Origins of selectivity for the [2+2] cycloaddition of α,β- unsaturated ketones within a porous self-assembled organic framework

Article abstract of DOI:10.1021/ja076001+

This article studies the origins of selectivity for the [2+2] cycloadditions of α,β-unsaturated ketones within a porous crystalline host. The host, formed by the self-assembly of a bis-urea macrocycle, contains accessible channels of ～6 A diameter and forms stable inclusion complexes with a variety of cyclic and acyclic α,β-unsaturated ketone derivatives. Host 1 crystals provide a robust confined reaction environment for the highly selective [2+2] cycloaddition of 3-methyl-2-cyclopentenone, 2-cyclohexenone, and 2-methyl-2-cyclopentenone, forming their respective exo head-to-tail dimers in high conversion. The products are readily extracted from the self-assembled host and the crystalline host can be efficiently recovered and reused. Molecular modeling studies indicate that the origin of the observed selectivity is due to the excellent match between the size and shape of these guests to dimensions of the host channel and to the preorganization of neighboring enones into favorable reaction geometries. Small substrates, such as acrylic acid and methylvinylketone, were bound by the host and were protected from photoreactions. Larger substrates, such as 4,4-dimethyl-2-cyclohexenone and mesityl oxide, do not undergo selective [2+2] cycloaddition reactions. In an effort to understand these differences in reactivity, we examined these host-guest complexes by thermogravimetric analysis (TGA), NMR, powder X-ray diffraction (PXRD) and molecular modeling.

Full text of DOI:10.1021/ja076001+

Published on Web 12/21/2007
Origins of Selectivity for the [2+2] Cycloaddition of
r,â-unsaturated Ketones within a Porous Self-assembled
Organic Framework
Jun Yang,† Mahender B. Dewal,† Salvatore Profeta, Jr.,† Mark D. Smith,†
Youyong Li,‡ and Linda S. Shimizu*,†
Department of Chemistry and Biochemistry, UniVersity of South Carolina, Columbia,
South Carolina 29208, Materials and Process Simulation Center,
California Institute of Technology, California 91125
Received August 9, 2007; E-mail: shimizul@mail.chem.sc.edu
Abstract: This article studies the origins of selectivity for the [2+2] cycloadditions of R,â-unsaturated ketones
within a porous crystalline host. The host, formed by the self-assembly of a bis-urea macrocycle, contains
accessible channels of ∼6 Å diameter and forms stable inclusion complexes with a variety of cyclic and
acyclic R,â-unsaturated ketone derivatives. Host 1 crystals provide a robust confined reaction environment
for the highly selective [2+2] cycloaddition of 3-methyl-2-cyclopentenone, 2-cyclohexenone, and 2-methyl-
2-cyclopentenone, forming their respective exo head-to-tail dimers in high conversion. The products are
readily extracted from the self-assembled host and the crystalline host can be efficiently recovered and
reused. Molecular modeling studies indicate that the origin of the observed selectivity is due to the excellent
match between the size and shape of these guests to dimensions of the host channel and to the
preorganization of neighboring enones into favorable reaction geometries. Small substrates, such as acrylic
acid and methylvinylketone, were bound by the host and were protected from photoreactions. Larger
substrates, such as 4,4-dimethyl-2-cyclohexenone and mesityl oxide, do not undergo selective [2+2]
cycloaddition reactions. In an effort to understand these differences in reactivity, we examined these host-
guest complexes by thermogravimetric analysis (TGA), NMR, powder X-ray diffraction (PXRD) and molecular
modeling.
reaction environments.4 Often, the reactions inside these de-
signed environments proceed at enhanced rates and exhibit
Introduction
unusual selectivity,1a which is generally attributed to entropic
effects.5 Molecular hosts, though often challenging to synthesize,
allow exquisite control of the cavity dimensions and properties
that may translate into control of the reaction geometry and
selectivity. Conversely, porous materials, such as zeolites,6
mesoporous silica,7 and coordination polymers8 are readily
There is great interest in developing synthetic hosts that
possess the extraordinary efficiency and specificity of enzymes.1
A number of groups have designed and synthesized hollow host
molecules2,3 to facilitate the reaction of encapsulated guests.
Others have explored the use of porous materials as confined
† University of South Carolina.
‡ California Institute of Technology.
(4) (a) Turro, N. J. Photochem. Photobiol. A 1996, 100, 53-56. (b) Rama-
murthy, V.; Eaton, D. F.; Caspar, J. V. Acc. Chem. Res. 1992, 25, 299-
307. (c) Hashimoto, S. J. Photochem. Photobiol., C. 2003 4, 19-49. (d)
Garcia, H.; Roth, H. D. Chem. ReV. 2002, 102, 3947-4007. (e) Tung, C.
H.; Wu, L. Z.; Zhang, L. P.; Chen, B. Acc. Chem. Res. 2003, 36, 39-40.
(f) Kaupp G. Top. Curr. Chem. 2005, 254, 95-183. (g) MacGillivray, L.
R.; Papaefstathious, G. S.; Friscic, T.; Varshney, D. B.; Hamilton, T. D.
Top. Curr. Chem. 2004, 248, 201-221. (h) Tanaka, K.; Mochizuki, E.;
Yasui, N.; Kai, Y.; Miyahara, I.; Hirotsu, K.; Toda, F. Tetrahedron 2000,
56, 6853-6865. (i) Yoshizawa, M.; Takeyama, Y.; Okano, T.; Fujita, M.
J. Am. Chem. Soc. 2003, 125, 3243-3247. (j) Madhavan, D.; Pitchumani,
K. Photochem. Photobiol. Sci. 2002, 1, 991-995. (k) Usami, H.; Takagi,
K.; Sawaki, Y. Chem. Lett. 1992, 1405-1408.
(1) (a) Vriezema, D. M.; Aragones, M. C.; Elemans, J. A. A. W.; Cornelissen,
J. J. L. M.; Rowan, A. E.; Nolte, R. J. M. Chem. ReV. 2005, 105, 1445-
1489. (b) Kirby, A. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 707-24.
(2) (a) Natarajan, A.; Kaanumalle, L. S.; Jockusch, S.; Gibb, C. L. D.; Gibb,
B. C.; Turro, N. J.; Ramamurthy, V. J. Am. Chem. Soc. 2007, 129, 4132-
4133. (b) Rebek, J. J. Angew. Chem., Int. Ed. 2005, 44, 2068-2078. (c)
Kang, J.; Rebek, J., Jr. Nature 1997, 385, 50-52. (d) Takahashi, K. Chem.
ReV. 1998, 98, 2013-2033. (e) Yoshizawa, M.; Fujita, M. Pure Appl. Chem.
2005, 77, 1107-1112. (f) Breslow, R.; Dong, S. D. Chem. ReV. 1998, 98,
1997-2011. (g) Marty, M.; Clyde-Watson, Z.; Twyman, L. J.; Nakash,
M.; Sanders, J. K. M. Chem. Comm. 1998, 2265-2266. (h) Nakash, M.;
Sanders, J. K. M. J. Org. Chem. 2000, 65, 7266-7271. (i) Leung, D. H.;
Fielder, D.; Bergman, R. G.; Raymond, K. N. Ang. Chem. Int. Ed. 2004,
43, 963-966. (j) Kang, Y.; Zyryanov, G. V.; Rudkevich, D. M. Chem.
Eur. J. 2005, 11, 1924-1932. (k) Warmuth, R.; Makowiec, S. J. Am. Chem.
Soc. 2005, 127, 1084-1085.
(5) Cacciapaglia, R.; Di Stefano, S.; Mandolini, L. Acc. Chem. Res. 2004, 37,
113-122.
(6) (a) Tao, Y. S.; Kanoh, H.; Abrams, L.; Kaneko, K. Chem. ReV. 2006, 106,
896-910. (b) Cundy, C. S.; Cox, P. A. Microporous Mesoporous Mater.
2005, 82, 1-78.
(3) (a) Yoshizawa, M.; Fujita, M. Pure Appl. Chem. 2005, 77, 1107-1112.
(b) Nishioka, Y.; Yamaguchi, T.; Yoshizawa, M. Fujita, M. J. Am. Chem.
Soc. 2007, 129, 7000-7001. (c) Karthikeyan, S.; Ramamurthy, V. J. Org.
Chem. 2007, 72, 452-458. (d) Wu, C.-D.; Lin, W. Angew. Chem., Int. Ed.
2007, 46, 1075-1078. (e) Dybstev, D. N.; Nuzhdin, A. L.; Chun, H.;
Bryliakov, K. P.; Talsi, E. P.; Fedin, V. P.; Kim, K. Angew. Chem., Int.
Ed. 2007, 45, 916-920.
(7) Vinu, A.; Hossain, K. Z.; Ariga, K. J. Nanosci. Nanotech. 2005, 5, 347-
371.
(8) (a) Suslick, K. S.; Bhyrappa, P.; Chou, J. H.; Kosal, M. E.; Nakagaki, S.;
Smithenry, D. W.; Wilson, S. R. Acc. Chem. Res. 2005, 38, 283-291. (b)
Ockwig, N. W.; Delgado-Friedrichs, O.; O’Keefe, M.; Yaghi, O. M. Acc.
Chem. Res. 2005, 28, 176-182.
9
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J. AM. CHEM. SOC. 2008, 130, 612-621
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Porous Organic Crystals
A R T I C L E S
Figure 1. Schematic representation of the self-assembly of macrocycle 1 into crystalline host 1, containing columnar channels. The porous crystals can
reversibly absorb a variety of guests including 2-cyclohexenone. UV-irradiation of included guests yields a photodimer in high conversion and selectivity.
The guests can be readily extracted from the crystals, and the crystals can be reused.
synthesized, but it is often more difficult to control and tailor
their cavity dimensions and properties. We have taken a hybrid
approach of using a rigid molecular host that self-assembles
into a porous material. This hybrid approach allows for readily
synthesizing large quantities of porous materials with well-
defined channels of predetermined dimensions for use as
confined reaction environments.
of products, and product distributions are very sensitive to the
surrounding reaction environment.13 The major products are the
exo and endo head-to-tail (HT) and head-to-head (HH) products.
These products are formed when two alkenes are brought
together in a suprafacial orientation within 4.2 Å of each other.14
Other minor products are also observed including ring opened
dimers. In general, [2+2] cycloadditions of enones within a
zeolite or on a surface can result in selectivity for either HT or
the HH, depending on the individual enone structure. For
example, the [2+2] cycloaddition of 2-cyclohexenone within a
zeolite yields high selectivities for the HH product due to
coordination to the carbonyl oxygen and to steric factors.4j,15
Crystalline host 1 is unusual in two respects. First, it facilitates
the [2+2] cycloadditions reaction with high conversion and high
selectivity. Second, it yields selectively the exo HT dimer, in
contrast to most previous host systems that favored the exo HH
product.4,15
To investigate the origins of selectivity and also the utility
of host 1 as a confined reaction environment, we examined a
range of R,â-unsaturated ketones in terms of size and shape.
First, we examined the ability of the synthetic host framework
to selectively absorb and release the reactants. These binding
experiments were carried out by following the absorption and
desorption, using TGA and NMR. Second, we examined the
shape and symmetry of the host environment using powder
X-ray diffraction and computer modeling. Third, we examined
the product distribution and yields of the cycloaddition products.
High selectivity and conversion was observed for the medium
sized enones because they were complementary to the reaction
We have developed macrocyclic bis-urea 1 that stacks into
columns, forming crystalline host 1 with guest accessible
channels (Figure 1).9 Crystalline host 1 can selectively bind
guests10 and facilitates the [2+2] cycloaddition of included
2-cyclohexenone to selectively yield the head-to-tail photodimer
in high conversion.11 Not only does host 1 induce a highly
selective reaction, but it also allows the product to be easily
isolated by extraction and facilitates efficient recovery of the
crystalline host for reuse. We are interested in understanding
the unique features of our system that lead to such high
selectivity and conversion. Specifically, we will use a range of
different R,â-unsaturated ketones to probe the origins of the
exclusive formation of the exo head-to-tail [2+2] product in
high conversion. In addition, molecular modeling will be used
to try to understand the reasons behind the observed products
and to see if one can develop a predictable model for this system.
The [2+2] cycloaddition reaction was chosen because it is
an excellent probe of the shape, symmetry, and homogeneity
of our self-assembled reaction environment. The [2+2] cy-
cloaddition reaction has proven to be a key transformation in
the synthesis of a number of natural products and pharmaceu-
ticals.12 Therefore, the ability to better control the selectivity
and efficiency of this reaction would enhance its synthetic utility.
The [2+2] cycloaddition reactions are known to give a range
(12) (a) Mascitti, V.; Corey, E. J. J. Am. Chem. Soc. 2006, 128, 3118-3119.
(b) Iriondo-Alberdi, J.; Greaney, M. F. Eur. J. Org. Chem. 2007, 4801-
4815. (c) Pirrung, M. C. J. Am. Chem. Soc. 1981, 103, 82-87. (d) Simmons,
P. G. Quarterly ReV. 1970, 1, 37-68.
(9) (a) Shimizu, L. S.; Hughes, A. D.; Smith, M. D.; Davis, M. J.; Zhang, B.
P.; Zur Loye, H. C.; Shimizu, K. D. J. Am. Chem. Soc. 2003, 125, 14972-
14973. (b) Shimizu, L. S.; Hughes, A. D.; Smith, M. D.; Samuel, S. A.;
Ciurtin-Smith, D. Supramol. Chem. 2005, 17, 27-30.
(13) (a) Lam, E. Y. Y.; Donald, V.; Hammond, G. S. J. Am. Chem. Soc. 1967,
89, 3482-3487. (b) Wagner, P. J.; David, J. B. J. Am. Chem. Soc. 1969,
91, 5090-5097.
(10) Dewal, M. B.; Lufaso, M. W.; Hughes, A. D.; Samuel, S. A.; Pellechia,
P.; Shimizu, L. S. Chem. Mater. 2006, 18, 4855-4864.
(14) Schmidt, G. M. J. Pure Appl. Chem. 1971, 27, 647-678.
(15) (a) Lem, G.; Nikolas, K. A.; Schuster, D. I.; Ghatlia, N. D.; Turro, N. J. J.
Am. Chem. Soc. 1993, 115, 7009-7010. (b) Fox, M. A.; Cardona, R.;
Ranade, A. C. J. Org. Chem. 1985, 50, 5016-5018.
(11) Yang, J.; Dewal, M. B.; Shimizu, L. S. J. Am. Chem. Soc. 2006, 128, 8122-
8123.
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A R T I C L E S
Yang et al.
Scheme 1. Photodimerization of 2-Cyclohexenone in the Presence
of Host 1
Preparation of Macrocycle 1. Macrocycle 1 was prepared
as previously described and was self-assembled from super-
heated glacial acetic acid (AcOH), forming the 1:1 inclusion
crystals host 1‚AcOH. The AcOH guests were removed by
heating at 120 °C for 2 h to yield empty host 1. The crystalline
structure is directed exclusively by the host. Thus, like zeolites,
the fidelity of the assembled structure is not changed dramati-
cally by the presence of different guests. Guests can be bound
and removed without destroying the self-assembled porous
framework. We have demonstrated this with a range of different
small molecule guests.10
environment. Larger substrates that could not fit into the
channels showed no selectivity. Smaller guests were bound into
the cavity but were unreactive, presumably because they were
bound in an orientation in which the adjacent enones were >4.2
Å apart or were not in the preferred suprafacial geometry.
Together, these studies gave us a clear picture of the nature of
the channels within host 1 and the factors that are involved in
organizing guests within these channels.
Scope of the [2+2] Cycloaddition Reaction in the Presence
of Host 1. Each of the 10 different guests (Table 1) was tested
for their ability to diffuse into the host framework. Crystals of
empty host 1 were sealed in a container in which the headspace
was saturated with guest vapor. Guest absorption was followed
1
Results and Discussion
by H NMR and TGA for 12 h to 14 days, until the system
reached an equilibrium, which generally took between 1 and 7
days. Empty host 1 displayed rapid uptake of the small acyclic
derivatives 2 and 3 upon vapor treatment and appeared to reach
a binding equilibrium (host 1: enone) within 24 h. Interestingly,
the absorption of both the small and medium cyclic enones (4-
7) were kinetically slow, requiring 5-7 days to reach equilib-
rium. The largest enones that could be absorbed by crystalline
host 1 by vapor treatment were 8 and 9 that have molecular
volumes of 107 Å3 and 114 Å3, respectively. None of the other
large substrates were absorbed even upon prolonged vapor
treatment (2 weeks). The uptake of guest by host 1 to form
host 1‚guest was monitored by two independent methods: (1)
dissolution of a sample in d6-DMSO and integration of the
monomer peaks for host and guest in the 1H NMR spectra; and
(2) heating and measuring the change in weight by TGA upon
loss of the included guest.
For the reasons above, we were interested in testing if self-
assembled host 1 could provide a highly selective confined
environment in which to carry out [2+2] cycloaddition
reactions. The first example that we examined was the [2+2]
cycloaddition of 2-cyclohexenone (Scheme 1). The 2-cyclo-
hexenone was bound into the host structure by exposing the
empty host 1 to 2-cyclohexenone vapor, resulting in the
formation of a 2:3 host:guest complex.11 The reaction was
carried out in the solid-state by UV-irradiation of the guest
filled crystals. The reaction proceeded with excellent selectivity,
giving almost exclusively the exo HT product with no starting
material left after 24 h. This was impressive for two reasons.
First, all of the 2-cyclohexenone could be converted selectively
into a single product. Second, all of the product could be
removed from the framework via extraction, and the porous
crystals recovered and reused without loss of selectivity.
Goals and Organization of This Study. On the basis of the
above results, we were interested in whether host 1 could be
used to carry out [2+2] cycloaddition reactions with small,
medium, and large R,â-unsaturated ketones. We were also
interested in trying to understand the unique features of our
system that facilitated exclusive formation of the exo HT
product. In these studies, ten different enones of different size,
shape, and symmetry were examined. These enone substrates
can be divided into three groups with respect to their molecular
volume relative to 2-cyclohexenone. The first substrates are the
guests smaller than 2-cyclohexenone 5 (acrylic acid 2, methyl-
vinylketone 3 (MVK), and 2-cyclopentenone 4) have calculated
molecular volumes ranging from 66 to 80 Å3.16 The second
group contains enones that are similar in size (∼96 Å3) to 5
(3-methyl-2-cyclopentenone 6, 2-methyl-2-cyclopentenone 7).
Finally, the last set of five substrates are larger than 2-cyclo-
hexenone (mesityl oxide 8, 2,3-dimethyl-2-cyclopentenone 9,
3-methyl-2-cyclohexenone 10, 4,4-dimethyl-2-cyclohexenone 11
and 3,5-dimethyl-2-cyclohexenone 12). Each set of enones was
tested for their ability to be absorbed by the host framework.
Next, the conversion of these enones into their photodimer
products was examined. The selectivity of their [2+2] cycload-
dition reactions within host 1 was studied. Finally, the structure
of the bound substrates within host 1 was examined by powder
X-ray diffraction and molecular modeling.
Once loading was complete, the inclusion crystals were
removed and immediately subjected to UV-irradiation using a
450 W Hannovia high-pressure mercury vapor lamp at ∼30 °C
1
for 24 h. The reaction was monitored at 2, 12, and 24 h by H
NMR. The reaction products were removed from the porous
framework by washing the crystals with solvent (CH2Cl2 or
CDCl3). Note that solvent does not dissolve the framework, and
the empty host could be efficiently recovered and reused. The
conversion observed for each enone and binding ratio (host:
guest) is reported in Table 1.
Conversion and Selectivity Patterns. Table 1 shows clear
trends in terms of the size of the enone with respect to their
reactivity within the highly confined environment of host 1.
None of the smaller substrates 2-4 reacted in the presence of
host 1, despite the fact that each of these neat substrates
undergoes rapid [2+2] cycloaddition reactions. For example,
both acrylic acid 217 and MVK 318 form polymeric materials in
>90% conversion after 12 h of UV-irradiation. These control
reactions were carried out by UV-irradiation of the liquid
enone. Each of these small guests was bound by host 1 in ratios
ranging from 5:2 to 1:2 host:guest. Yet within the complex,
they could be subjected to UV-irradiation for up to 48 h without
any reaction. After irradiation, the starting materials (2-4) could
(17) (a) Eastmond, G. C.; Haigh, E.; Taylor, B. Trans. Faraday Soc. 1969, 65,
2497-2502. (b) Muthukrishnan, S.; Pan, E. H.; Stenzel, M. H.; Barner-
Kowollik, C.; Davis, T. P.; Lewis, D.; Barner, L. Macromolecules 2007,
40, 2978-2980.
(16) The molecular volumes were calculated using Macromodel 5.5: Columbia
University: New York, 1996.
(18) White T.; Haward, R. N. J. Chem. Soc. 1943, 25-31.
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A R T I C L E S
Table 1. Host:Guest Ratios of the Unsaturated Ketones Inclusion Complexes with Crystalline Host 1 and the Control Reactions after 24 h
of UV-Irradiation
a Control reactions were monitored at 12 h. b Control substrates reacted to give polymers.
be isolated from the host 1 crystals by extraction, and the crystals
reused. These results indicate that host 1 safely stores and
protects these reactive enones from UV-irradiation. The
medium-sized substrates 5-7 selectively form the HT [2+2]
dimerization products in good yield. Of the large substrates,
host 1 only absorbed guests 8 and 9. The host 1‚8 complex did
not react upon prolonged UV-irradiation. The host 1‚9 complex
reacted upon UV-irradiation, with 55% of the starting enone
converted to a complex mixture of products within 24 h.
Next, we examined the distribution of the photodimeric
products of the [2+2] cycloaddition in the presence and absence
of host 1. Table 2 shows the product distribution for enones
that selectively formed the exo HT dimer and compared with
the control reactions carried out without host 1. Examination
of the reactions in Table 2 reveals the unusually high conversion
(100%) and selectivity (96%) for the exo HT dimer initially
observed for 5 was also observed for the other medium-sized
substrates 6 and 7. These enones have nearly identical molecular
volumes (97 Å3) as calculated by Macromodel16 to that of the
original substrate 5 (96 Å3); however, they have different
Table 2. Selectivity of the [2+2] Cycloaddition after 24 h of
UV-Irradiation
dimensions as estimated by molecular length and width.
Substrate 6 (4.2 Å × 4.7 Å) closely matches the dimensions of
the original 2-cyclohexenone (4.2 Å × 4.7 Å) and showed
similarly high selectivity (98%) and conversion (80%) for the
exo HT dimer. Substrate 7 (4.3 Å × 4.8 Å) showed high
9
J. AM. CHEM. SOC. VOL. 130, NO. 2, 2008 615

A R T I C L E S
Yang et al.
1
Figure 2. Photolysis product of enone 6 with host 1. (a) H NMR of the product in CDCl3; (b) GC-MS of reaction mixture at 24 h. (c) ORTEP X-ray
crystal structure of the product.
Scheme 2. Photodimerization of 2 in the Presence and Absence of Host 1
a Structures of minor products suggested in literature.
conversion (95%) with slightly lower selectivity (80%) for the
exo HT dimer.
to 6b is 27:52, in good agreement with literature reports.20 In
summary, the [2+2] photodimerization of 6 proceeded at higher
conversion in the presence of host 1 and favors the exo HT
product (98%).
Next, we studied whether the manner by which the enone
was loaded into the crystalline host altered the reactivity or
selectivity. Enone 6 can also be loaded into the host 1 by soaking
the crystals in neat enone.21 Irradiation of the soaked complex
gave a slightly better conversion of enone (87% at 24 h) as
compared with the vapor loaded material and correspondingly
high selectivity (98%) for 6a was also observed. The soaking
method proved to be a more efficient strategy for guest loading,
and we plan to further investigate this loading method for other
enones.
The data in Table 2 was measured as exemplified by the
procedure for enone 6 shown below. Crystalline host 1‚6
complex was UV irradiated for 24 h and the product was
extracted and characterized without further purification. 1H
NMR of the crude extract revealed the high selectivity of the
reaction, and the spectrum agrees well with the reported data
of exo HT product 6a,19 displaying only one singlet peak at δ
1.16 ppm, corresponding to a single methyl group and Ha signal
at 2.34 ppm (Figure 2a). Slow evaporation of CH2Cl2 from the
extract yielded crystals suitable for the first reported X-ray
crystallographic structure of this isomer and confirmed the
structure of 6a as the exo HT dimer (Figure 2c). A more careful
analysis by GC-MS (Table 2) established that the cycloaddition
of host 1‚6 is highly selective for 6a (98%) and shows 80%
conversion after 24 h of UV-irradiation (Figure 2c). Only 2%
of the HH isomer was observed and less than 1% of one other
product. The structures of the other isomers 6c-f (Scheme 2)
were previously proposed by Schaffner.19b GC-MS suggests
that the trace product is 6c (<1%), as it is less polar and elutes
slightly ahead of 6a, consistent with the assignment of the
products in the 2-cyclohexenone series. In comparison, the
control reaction of 6 is both kinetically slow, displaying only
31% conversion after 24 h, and is unselective. The control
reaction yields a mixture of 6 products each of which displays
the expected MW of the dimer 192 g/mol. The ratio of the 6a
Although similar in molecular volume, enone 7 (4.3 × 4.8
Å) is shorter and wider than 5 and 6. This difference in shape
affects the uptake of 7, yielding a lower 5:2 host‚guest
stoichiometry. A rapid [2+2] cycloaddition was observed upon
UV-irradiation of the complex and again favored the exo HT
isomer (Scheme 3), similar to what is observed in photodimer-
1
ization of solid-state SnCl4 complexes of 7.19d After 24 h, H
NMR analysis showed that only trace amounts of the starting
enone 7 remained in the host in addition to the two photolysis
products. These were assigned based on the chemical shift of
the methyl groups at 1.16 and 0.98 ppm (Figure 3a). Analysis
by GC-MS revealed that 7 reacted to yield the photodimers in
95% conversion, forming 7a with 80% yield and the HH isomer
(20) Anklam, E.; Konig. W. A.; Margaretha, P. Tetrahedron Lett. 1983, 24,
5851-5854.
(21) Host 1 crystals were soaked for 2 h in the liquid enone. The host 1‚6
complex was then recovered by filtration and air-dried for 5 min. This
method of loading produced the same 2:3 host:guest ratio as measured by
TGA.
(19) (a) Mark, G.; Matthaeus, H.; Mark, F.; Leitich, J.; Henneberg, D.;
Schomburg, G.; Von Wilucki, I.; Polansky, O. E. Monatsh. Chem. 1971,
102, 37-50. (b) Reinfried, R.; Bellus, D.; Schaffner, K. HelV. Chim. Acta
1971, 54, 1517-1531. (c) Yvon, K. Acta Cryst. 1974, 30, 1638-1640. (d)
Rao, V. P.; Fech, J. J. Photochem. Photobiol. A: Chem. 1992, 67, 51-56.
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A R T I C L E S
Scheme 3. Photodimerization of 7 in the Presence and Absence
of Host 1
instead from the reaction of disordered enone on the surface of
the crystals. This is consistent with the similar distributions of
the products for 10, 11, and 12 in the presence and absence of
host 1 (Table 3).
It is apparent that the size and shape of the guest dramatically
affect the absorption of the guest into the host, as well as the
efficiency and selectivity of the [2+2] cycloaddition. To
understand the origins of these effects, we studied the structure
and stoichiometry of the host:guest inclusion complexes, using
TGA, PXRD and molecular modeling. For promotion of
selective [2+2] cycloaddition, it is likely that the guest enones
must (1) be absorbed in significant quantity into the channels
of host 1, forming well-ordered materials; and (2) be oriented
in a favorable geometry with the double bonds positioned <4.2
Å to allow photodimerization.
7b with 20% yield (Figure 3b). Confirmation of the isomeric
assignments was provided by crystallographic analysis. Single
crystals of the major product formed from slow evaporation of
the CH2Cl2 extract. The crystal structure confirmed the structure
of 7a as the exo-HT dimer (Figure 3c). For comparison, the
[2+2] photodimerization reaction of the neat enones was carried
out in the absence of host 1. The control reaction of 7 proceeded
markedly slower with only 26.8% conversion by 24 h affording
the opposite selectivity. The HH dimer 7b was the major product
(72%) and 7a (28%) was the minor product. No additional
cycloaddition or ring-open products were observed for either
the host 1‚7 complex or the control reactions.
With the larger substrates, only mesityl oxide 8 (107 Å3) and
2,3-dimethyl-2-cyclopentenone 9 (114 Å3) could be loaded into
host 1 by vapor treatment and only host 1‚9 underwent reaction
upon UV-irradiation. After 24 h of UV-irradiation, 55% of
the starting enone was converted into a complex mixture of 8
isomers, each of which displayed the expected molecular weight
of the photodimer (220 g/mol). This conversion was distinctly
higher than the control reaction, which showed only 3.3%
conversion at 24 h.22 Mesityl oxide 8 formed a 5:1 complex
with host 1. This complex was stable to prolonged UV-
irradiation (48 h). This stability is not surprising given the low
reactivity of neat mesityl oxide. The control reaction of neat
mesityl oxide displayed <10% conversion after 24 h of UV-
irradiation.22
All of the small- and medium-size substrates (2-7) formed
stable host 1‚guest complexes with reproducible host: guest
ratios at room temperature. Investigation of these complexes
by TGA showed that the complexes displayed different tem-
perature stabilities. The literature provides abundant examples
of the use of TGA to characterize inclusion complexes.24 The
temperature range at which guest desorption occurs indicates
the stability of the complex.25 The temperature at which half
the guest is lost (t1/2) provides a measure of complex stability.
The desorption of the enones from the inclusion complexes,
host 1‚enone was followed by TGA (Figure 4), and the measured
weight loss corresponds to the amount of guest bound, allowing
calculation of the host:guest binding ratio (Table 1). The
complexes with acyclic guests (host 1‚acrylic acid (2) and host
1‚MVK (3)) displayed a gradual one-step desorption curve from
∼40 °C to 110 °C (Figure 4a). For these acyclic guests, t1/2
ranged from 72 to 81 °C. In comparison, the host:guest
complexes of the cyclic enones were markedly more stable,
displaying no desorption of guest below 65 °C. For example,
the host 1‚2-cyclopentenone inclusion complex displayed
a sharp, one-step weight loss (26.4%) between 80 °C and
100 °C, with t1/2 ) 93.1 °C. The increase in stability of the
cyclic enones complexes over the acyclic enone complexes does
not appear to correlate with their boiling points but is instead
loosely correlated with their molecular dipole moments (Sup-
porting Information). The sharp desorption curves observed for
the cyclic enones complexes may indicate that the individual
guest molecules are bound more homogeneously within host 1.
The amount of guest that is absorbed into host 1 varies
dramatically over the 10 substrates tested and is associated with
size, shape, and polarity of the guest. For example, acrylic acid
and MVK have similar sizes (∼70 Å3 volume) and shapes (∼5.0
Å × 3.0 Å, Table 1). However, the more polar acrylic acid 2
was bound with a higher 3:2 host:guest stoichiometry than with
the less polar MVK, which was bound in a 5:2 host:guest
stoichiometry. Not only is size and polarity important but shape
also appears to be important for efficient guest loading. For
example, the absorption of the larger by volume (80 Å3)
2-cyclopentenone 4 (4.0 Å × 4.2 Å) displayed much higher
The three large substrates (10-12) with molecular volumes
estimated16 between 114 and 130 Å3 were not absorbed by host
1 even upon prolonged vapor treatment (>2 weeks), showing
that both molecular shape and size (volume) influence binding.
To test if these substrates could be absorbed under more forceful
conditions, host 1 was soaked in the liquid enones at room
temperature for 2 h. After filtration and air-drying, the resulted
1
materials were characterized by H NMR. Unlike the smaller
substrates, which all formed host:guest complexes with repro-
ducible host:guest ratios, these soaked materials did not exhibit
steady host:guest ratios and the measured ratios appeared to be
dependent on drying time and crystal size. Regardless of the
initial host:guest ratio, UV-irradiation of these crystals resulted
in photodimerization reactions that were unselective (Table 3).
The product distributions were similar to the corresponding
control reactions run in the absence of host 1.23 Therefore, we
assume that these large substrates are not loaded within the
channels of host 1 and the unselective reactions observed result
(24) (a) Nassimbeni, L. R.; Su, H. J. Phys. Org. Chem. 2000, 13, 368-371. (b)
Phyongtamrun, S.; Tashiro, K.; Miyata, M.; Chirachanchaik, S. J. Phys.
Chem. B 2006, 110, 21365-21370. (c) Dey, S.; Pal, K.; Sarkar, S.
Tetrahedron Lett. 2007, 48, 5481-5485.
(25) Nassimbeni, L. R. In Crystallography of Supramolecular Compounds;
Tsoucaris, G., Atwood, J. L., Lipkowski, J., Eds.; NATO ASI Series C:
Mathematical and Pysical Sciences, Vol 480, Kluwer Academic Publish-
ers: Dordrecht, 1995, p 285-305.
(22) Yang, N.-C.; Thap, D. M. J. Org. Chem. 1967, 32, 2462-2465.
(23) (a) Ziffer, H.; Fales, H. M.; Milne, G. W. A.; Field, F. H.; J. Am. Chem.
Soc. 1970, 92, 1597-1600. (b) Schuster, D. I.; Greenberg, M. M.; Nunez,
I. M.; Tucker, P. C. J. Org. Chem. 1983, 48 2615-2619.
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A R T I C L E S
Yang et al.
1
Figure 3. Photolysis product of enone 7 with host 1. (a) H NMR of the product; (b) GC-MS of reaction mixture at 24 h. (c) X-ray crystal structure of
the exo head-to-tail product 7a.
Table 3. UV-Irradiation of Host 1 Crystals Soaked in Liquid
Enones
host 1‚MVK complex is unreactive also suggests that the bound
MVK does not have much mobility within the solid complex
because the neat MVK rapidly polymerizes on UV-irradia-
tion.18
Most of the host 1‚guest complexes were well-ordered
crystalline materials with distinct PXRD patterns. Unfortunately,
it is currently difficult to predict the molecular structure from
the PXRD pattern for such complex organic structures. To gain
further insight into the structure of the inclusion complexes,
we investigated the heptameric assemblies of three of the
inclusion complexes: host 1‚4, host 1‚5, and host 1‚6 using
the molecular modeling program Spartan.27 The first complex
host 1‚4 is unreactive, whereas the second two complexes
undergo selective [2+2]-cycloadditions upon UV-irradiation.
These three guests (4-6) are bound in high host to guest ratios
that should facilitate reaction. In addition, each of these three-
host guest complexes show well-defined PXRD patterns,
indicating that these guests are bound in well-ordered conforma-
tions. These two features increase the probability that our
molecular models will provide insightful analysis of the structure
of these complexes. It is our hypothesis that the selectivity of
the reaction is due to the confined environment of the channels.
Assuming that there are only minor structural differences
between the filled host 1‚AcOH and the empty host 1, we can
approximate the structure of empty host 1 (Figure 6), using the
atomic coordinates from the single-crystal structure of host 1‚
AcOH with the guest AcOH omitted.9 The channel is not straight
and alternates back and forth due to alternating edge to face
aryl stacking interactions between the macrocycle layers. The
channel contains wider openings above and below the plane of
the macrocycle alternating with the narrow aperture within the
plane of the macrocycle. The distance between the van der
Waals surfaces of the carbonyl group (C16A) and phenyl
hydrogen (H8) is 4.8 Å and 3.8 Å between phenyl hydrogens
(H7 to H23). This model is consistent with the experimental
evidence that the empty host 1 does not collapse and displays
permanent porosity, showing a type 1 gas adsorption isotherm
with CO2 at 0 °C, with an average pore size of <6.5 Å
diameter.10
guest loading of 1:2. Given the relatively high loading of 2 and
4, it is quite surprising that neither of these guests undergo
cycloadditions reaction upon UV-irradiation. In comparison
host 1‚5, in which the guest 5 contains an additional methylene
group compared to 4, displayed a lower loading of 2:3 host:
guest and yielded an efficient [2+2] cycloaddition reaction.
To investigate if the inclusion complexes are well-ordered
materials, the complexes were ground to a powder and examined
by powder X-ray diffraction (PXRD). Figure 5 compares the
PXRD patterns of empty host 1 with four host 1‚guest
complexes. Inclusion complexes formed from the cyclic enones,
2-cyclohexenone (a), 3-methyl-2-cyclopentenone (b), and 2-cy-
clopentenone (c) are all highly crystalline, displaying well-
defined PXRD patterns that are distinct from each other and
from the empty host 1. This suggests that these guests are well-
ordered within the framework of host 1.26 When the guests are
removed from bulk powder by heating, the empty powder
displays a PXRD pattern with peak positions and intensities
matching the original empty host 1 (e). In this series, only the
host 1‚MVK complex exhibited a PXRD pattern (Figure 5d)
similar to the empty host 1. The PXRD pattern could reflect
the lower loading of this guest (1:MVK 5:2) in the complex, or
more likely means that the guest is disordered. The low loading
of this small guest is probably the reason that no reaction is
observed even after 48 h of UV-irradiation. The fact that the
A model of the framework of host 1 containing a single
column with seven macrocycles was generated, using the atomic
coordinates from host 1‚AcOH. Dynamic simulations on the
empty single column of 7 macrocycles in vacuo using Spartan27
indicated that the major freedom of motion is the tilting of the
plane of the aromatics by up to 30°. This type of motion is
(26) (a) Hasegawa, S.; Horike, S.; Matsuda, R.; Furukawa, S.; Mochizuki, K.;
Kinoshita, Y.; Kitagawa, S. J. Am. Chem. Soc. 2007, 129, 2607-2614. (b)
Dalrymple, S. A.; Shimizu, K. H. G. Chem. Comm. 2006, 956-959. (c)
Tanaka, T.; Tasaki, T.; Aoyama, Y. J. Am. Chem. Soc. 2002, 124, 12453-
12462.
(27) Spartan 04 for Macintosh, v. 1.1.1, 2007, Wavefunction, Inc. Irvine, CA.
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A R T I C L E S
Figure 4. TGA desorption curves for the host 1‚enone complexes with (a) small substrates; (b) medium substrates.
is relatively small compared to the large guest, limiting the
number of possible conformations. Enone 5 fits snugly into the
cavity, showing a number of close contacts (3-4 Å) between
guest and framework atoms. For example, the average distance
between the enone oxygen and the urea carbonyl carbons in
the heptameric model is 3.7 Å. The alignment of neighboring
enone molecules effectively preorganizes the alkenes for a
selective [2+2] cycloaddition. Molecular orbital surface calcula-
tions using Spartan suggest that the HOMO of one enone and
the LUMO of the neighboring enone were aligned in a
suprafacial manner with the carbons of the alkene approaching
within 3.4 Å, which is well within the optimal distance for the
[2+2] photoaddition.14
The inclusion complex host 1‚6 structure (Figure 7b) was
constructed via an identical procedure until no further guests
could be incorporated into the framework. This yielded a 1:1
host:guest complex, which is a slightly lower loading than the
experimentally observed 2:3 host:guest ratio. These molecular
mechanics simulations using MMFF suggest that enone 6 is
also organized in an alternating antiparallel geometry that favors
the formation of the HT dimer, with the enone oxygen pointing
generally toward the urea network. In the heptameric model of
host 1‚6, the enone carbonyl was skewed toward the pocket
created by the neighboring aromatic moieties that lie parallel
to the column axis. These aryl groups define the pore of the
macrocycle and both the ketone from one molecule of 6 and
the methyl from the neighboring molecule of 6 fit within this
opening. Molecular orbital surface calculations using Spartan
predict that the HOMO and the LUMO of the neighboring
enones were aligned in a suprafacial manner. Two of the reacting
carbons are positioned more closely (∼3.5 Å), with the
remaining two slightly further apart at 4.2 Å. All were within
the required distance for the [2+2] addition to yield the exo
HT product.14 The large guest 6 fills up much of the small cavity
and again many close contacts between the guest and host are
observed, including close packing of the enone oxygen of the
guests within 3-4 Å of the urea nitrogens and carbonyl carbon
of the host. These structures indicate that electrostatic and van
der Waals interactions play a large role in orienting the guest
within the cavity.
Figure 5. PXRD patterns of (a) host 1‚2-cyclohexenone (5), (b) host 1‚
3-methyl-2-cyclopentenone (6), (c) host 1‚2-cyclopentenone (4), (d) host
1‚methylvinylketone (3), and (e) the empty host 1.
likely to be tempered within the crystalline solid. For a first
approximation of the filled structure of host 1‚2-cyclohexenone
(5), the structure of the host was “frozen” so that no movement
was allowed in the macrocycle framework. A single guest 5
was added, and the guest was allowed to move to an energy
minimum orientation inside the static host structure. Next, a
second guest was added, and again with the frozen host, the
guests were allowed to move to an energy minimum orientation.
The process was repeated until incorporation of further guests
caused a guest to be ejected from the ends of the heptamer
during minimization. The maximum loading of guests in these
short heptamers was 1:1 host:guest, which is a slightly lower
loading than the 2:3 host:guest ratio observed experimentally
for host 1‚5. This might be due to edge effects, which are a
result of the small size of the modeled structure. For viewing
clarity, the three macrocycles in the center of the modeled
structure and two encapsulated 2-cyclohexenone guests are
shown in Figure 7a. Monte Carlo searching of the conformer
distributions at ground state with Molecular Mechanics (MMFF)
suggests that the lowest energy structures have the 2-cyclohex-
enone guests loaded in an alternating antiparallel geometry with
the carbonyl of the enone pointing toward the ureas. The channel
An identical procedure was used to construct a model of host
1‚2-cyclopentenone (4) complex (Figure 7c). This enone was
protected from photoreaction in the presence of host 1. Again,
the simulation did not permit the small host oligomer to be
loaded past a 1:1 host:guest ratio; although for this guest, a
higher loading (1:2) was observed, experimentally. These
molecular mechanics simulations using MMFF suggest that 4
is organized in an alternating antiparallel geometry; however,
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A R T I C L E S
Yang et al.
Figure 6. Representation of the guest-accessible channels using the single-crystal structure of 1, with guest AcOH omitted (left). A view of the narrow
aperture within the plane of a single macrocycle (right). The distance between the van der Waals surfaces of the carbonyl group (C16A) and phenyl hydrogen
(H8) is 4.8 Å and 3.8 Å between phenyl hydrogens (H7 to H23).
reactions. We are attempting to grow large single crystals of
these complexes to elucidate their structures by X-ray diffraction
and to compare with the molecular modeling studies.
In summary, host 1 crystals formed by self-assembly of a
simple macrocycle provide a robust confined reaction environ-
ment for the highly selective [2+2] cycloaddition of 3-methyl-
2-cyclopentenone, 2-cyclohexenone, and 2-methyl-2-cyclopen-
tenone, forming their respective exo HT dimers in high
conversion. The products are readily extracted from the self-
assembled host, and the crystalline host readily recovered and
reused. Molecular modeling indicates that origin of this observed
selectivity is likely due to the excellent match between the size
and shape of these guests to the dimensions of the host channel.
The substrates that undergo selective reaction appear to be
effectively preorganized within the host channel adopting
alternating orientation of neighboring enones, which gives rise
to the formation of the observed HT dimer. Substrates of smaller
size and molecular volume are also bound within host 1;
however, the host protects these smaller enones from prolonged
UV-irradiation. Further examination of one of these smaller
complexes, host 1‚2-cyclopentenone by PXRD and molecular
modeling indicates that this complex is highly ordered with the
host effectively constraining the reactive alkenes in a conforma-
tion where the [2+2] cycloaddition is no longer favored. Large
substrates either do not form reproducible host:guest complexes
or show no difference in selectivity in the presence or absence
of host 1. Presumably, the size and shape of these enones
precludes their absorption within the confined channel of host
1. We are currently examining the use of host 1 as a confined
reaction environment for other [2+2] cycloadditions and uni-
molecular rearrangements and will report on these in due course.
Figure 7. Models of the inclusion complexes constructed using Spartan.
The hydrogens of the host were omitted for clarity: (a) host 1‚2-
cyclohexenone (5), (b) host 1‚3-methyl-2-cyclopentenone (6), (c) host 1‚
2-cyclopentenone (4). The HOMO and LUMO of two neighboring enone
molecules and the distances between double bonds were calculated using
Spartan with MMFF.
the plane of the alkenes no longer approaches each other in the
preferred suprafacial orientation. In this case, the two olefins
are tilted, nearly 58° in a geometry that is no longer favorable
for the [2+2] photocycloaddition reaction. Molecular orbital
surface calculations using Spartan show that the HOMO and
the LUMO of the neighboring enone were not properly aligned
for the reaction.
Taken together, these modeling studies predict that the enones
are bound with well-defined geometries within the narrow, zig-
zag shaped channels of host 1. Small changes in the orientation
of the enones within the confined environment of the channel
greatly influence the outcome of the [2+2] cycloaddition. For
example, 4 did not react after 24 h of UV-irradiation; whereas
both 5 and 6 displayed selective conversion to their respective
HT dimers in high yield. These simple models using a static
host scaffold suggest that in the future it may be possible to
predict not only which reactants will bind in the channels of
the host but also which complexes might show selective
Experimental Section
General Information. All chemicals were obtained from Sigma-
Aldrich Chemical Company and used without further purification. The
enone guests were purchased as reagent grade.
Preparation of Host 1. Macrocycle 1 was synthesized and crystal-
lized as previously described.9 Ground or unground crystals of 1‚AcOH
were evacuated by heating at 120 °C to form the empty host 1, which
was cooled in a desiccator to room temperature. The loading of enone
guests was carried out in the dark in vessels covered with aluminum
foil.
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Porous Organic Crystals
A R T I C L E S
Loading of Guests into Host 1. Crystals of host 1 (116 mg) were
added to a 20-mL scintillation vial and exposed to guest vapor (10 g)
in a sealed vessel for between 12 h and 2 weeks. Small amounts (1-2
mg) of the solid material were taken to check the 1H NMR every 24 h
until the system reached an equilibrium. Loading of the guest vapor
was time-dependent and appeared to reach a maximum at 5-7 days
for the cyclic enones. Loading of acyclic substrates was more rapid,
reaching a maximum in 24 h. The host:guest binding ratio was
borosilicate immersion well, and the entire apparatus was placed
in a UV shielded and refrigerated reaction chamber. The starting
temperature was 0 °C, and the final temperature did not increase above
30 °C after 24 h of irradiation. A 20 mL scintillation vial containing
50 mg host-guest complex or a 4 mL glass vial containing 100 mg
neat enone liquid were placed in proximity to the lamp (3∼5 cm) and
irradiated for 24 h. After the irradiation, small samples of host-guest
complex and the control were studied by 1H NMR. The control reactions
were dissolved directly in CDCl3 and the solutions were also analyzed
GC-MS. For the complex, crystals were either dissolved in d6-DMSO
or shaken with 1 mL CDCl3 for 1 h. The empty host 1 was recovered
by filtration and washed with CDCl3 (2 × 0.5 mL). The recovered
host 1 was dissolved in d6-DMSO for 1H NMR analysis. There was no
detectable enone and dimer product in the washed host. The CDCl3
filtrate was analyzed by 1H NMR and GC-MS. Single crystals of the
dimerization products were obtained upon slow evaporation from this
solution and used for X-ray crystal structure analysis.
1
determined by both TGA and H NMR.
NMR Studies. Samples of host 1 were transferred directly into an
NMR tube and dissolved in 1 mL of d6-DMSO solvent. The NMR
tube was sonicated until all the material was dissolved. The NMR
spectra were recorded using a 300-MHz Mercury Varian NMR
spectrometer. The macrocycle:guest ratios were determined by the 1H
NMR integration. Delay times were optimized for integration.
PXRD Studies. X-ray powder diffraction data were collected either
on a Rigaku DMAX-2100 or Rigaku DMAX-2200 powder X-ray
diffractometer using Cu KR1 radiation with graphite monochromator.
Data were collected at an increment of 0.05° and an exposure time of
5 s/step in the angular range 2-20° 2θ at ambient temperature. The
GC-MS spectra were obtained with Micromass VG70S magnetic sector
mass spectrometer, Column: Restek RTX-5, 30 m × 0.25 mm, 0.25-
µm film thickness.
TGA Studies. Guest desorption studies were carried out on 5-10
mg of empty host 1 after equilibration with each guest in the vapor
chamber. Thermogravimetric analyses (TGA) were performed using a
TA Instruments Q600 simultaneous DTA-TGA. All samples were
analyzed, using the same method with a heating rate of 4 °C/min from
25 to 140 °C under helium. Upon completion, each sample was
recollected for the next absorption/desorption cycle.
Acknowledgment. This work was supported by the NSF
(CHE-071817), by the Petroleum Research Fund (44682), and
by a grant from the University of South Carolina, Office of
Research and Health Sciences Research Funding Program.
Supporting Information Available: Experimental details, GC/
MS data, and full characterization of the major cycloaddition
products including crystallographic information files. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Photoreaction. Photocycloaddition of enones were carried out, using
a Hanovia medium-pressure 450-W mercury arc lamp cooled in a
JA076001+
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