Microenvironmental control of enantiodifferentiating photocyclization of 5-hydroxy-1,1-diphenylpentene through selective solvation

Article abstract of DOI:10.1002/chir.22004

For mechanistic elucidation of the photosensitized cyclization of 5-hydroxy-1,1-diphenylpentene (1), its methyl ether (4) was synthesized as an unreactive dummy substrate and used as a quencher of the sensitizer fluorescence to reveal the intervention of an exciplex intermediate that was unable to detect when reactive substrate 1 was used as a quencher/reactant In the enantiodifferentiating photocyclization of 1 to 2-(diphenylmethyl) tetrahydrofuran (2) sensitized by a chiral saccharide ester of 1,4-naphthalenedicarboxylate (3), the enantiomeric excess (ee) of chiral product 2 obtained in methylcyclohexane (MCH) at 25 °C was significantly enhanced from 20% to 35% upon 10-fold dilution of the sample solution by MCH, for which the reduced solvent polarity, discouraging dissociation of the intervening radical ionic exciplex, is likely to be responsible. Further attempts to microenvironmentally control the photochirogenic reaction and enhance the product's ee through selective solvation of polar cosolvent to the diastereomeric exciplex pair in nonpolar solvent were not successful probably due to the inherently high local polarity around the exciplex of saccharide-appended 3 with alcoholic substrate 1.

Full text of DOI:10.1002/chir.22004

CHIRALITY 24:400–405 (2012)
Microenvironmental Control of Enantiodifferentiating Photocyclization
of 5-Hydroxy-1,1-diphenylpentene through Selective Solvation
3
YASUHIRO NISHIYAMA,1 TAKEHIKO WADA,2 KIYOMI KAKIUCHI,1 AND YOSHIHISA INOUE
*
1Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST), Ikoma, Japan
2Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira, Sendai, Japan
3Department of Applied Chemistry, Osaka University, Suita, Japan
ABSTRACT
For mechanistic elucidation of the photosensitized cyclization of 5-hydroxy-1,
1-diphenylpentene (1), its methyl ether (4) was synthesized as an unreactive “dummy” substrate
and used as a quencher of the sensitizer fluorescence to reveal the intervention of an exciplex
intermediate that was unable to detect when reactive substrate 1 was used as a quencher/
reactant In the enantiodifferentiating photocyclization of 1 to 2-(diphenylmethyl)tetrahydrofuran
(2) sensitized by a chiral saccharide ester of 1,4-naphthalenedicarboxylate (3), the enantiomeric
excess (ee) of chiral product 2 obtained in methylcyclohexane (MCH) at 25 ꢀC was significantly
enhanced from 20% to 35% upon 10-fold dilution of the sample solution by MCH, for which the
reduced solvent polarity, discouraging dissociation of the intervening radical ionic exciplex, is
likely to be responsible. Further attempts to microenvironmentally control the photochirogenic
reaction and enhance the product’s ee through selective solvation of polar cosolvent to the
diastereomeric exciplex pair in nonpolar solvent were not successful probably due to the
inherently high local polarity around the exciplex of saccharide-appended 3 with alcoholic
substrate 1. Chirality 24:400–405, 2012. © 2012 Wiley Periodicals, Inc.
KEY WORDS: photochirogenesis; enantioselectivity; photosensitization; solvent polarity
INTRODUCTION
1-diphenylpentene (1), which is known to cyclize to 2-(diphe-
nylmethyl)tetrahydrofuran (2) upon photosensitization
with electron-accepting sensitizers,17,18 as a “self-containing”
substrate for the enantiodifferentiating photocyclization
sensitized by bis(1,2;4,5-di-O-isopropylidene-a-fructopyranosyl)
1,4-naphthalenedicarboxylate (3) (Scheme 1) in supercritical
carbon dioxide (scCO2).16 Possessing a built-in hydroxyl, this
substrate allowed us to closely investigate the effects of
diethyl ether added as an entrainer (cosolvent) to scCO2 on
the enantiodifferentiating photocyclization of 1, revealing that
the addition of ether significantly enhances the ee of cyclization
product 2 as a result of the clustering of ether molecules
around the exciplex intermediate in less polar scCO2. This
intriguing result prompted us to expand the concept of
the microenvironmental control in scCO2 to the chiral
photoreaction in conventional media exploiting the selective
solvation of polar cosolvent in nonpolar solvent; the results of
which will be reported in the following text.
Chiral photochemistry, or photochirogenesis, becomes
more popular, and a variety of molecular and supramolecular
photochirogenic reactions have been investigated particularly
in recent years.1–5 Nevertheless, precisely controlling
photochirogenic process is still a significant challenge, and
indeed the optical yields reported so far are generally
modest in particular for the most chiral source-efficient
enantiodifferentiating photosensitizations,1–5 indicating that
both general strategies and practical tactics are definitely
needed for understanding the factors and mechanisms
operating in photochirogenic processes and improving the
optical yields derived therefrom.
In a series of studies, we have demonstrated that various
entropy-related factors, such as temperature,6–8 pressure,9–12
and solvation,13–15 play vital roles in the essential enantiodiffer-
entiating steps of various chiral photosensitizations to critically
manipulate the relative stability and/or reactivity of the
diastereomeric exciplex pair of chiral sensitizer with prochiral
substrate.2 In particular, the selective solvation to exciplex
becomes a dominant factor determining product’s enantio-
meric excess (ee), when the exciplex is polarized or radical
ionic in nature.13–15 Thus, the chiral sense of product obtained
in the photoisomerization of (Z)-cyclooctene sensitized by
chiral pyromellitates is dramatically switched from R to S upon
addition of diethyl ether to the pentane solution.13
MATERIALS AND METHODS
General
Mass spectra were recorded on a JEOL (Akishima, Japan) JMS-700 instru-
ment with electron impact ionization and 1H NMR spectra at 500 MHz on a
JEOL JNM-ECP500 instrument. Fluorescence spectra were measured on a
Contract grant sponsor: Japan Society for the Promotion of Science (Y.N. and
Y.I.) and Kansai Research Foundation for Technology Promotion (Y.N.);
Contract grant number: Grant-in-aid for Research Activity Start-up, No. 22850011
(Y.N.) and Grant-in-aid for Scientific Research (A), No. 21245011 (Y.I.).
*Correspondence to: Y. Inoue, Department of Applied Chemistry, Osaka
University, Yamada-oka, Suita 565-0871, Japan. E-mail: inoue@chem.eng.
osaka-u.ac.jp
Received for publication 06 December 2011; Accepted 16 January 2012
DOI: 10.1002/chir.22004
Published online 19 April 2012 in Wiley Online Library
(wileyonlinelibrary.com).
The enantiodifferentiating polar addition of alcohol to 1,
1-diphenylalkene in methylcyclohexane (MCH) sensitized by
chiral naphthalene(di)carboxylates is also sensitive to the
solvent polarity, affording higher ee at lower concentration of
alcohol added as a reagent.14,15 However, the detailed examina-
tion of selective solvation was not feasible in this system
because of the presence of the alcohol reagent inevitably
added to the solution. We therefore employed 5-hydroxy-1,
© 2012 Wiley Periodicals, Inc.

ENANTIODIFFERENTIATING PHOTOCYCLIZATION
401
The ee of product 2 was determined by chiral high-performance
liquid chromatography on a JASCOplus instrument equipped with a
UV detector (detection wavelength: 220 nm).16 The chiral high-
performance liquid chromatography analysis was run at 5 ꢀC on a Daicel
(Osaka, Japan) Chiralpak IB column (5 mm particles, 4.6 mm
f  250 mm) eluted with a 98:1:1 mixture of n-hexane/isopropanol/1,2-
dichloroethane at a flow rate of 0.3 ml/min under the isocratic condition.
The enantiomer peaks were well separated at retention times 22 and 25
min, from the integrated areas of which the product’s ee was calculated
with an error of Æ2% ee.
RESULTS AND DISCUSSION
Fluorescence Quenching
In our previous study,16 we found that the fluorescence of
sensitizer 3 was efficiently quenched upon addition of
substrate 1 to give cyclization product 2 in good yield but failed
to unambiguously prove the intervention of an exciplex
intermediate in the photocyclization process by detecting the
exciplex fluorescence. The lack of fluorescence is presumably
due to the fast intramolecular nucleophilic attack of the
terminal hydroxyl to the radical-cationic olefin moiety of 1,
leading to cyclization product 2 (Scheme 1). If this is indeed
the case, the exciplex lifetime is expected to be appreciably
elongated by blocking the cyclization path to 2 through
methylation of the terminal OH of 1. In the present study,
we therefore employed 5-methoxy-1,1-diphenylpentene (4)18
(Scheme 2) as an unreactive “dummy” substrate that possesses
the same donor moiety as 1 but never yields the cyclization
product and compared its fluorescence quenching behavior
with that of intact substrate 1.
Scheme 1. Enantiodifferentiating photocyclization of 5-hydroxy-1,
1-diphenylpentene (1) to chiral cyclization, product (2) sensitized by bis(1,2;4,
5-di-O-isopropylidene-a-fructopyranosyl) 1,4-naphthalenedicarboxylate (3).
JASCO (Hachioji, Japan) FP-6500 spectrofluorimeter or on an Edinburgh
FL920S instrument. Fluorescence lifetimes were determined by the time-
correlated single-photon-counting technique, using an Edinburgh FL920S
instrument equipped with a pulsed H2 light source or a Hamamatsu C4334
instrument equipped with an N2 laser (Usho KEC-160, Osaka, Japan).
All chemicals were purchased from Wako (Osaka, Japan) and used without
further purifications. Spectrograde solvents were used throughout the work.
5-Hydroxy-1,1-diphenylpentene (1) was prepared as reported previ-
ously.16 5-Methoxy-1,1-diphenylpentene (4) employed as a “dummy”
substrate was prepared from 1 by the Williamson ether synthesis by
using iodomethane and sodium hydride (Scheme 2);18 1H NMR (CDCl3):
d 1.72 (tt, J = 7.1 Hz, 2H), 2.18 (dt, J = 7.6 Hz, 2H), 3.29 (s, 3H), 3.36
(t, J = 6.6 Hz, 2H), 6.09 (t, J = 7.5 Hz, 1H), 7.17–7.38 (m, 10H); mass
spectrometry (electron impact ionization) m/z (relative intensity) 252
(M+, 4), 236 (30), 207 (41), 166 (100),77 (28); high-resolution mass spec-
trometry Calcd for C18H20O (M+): 252.1514. Found: 252.1514.
We first examined the fluorescence quenching behavior
of sensitizer 3 with substrate 1 in diethyl ether at room
temperature. As shown in Figure 1(a), gradual addition of 1
of up to 10 mM to an ether solution of 3 (10 mM) led to an
efficient fluorescence quenching. According to the Stern–
Volmer (S–V) equation, I0F/IF = 1 + kQt0[Q], where kQ denotes
the apparent quenching rate constant and t0 the natural lifetime
of 3; the relative fluorescence intensity (I0F/IF) was plotted
against the quencher concentration [Q] (Q = 1) to give a
straight line (Fig. 1(b)). The S–V constant, defined as the slope
of the S–V plot, is a product of the apparent quenching rate
constant (kQ) and the inherent lifetime (t0) of fluorophore 3.
The t0 value was independently determined as 8.7 ns by using
the single-photon counting technique in the absence of a
quencher under a comparable condition. From the S–V
constant (kQt0) and the lifetime (t0), we obtain the quenching
rate constant: kQ = 7.9 Â 109 MÀ1 sÀ1 (Table 1).
Photolysis and Product Analysis
Solutions of substrate 1 (2 or 20 mM) and sensitizer 3 (0.3 or 3 mM) in
quartz cells were purged with nitrogen gas at 0 ꢀC, placed in a Unisoku
(Hirakata, Japan) CoolspeK cryostat maintained at a given temperature
and then irradiated at wavelengths >320 nm (effective wavelength: 313
nm) with a 500-W high-pressure mercury lamp through a 5-cm water
layer and a Toshiba (Tokyo, Japan) UV-31 or UV-D36B filter.
Irradiated samples were subjected to gas chromatographic (GC) analysis
on a Zebron (Torrance, CA, USA) ZB-WAXplus (0.25 mm f  30 m) or GL
Science TC-1 column (0.25 mm f  30 m) to determine the conversion (con-
sumption of 1) and chemical yield of 2 on the basis of consumed 1.15 The GC
analyses were performed at a head pressure of 100 kPa with a temperature
program, where the column temperature was kept at 180 ꢀC for first 8 min,
raised to 220 ꢀC at a rate of 20 ꢀC/min, and then hold at that temperature
for 40 min. Under the condition employed, the retention times of substrate
1 and product 2 were 36 min and 13 min, respectively, on the ZB-WAXplus
column and 15 min and 13 min, respectively, on the TC-1 column.
Similar fluorescence quenching experiments were performed
with “dummy” substrate 4 in MCH, toluene, diethyl ether, and
acetonitrile and also in MCH-containing acetonitrile (0.6 M) or
propionitrile (0.1-0.6 M) as a cosolvent to give the quenching
parameters summarized in Table 1.
Scheme 2. Synthesis of 5-methoxy-1,1-diphenypentene (4).
Chirality DOI 10.1002/chir

402
NISHIYAMA ET AL.
Fig. 1. (a) Fluorescence quenching of sensitizer 3 (0.01 mM) by substrate 1 (0–10 mM, from top to bottom) in diethyl ether at room temperature, excitation
wavelength: 340 nm, and (b) the Stern–Volmer plot obtained therefrom.
TABLE 1. Fluorescence maxima (lmax), Stern–Volmer constants (kQt), fluorescence lifetimes (t0), and quenching rate
constants (kQ) obtained upon fluorescence quenching of chiral sensitizer 3 (10 mM) with substrate 1 (0–10 mM) and “dummy”
substrate 4 (0–7.2 mM) in various solvents at room temperature in the presence and absence of cosolvent
Quencher
Solvent
Cosolvent
lmax/nm
kQt0/MÀ1
t0/ns
kQ/109 MÀ1 sÀ1
1
4
Et2O
none
none
405
396
402
397
400
404
423
405
419
69
30
36
34
38
40
17
51
66
8.7
5.8
7.1
6.4
6.6
6.8
11.6
8.7
7.9
5.2
5.1
5.3
5.8
5.9
1.5
5.9
6.3
MCHa
ANa (0.6 M)
PNa (0.1 M)
(0.3 M)
(0.6 M)
none
toluene
Et2O
none
none
ANa
10.5
aMCH, methylcyclohexane; AN, acetonitrile; PN, propionitrile; cosolvent concentration in the parentheses.
In contrast to the monotonous decrease of fluorescence
intensity over the entire wavelength range (360–500 nm) upon
addition of reactive substrate 1 (0–10 mM) (Fig. 1(a)), the
addition of “dummy” substrate 4 (0–7.2 mM) quenched the
fluorescence at the main band but induced a new weak
emission at >490 nm with accompanying isoemissive point at
ca. 490 nm (Fig. 2(a), inset), which is assignable to an exciplex
of sensitizer 3 with “dummy” substrate 4. The elongated
lifetime and/or enhanced fluorescence efficiency, as a
consequence of the blockage of the subsequent cyclization
path, are likely to be responsible for the successful detection
of the exciplex fluorescence. Unfortunately, the intensity of
the exciplex fluorescence was too weak to determine its
lifetime.
Fig. 2. (a) Fluorescence quenching of sensitizer 3 (0.01 mM) by “dummy” substrate 4 (0–7.2 mM, from top to bottom) in methylcyclohexane at room temper-
ature, excitation wavelength: 340 nm, and (b) the Stern–Volmer plot obtained therefrom.
Chirality DOI 10.1002/chir

ENANTIODIFFERENTIATING PHOTOCYCLIZATION
403
It is to note however that the kQ value obtained for “dummy”
substrate 4 in ether reaches 5.9 Â 109 MÀ1 sÀ1, which
is only 25% smaller than that for reactive substrate 1 (7.9 Â
109 MÀ1 sÀ1); see Table 1. Furthermore, the fluorescence
quenching turned out to be less sensitive to the solvent polarity,
affording comparable kQ values of 5.2-6.3 Â 109 MÀ1 sÀ1 for
MCH, ether, and acetonitrile. Another crucial finding coherent
to this is the effect of polar cosolvents added to MCH. As shown
in Table 1, the addition of 0.6 M acetonitrile to MCH did not
appreciably alter the original kQ value, and the addition of
0.1–0.6 M propionitrile only slightly elongated the kQ
value from 5.2 to 5.3–5.9 MÀ1 sÀ1. These observations are
rationalized by assuming that the cyclization path is not a
dominant decay route of the exciplex, and the apparent
quenching rate constant kQ is governed not only by the
chemical and physical decay processes but also by the reverse
reaction regenerating excited sensitizer and ground-state
substrate, as clearly demonstrated for the polar photoaddition
of methanol to 1,1-diphenylpropene.14
The only exception was toluene, which substantially reduced
the kQ value down to 1.5 Â 109 MÀ1 sÀ1. This may be attributed
to the p–p stacking solvation to excited 3, which energetically
stabilizes the excited state and also hinders the attack of
substrate. This rationale is experimentally supported by the
bathochromic shift of the fluorescence to 423 nm and the
elongated lifetime of 11.6 ns in toluene, both of which are
greater than the corresponding values in polar acetonitrile
(Table 1).
produced. An analogous general diastereodifferentiating
mechanism may operate in the present case, excepting that
the hydroxyl group introduced to the substrate is expected
to stabilize the exciplex intermediate, facilitate its charge
separation, and eventually accelerate the subsequent
cyclization process, as demonstrated by the fluorescence
quenching experiments described earlier.
The enantiodifferentiating photocyclization of 1 was first
examined in MCH at a relatively high substrate concentration
of 20 mM to afford cyclic ether 2 in ꢀmodest 20%–26% ee at
temperatures ranging from 25 to À20 C (Table 2, runs 1–3).
ꢀ
The photocyclization in toluene at 25 C (run 9) and in ether
ꢀ
from 25 to À20 C (runs 10–12) afforded 2 in higher ee’s of
28% and 22%–35%, respectively. However, the use of more polar
acetonitrile as a solvent led to the formation of almost racemic
product (0%–5% ee) from 25 to À20 ꢀC (runs 13–15). This
somewhat irregular trend of the product’s ee seems reasonable
because the radical cationic nature of 1 in the exciplex interme-
diate is promoted by increasing the solvent polarity to acceler-
ate the cyclization to 2, whereas the diastereodifferentiating
interaction of substrate with chiral sensitizer in the exciplex
is maintained in less polar solvents such as toluene and
ether but damaged in a polar solvent like acetonitrile by the
dissociation or solvent separation of the radical ionic exciplex.
When ether (0.6 M) was added to the MCH solution as a
cosolvent, the product’s ee obtained was appreciably improved
from 20% to 27% at 25 ꢀC and from 26% to 30% at 0 ꢀC; compare
runs 4 and 5 with runs 1 and 2. This ee enhancement is
presumably due to the selective solvation of added ether to
the radical cationic exciplex, which enhances the local polarity
around the exciplex to promote its charge separation and
facilitate the intramolecular attack of the terminal hydroxyl,
whereas its dissociation to a solvent-separated or free radical
ion pair is discouraged by the low bulk polarity of MCH.
Because the radical cationic exciplex is indeed a pair of re-face
and si-face stacked diastereomeric isomers, the relative stability
and/or cyclization rate should be critically affected by the
microenvironmental change caused by the selective solvation.
More polar acetonitrile added to MCH as a cosolvent was
apparently not effective in enhancing the enantioselectivity,
affording comparable 19%–23% ee upon addition of 0.3–0.6 M
Photoreaction
The photosensitized polar addition of alcohols to 1,1-
diarylalkenes proceeds through a radical ionic exciplex and is
facilitated in polar solvents.12,14,15 When chiral sensitizer
and prochiral substrate are employed, the exciplex-derived
therefrom becomes a pair of diastereomers (re-Ex and si-Ex),
as illustrated in Scheme 3, in which either re-face or si-face of the
olefin moiety of 1 is open and therefore attacked intramolecu-
larly by the terminal hydroxyl group. The relative stability of
two diastereomeric exciplexes (KR/KS) and the relative rate
constant of the subsequent cyclization (kR/kS) are the two
dominant factors determining the ee of the alcohol adduct
Scheme 3. Mechanism of the enantiodifferentiating photocyclization of 1 to enantiomeric 2 via a diastereomeric exciplex pair (re-Ex and si-Ex), which either
dissociates to singlet-excited sensitizer (1S*) and 1 or suffers intramolecular attack of the terminal OH from the open re-face or si-face of radical cationic 1d+ to afford
(R)-2 or (S)-2.
Chirality DOI 10.1002/chir

404
NISHIYAMA ET AL.
TABLE 2. Enantiodifferentiating polar photocyclization of 1 to 2 sensitized by 3 in various solvents with and without added cosolventa
Run
1b
1/mM
3/mM
Solvent
MCHc
Cosolvent
none
Temperature/ꢀC
Conversion/%
Yield/%
ee/%
20
3
25
0
À20
20
0
25
0
25
25
25
0
d
d
d
d
d
d
d
d
24
68
30
63
18
30
33
23
51
37
9
33
39
24
18
14
4
d
d
d
d
d
d
d
d
25
12
13
6
14
13
12
13
18
24
67
18
31
42
44
43
d
20
26
21
27
30
19
23
19
28
22
33
35
5
2
3
4b
Et2O (0.6 M)
ANc (0.3 M)
5
6
7
8
(0.6 M)
none
none
9b
toluene
Et2O
10b
11
12
13b
14
15
16
17
18
19
20
21
22
23
24
25
26
27
À20
25
0
ANc
none
1
0
0
À20
Et2O (0.6 M)
none
0
2
0.3
MCHc
25
0
À20
25
25
0
25
0
À20
25
0
35
33
33
33
33
33
28
24
9
PNc (0.1 M)
(0.3 M)
(0.6 M)
Et2O
none
36
12
31
25
28
35
aIrradiated at 313 nm for 2 h.
bData cited from Reference 16.
cMCH, methylcyclohexane; AN, acetonitrile; PN, propionitrile.
dNot determined.
acetonitrile (runs 6–8). However, these modest ee’s are rather
extraordinary in view of the extremely low 0–5% ee obtained
in pure acetonitrile (runs 13–15) and in an acetonitrile–ether
mixture (run 16) and indicate that acetonitrile added to MCH
solvates selectively to the radical cationic exciplex, whereas
the low bulk polarity of MCH confines the radical cationic
exciplex in a polar solvation shell of acetonitrile surrounded
by bulk MCH to eventually afford the ee’s comparable with
those obtained in pure MCH.
Unexpectedly, the product’s ee obtained upon photolysis in
MCH from 25 to À20 ꢀC was significantly enhanced from
20%–26% (Table 2, runs 1–3) to 33%–35% (runs 17–19) by simply
diluting the sample solution by 10 times to 2 mM substrate and
0.3 mM sensitizer concentrations. Intriguingly, this apparently
strange concentration dependence of ee seems specific to the
photocyclization in MCH. When the photocyclization was
performed in ether at 0–25 ꢀC, the ee was only slightly
improved from 22%–33% (runs 10 and 11) to 28%–35% (runs 26
and 27) by reducing the substrate concentration from 20 mM
to 2 mM. On the other hand, the product becomes almost
racemic upon irradiation in polar acetonitrile (runs 13–15), as
stated earlier. Thus, the lower ee’s obtained in MCH at a higher
substrate concentration (20 mM) may be attributed at least,
in part, to the increased polarity of solvent MCH mixed with
inherently polar alcoholic substrate 1. Other possible
explanations for the concentration effect, including the
hydrogen-bonding self-aggregation of substrates and the
hydrogen-bonding interaction between the substrate’s OH
and the sensitizer’s carbonyl in the ground state, may be ruled
Chirality DOI 10.1002/chir
out because the addition of good hydrogen-bond acceptor, such
as ether (0.6 M) or acetonitrile (0.3–0.6 M), to MCH did not
influence the product’s ee (Table 2, runs 4–8).
We therefore re-examined the effects of selective solvation
on the enantioselectivity of photocyclization under the dilute
condition by using less polar propionitrile as a cosolvent. As
shown in Table 2, the product’s ee was not appreciably affected
by the addition of 0.1–0.3 M propionitrile (runs 20–22), holding
the original 33%–35% obtained in pure MCH (runs 17–19).
Furthermore, the addition of 0.6 M propionitrile noticeably
reduced the ee to 28% at 25 ꢀC, to 24% at 0 ꢀC, and even to 9%
ꢀ
at À20 C (runs 23–25), which may be attributed to a greater
contribution of the solvent-separated radical ion pair facilitated
by the high local polarity caused by excessive solvation around
the exciplex upon addition of 0.6 M propionitrile, in particular,
at lower temperatures. It is concluded therefore that the
concept of microenvironmental polarity control is of great
importance for the enantiodifferentiating polar photoaddition/
cyclization of diphenylalkene derivatives lacking polar substitu-
ent but does not contribute as a convenient effective tool for
enhancing the product’s ee for such substrates with polar
substituent(s).
CONCLUSION
In this study to microenvironmentally control the
photochirogenic reaction, we first obtained the evidence that
supports the intervention of an exciplex intermediate in
the photocyclization of 5-hydroxy-1,1-diphenylpentene 1 by

ENANTIODIFFERENTIATING PHOTOCYCLIZATION
405
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using a “dummy” substrate 4. The enantiodifferentiating
photocyclization of 1 sensitized by chiral naphthalene
derivative 3 turned out to be significantly dependent on the
substrate concentration, affording enantiomeric ester 2 in
20% ee at 20 mM but much higher 35% ee at 2 mM, which is
probably attributable to the reduced solvent polarity upon
10-fold dilution of the polar substrate. However, the attempts
to enhance the product’s ee by selective solvation to the
intervening diastereomeric exciplex pair were not successful,
which is presumably due to the inherently augmented local
polarity around the exciplex as a result of intramolecular
solvation of the built-in hydroxyl group to the radical cationic
olefin part of substrate 1. This is a bitter but valuable lesson,
which should be taken into account in designing such chiral
photoreaction systems that involve polarized or radical ionic
exciplex intermediates.
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control of enantiodifferentiating polar addition of 1,1-diphenylpropene
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Chirality DOI 10.1002/chir