 1.
There have been several studies on the effect of substituent
groups attached to carbon-centered radicals [27–30]. They have
revealed that synergistic (captodative) effect caused by an electron
donor-acceptor pair directly attached to a CH• radical enhances
the stability of the radical to a greater extent, as compared to a
donor–donor pair or an acceptor–acceptor pair. We believe that a
combination of CF3 (electron acceptor) and OR (electron donor)
attached to the CH• radical enhances the stability of BR-2 and
extends its biradical lifetime by a factor of eight as compared to
the stability of BR-1. It should be noted that as the opposite par-
tial charges on the two radical centers of BR-2 because of CF3 and
OH/Ph increase the spin–orbitcoupling, theyareexpected to reduce
the lifetime of BR-2. However, this effect seems insignificant as
compared to the synergistic effect discussed above [31].
Fig. 3. Time-resolved transient absorption spectra of 5 mM o-ethoxybenzophenone
(a) and o-2,2,2-trifluoroethoxybenzophenone (b) in cyclohexane solutions of 0.7 M
pyridine, measured at time delays of 2 ns (i) and 50 ns (ii) after excitation at 355 nm.
ate, respectively [17,18]. The transient-absorption spectra of R-2
in Fig. 3b exhibit two absorption bands at 550 nm and 580 nm.
The 550 nm absorption band is ascribed to the triplet-state charge-
separated species leading to the formation of BR-2 because it
decays faster than the 580-nm absorption band arising from BR-
2. The kinetic profile in Fig. 4b (see below) agrees well with the two
absorption bands with a fast component (7 ns) and a slow com-
ponent (200 ns) resulting from the triplet-state charge-separated
species and the biradical intermediate, respectively. We attribute
the red shifts of BR-2 and the triplet-state charge-separated species
to electronegative fluorines.
Fig. 4 shows the transient-absorption kinetic profiles of biradical
intermediates derived from the reactant compounds in cyclohex-
ane solutions of 0.7 M pyridine, measured at 550 nm after excitation
at 355 nm. The best-fit curve of the kinetic profile in Fig. 4a exhibits
a single rise (7 ns) and a single decay (25 ns) while that in Fig. 4b
The diastereomeric ratio of P-1 and P-2 can be explained in
terms of their relative energies produced by the steric effects
between the phenyl and methyl groups as well as their transition
states leading to cyclization. Our preliminary calculations suggest
that the diastereoselectivity of the photoproducts exists in the
biradical intermediate before cyclization because the energy dif-
ference between the two diastereomeric products is smaller than
the energy difference between their transition states leading to the
diastereomeric products. The energy difference between Z (P-1)
and E (P-1) is 0.9 kcal/mol, whereas the energy difference between
the transition states leading to Z (P-1) and E (P-1) is 19.1 kcal/mol at
the B3LYP/3-21G computational level. Under these circumstances,
diastereoselectivity is pronounced if the rotational barrier is high
and the lifetime of the biradical intermediate is short because a
conformational equilibrium is not achieved within a short lifetime.
The rotation time of the C–C bond arising from a phenyl-CH• rad-
ical has been deduced from the mechanistic study of o-alkylphenyl
Fig. 4. Transient-absorption kinetic profiles, excited at 355 nm and
monitored at 550 nm, of 5 mM o-ethoxybenzophenone (a) and o-2,2,2-
trifluoroethoxybenzophenone (b) in cyclohexane solutions of 0.7 M pyridine.

H. Kim et al. / Journal of Photochemistry and Photobiology A: Chemistry 218 (2011) 174–177
177
ketones to be 30–50 ns [32]. In the present study, the rotation of
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Acknowledgements
This research was supported by the Duksung Women’s Uni-
versity Research Grant 3000001300. We also acknowledge the
research grants of 2010-0015806 and 2010-0001635 funded
through the National Research Foundation of Korea by the Ministry
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