Templating photodimerization of trans-cinnamic acids with cucurbit[8]uril and γ-cyclodextrin

Article abstract of DOI:10.1021/ol047866k

(Chemical Equation Presented) Cucurbit[8]uril and γ-cyclodextrin are able to align two olefin molecules in a head-head fashion within their large cavities. Excitation of such templated olefins results in syn head-head cyclobutanes in nearly quantitative yields. The methodology revealed here works with trans-cinnamic acids that do not dimerize either in solution or in the solid state and with the ones that yield only anti head-tail dimer in the solid state.

Full text of DOI:10.1021/ol047866k

ORGANIC
LETTERS
2005
Vol. 7, No. 4
529-532
Templating Photodimerization of
trans-Cinnamic Acids with
Cucurbit[8]uril and
γ-Cyclodextrin
Mahesh Pattabiraman, Arunkumar Natarajan, Lakshmi S. Kaanumalle, and
V. Ramamurthy*
Department of Chemistry, Tulane UniVersity, New Orleans, Louisiana 70118
murthy@tulane.edu
Received October 15, 2004 (Revised Manuscript Received December 29, 2004)
ABSTRACT
Cucurbit[8]uril and
γ
-cyclodextrin are able to align two olefin molecules in a head−head fashion within their large cavities. Excitation of such
templated olefins results in syn head
−head cyclobutanes in nearly quantitative yields. The methodology revealed here works with trans-
cinnamic acids that do not dimerize either in solution or in the solid state and with the ones that yield only anti head
state.
−tail dimer in the solid
The reactions of trans-cinnamic acids are examples of [2 +
2] photodimerization that have been investigated extensively
since 1889.1 Some of these acids exhibit a dual behavior on
photolysis dependent on the reaction medium. While in
solution trans-cis isomerization occurs exclusively, on
photolysis of the crystal these acids react to give dimeric
products under conditions where the two reactive CdC bonds
are within the topochemically stipulated distance (<4.2 Å)
and parallel (Scheme 1).2,3 Most of the current efforts in
solid-state photochemistry are devoted to establishing reliable
strategies that would steer molecules so as to obtain a crystal
structure that would favor photodimerization.4 In this paper,
we establish the utility of cucurbit[8]uril (CB[8])5 and
γ-cyclodextrin (γ-CD) in templating photodimerization of a
variety of trans-cinnamic acids to a single isomer (syn head-
head dimer) both in solution and the solid state. Remarkably,
the methodology reported here with CB[8] and γ-CD is
general and works with a number of cinnamic acids that do
not dimerize (γ-packing) and also with the ones that give
anti head-tail dimers (R-packing) in solid state. Since
CB[8] is known to include mostly cationic guest molecules,
until now its scope as a reaction medium has been limited.
Photodimerization of C2-symmetric trans-diaminostilbene
hydrochloride within CB[8] has recently been reported.6 As
far as we are aware, neither neutral olefins nor olefins with
different substituents have been included and aligned within
CB[8]. We show in this report that CB[8] can include neutral
(4) (a) Toda, F. Acc. Chem. Res. 1995, 28, 480. (b) Ito, Y.; Kitada, T.;
Horiguchi, M. Tetrahedron 2003, 59, 7323. (c) Ito, Y.; Borecka, B.; Totter,
J.; Scheffer, J. R. Tetrahedron Lett. 1995, 36, 6083. (d) MacGillivray, L.
R.; Reid, J. L.; Ripmeester, J. A. J. Am. Chem. Soc. 2000, 122, 7817. (e)
Gao, X.; Friscic, T.; MacGillivray, L. R. Angew. Chem., Int. Ed. 2003, 43,
232. (f) Papaefstahiou, G. S.; Zhong, Z.; Geng, L.; MacGillivray, L. R. J.
Am. Chem. Soc. 2004, 126, 9158. (g) Caronna, T.; Liantonio, R.; Logothetis,
T. A.; Metrangolo, P.; Pilati, T.; Resnati, G. J. Am. Chem. Soc. 2004, 126,
4500. (h) Shan, N.; Jones, W. Tetrahedron Lett. 2003, 44, 3687.
(5) (a) Mock, W. L. Top. Curr. Chem. 1995, 175, 1. (b) Day, A.; Arnold,
A. P.; Blanch, R. J.; Sunshall, B. J. Org. Chem. 2001, 66, 8094. (c) Kim,
J.; Jung, I.-S.; Kim, S.-Y.; Lee, E.; Kang, J.-K.; Sakamoto, S.; Yamaguchi,
K.; Kim, K. J. Am. Chem. Soc. 2000, 122, 540.
(1) (a) Liebermann, C. Chem. Ber. 1989, 122, 124. (b) Liebermann, C.
Chem. Ber. 1989, 122, 782.
(2) (a) Cohen, M. D.; Schmidt, G. M. J. J. Chem. Soc. 1964, 1996. (b)
Cohen, M. D.; Schmidt, G. M. J. J. Chem. Soc. 1964, 2000. (c) Schmidt,
G. M. J. J. Chem. Soc. 1964, 2014.
(3) Ramamurthy, V.; Venkatesan, K. Chem. ReV. 1987, 87, 433.
10.1021/ol047866k CCC: $30.25
© 2005 American Chemical Society
Published on Web 01/21/2005

Scheme 1
Table 2. Photochemistry of trans-Cinnamic Acids That Yield
Anti H-T Dimer upon Irradiation in the Solid State
anti H-Tb syn H-Hb cisb
host/guest
guest/hosta
(%)
(%)
(%)
4-Me-t-CA (1d)
crystals
CB[8] solid state
100
66
46
32
80
1:1
1:3
1:5
1:1
2:1
15
26
39
19
28
29
20
CB[7] solid state
γ-CD solid state
t-CA (1e)
100
crystals
100
CB[8] solution
CB[8] solid state
CB[7] solid state
γ-CD solid state
4-HO-t-CA (1f)
crystals
CB[8] solution
CB[8] solid state
γ-CD solid state
4-NH3+ Cl- (1g)
crystals
2:1
1:5
1:1
2:1
54
29
46
52
32
1
19
68
99
100
24
2:1
1:3
2:1
38
48
99
62
28
1
100
68
CB[8] solution
CB[8] solid state
1:2
1:1
88
14
12
18
guest molecules such as cinnamic acids and that the resulting
host-guest complexes are soluble enough in water to conduct
photochemical studies (Tables 1 and 2). We further provide
a Mixing ratios of host and guest; stoichiometry of the complexes are
unknown at this time. b Yields reported are based on NMR integration at
100% conversion; 1H NMR spectra of the irradiated samples are provided
in the Supporting Information.
Table 1. Photochemistry of trans-Cinnamic Acids That Are
Photoinactive in the Solid State
host/guest
guest/hosta
syn H-Hb (%)
cisb (%)
3-MeO-t-CA (1a)c
CB[8] solution
CB[8] solid state
γ-CD solid state
3-Me-t-CA (1b)c
CB[8] solution
CB[8] solid state
γ-CD solid state
4-MeO-t-CA (1c)c
CB[8] solution
CB[8] solid state
γ-CD solid state
2:1
1:1
2:1
72
78
96
28
22
4
2:1
1:1
2:1
83
45
99
17
55
1
2:1
1:1
2:1
72
48
100
28
52
Figure 1. 1H NMR spectrum of 1g: (a) in D2O; (b) in the presence
of 2 equiv of CB[7]; (c) in the presence of 1.5 equiv of CB[8].
a Mixing ratios of the host and the guest; stoichiometry of the complexes
are unknown at this time. b Yields reported are based on NMR integration
at 100% conversion; 1H NMR spectra of the irradiated samples are provided
in the Supporting Information. c Irradiation in the crystalline state leads to
no photoreaction.
within the cavities of cucurbiturils are consistent with the
literature reports on cucurbituril complexes of viologens7 and
trans-diaminostilbene hydrochloride.6 Irradiation of trans-
a simple technique to include even water-insoluble neutral
guests within CB[8] to pursue photochemistry in the solid
state. trans-4-Aminocinnamic acid hydrochloride 1g is a
(6) (a) Lee, J. W.; Samal, S.; Selvapalam, N.; Kim, H.-J.; Kim, K. Acc.
Chem. Res. 2003, 36, 621. (b) Jon, S. Y.; Ko, Y. H.; Park, S. H.; Kim,
H.-J.; Kim, K. Chem. Commun. 2001, 1938. (c) Choi, S.; Park, S. H.;
Zigamshina, A. Y.; Ko, Y. H.; Lee, J. W.; Kim, K. Chem. Commun. 2003,
2176.
(7) (a) Ong, W.; Gomez-Kaifer, M.; Kaifer, A. E. Org. Lett. 2002, 4,
1791. (b) Kim, H.-J.; Heo, J.; Jeon, W. S.; Lee, E.; Kim, J.; Sakamoto, S.;
Yamaguchi, K.; Kim, K. Angew. Chem., Int. Ed. 2001, 40, 1526. (c) Kim,
H.-J.; Jeon, W. S.; Ko, Y. H.; Kim, K. Proc. Natl. Acad. Sci. U.S.A. 2002,
99, 5007.
1
highly water-soluble cationic olefin. A comparison of H
NMR spectra of this compound in D2O, D2O-CB[7], and
D2O-CB[8] presented in Figure 1 suggests the inclusion of
this olefin into the cavities of host CB[7] and CB[8].
Observed upfield shifts of olefinic as well as aromatic protons
of trans-4-aminocinnamic acid hydrochloride upon inclusion
530
Org. Lett., Vol. 7, No. 4, 2005

4-aminocinnamic acid hydrochloride in aqueous solution
yields the corresponding cis isomer, and upon irradiation as
crystals the only product obtained was the anti head-tail
dimer (Table 2). Remarkably, irradiation of trans-4-amino-
cinnamic acid hydrochloride (0.02 M) included in CB[8]
(0.01 M) in aqueous solution gave the syn head-head dimer
along with the corresponding cis isomer of the olefin. It is
thus clear that the larger cavity of CB[8] accommodates two
molecules of trans 4-aminocinnamic acid hydrochloride and
aligns them in a geometry favorable for formation of the
syn head-head dimer. As expected, irradiation of trans-4-
aminocinnamic acid hydrochloride-CB[7] complex, a host
with a smaller cavity (similar to that of â-cyclodextrin),
produced only the corresponding cis isomer.
Computed structures at the AM1 level for complexes of
trans-4-aminocinnamic acid hydrochloride (and dimers) with
CB[7] and CB[8] are provided in Figures 2 and 3.8
Figure 3. Computed structures (at the AM1 level) of complexes
of (top) syn head-head and (bottom) anti head-tail dimers of trans-
4-aminocinnamic acid hydrochloride within CB[8]. Note that while
the syn head-head dimer fits nicely within CB[8], in the case of
the anti head-tail dimer half the molecule projects outside the
cavity.
include only one molecule whereas CB[8] accommodates
two (Figure 2). (b) As per computations, alignment of two
olefins in a head-head fashion is favored within a CB[8]
cavity. (c) When a structure with head-tail arrangement was
minimized, one of the olefins tended to stay at the rim of
CB[8] suggesting that host-guest complexes do not prefer
head-tail arrangement of cinnamic acids. (d) While the syn
head-head dimer easily fits within CB[8], the anti head-
tail dimer does not (Figure 3). Qualitative reasoning based
on AM1 calculations is consistent with the model that
CB[8] can template cinnamic acids to form syn head-head
dimers.
Figure 2. Computed structures at the AM1 level for complexes
of trans-4-aminocinnamic acid hydrochloride with (top) CB[7] and
(bottom) CB[8]. Note that only one molecule fits within CB[7] and
two molecules in a head-head geometry within CB[8].
In Tables 1 and 2 are presented the results of seven
cinnamic acids based on their solid-state reactivity. The first
group of cinnamic acids, 3-methoxy-, 3-methyl-, and 4-meth-
oxycinnamic acids, do not dimerize or isomerize in the solid
state. They only isomerize in solution (Table 1). However,
irradiation of the host-guest complexes of cinnamic acids
(6 × 10-5 M) in CB[8] (3 × 10-5 M) both in solution and
in the solid state resulted in a single dimer (syn head-head)
(>70%). Although minor amounts (30%) of cis isomer were
also formed no other dimers were detected by 1H NMR. The
host-guest complex was obtained by sonication (30 min)
of the water-insoluble CB[8] in an aqueous solution of the
above cinnamic acids. The clear solution obtained indicated
the complexation of the water-soluble neutral guests with
the water insoluble host. Consistent with the model that larger
cavities of CB[8] is critical to inclusion and alignment of
These structures are revealing in terms of what can be
accomplished with CB[7] and CB[8]: (a) CB[7] is able to
(8) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
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D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
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Org. Lett., Vol. 7, No. 4, 2005
531

two molecules, use of CB[7] as the host gave only the cis
isomer. To establish the generality of CB[8] as a templating
agent we explored the use of solid complexes. The complex
was prepared by mechanically grinding of the host CB[8]
(80 mg; 6 × 10-4 mol) and the guest cinnamic acids (10
mg; 1.5 × 10-5 mol) together with an agate pestle and
mortar.9 Irradiation of these solid complexes gave only the
syn head-head dimer with minor amounts (15%) of the cis
olefin. Irradiation of complexes of these cinnamic acids in
CB[7] accomplished by a similar grinding method gave the
cis olefins only. The absence of any product on irradiation
of pure olefin crystals and the syn head-head dimers and
cis olefins obtained as complexes of CB[8] and CB[7] clearly
indicate inclusion of the cinnamic acids within these hosts
through the solid-state grinding technique.
The second group of olefins consists of 4-methyl- and
4-hydroxycinnamic acid derivatives that yield the anti head-
tail dimer in the crystalline state (Table 2). Of these, the
host-guest complex of 4-methylcinnamic acid that is not
soluble in water could only be prepared by the “grinding”
technique. Consistent with the above observations, irradiation
of CB[8] complexes of cinnamic acid and 4-hydroxycinnamic
acid in water and as solid complexes gave the corresponding
syn head-head dimer along with the cis isomer of the olefin
(Table 2). Since the uncomplexed crystals gave anti head-
tail dimer, to avoid complication from photoreactions from
pure crystals that produce anti head-tail dimer use of excess
host that would eliminate any uncomplexed crystalline guest
was attempted. Although the yields of syn head-head dimer
depend on the amount of the host, even the 5-fold excess of
the host failed to eliminate completely formation of the anti
head-tail dimers (Table 2, CB[8] solid-state entries). The
fact that the amount of syn head-head dimer increased with
the host amount we believe that CB[8] is orienting even these
olefins in a head-head fashion. Only crystal structure
determination of the complexes would unequivocally solve
this problem. Irradiation of CB[7] complexes with all seven
cinnamic acids listed in Tables 1 and 2 resulted in the cis
isomer only reinforcing the requirement of a larger cavity
for dimerization.
From the presentation above it is clear that the CB[8]
cavity dimension similar to that of γ-CD has the ability to
include two molecules of cinnamic acids and align them in
such a way to yield only a syn head-head dimer. Now the
question arises whether γ-CD itself can behave like CB[8].
All six neutral cinnamic acids investigated here formed
complexes with γ-CD but these were not soluble in water.
Therefore, irradiation of these as solids gave the syn head-
head dimer in very high yield (>95%). Unlike in the case
of CB[8] geometric isomerization was only a very minor
pathway (<5%; Tables 1 and 2). Cyclodextrin complexes
could not be formed by grinding cinnamic acids with γ-CD
although they are readily prepared by stirring aqueous
solutions of γ-CD with saturated ethyl acetate solution of
the guest. Cavities of CB[8] and γ-CD can preorganize
cinnamic acids toward a single dimer, and this approach
compliments the novel methods reported recently for pre-
organizing C2-symmetric olefins.4 The method reported here
for templating nonsymmetric olefins is superior to the ones
reported previously where only partial success has been
achieved.10
Acknowledgment. V.R. thanks A. Kaifer for useful
discussions and NSF for financial support (CHE-9904187
and CHE-0212042).
Supporting Information Available: Experimental de-
tails, NMR spectral data for photodimers, molecular struc-
tures of the hosts and details of AM1 computation are
provided in the Supporting Information. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL047866K
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