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A.R. Clements, M. Pattabiraman / Journal of Photochemistry and Photobiology A: Chemistry 297 (2014) 1–7
significant research activity exploring the macromolecular host
mediatedphoto-heterodimerizationsincethen.Consideringthelack
of research activity in this area despite the need for developing new
strategies for photodimerization, and inspired by the report by
Yoshizawa et al., we endeavored to study heterodimerizationwithin
a readily available and environmentally benign macromolecular
isolated through flash column chromatography and characterized
further using COSY (Fig. 2) in which the cross-peaks between the
pseudo triplets further confirmed that the isolated product is in
fact a heterodimer.
Based on the 1H NMR profile, peak integrations, and correlation
between the cyclobutane signals in COSYanalysis, the compound is
ascertained to be the 6-methyl coumarin–cinnamic acid hetero-
dimer. We are not able to identify the stereochemistry of the
heterodimer through spectroscopy alone. However, we will
attempt to deduce it based on the known host–guest chemistry
of cyclodextrin complexes and computational analysis of the
inclusion complexes (vide infra). Irradiation of mechanically
ground mixture of the two alkenes without subjecting it to the
complexation process, used as the control, did not yield the hetero-
dimer in any significant quantity (Fig. 1, top spectrum). The homo-
dimers were the predominant products which presumably
resulted from the topochemical reactivity of the respective alkenes
in solid-state; the neat solids of cinnamic acids and coumarins are
known to yield various photodimers depending on the packing in
solid-state.
host–
Cyclodextrins are a family of macrocyclic cavitands known for
their versatile host–guest chemistry [12]. The ability of -cyclo-
dextrin ( -CD) to encapsulate two alkenes simultaneously to form
g-cyclodextrin.
g
g
1:2 inclusion complexes has been employed to direct stereo-
selective photodimerization in solution phase and in the solid-
state [6b,8b,10a–d]. However, photo-heterodimerization within
g
-CD has not been demonstrated. In addition, g-CD possesses
advantages over the nanocage due to its low cost, ready
availability, and lack of aromatic chromophores. In this communi-
cation, we report the successful selective photo-heterodimeriza-
tion between substituted cinnamic acids and coumarins directed
by g-CD, in which the physicochemical complementarity between
non-identical alkenes has been utilized to direct selectivity.
Intrigued by the strategy employed by Yoshizawa et al., we
reasoned that spatial and electronic complementarity between
alkenes could be realized when alkenes are confined to the limited
The heterodimer was the major product in the reaction (60%)
followed by significantly lesser amount of the 6-methyl coumarin
homodimer. The homodimer of cinnamic acid and cis-cinnamic
acid were minor products. Mass balance for the reaction at around
85% conversion was greater than 93%. This indicated that the
observed selective formation of heterodimer as the major product
is due to the overall reactivity of the alkenes in the bulk of the
sample, and not due to uneven reactivity from multiple alkene
orientations or selective extraction of the heterodimer from the
product mixture.
As both alkenes are photoactive, a total of twelve homo- and
heterodimers are possible in the reaction, in addition to the
isomerization product; it is remarkable to observe that the 1H NMR
spectrum of the reaction mixture is much cleaner signifying the
extent of reaction control achieved through the cavity directed
strategy. In order to better understand the reaction outcome and
deduce the heterodimer structure, we decided to study the
structure of heterodimer included within the cyclodextrin cavity
computationally. Geometry optimized structures of inclusion
complexes of the four possible coumarin–cinnamic acid hetero-
cavity volume of g-CD through inclusion complex formation. This
idea is summarized in Scheme 1 wherein two large guest
molecules are unable to be fit within a cavity. This drives the
complexation toward the 1:1:1 complex. Thus, the hetero-guest
pair complex, which is more favorable, is expected to be present in
higher proportion(s) than the homo-guest pair complexes yielding
predominantly heterodimers upon irradiation (Scheme 1). We
chose to study the cross-dimerization between cinnamic acids [13]
and coumarins [14] as their individual photochemistries are well
documented in literature. Given the practical significance of the
two alkene systems, the cross-photodimerization between them is
expected to be of importance.
2. Results and discussion
We initiated our investigation with the 6-methyl coumarin–
cinnamic acid pair. The choice of alkenes was based on the possible
steric complementarity between 6-methyl coumarin (6-MeCU)
with a bulky methyl group, compared to than the unsubstituted
cinnamic acid (CA) (Scheme 2). Sonication of an equimolar mixture
dimers included within g-CD performed using the semi-empirical
PM3 method built in Gaussian1 09 program [15] are presented in
Fig. 3. Optimizations were performed on initial structures in which
both the aromatic groups were included within the cavity, without
regard to the van der Waals radii. Among the optimized four
inclusion complexes, the syn H–H dimer was the only dimer
complex in which both the hydrophobic aromatic rings were
included well within the cavity, while the hydrophilic carboxy
groups of cinnamic acid and coumarin protruded outward. In all
other cases, despite lack of any bulky substituents in the aromatic
ring, only one of the aromatic rings remained included within the
cavity, while the other was expelled. This is presumably so because
the syn H–H dimer was compact enough to fit both the aromatic
rings within the cavity, while the other three heterodimers consist
of aromatic rings that are spaced much farther away to be
simultaneously included within the cavity. As the inclusion
of 6-methyl coumarin, cinnamic acid, and g-CD in water yielded a
white precipitate which was filtered, washed with water and
organic solvents, dried, and irradiated between glass plates using a
medium pressure mercury vapor lamp.
1H NMR analysis of the photoproduct mixture isolated using
biphasic extraction showed the presence of four distinct pseudo-
triplet signals of equal intensity (Fig. 1, bottom spectrum) in the
typical cyclobutane region (3–5 ppm); the signals were present
alongside the syn H–H homodimers of cinnamic acid and 6-methyl
coumarins which are known to be formed within
g-CD [8b,10c].
The pseudo-triplets corresponded to the multiplicity pattern of
cyclobutane skeleton with non-equivalent protons, as is expected
in a heterodimer. The compound corresponding to the signal was
Scheme 1. Depiction of the strategy employed for directing heterodimerization based on size complementarity.