Stereoselective Photodimerization of (E)-Stilbenes in Crystalline γ-Cyclodextrin Inclusion Complexes

Article abstract of DOI:10.1021/jo9903149

Solid-state irradiation of the crystalline inclusion complex of (E)-stilbene in γ-cyclodextrin (γ-CD) yields a single isomer of syn-tetraphenylcyclobutane stereoselectively in high yield. In contrast, the photodimerization of stilbene in solution is very inefficient and unselective, and no photodimer is observed even upon prolonged irradiation of pure crystals. The monosubstituted stilbenes form a pair of photodimers stereoselectively, viz. the syn head-to-head and syn head-to-tail isomers, in comparable yields. The photodimer yields of about 70% and the biphasic decay kinetics of the excited stilbene (as established by picosecond time-resolved diffuse-reflectance spectroscopy) indicate that the stilbene guests are located in at least two distinct sites in the γ-CD crystal lattice, i.e., a dimerization site where excited stilbene is in close reach of another stilbene guest molecule and an isomerization site where excited stilbene does not find a close neighbor for dimerization and thus undergoes trans → cis isomerization only.

Full text of DOI:10.1021/jo9903149

8098
J . Org. Chem. 1999, 64, 8098-8104
Ster eoselective P h otod im er iza tion of (E)-Stilben es in Cr ysta llin e
γ-Cyclod extr in In clu sion Com p lexes
K. S. S. P. Rao, S. M. Hubig,* J . N. Moorthy, and J . K. Kochi
Department of Chemistry, University of Houston, Houston, Texas 77204-5641
Received February 18, 1999
Solid-state irradiation of the crystalline inclusion complex of (E)-stilbene in γ-cyclodextrin (γ-CD)
yields a single isomer of syn-tetraphenylcyclobutane stereoselectively in high yield. In contrast,
the photodimerization of stilbene in solution is very inefficient and unselective, and no photodimer
is observed even upon prolonged irradiation of pure crystals. The monosubstituted stilbenes form
a pair of photodimers stereoselectively, viz. the syn head-to-head and syn head-to-tail isomers, in
comparable yields. The photodimer yields of about 70% and the biphasic decay kinetics of the excited
stilbene (as established by picosecond time-resolved diffuse-reflectance spectroscopy) indicate that
the stilbene guests are located in at least two distinct sites in the γ-CD crystal lattice, i.e., a
dimerization site where excited stilbene is in close reach of another stilbene guest molecule and an
isomerization site where excited stilbene does not find a close neighbor for dimerization and thus
undergoes trans f cis isomerization only.
In tr od u ction
Cyclodextrins (CDs) form cage-type or channel-type
crystal lattices depending on whether they crystallize
from water as hydrates or in the presence of excess guest
molecules as inclusion complexes.1 As a result, CD crystal
structures exhibit well-defined cavities of varying sizes
and shapes that can be occupied by a variety of organic
and inorganic guest molecules2,3 and are thus utilized as
rigid microvessels for thermal as well as photochemical
reactions.4 Crystalline cyclodextrins are typical examples
of highly organized and constrained reaction media that
are frequently exploited to improve the efficiency and
selectivity of photoreactions.4-6 However, only a few
studies on bimolecular photoreactions in solid CD inclu-
sion complexes have been reported that clearly demon-
strate improved stereo- and/or regioselectivity (including
cycloadditions and photoreductions)7-9 as compared to the
corresponding reactions carried out in solution.
In this study, we report the effects of the crystalline
γ-cyclodextrin environment (see Figure 1) on the ef-
ficiency and stereoselectivity of the photodimerization of
stilbene and its derivatives. Stilbenes are excellent
candidates to demonstrate the modulation of photochemi-
cal reactivity by solid-state host/guest interactions for the
following reasons: (i) Stilbenes exhibit a diverse photo-
chemical behavior in solution that includes reversible
F igu r e 1. Schematic presentation of (left) the toroidally
shaped structure of γ-cyclodextrin and (right) the channel-type
crystal lattice of its inclusion complexes.
trans f cis isomerization, cyclization to dihydrophenan-
threne, and dimerization to yield tetraphenylcyclobutane
products.10,11 The latter pathway is extremely inefficient
in solution;12 it leads to a mixture of stereoisomers of
tetraphenylcyclobutanes in low yields12-14 and is thus a
good proving ground to test enhanced efficiency and
selectivity in the solid state. (ii) Stilbenes form readily
inclusion complexes with cyclodextrins,15,16 which can be
isolated in crystalline form as shown in this study. (iii)
Irradiation of diammonium-substituted stilbene in aque-
(1) For a review, see: Saenger, W.; J acob, J .; Gessler, K.; Steiner,
T.; Hoffman, D.; Sanbe, H.; Koizumi, K.; Smith, S. M.; Takha, T. Chem.
Rev. 1998, 98, 1787.
(2) Atwood, J . L., Davis, J . E. D., MacNicol, D. D., Eds. Inclusion
Compounds; Academic Press: London, 1984; Vols. 2-3.
(3) Wenz, G. Angew. Chem., Int. Ed. Engl. 1994, 33, 803.
(4) Ramamurthy, V., Scheffer, J . R., Turro, N. J ., Eds. Organic
Chemistry in Anisotropic Media. Tetrahedron 1987, 43(7).
(5) Kalayasundaram, K. Photochemistry in Microheterogeneous
Systems; Academic Press: London, 1987.
(10) Lewis, F. D. Adv. Photochem. 1986, 13, 165.
(11) Lewis, F. D. Acc. Chem. Res. 1979, 12, 152.
(12) (a) Even at concentrations as high as 0.5 M, irradiations of (E)-
stilbene in benzene for 2 months yielded only 27% conversion into
cyclobutane products.13 (b) Note that somewhat better dimerization
efficiencies have been achieved in water16a and in other hydroxylic
solvents such as methanol14 due to the hydrophobic effect.12c (c)
Tanford, C. The Hydrophobic Effect; Wiley: New York, 1980.
(13) (a) Shechter, H.; Link, W. J .; Tiers, G. V. D. J . Am. Chem. Soc.
1963, 85, 1601. (b) See also ref 19.
(6) Ramamurthy, V. Photochemistry in Organized and Constrained
Media; VCH: New York, 1991.
(7) Moorthy, J . N.; Venkatesan, K.; Weiss, R. G. J . Org. Chem. 1992,
57, 3292.
(14) Ito, Y.; Kajita, T.; Kunimoto, K.; Matsuura, T. J . Org. Chem.
1989, 54, 587.
(15) Herrmann, W.; Wehrle, S.; Wenz, G. J . Chem. Soc., Chem.
Commun. 1997, 1709.
(8) Tanaka, Y.; Sasaki, S.; Kobayashi, A. J . Inclusion Phenom. 1984,
2, 851.
(9) Mir, M.; Margret, J .; Cayon, E. Tetrahedron Lett. 1992, 46, 7053.
(16) (a) Syamala, M. S.; Ramamurthy, V. J . Org. Chem. 1986, 51,
3712. (b) Syamala, M. S.; Devathan, S.; Ramamurthy, V. J . Photochem.
1986, 34, 219.
10.1021/jo9903149 CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/14/1999

Stereoselective Photodimerization of (E)-Stilbenes
J . Org. Chem., Vol. 64, No. 22, 1999 8099
Ch a r t 1
Ch a r t 2
Ta ble 1. Isola tion of γ-CD/Stilben e In clu sion Com p lexes
4.9 ppm)17 of the C1H protons of the glucose units in the
γ-CD were quantitatively compared with the signals of
the aromatic protons of stilbene 1a , which led to a host/
guest ratio of 1:1.75. This host/guest ratio was in reason-
able agreement with the ratio of 1:1.60 obtained from the
mass analysis of the (E)-stilbene extracted from the pure
complex. Similar procedures were applied for the prepa-
ration and analysis of the γ-CD inclusion complexes of
the other (substituted) stilbenes in Chart 1, and the
molar host/guest ratios and yields of the inclusion
complexes are given in Table 1. In all cases, the γ-cyclo-
dextrin and stilbene solutions were mixed together in a
molar ratio of 1:2.3. Slightly lower host/guest ratios were
obtained when the stilbene and the γ-CD were added in
a precise 2:1 molar ratio. On the other hand, addition of
stilbene in a higher excess than a factor of 2.3 did not
increase the host/guest ratios in Table 1. Interestingly,
the host/guest ratios obtained for the stilbenes 2 and 3
in Chart 1 did not exceed 1:0.90 and 1:0.85, respectively.
II. P h otod im er iza tion of Stilben e in th e γ-CD
In clu sion Com p lexes a n d Ch a r a cter iza tion of th e
Cyclobu ta n e P h otop r od u cts. The microcrystalline
γ-CD complex of (E)-stilbene (1a , 770 mg) was irradiated
in a Rayonet photochemical reactor at λ ) 330 nm. After
24 h of photolysis, the complex was dissolved in 30 mL
of distilled water saturated with NaCl at 50 °C, and the
organic contents were extracted into chloroform. Analysis
a n d Host/Gu est Ra tiosa
host/guest molar ratio
stilbeneb
method Ac
method Bd
mass balancee (%)
1a
1b
1c
1d
1e
1f
2
1:1.75
1:1.70
1:1.80
1:1.95
1:1.77
1:1.80
1:0.90
1:0.85
1:1.60
1:1.65
1:1.70
1:1.85
1:1.70
1:1.70
1:0.95
1:0.86
92
91
94
83
90
88
48
43
3
a
Inclusion complexes were prepared by the addition of γ-CD
b
and stilbene in a molar ratio of 1:2.3. Identified in Chart 1.
c Ratios determined from the 1H NMR spectra of the inclusion
d
complexes. Ratios obtained from the relative masses of γ-CD and
stilbene in the inclusion complex. e Mass balance of the precipi-
tated inclusion complex: % mass balance ) 100 × (mg inclusion
complex/mg γ-CD + mg stilbene).
ous γ-CD solution yields two stereoisomeric cyclobutane
products in good yields.15 (iv) All stilbenes in this study
do not undergo photodimerizations in the neat crystalline
state (see the Discussion).28 Thus, a series of crystalline
γ-CD inclusion complexes with the substituted stilbenes
in Chart 1 are irradiated by steady-state and time-
resolved (diffuse-reflectance) techniques to explore the
stereo- and regioselectivity in the formation of the cyclo-
butane photoproducts as well as the reaction dynamics
of excited stilbene in the solid-state inclusion complexes.
1
of the crude reaction mixture by GC and H NMR (vide
infra) indicated the formation of the photodimer 1,2,3,4-
tetraphenylcyclobutane and (Z)-stilbene. Separation of
the crude reaction mixture by column chromatography
yielded the photodimer and (Z)-stilbene in 48% and 10%
yield, respectively. Prolonged irradiation (up to 72 h) of
the stilbene/γ-CD complex did not further improve the
yields. Most importantly, only one (out of four possible)
tetraphenylcyclobutane isomer was found as photoprod-
uct, and it was identified as the syn isomer (see Chart 2)
by 1H NMR spectroscopy and X-ray crystallography.
Thus, the NMR spectrum showed a singlet at δ 4.5 ppm,
which was characteristic of cyclobutane protons,13a and
the syn stereochemistry was unambiguously determined
by X-ray structural analysis of a single crystal (see the
Experimental Section).18 Similarly, photolysis of the
microcrystalline complexes of γ-CD with stilbene 1b and
the monosubstituted (E)-stilbenes (1c-f) afforded pho-
todimers as the major products in addition to small
amounts (<10%) of the corresponding (Z)-stilbenes, which
were also isolated (see Table 2). On the basis of the
chemical shift of the cyclobutane protons in the NMR
spectra, the syn configuration was assigned to all pho-
todimer products (see the Experimental Section).13,14,19,20
Resu lts
I. F or m a tion a n d Ch a r a cter iza tion of th e Cr ys-
ta llin e Stilben e/γ-Cyclod extr in (γ-CD) In clu sion
Com p lexes. When a concentrated solution of (E)-stilbene
(1a , 1.6 mmol) in ethanol (10 mL) was added to a
saturated solution of γ-cyclodextrin (γ-CD, 0.7 mmol) in
water and stirred for 12 h, a fine white microcrystalline
precipitate formed, which was isolated after thorough
washing with ether and cold water. This white precipitate
was considered to be the stilbene/γ-CD inclusion complex
since (i) the stilbene/γ-CD molar ratio was highly repro-
ducible from batch to batch (vide infra) and (ii) the
stilbene component could not be removed by extensive
washing with ether. The mass balance between the
starting material and the isolated precipitate revealed
the inclusion complex of stilbene (1a ) in γ-CD to be
formed in 92% yield (see Table 1).
The molar ratio between the γ-CD host and the stilbene
1
guest was determined by both the H NMR spectroscopic
analysis (method A)16,17 and from the mass of the (E)-
stilbene in the precipitate as determined by decomplex-
ation (method B, see the Experimental Section). For
example, the characteristic NMR signals (doublets at δ
(18) Margulis, T. N. Acta Crystallogr. 1965, 19, 857.
(19) Ulrich, H.; Rao, D. V.; Stuber, F. A.; Sayigh, A. A. R. J . Org.
Chem. 1970, 35, 1121.
(17) Schneider, H.-J .; Hacket, F.; Rudiger, V. Chem. Rev. 1998, 98,
1755.
(20) Green, B. S.; Heller, L. J . Org. Chem. 1974, 39, 196.

8100 J . Org. Chem., Vol. 64, No. 22, 1999
Rao et al.
Ta ble 2. Stea d y-Sta te P h otolysis of Stilben e/γ-CD
In clu sion Com p lexesa
isolated yieldc (%)
photo-
dimer
stilbeneb stilbene stilbene photodimer H-T:H-Hd yielde (%)
(E)-
(Z)-
syn
1a
1b
1c
1d
1e
1f
2
22
40
38
36
29
22
23
66
10
9
6
(trace)
10
9
64
18
48
42
46
52
42
60
0
f
f
61
70
72
79
59
76
0
57:43
55:45
60:40
54:46
g
3
0
g
0
a
Photolysis (λ ) 330 nm) of the inclusion complexes was carried
out for 24 h at room temparature. Identified in Chart 1. c Based
b
on the amount of stilbene present in the inclusion complex prior
d
to irradiation. Molar ratio between head-to-tail and head-to-head
isomers as determined by gas chromatography using p-methyl-
anisole as internal standard. e Based on the conversion of stilbene
in the photoreaction. f No distinction between H-H and H-T
g
isomers. No photodimers obtained.
F igu r e 2. Transient absorption spectra recorded at (top-to-
bottom) 50, 350, 1000, and 4000 ps following the 25-ps laser
excitation (at 355 nm) of crystalline stilbene1a /γ-CD inclusion
complex showing the decay of stilbene excited singlet state.
Ch a r t 3
In contrast, photolysis of (Z)-stilbene (2) and the
trimethyl-substituted stilbene (3) as crystalline γ-CD
complexes resulted in the formation of isomerization
products only, and no photodimers were found in the
reaction mixture even after prolonged irradiation periods.
Note that in these complexes the host/guest molar ratio
was about H:G ≈ 1:1 as opposed to that of the other
stilbenes (H:G ≈ 1:2, see Table 1). All stilbenes in Table
2 were also irradiated under the same conditions as (i)
neat crystals and (ii) dissolved in benzene solution (0.3
M). However, no photoproducts were obtained in the solid
state, and inefficient, unselective photoreactions were
observed in solution.12,13
III. P icosecon d Tim e-Resolved La ser F la sh P h o-
tolysis. The crystalline inclusion complex of stilbene (1a )
in γ-CD was exposed to the third-harmonic (355 nm) laser
pulse of a mode-locked Nd:YAG laser (25-ps pulse width).
At this wavelength, only stilbene absorbed the laser light.
The transient absorption spectra were recorded in the
diffuse-reflectance mode (see the Experimental Section)
at various times after the laser excitation. As shown in
Figure 2, the transient spectra showed a broad absorption
band with maximum at 570 nm and a tail reaching far
into the red wavelength region beyond 700 nm. At shorter
wavelengths (below 480 nm), a strong emission was
detected, which appeared to extend beyond the blue edge
of the detection system (at 400 nm). On the basis of the
similarity with the transient absorption spectra of excited
(E)-stilbene recorded in dichloromethane solution (λmax
) 590 nm, see Table 3), in heptane solution (λmax ) 580
nm),21 and in acetonitrile solution (λmax ) 575 nm),22 we
assign the absorption signals to the excited singlet state
of (E)-stilbene (1a ). Interestingly, no emission was ob-
served in dichloromethane solution. Instead, a second
(weaker) absorption band at 480 nm was observed.22
Whether a similar 480-nm absorption band was or was
GC analysis revealed that monosubstituted stilbenes
formed two distinct syn-cyclobutane isomers in about
equal amounts. These two photodimers were identified
as the syn head-to-head (H-H) and the syn head-to-tail
(H-T) isomers (see Chart 3) by a careful analysis of the
fragmentation pattern of their mass spectra as follows:
The H-H isomers showed three major components in
their mass spectra that were assigned to the unsubsti-
tuted, monosubstituted, and disubstituted stilbene as the
result of fragmentation of the cyclobutane isomer A along
the wavy lines in Chart 3. In contrast, isomer B (see
Chart 3) could only form one (monosubstituted) stilbene
fragment regardless of the fragmentation mode.
In the case of the p-cyanostilbene/γ-CD complex, the
two isomers (syn H-H and syn H-T) could be separated
by column chromatography (see the Experimental Sec-
tion). In addition to the mass-spectral fragmentation
1
pattern, H NMR spectroscopy was utilized to identify
the isomers. Thus, the cyclobutane protons of the syn
H-T dimer appeared as a singlet at δ 4.55 ppm, whereas
those of the syn H-H dimer exhibited an A2B2 pattern
with two doublets centered at δ 4.40 and 4.60 ppm in
good agreement with the spectra reported in the litera-
ture.14 In all cases, the two syn photodimers (H-H and
H-T) were formed in comparable yields (see Table 2).
In addition, the ratio of syn (H-H) and syn (H-T)
isomers did not change with time over prolonged irradia-
tion periods as established for the p-methylstilbene/γ-
CD complex.
(21) Shkurinov, A. P.; Koroteev, N. I.; J onusauskas, G.; Rulliere, C.
Chem. Phys. Lett. 1994, 223, 573.
(22) As a possible assignment for this absorption band, the stilbene
excimer has been considered, but no unambiguous experimental proof
could be provided. See: Peters, K. S.; Freilich, S. C.; Lee, J . J . Phys.
Chem. 1993, 97, 5482.

Stereoselective Photodimerization of (E)-Stilbenes
J . Org. Chem., Vol. 64, No. 22, 1999 8101
Ta ble 3. Sp ectr a l Da ta a n d Deca y Kin etics of th e Stilben e (Sin glet) Excited Sta tes in Dich lor om eth a n e (DCM) a n d in
γ-CD In clu sion Com p lexesa
decay rate constants (s-1
)
transient absorption maximum (nm)
γ-cyclodextrin
DCM
c,f
d,f
stilbeneb
γ-CD
DCM
590
k1
k2
Re,f
1a
565
g4.0 × 1010
2.9 × 109
(3.0 × 109)
4.6 × 109
6.8 × 109
6.2 × 109
(5.5 × 109)
1.5 × 109
(1.5 × 109)
3.3 × 109
(5.3 × 109)
1.4 × 109
1.8 × 108
(2.0 × 108)
4.1 × 108
1.8 × 108
5.9 × 108
(3.1 × 108)
1.3 × 108
(-)
20:80
(57:43)
26:74
21:79
52:48
(80:20)
45:55
(100:0)
40:60
(67:33)
69:31
1b
1c
1d
580
600
565
g
590
600
g
g4.0 × 1010
2.4 × 1010
1e
1f
3
580
580
576
560
550
g
1.6 × 1010
g4.0 × 1010
g
2.9 × 108
(7.0 × 108)
1.7 × 108
Measured by time-resolved (ps) spectroscopy upon 25-ps laser excitation at 355 nm. Identified in Chart 1. c First-order rate constant
a
b
for fast decay component. First-order rate constant for slow decay component. e Ratio of fast and slow component as determined by
d
their initial relative absorbance (A0) at time t ) 0 ps (R ) A0,fast (%):A0,slow (%)). f Values for preirradiated samples in parentheses (see
g
text). Not measured in DCM.
solution decayed following first-order kinetics, and rate
constants of 1.6 × 1010 and 2.4 × 1010 s-1 were deter-
mined, respectively. In contrast, the decay traces in the
γ-CD samples exhibited a biphasic behavior as observed
for unsubstituted stilbene in Figure 3, and the rate
constants for the fast and the slow decay components
differed by about 1 order of magnitude (see Table 3). Also
shown in Table 3 are the ratios R between the absorbance
of the fast component and that of the slow component,
which varied substantially for the various stilbenes. In
general, the lifetimes of the excited stilbenes in dichlo-
romethane solution were within or close to the time
resolution of the kinetic spectrometer (25 ps), and the
rate constants determined in the crystalline γ-CD samples
were at least 1 order of magnitude slower than those
measured in dichloromethane solution (see Table 3). In
both media, the rate constants varied somewhat with the
stilbene substituents, but did not reveal any perceptible
trend. In no case did the transient absorption signals
persist beyond 5 ns.
F igu r e 3. Biphasic decay of stilbene excited singlet state in
The time-resolved diffuse-reflectance measurements
were also carried out with preirradiated samples of
crystalline stilbene/γ-CD inclusion complexes.23 For a
complete comparison, new batches of stilbene/γ-CD com-
plexes were prepared and divided into three samples. The
first sample was used to determine the host/guest ratios
which were in close agreement with those determined
earlier (see Table 1). The second sample was irradiated
for 72 h prior to time-resolved diffuse-reflectance mea-
surements, and the photodimer yields were determined
by quantitative NMR measurements. The third sample
was examined by laser flash photolysis without preirra-
diation. A careful comparison of the biphasic decays
observed upon laser photolysis of preirradiated and
unirradiated samples revealed that the relative amounts
of the slow component decreased at least by 50% upon
preirradiation, whereas the decay rate constants re-
mained more or less the same (see Table 3). In fact, in
the case of methoxystilbene (1e) the slow component
disappeared completely in the decay kinetics of the
preirradiated sample, and a monoexponential decay was
observed with a rate constant of k ) 1.5 × 109 s-1, which
was identical to that of the fast component in the biphasic
decay of the corresponding unirradiated sample.
the crystalline stilbene/γ-CD inclusion complex. The solid lines
represent the best exponential fits of the data points for the
fast and slow decay component.
not present in the transient diffuse-reflectance spectrum
of the solid-state stilbene/γ-CD complex could not be
examined owing to the strong emission that interfered
with the detection of transient absorption signals below
490 nm (see Figure 2).
The transient spectra of excited stilbene in the γ-CD
inclusion complex decayed completely to the spectral
baseline on the picosecond and early nanosecond time
scale in a biphasic manner (see Figure 3), and the
biexponential fit of the data points yielded two first-order
rate constants of kfast ) 2.9 × 109 s-1 and kslow ) 1.8 ×
108 s-1. In contrast, the transient absorption spectra of
excited stilbene in dichloromethane decayed very rapidly
with a rate constant exceeding the time resolution of the
laser spectrometer (k > 4 × 1010 s-1). Similar transient
spectra were obtained for the substituted stilbenes (1b-
f) in γ-CD, and they closely resembled the corresponding
spectra in dichloromethane solution (see Table 3). A
comparison of the decay patterns of the transient spectra
in crystalline γ-CD and in dichloromethane solution
again revealed characteristic differences in the kinetics.
For example, stilbenes 1d and 1e in dichloromethane
(23) We thank one of the reviewers for suggesting this experiment.

8102 J . Org. Chem., Vol. 64, No. 22, 1999
Rao et al.
Discu ssion
crystallographic studies on various stilbenes uniformly
reveal that the lack of dimerization reactivity is due to
the large distance (d > 5 Å) and frequently nonparallel
orientation of the olefinic double bonds of the stilbenes
in crystal lattices.29 Thus, in accord with the topochemical
postulates established by Schmidt and co-workers,30 a [2
+ 2] cycloaddition to yield tetraphenylcyclobutane would
require too large a movement of atoms in the stilbene
crystal lattices.31
Photodimerization of (E)-stilbene to yield tetraphenyl-
cyclobutane dimers can be achieved in good yields and
with excellent (syn) stereoselectivity by prior incorpora-
tion of the substrates into crystalline γ-cyclodextrin
matrixes as inclusion complexes with a host/guest ratio
of about 1:2.
I. Syn th etic Releva n ce. A. P h otod im er iza tion in
Solu tion . The photodimerization of stilbene in organic
solvents is an extremely inefficient and unselective
process which results in a variety of stereo- and regio-
isomeric photoproducts in very low yields.12,13 Thus, even
at stilbene concentrations as high as 0.5 M, this bimo-
lecular photoreaction cannot compete with the (uni-
molecular) trans f cis photoisomerization and subse-
quent cyclization of the stilbene, which results in (Z)-
stilbene and phenanthrene formation, respectively.13
Since both reaction pathways originate from the excited
singlet state of stilbene as the common precursor,10,11 the
predominance of the photoisomerization is solely due to
its rapid rate24 as compared to that of the diffusion-
limited photodimerization. In fact, the excited singlet
state of all stilbene derivatives decayed with rate con-
stants k > 1010 s-1 in dichloromethane solution (see Table
3). Thus, even in the best case of diffusion-limited
dimerization (i.e., kdim ≈ 1010 M-1 s-1),25 this pathway can
only effectively compete with the other fast decay routes
of excited stilbene if stilbene concentrations [S] . 1 M
are applied.
B. Th e Solid -Sta te Ap p r oa ch . In general, rate-
limiting diffusional processes prior to reaction are readily
obviated in organized and constrained media in which
the reactants are permanently positioned at close dis-
tance. Such a pre-assembly of the reaction partners not
only improves the efficiency of a bimolecular photoreac-
tion that must compete with rapid unimolecular path-
ways but also generally enhances its stereo- and/or
regioselectivity (as compared to the corresponding reac-
tion in solution) owing to the fixed relative orientation
of the substrates in a rigid microenvironment. Accord-
ingly, numerous photochemical reactions have been car-
ried out in the solid crystalline state to improve efficiency
and selectivity.26 In fact, there are even reports of
bimolecular photoreactions that exclusively occur in the
crystalline state and not in solution.27
C. Efficien t P h otod im er iza tion in Cr ysta llin e
γ-Cyclod ext r in In clu sion Com p lexes. As demon-
strated in this study, the incorporation of stilbene
molecules into the rigid cavities of crystalline γ-cyclo-
dextrin is the method of choice to overcome the above-
described problems in solution as well as in neat crystals.
Thus, stilbene photodimer yields as high as 79% (see
Table 2) are obtained, and most importantly, absolute
syn- stereoselectivity is achieved whereas stilbene pho-
todimerizations in organic solvents12-14 or aqueous γ-CD
solution15 result in syn- and anti-cyclobutane products.
We conclude that in the crystalline inclusion complexes
with host/guest ratio of 1:2 most stilbene molecules are
positioned in close distance and fixed orientation to each
other and thus readily dimerize upon photoexcitation to
yield stereoselectively syn-tetraphenylcyclobutane.33 In-
terestingly, the monosubstituted stilbenes 1c-f form two
regioisomeric cyclobutane photoproducts in comparable
yields (see Table 2, column 5). We conclude that there is
no preferred (H-H or H-T) orientation of these stilbene
molecules in the cyclodextrin cavities prior to photo-
dimerization, and thus, the H-H/H-T ratios in Table 2
are close to a statistical distribution of 50:50.
The relatively low yields (<18%) of (Z)-stilbene forma-
tion from the (E)-stilbenes 1a -f and 3 in Table 2 reveal
that the rigid cyclodextrin matrix strongly impedes the
(29) (a) Bouwstra, J . A.; Schouten, A.; Kroon, J . Acta Crystallogr.,
Sect. C 1984, 40, 428. (b) Hoekstra, H. A.; Meertens, P.; Vos, A. Acta
Crystallogr. 1975, B31, 2813. (c) Bernstein, J . Acta Crystallogr. 1975,
B31, 1268. (d) Finder, C. J .; Newton, M. G.; Allinger, N. L. Acta
Crystallogr. 1974, B31, 411. (e) Robertson, J . M.; Woodward, I. Proc.
R. Soc. London, Ser. A 1937, 162, 568.
(30) Schmidt. G. M. J . Pure Appl. Chem. 1971, 27, 647.
(31) On the basis of photodimerization studies with cinnamic acid
derivatives, Schmidt and co-workers empirically determined an upper
limit of d e 4.2 Å for the distance between olefinic double bonds that
can undergo [2 + 2] cycloadditions.30 However, there are contradictory
reports of photoinduced dimerizations of olefins over distances of more
than 4.4 Å.32
However, the photodimerization of stilbenes is gener-
(32) Gnanaguru, K.; Ramasubbu, N.; Venkatesan, K.; Ramamurthy,
V. J . Photochem. 1984, 27, 355.
(33) On the basis of purely geometrical constraints, a pair of trans-
stilbene molecules can stack in the 8-Å channels33b of γ-CD in several
ways: either with the same orientation (i.e., the double bonds more
or less lined up parallel as in A) or with an inverted orientation (i.e.,
the double bonds crossed as in B), i.e.
ally suppressed in the crystalline solid-state.28 X-ray
(24) (a) Saltiel, J .; D’Agostino, J .; Megarity, E. D.; Metts, L.;
Neuberger, K. R.; Wrighton, M.; Zafiriou, O. C. Organic Photochem-
istry; Dekker: New York, 1973; Vol. 3, p 1. (b) Saltiel, J .; Chang, D.
W. L.; Megarity, E. D.; Rousseau, A. D.; Shannon, P. T.; Thomas, B.;
Uriarte, A. K. Pure. Appl. Chem. 1975, 41, 559.
(25) Moore, J . W.; Pearson, R. G. Kinetics and Mechanism, 3rd ed.;
Wiley: New York, 1981; p 239.
(26) For reviews, see: (a) Ito, Y. Synthesis 1998, 1. (b) Leibovitch,
M.; Olovsson, G.; Scheffer, J . R.; Trotter, J . Pure Appl. Chem. 1997,
69, 815. (c) Gamlin, J . N.; J ones, R.; Leibovitch, M.; Patrick, B.;
Scheffer, J . R.; Trotter, J . Acc. Chem. Res. 1996, 29, 203. (d) Toda, F.
Acc. Chem. Res. 1995, 28, 480. (e) Green, B. S.; Lahav, M.; Rabinovich,
D. Acc. Chem. Res. 1979, 12, 191. (f) Green, B. S.; Aradyellin, R.; Cohen,
M. Top. Stereochem. 1986, 16, 131.
(27) (a) Haga, N.; Nakajima, H.; Takayanagi, H.; Tokumaru, K. J .
Chem. Soc., Chem. Commun. 1997, 1171. (b) Haga, N.; Nakajima, H.;
Takayanagi, H.; Tokumaru, K. J . Org. Chem. 1998, 63, 5372.
(28) Note that 1,2,3,4,5-pentafluorostilbene, which crystallizes in
tightly packed π-stacks with an intermolecular distance of about 3.5
Å, is the only stilbene derivative that photodimerizes in the crystalline
state (in a head-to-tail configuration). See: Coates, G. W.; Dunn, A.
R.; Henling, L. M.; Ziller, J . W.; Lobkowsky, E. B.; Grubbs, R. H. J .
Am. Chem. Soc. 1998, 120, 3641.
Concerted [2 + 2] cycloaddition of trans-stilbene with preorientation
A will lead to the formation of the syn-cyclobutane.28,33c,d On the other
hand, if preorientation B is photoactive (it may not undergo photocy-
cloaddition due to insufficient π-orbital overlap between the crossed
double bonds), it will result in the formation of the anti-cyclobutane.
Thus, the fact that syn-cyclobutanes are obtained stereoselectively in
good yields suggests that the stilbene guests in the γ-CD channels
preferentially stack with parallel orientation (A). (b) Ding, J .; Steiner,
T.; Saenger, W. Acta Crystallogr. Sect. B 1991, 47, 731. (c) Fleming,
S. A.; Ward, S. C. Tetrahedron Lett. 1992, 33, 1013. (d) Inokuma, S.;
Yamamoto, T.; Nishimura, J . Tetrahedron Lett. 1990, 31, 97.

Stereoselective Photodimerization of (E)-Stilbenes
J . Org. Chem., Vol. 64, No. 22, 1999 8103
trans f cis isomerization. This is particularly true for
the cases where the CD cavities are “stuffed” with
approximately two stilbenes per host molecules (see 1a -f
in Table 1). Importantly, stilbenes 2 and 3 do not undergo
photodimerization if irradiated as γ-CD inclusion com-
plexes. In both cases, a host/guest ratio of approximately
1:1 was determined for the inclusion complexes (see Table
1) even when the stilbene guests were applied in more
than 2-fold excess as compared to the CD host. Obviously,
both stilbenes are too bulky to be packed more tightly in
the γ-CD cavities. As a result, the two substrates 2 and
3 lack a stilbene neighbor in close reach to undergo
cycloaddition, and thus no photodimers are found. In-
stead, photoisomerization is the only reaction route
available for these stilbenes, and moderate yields of 23%
and 18% are obtained for stilbenes 2 and 3, respectively.
II. Th e Micr oen vir on m en t of Excited Stilben e in
th e γ-CD Cr ysta l La ttice. A revealing result of this
investigation is the fact that we are unable to achieve
quantitative yields of photodimerization even after pro-
longed irradiation. Instead, the photodimer yields aver-
age around 70%, which is more or less reproducible from
batch to batch (see Table 2). Thus, we conclude that most
but not all stilbene molecules are located at sites within
the γ-CD channels where a neighbor stilbene molecule
is in close reach. In other words, part of the excited
stilbene guests are unable to dimerize and thus decay
by either isomerization or other (radiative or nonradia-
tive) deactivation routes.34 The concept of (at least) two
different environments for the excited stilbene molecules
in the crystal lattice, i.e., with or without a stilbene
neighbor, is confirmed by the fact that, in all time-
resolved experiments, the excited stilbene decays in first
approximation35 with biphasic kinetics. Since the slow
component in the biphasic decays is substantially reduced
or even disappears in the preirradiated samples (see
Table 3), we propose to assign the slow decay to that of
excited stilbenes with a neighbor in close reach. These
excited stilbene molecules dimerize or decay by radiative
or nonradiative deactivation, but they cannot easily
isomerize to the (Z)-stilbene as revealed by the low
isomerization yields.36 On the other hand, the fast decay
is tentatively assigned to excited stilbenes without close
neighbors, which cannot dimerize but readily undergo
trans f cis isomerization with relatively fast rates.
Despite the fact that excited stilbene 3 does not dimerize
in crystalline γ-CD channels, its biphasic decay suggests
two environments in the γ-CD channels, one where it can
isomerize (fast component) and one where isomerization
is inhibited and merely radiative and nonradiative
deactivation of the excited stilbene state is observed.
In summary, the microenvironment of the γ-CD crystal
lattice has the following effects on the predominant
reaction pathway of photoexcited stilbene: (i) There are
(at least) two sites for stilbene guests in the γ-CD
channels, which cause the excited stilbene to decay at
two (independent) rates. (ii) Isolated stilbene molecules
can isomerize with rates of kfast ≈ 109 s-1, which are about
1 order of magnitude slower as compared to those in
solution. (iii) Isomerization is suppressed wherever a
stilbene neighbor is in close reach and dimerization
occurs instead leading to cyclobutane photoproducts in
high yields and with absolute syn stereoselectivity.
Exp er im en ta l Section
I. Ma ter ia ls a n d Meth od s. (E)-Stilbenes (1a , and 1b) and
(Z)-stilbene (2) were used as received from Aldrich. The
stilbenes 1c-f were prepared following literature procedures37
and recrystallized from ethanol. γ-Cyclodextrin was obtained
as a gift from Cerestar Co. and used as received. Dichloro-
methane was purified by standard procedures.38 1H NMR
spectra were recorded in CDCl3 on a General Electric QE-300
spectrometer, and the chemical shifts are reported in ppm
units downfield from internal standard tetramethylsilane.
GC-MS analyses were carried out on a HP 5890 gas chro-
matograph interfaced to a HP 5970 mass spectrometer (EI,
70 eV). Melting points were measured on a Mel-Temp (Labo-
ratory Devices) apparatus and are uncorrected.
II. P r ep a r a tion of th e Stilben e/γ-CD In clu sion Com -
p lexes a n d Det er m in a t ion of t h e H ost /Gu est R a t ios.
Solid-state γ-CD complexes of the stilbenes 1a -f, 2, and 3 were
prepared following the reported procedure.39 In a typical
experiment, 1.5 mmol (0.280 g) of the (E)-stilbene (1a ) dis-
solved in ethanol was added to an aqueous solution of 0.77
mmol (1.00 g) of γ-CD. The solution turned cloudy im-
mediately, and subsequently, a white precipitate formed over
a period of 12-16 h while the suspension was stirred. The
precipitate was filtered, washed with ether followed by cold
water, and dried at 50 °C for 10 h. Part of the microcrystalline
powder was subsequently dissolved in deuterated DMSO, and
the molar ratio (1:1.75) between host (γ-CD) and guest
(stilbene) was determined by 1H NMR spectroscopy. The ratio
of the relative masses of γ-CD and (E)-stilbene were deter-
mined as follows: 0.250 g of the inclusion complex was
subjected to the decomplexation by dissolving it in a saturated
solution of NaCl in water. (E)-Stilbene was extracted from the
aqueous solution with chloroform, the solvent was evaporated
under reduced pressure, and the mass of the (E)-stilbene was
determined after drying for 10 h at 80 °C. The mass of γ-CD
was taken as the difference between the mass of stilbene and
that of the inclusion complex (0.250 g), and a molar ratio of
1:1.6 was calculated that was in good agreement with that
1
obtained from the H NMR spectrum of the inclusion complex.
III. Stea d y-Sta te P h otolysis of th e In clu sion Com -
p lexes a n d Ch a r a cter iza tion of th e P r od u cts. A 700 mg
portion of finely ground solid-state γ-CD inclusion complex of
the (E)-stilbene (1a ) was irradiated in a Rayonnet photochemi-
cal reactor with UV light at λ ) 330 nm. The sample was
occasionally agitated to ensure uniform exposure to light. After
irradiation of the complex for 24 h, the sample was suspended
in 50 mL of distilled water saturated with sodium chloride.
After warming of the solution at 50 °C for 1 h, the organic
contents were extracted into chloroform. The chloroform
extracts were dried over anhydrous sodium sulfate, concen-
trated in vacuo, and purified by column chromatography. The
photodimer was isolated in 48% yield by elution with 10%
chloroform in hexane on silica gel. The 1H NMR and GC/MS
spectral data13 are as follows: mp 164-165 °C (lit.13 mp 165
°C); 1H NMR (CDCl3) δ 4.45 (s, 4H), 7.10-7.20 (m, 12 H), 7.30-
7.50 (m, 8H); GC/MS m/z (relative intensity) 180.25 (100).
X-ray crystallographic examination of a single crystal yielded
cell parameters identical with those previously published.18
Similar irradiation procedures were applied to the inclusion
complexes with the other stilbenes (1b-f), and the photo-
(34) Owing to the channel-type arrangement of γ-CD inclusion
complexes in the crystalline state (see Figure 1), we avoid the
misleading picture of separated 1:1 and 2:1 complexes of stilbene with
cyclodextrin in the crystal lattice and prefer the simple distinction
between stilbene guests with and without a close neighbor.
(35) The possibility of more than two distinct locations for the
stilbene cannot be excluded since the kinetic traces can also be fitted
with more than two exponentials.
(37) Sues, E. J .; Wilson, C. V. J . Org. Chem. 1961, 26, 5243.
(38) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon: Oxford, 1988.
(39) Takahashi, K. Chem. Rev. 1998, 98, 2013 and references
therein.
(36) In fact, (E)-stilbene does not photoisomerize at all as 2:1
complex with γ-CD in aqueous solution.15

8104 J . Org. Chem., Vol. 64, No. 22, 1999
Rao et al.
dimers were purified by column chromatography. The spectral
data of the photodimers are as follows. P h otod im er of 1b:16a
1H NMR (CDCl3) δ 3.65 (m, 12H), 4.30 (s, 4H), 7.20-7.30 (m,
8H), 7.40-7.50 (m, 8H); GC/MS m/z (relative intensity) 240.15
(100). In the case of 1c-e, the syn H-H and syn H-T isomers
were obtained as a mixture, which could not be separated
either by column chromatography or by preparative TLC.
P h otod im er s of 1c:16a 1H NMR (CDCl3) δ 1.85 (s, 6H), 4.30
(s, 4H), 7.10-7.20 (m, 10H), 7.55-7.75 (m, 8H); GC/MS of syn
H-H photodimer m/z (relative intensity) 208 (55), 194 (100),
180 (50); GC/MS of syn H-T photodimer m/z (relative inten-
sity) 194 (100). P h otod im er s of 1d :16a 1H NMR (CDCl3) δ 4.40
(s, 4H), 7.15-7.25 (m, 10H), 7.50-7.70 (m, 8H); GC/MS of syn
H-H photodimer m/z (relative intensity) 249.5 (62), 214.5
(100), 180 (45); GC/MS of syn H-T photodimer m/z (relative
intensity) 214.5 (100). P h otod im er s of 1e:16a 1H NMR (CDCl3)
δ 3.60 (s, 6H), 4.35 (s, 4H), 7.10-7.20 (m, 10H), 7.55-7.75 (m,
8H); GC/MS of syn H-H photodimer m/z (relative intensity)
240 (63), 210 (100), 180 (50); GC/MS of syn H-T photodimer
m/z (relative intensity) 210 (100). P h otod im er s of 1f.14 In
the case of 1f, the H-H and the H-T isomers could be readily
separated by column chromatography using CHCl3/hexanes
(25:75) as eluent on 200 mesh silica gel, and the spectral data
are as follows: Syn H-H p h otod im er of 1f: 1H NMR (CDCl3)
δ 4.45-4.46 and 4.55-4.60 (A2B2, 4H), 7.10-7.20 (m, 14H),
7.45-7.55 (m, 4H); GC/MS m/z (relative intensity) 230 (34)
205 (100), 180 (23). Syn H-T p h otod im er of 1f: 1H NMR
(CDCl3) δ 4.50 (s, 4H), 7.10-7.20 (m, 14H), 7.50-7.55 (m, 4H);
GC/MS m/z (relative intensity) 205 (100).
IV. La ser F la sh P h otolysis. The diffuse-reflectance laser
photolysis setup has been described previously in detail.40
Briefly, the third-harmonic output (355 nm, 25 ps) of a mode-
locked Nd:YAG laser (QUANTEL, YG 501-C) was used as the
excitation source. The fundamental laser pulse (1064 nm) was
focused into a 10-cm cuvette containing a 1:1 mixture of H2O
and D2O to generate a white continuum pulse of 25-ps
duration, which was utilized as the analyzing light pulse. The
continuum light was split into two beams, which were used
as reference light and probe light for the crystalline sample
stored in a 1-mm cuvette. The diffuse-reflected probe light was
collected by fiber optics and detected by an unintensified dual-
diode-array detector (Princeton Instruments) attached to a flat-
field spectrograph (Instrument S.A.). The diffuse-reflectance
transient absorption spectra, which represent the average over
100-300 laser shots, are presented as percentage absorption:
% ABS ) 100 × (1 - R/R0), with R and R0 representing the
diffuse-reflected sample light and the reference light, respec-
tively.
V. X-r a y Diffr a ction Stu d ies. To determine the mode of
stilbene stacking within γ-CD channels, single crystals (suit-
able for X-ray structural analysis) of various stilbene/γ-CD
inclusion complexes were obtained as follows.
Gen er a l P r oced u r e. For example, a solution of (E)-stilbene
(17 mmol) in diethyl ether (10 mL) was mixed with a saturated
aqueous solution of γ-CD (7.7 mmol in 10 mL) and the mixture
deposited a well-formed crop of transparent crystals during
48 h (at 22 °C). These crystals were dissolved in DMSO-d6,
1
and H NMR spectroscopy established the molar ratio of 1:1.80
between host (γ-CD) and guest (stilbene).
The X-ray data collected from several well-faced transparent
single crystals at -150 °C showed poor diffracting ability, and
no high-angle reflections above sin θ/λ >0.3 were obtained.
However, a comparison of several single crystals (with different
stilbenes) indicated that all crystals exhibited tetragonal
symmetry and were isomorphous with γ-CD dodecahydrate
and other related complexes.33b,41 On the basis of the observed
isomorphism, the coordinates of the γ-CD atoms were taken
from an earlier study33b to perform data refinement that
converged at R ∼0.25. This result indicates that the γ-CD host
structure of the stilbene inclusion complex is very similar to
that of γ-CD clatherates.33b,41 However, attempts to localize
the stilbene guests within the more or less ordered γ-CD lattice
failed due to total disorder even with the heavy-atom deriva-
tive 4,4′-dibromo (E)-stilbene. Such a massive disorder, which
is not observed in γ-CD crystals of tetragonal symmetry
containing other guest molecules such as water or alcohol, as
well as the poor diffracting ability of these crystals, indicates
that the stilbene molecules populate the γ-CD channels in a
highly irregular manner.34,35
Ack n ow led gm en t. We thank Cerestar Co. for pro-
viding free samples of γ-cyclodextrin, T. Dhanasekaran
for assistance with the laser experiments, S. V. Linde-
man for the X-ray crystallographic studies, and the
National Science Foundation and Robert A. Welch
Foundation for financial support.
J O9903149
(40) Yoon, K. B.; Hubig, S. M.; Kochi, J . K. J . Phys. Chem. 1994,
98, 3865.
(41) (a) Lindner, K.; Saenger, W. Biochem. Biophys. Res. Commun.
1980, 92, 933. (b) Harata, K. Bull. Chem. Soc. J pn. 1987, 60, 2763.