Recyclable nitrate-templated photochemical [2+2] cycloaddition reaction promoted by a tripodal receptor

Article abstract of DOI:10.1039/c3cc41268g

A nitrate-templated stereoselective photochemical [2+2] solid-state synthesis that is promoted by a supramolecular encapsulation/release of the anion template is reported. The complete reaction process with the same nitrate template can be recycled in a repetitive manner. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc41268g

Showcasing work from the laboratory of
Prof. Shih-Sheng Sun at Academia Sinica, Taippei,
Taiwan, Republic of China.
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Recyclable nitrate-templated photochemical [2+2] cycloaddition
reaction promoted by a tripodal receptor
A nitrate-templated stereoselective photochemical [2+2]
solid-state synthesis that is promoted by a supramolecular
encapsulation/release of the anion template is reported.
The complete reaction process with the same nitrate
template can be recycled in a repetitive manner.
See Shih-Sheng Sun,
Chem. Commun., 2013, 49, 10070.
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Recyclable nitrate-templated photochemical [2+2]
cycloaddition reaction promoted by a tripodal
receptor†
Cite this: Chem. Commun., 2013,
49, 10070
Received 18th February 2013,
Accepted 17th May 2013
Ashutosh S. Singh and Shih-Sheng Sun*
DOI: 10.1039/c3cc41268g
www.rsc.org/chemcomm
A nitrate-templated stereoselective photochemical [2+2] solid-state cycloaddition reactions in the solid state provide an easy way to
synthesis that is promoted by a supramolecular encapsulation/release isolate the target compound simply by washing the crude product
of the anion template is reported. The complete reaction process with with a base. However, cyclobutane derivatives containing pyridyl
the same nitrate template can be recycled in a repetitive manner.
groups are sensitive towards base or heating and known to undergo
isomerization in solution.13,15 Moreover, environmental issues
The dynamic modes of action of enzymes using hydrophobic must be taken into account in preparing fine chemicals in bulk.
pockets to catalyze/promote bond formation/cleavage1 have Therefore, it is highly desirable to develop a prototype reaction
inspired scientists to design various constrained environments scheme where environmentally hazardous anions can be utilized in
such as hydrogen-bonded cocrystals,2 liquid crystals,3 coordination a minimal amount and recycled.
polymers,4 zeolites,5 and discrete hosts (capsules or cages)6 etc. to
Previously, we have shown the selective recognition, encapsula-
facilitate chemical transformations with high effective molarity. tion and sensing of weakly coordinating perchlorate and nitrate
Inspired by natural systems, ditopic organic receptors have also anions by highly flexible neutral receptors.16 The binding of nitrate
been reported for catalyzing stereoselective C–C bond formation in can be reversibly controlled by changing the polarity of the solvent
2a,7
¨
the solid state by the groups of MacGillivray and Warnmark.
medium through dynamic self-assembly via the formation of a
It is known that many of the bond formation/cleavage processes hydrogen bonded dimeric capsule.17 Allosteric modulation of a
in biological systems are catalyzed or promoted by anions8 where the catalytic centre by reversible uptake of anions or small molecules
active sites are reported to be hydrophobic and the effective has been recently reported by Mirkin’s group to control the length of
dielectric constants within the active centers resemble those of a desired polymer.18 Motivated by these results we take one step
organic solvents rather than that of water.9 The low dielectric further to utilize the liberated nitrate anion from a nitrate complex
constants of the enzyme active centers stabilize ion–ion and ion– for anion-templated [2+2] photochemical cycloaddition reactions.
dipole interactions that further facilitate chemical transformations A proof-of-concept process to reversibly uptake substrates for the
to occur inside the hydrophobic pockets of enzymes.10 However, due photochemical dimerization and release the product by solvent
to the large variations in hydration energy, size and shape, basicity polarity modulation is designed. Herein, we report a nitrate anion-
and pH dependence of anions, anion recognition and designing promoted photochemical [2+2] cycloaddition reaction of trans-1,2-
anion promoted or catalyzed C–C bond formation platforms in bis(4-pyridyl)ethylene (4,40-bpe) at room temperature assisted by a
artificial systems is a difficult and very challenging task.11
tripodal receptor that leads to the formation of a single stereoisomer
The role of cationꢀ ꢀ ꢀp interactions explored by the Yamada rctt-tetrakis(4-pyridyl)cyclobutane (4,40-tpcb) in 100% yield (Fig. 1).
group12 and the use of anions as templates for C–C bond
A suitable crystal for single-crystal X-ray diffraction of
formation through photochemical [2+2] cycloaddition reactions 4,40-bpeꢀ2HNO3 was obtained as a thick needle by slow evaporation
as studied by the Teramae and Vittal groups13 have fulfilled the of a solution of 4,40-bpe in methanol and 20% nitric acid at
required criteria for [2+2] cycloaddition reactions.14 The utilization room temperature for 6–8 h. In the crystal packing diagram of
of cationꢀꢀꢀp interactions or anion template methods to perform 4,40-bpeꢀ2HNO3, both pyridyl moieties and the double bond lie
at an equidistance of 3.665 Å, which is suitable for photochemical
Institute of Chemistry, Academia Sinica, 115 Nankang, Taipei, Taiwan,
Republic of China. E-mail: sssun@chem.sinica.edu.tw; Fax: +011-2-27831237;
Tel: +011-886-2-27898596
cycloaddition reaction with its neighboring molecules.14,19 The
transparent single crystal of 4,40-bpeꢀ2HNO3 became opaque after
irradiation with UV-light at 365 nm and not suitable for single-
crystal X-ray diffraction. A single crystal of the photo-product
4,40-tpcbꢀ4HNO3 was obtained after slow evaporation of its aqueous
methanolic solution at room temperature for 4–5 days.
† Electronic supplementary information (ESI) available: Experimental procedure,
characterization data and titration spectra and crystallographic details. CCDC
902210–902212. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c3cc41268g
c
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Fig. 1 A schematic representation of tripodal receptor assisted nitrate anion
promoted photochemical transformation.
To illustrate the nitrate anion promoted chemical transforma-
tion, two parallel and independent experiments were performed
and the reversibility of the complete reaction cycle was demon-
strated with 1H NMR titration experiments. In one experiment, the
nitrate adduct of trans-1,2-bis(4-pyridyl)ethylene, 4,40-bpeꢀ2HNO3
was isolated as a crystalline solid from a methanolic solution of
4,40-bpe with addition of 20% nitric acid in methanol at room
temperature. In another experiment, 4,40-bpeꢀ2HNO3 was prepared
by addition of 4,40-bpe to a stirred solution of nitrate complex 1b in
wet CHCl3 at room temperature. The precipitate was collected, and
Fig. 2 Partial 1H NMR titration spectra (400 MHz, DMSO-d6, 25 1C) of nitrate
complex 1b (6.25 mM) in the presence of 4,40-bpe (3.12 mM) with varying
amounts of CDCl3. The spectrum in red was recorded after partial evaporation of
CDCl3 from the solution. Asterisks and circles marked in green and red represent
peaks for DMSO-d6 used as solvent and internal reference (TMS in DMSO-d6),
respectively. The arrow in blue represents the shifting of the CDCl3 peak.
peak for proton ‘‘a’’ of 4,40-bpe shifted gradually upfield. The
downfield shift of the peak for proton ‘‘h’’ of nitrate complex 1b
with an increasing amount of CDCl3 was previously assigned to
the formation of a self-assembled capsule with subsequent
release of the nitrate anion in its protonated form (see
Table 1 and Scheme S3, ESI†).17 Here, hydrogen bonded self-
assembled capsule formation occurs with simultaneous proto-
nation of 4,40-bpe. The upfield shift of the peak for proton ‘‘a’’
of 4,40-bpe was observed because of the decrease of the polarity in
solution.21 After partial evaporation of CDCl3 from the mixture, the
resulting spectrum (shown in red in Fig. 2) almost merged with that
of the parent spectrum. This observation suggests that the seaming
of hydrogen bonded capsule 10ꢀ10 was ruptured in a polar solvent
1
was identified by H NMR to be self-assembled capsule 10ꢀ10. The
filtrate was evaporated to obtain the nitrate adduct, 4,40-bpeꢀ2HNO3.
The nitrate adducts in solid form from both experiments were
1
separately irradiated with UV-light at 365 nm. H NMR spectra of
the crude products from both photochemical reactions showed the
formation of a single isomer and 100% conversion of 4,40-bpeꢀ2HNO3
to 4,40-tpcbꢀ4HNO3 within 2.5–3 h (Fig. S17 and S27, ESI†).
Subsequently, to an aqueous methanolic or ethanolic
solution containing receptor 10 or capsule 10ꢀ10 was added
4,40-tpcbꢀ4HNO3 and the mixture was stirred for 5–10 min at room
temperature. The yellowish white precipitate was collected and
confirmed to be complex 1b. The filtrate was evaporated to dryness
and was confirmed to be the anion free photocyclized product
4,40-tpcb (Fig. 1 and 2). The process was successfully repeated ten
times. The same adduct, 4,40-bpeꢀ2HNO3, was also obtained from
complex 1b if aqueous acetone or wet CH2Cl2 instead of wet CHCl3
was used as the solvent (see Table 1). Moreover, the employment of
acetone or CH2Cl2 provides the advantages of easy evaporation of
the solvent and facile precipitation of the self-assembled capsule
10ꢀ10 when compared to CHCl3.
Table 1 Chemical shifts of the a-proton of 4,40-bpe upon titration of DMSO-d6
solutions (0.4 mL) of 4,40-bpeꢀ2HNO3,a and a mixture of complexb 1b and
4,40-bpe with varying amounts of CDCl3 and acetone-d6, respectively
CDCl3 (mL)
da
db
Acetone-d6 (mL)
dc
dd
0
8.87
8.75
8.67
8.61
8.51
8.45
8.41
8.68
8.57
8.48
8.42
8.35
8.30
8.27
0
8.83
8.90
9.01
9.04
9.08
9.10
9.10
8.71
8.77
8.82
8.86
8.91
8.94
8.96
0.1
0.2
0.3
0.5
0.7
0.9
0.1
0.2
0.3
0.5
0.7
0.9
The mechanistic pathway and reversibility of the reaction
cycle shown in Fig. 1 have been confirmed through 1H NMR
titration experiments. A DMSO-d6 solution containing both
nitrate complex 1b and 4,40-bpe in a molar ratio of 2 to 1 was
titrated with CDCl3 (Fig. 2).20 In the presence of 4,40-bpe, the
peak for proton ‘‘h’’ of nitrate complex 1b shifted gradually
downfield with an increasing amount of CDCl3 whereas the
a
b
Titration of a DMSO-d6 solution of 4,40-bpeꢀ2HNO3 (3.12 mM). Titra-
tion of a DMSO-d6 solution of nitrate complex 1b (6.25 mM) and 4,40-bpe
(3.12 mM) with CDCl3. Conditions are similar to a with the titrations of
DMSO-d6 solutions carried out with acetone-d6. Conditions are similar
c
d
to b with the titrations of DMSO-d6 solutions carried out with acetone-d6.
c
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like DMSO-d6 after evaporation of CDCl3 from solution with this research. A.S.S. thanks the National Science Council of
subsequent protonation of the centrally bridged N-atom of Taiwan (Grant no 101-2811-M-001-131) for sponsorship of
receptor 10 and re-encapsulation of the nitrate anion to form a postdoctoral fellowship. Mass spectrometry analyses were
the discrete nitrate complex 1b again. The protonation of the performed by the Mass Spectrometry facility of the Institute
centrally bridged N-atom of receptor 10 (Fig. 2) after partial of Chemistry, Academia Sinica.
evaporation of CDCl3 was confirmed by merging peaks of
aliphatic protons close to the bridged N-atom (for protons
‘‘a’’ and ‘‘b’’) with those of the parent spectrum.
Table 1 summarizes the chemical shifts for the pyridyl
a-protons of 4,40-bpe upon titration of DMSO-d6 solutions of
Notes and references
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¨
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template. The present work is reminiscent of biological pro-
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proximity by polarity modulated proton-transfer between two
N-atoms of different basicity.9,10,22 The photochemical product
can be easily isolated from the nitrate template by precipitating
it as complex with a tripodal receptor from aqueous MeOH–
EtOH and the nitrate anion in its protonated form (template)
can be recycled in a repetitive manner. Such supramolecular
reaction cycle shown in Fig. 1 can be considered as a green
process as the key reaction is conducted in solid state and the
recyclability of the nitrate anion during the reaction process
renders the production of bulk fine chemicals with minimal
environmental impact.23 Work is in progress to apply a similar
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20 DMSO-d6 has been used for titration experiments due to the
excellent solubility of all components in the reaction scheme (see
Table S1, ESI†). CDCl3 was flashed over neutral alumina prior to use
for titration experiments.
21 A controlled experiment by titration of 4,40-bpeꢀ2HNO3 in DMSO-d6
with CDCl3 showed similar upfield shifts of the pyridyl signals; see
also Table 1 for the chemical shifts.
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We are grateful to the National Council of Taiwan (Grant no
(b) B. C. Kross, G. R. Hallberg, D. R. Bruner, K. Cherryholmes and
100-2113-M-001-024-MY3) and Academia Sinica for support of
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c
10072 Chem. Commun., 2013, 49, 10070--10072
This journal is The Royal Society of Chemistry 2013