Transition-metal-promoted chemoselective photoreactions at the cucurbituril rim

Article abstract of DOI:10.1002/anie.201005317

When included in a supramolecular barrel with transition-metal ions as lids, bicyclic azoalkanes undergo phase-selective photolysis to afford new photoproducts and photoproduct distributions. In the presence of the macrocycle cucurbit[7]uril and Ag⁺ ions, 2,3-diazabicyclo[2.2.1]hept-2-ene forms a ternary host-guest inclusion complex in which the cations are coordinated to the carbonyl rims of the host. Direct photolysis of this ternary complex provides cyclopentene as a new photoproduct.

Full text of DOI:10.1002/anie.201005317

DOI: 10.1002/anie.201005317
Nanoreactors
Transition-Metal-Promoted Chemoselective Photoreactions at the
Cucurbituril Rim**
Apurba L. Koner, Cesar Mꢀrquez, Michael H. Dickman, and Werner M. Nau*
Supramolecular systems which provide a confined nanospace
for the formation of discrete inclusion complexes with
reactive guests near active sites are presently of great
interest.[1] Supramolecular capsules[2] and coordination
cages[3] as well as macrocycles of the cyclodextrin[1] and
calixarene[4] types have been intensively investigated for their
functionalization with transition metals and the resulting
potential to promote the chemoselective and/or catalytic
reactions of substrates. Cucurbit[n]urils (CBn) are synthetic
macrocycles with an ever-expanding range of applications.[5]
They have already been investigated with respect to their
catalytic properties, starting from the early work of Mock on
[3+2] cycloadditions catalyzed by CB6[6] and, subsequently,
several other examples of photocycloadditions using CB7 and
CB8.[7] The hitherto reported catalytic applications have
mostly relied, like the elegant examples described for cyclo-
dextrins, particularly the larger g-cyclodextrin,[7d,e] capsules,[8]
and coordination cages,[9] on the ability of sufficiently large
hosts to accommodate two reactants within their inner
hydrophobic cavity and thereby facilitate stoichiometric
reactions. But cucurbiturils are multifunctional in the sense
that they possess not only a hydrophobic cavity, but also two
carbonyl rims with a known affinity for metals ions.[10] While
such metal ions have previously been regarded as “lids on the
barrel”, which could either compete with guest binding[11] or
further shield the guest,[12] we thought they could be
potentially regarded as self-assembling active sites, possibly
allowing catalysis in water. In fact, such ternary guest/
cucurbituril/metal-ion complexes have been implicated in
solution,[11–13] and they are documented in the solid state,[12a,14]
suggesting that the required proximity between a substrate as
a guest and the desired metal ion would be readily ensured.
We now report a chemoselective transformation of
included guests promoted by transition-metal ions coordi-
nated to the cucurbituril rim. Building on our conceptual
work with p-sulfonatocalix[4]arenes as macrocycles,[15] we
have realized a two-phase system (Figure 1), in which the host
acts formally as an inverse phase-transfer catalyst to bind a
Figure 1. Dynamic self-assembly of a ternary guest/host/metal-ion
complex and the transition-metal-promoted photoreaction.
photoreactive substrate by hydrophobic interactions in the
aqueous phase and allows the subsequent docking of metal
ions to the carbonyl rim through ion–dipole interactions. The
resulting ternary self-assembly is synergistically reinforced by
weak metal–ligand bonding interactions, which affect the
chemoselectivity in the spatially resolved laser photolysis of
the aqueous phase. The reaction is designed to afford a
photoproduct with reduced affinity to the macrocycle, which
accumulates in the organic phase, where the reaction mixture
is analyzed.
Specifically, we have investigated the influence of metal–
ligand bonding on the photodeazetation of the bicyclic
azoalkanes 2,3-diazabicylo[2.2.2]oct-2-ene (DBO) and 2,3-
diazabicylo[2.2.1]hept-2-ene (DBH) in the presence of CB7
(Figure 2). Addition of CB7 to aqueous solutions of DBO and
DBH causes characteristic bathochromic and hypochromic
shift in their UV spectra[16] as well as characteristic upfield
shifts in their 1H NMR spectra (see Figures S1–S3 and
Tables S1–S2 in the Supporting Information), which are
[*] Dr. A. L. Koner, Dr. C. Mꢀrquez, Dr. M. H. Dickman,
Prof. Dr. W. M. Nau
School of Engineering and Science
Jacobs University Bremen
Campus Ring 1, 28759 Bremen (Germany)
Fax: (+49)421-200-3229
E-mail: w.nau@jacobs-university.de
Homepage: http://www.jacobs-university.de/ses/wnau
[**] This work was supported by the DFG (NA-686/5-1), AGAUR (2009
PIV 00107, Visiting Professorship at ICIQ, Tarragona, Spain), and
the Fonds der Chemischen Industrie. We thank V. D. Uzunova for
the ITC measurements and R. Dsouza and A. Hennig for help with
graphics and photography.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201005317.
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545

Communications
the metal ion are formed, the fluorescence of DBO is
quenched, which provides another means of directly follow-
ing the docking process (see Figure S5b in the Supporting
Information).
It is important to note that metal–ligand bonds between
azoalkanes and transition metals are generally very
weak.[15a,17] The addition of the respective metal ions in low
millimolar concentrations does therefore not cause any UV-
spectral changes when CB7 is absent (insets in Figures S6 and
S7 in the Supporting Information). Only at very high metal-
ion concentrations and for very few metal ions[17] is it at all
possible to obtain evidence for the formation of metal–ligand
bonds to the free azoalkanes and to quantify the very low
binding constants; for example, values of (20 Æ 3)mÀ1 for
DBH and (10 Æ 5)mÀ1 for DBO were estimated from the
appearance of weak charge-transfer bands for Ag+. As can be
projected from all accessible binding constants (see the
Supporting Information), the ternary complexes form with
positive cooperativity, because the three types of supramolec-
ular interactions (Figure 1) add up: the ligation affinity of the
metal ion to the complexed azoalkane increases by about
three orders of magnitude as a consequence of the added ion–
dipole interactions to the host. In essence, CB7 serves as a
template for the formation of the metal–ligand bond to the
azoalkanes, and it is this positioning of the chromophore right
next to the metal ion which can be exploited to alter the
chemical reactivity of the encapsulated guest. The ternary
assemblies can in fact be viewed as simplistic but functional
metalloenzyme models, because they possess both an active
site and a hydrophobic pocket for selective substrate binding.
They differ conceptually from designed metallomacrocycles,
in which the transition metal is irreversibly incorporated
through the attachment of nitrogeneous ligands to the
macrocycle.[4]
Bicyclic azoalkanes are photoreactive and eliminate
nitrogen upon irradiation in their near-UV n,p* absorption
bands.[18] With the self-assembly of the ternary complexes
firmly established, we took advantage of the rapid supra-
molecular exchange dynamics and proceeded to screen the
photoreactivity of the encapsulated azoalkanes in the pres-
ence of different metal ions. Note that the photolysis of DBO
[Eq. (1)] is known to afford, with very low quantum yield, a
mixture of bicyclo[2.2.0]hexane and 1,5-hexadiene derived
from ring closure and opening of the intermediate 1,4-
cyclohexadiyl biradical, respectively.[18] The ring-opened
product arises preferably from the triplet excited state.[18b,19]
Photolysis of DBH [Eq. (2)], on the other hand, proceeds
with unit quantum efficiency and leads, from both the singlet
and triplet excited state, to the clean formation of bicyclo-
[2.1.0]pentane (housane) as the exclusive photoproduct.[18a]
In experimental detail, the reaction was performed in a
two-phase system[20] consisting of an aqueous solution con-
Figure 2. The host CB7 and the reactive guest molecules.
attributed to the formation of inclusion complexes driven by
hydrophobic interactions. The corresponding UV and inde-
pendent isothermal calorimetric titrations can be fitted
according to a 1:1 complexation model and afford high
binding constants of (5.8 Æ 0.2) ꢀ 106 mÀ1 for DBO and (3.8 Æ
0.2) ꢀ 105 mÀ1 for DBH.
The subsequent docking of the metal ions on the carbonyl
rim, driven by ion–dipole interactions, can be again moni-
tored by optical titrations (see Figures S4–S8 in the Support-
ing Information). For this purpose, solutions with the
respective metal salt are added to the azoalkane·CB7 binary
complexes (excess host). The docking of alkali ions, for
example, results in increased protection of the chromophore
from the aqueous solution, which is readily monitored
through an increase in the fluorescence intensity of DBO
(and fluorescence lifetime, see Figure S5a in the Supporting
Information). The docking of most multivalent transition-
metal ions such as Co2+, Ni2+, and Zn2+ results in a
hypsochromic shift of the UV absorption band, which is
diagnostic for the involvement of the azo group as a
monodentate ligand (see Figure S6 in the Supporting Infor-
mation).[15a] For Ag+ (and Tl+), hyper- and bathochromic UV
1
shifts as well as downfield H NMR shifts are observed (see
Figures S2, S3, and S7 in the Supporting Information). For
Ag+, these are assigned, bolstered by the precise binding
mode in the crystal structure of the DBO·CB7·Ag+ complex
(Figure 3), to the predominant involvement of the azo group
as a bidentate bridging ligand between two metal ions. In all
cases in which coordinative bonds between the azo group and
Figure 3. a) Top view and b) dissected side view of the crystal structure
of the ternary complex CB7·DBO·Ag+ showing one of three distinct
host–guest complexes in the asymmetric unit (magenta: cucurbituril
skeleton, green: guest carbon atoms, red: oxygen atoms, blue:
azoalkane nitrogen atoms, yellow: silver ions). Disordered silver atoms
are marked with a black (position with major occupancy) or white star
(minor occupancy). See the Supporting Information for all ternary
complexes.
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Angew. Chem. Int. Ed. 2011, 50, 545 –548

these only when CB7 was present, the chemoselectivity
increased strongly and afforded a five- to tenfold excess of the
diene (83–90%). Since actually the ternary DBO·CB7·metal-
ion complexes are being irradiated under these conditions,
and since the photoreactivity is unaffected by the macrocycle
complexation as such (see numerous control experiments in
the Supporting Information), we interpret the photoproduct
distributions as arising from an altered photoreactivity when
particular metal ions are coordinated to the cucurbituril rim.
The preferential formation of the diene is indicative of a
preferred reaction from the triplet excited state, presumably
caused by heavy-atom-induced intersystem crossing. Such
heavy-atom effects are reminiscent of (but much more
pronounced than) the effects observed in the DBO photolysis
in heavy-atom-doped zeolites.[19]
taining the water-soluble macrocyclic host and the metal salt,
and an organic layer (n-pentane for DBO and toluene for
DBH) containing the bicyclic azoalkane. The photolysis was
preferably conducted by phase-selective laser irradiation
(355 nm, Nd-YAG laser; Figure 4). Owing to the high
The results for the photolysis of DBH were even more
revealing (Table 2). DBH affords invariably 100% bicyclo-
[2.1.0]pentane in aqueous solution, in organic solution, and in
Table 2: Photoproducts of DBH under different conditions with and
without CB7 and metal ions[a]
Host Metal ion
BCP[b] CP[b]
Figure 4. Photograph of the phase-selective laser irradiation
(lexc =355 nm, third harmonic Nd-YAG laser, incident from the right)
of the DBO·CB7 complex in aqueous solution. The upper phase in the
cuvette neck contains n-pentane colorized with a trace amount of b-
carotene. Note the N2 bubbles resulting from photodeazetation.
-
–
100
100
100
0
0
0
CB7
–
–
alkaline (earth) metal ions, Fe3+, Co2+, Cu2+, Tl+,
Zn2+, Ag+
CB7 alkaline (earth) metal ions, Fe3+, Co2+, Cu2+, Tl+,
100
59[c]
0
Zn2+
solubility of the azoalkanes in water[21] we used an excess
(two equivalents) of the macrocycle to ensure quantitative
complexation and to avoid photolysis of residual uncom-
plexed azoalkane in the aqueous phase. We analyzed the
photoproduct distributions by GC analysis by drawing
aliquots from the upper organic phase. To exclude a
preferential complexation of one of the reaction products
with CB7, we added an excess of cadaverine (1,5-diamino-
pentane), a strong competitive binder,[5d] to the reaction
mixture after complete photolysis.[5d]
The photolysis of DBO in water as well as in organic
solvents (n-pentane), in the presence of only CB7, in the
presence of only metal ions, and in the presence of both CB7
and most metal ions produced about a two- to threefold
excess of 1,5-hexadiene (70 Æ 5%) over the bicyclic product
(Table 1 or Table S3 in the Supporting Information). But for
very few metal ions (Tl+, Fe3+, Co2+, Ni2+, Cu2+, Ag+) and for
CB7 Ag+
41[c]
[a] Concentrations: 2 mm DBH, 4 mm CB7, and 30 mm metal ion.
[b] Products correspond to bicyclo[2.1.0]pentane and cyclopentene, see
Equation (2). [c] Unselective irradiation of both phases in a photoreactor
afforded a product ratio (BCP/CP) of 73:27.
the presence of metal ions, CB7, and both—with one single
exception: This hit was found for the DBH·CB7·Ag+ ternary
complex, for which the significant formation of a new
photoproduct, cyclopentene, was observed [41%, Eq. (2)].
The presence of the macrocycle is, indeed, essential to
produce cyclopentene, since even the photolysis of DBH in
the presence of 1m AgNO3 did not lead to this unexpected
product. Even though our example lacks catalytic turnover
because excess CB7 and Ag+ ions are required, it is evident
that Ag+ ions promote the photochemical formation of
cyclopentene inside CB7.
While cyclopentene has not been observed previously in
the direct photolysis of DBH, this product can be formed
through the one-electron oxidation of DBH.[22] With this
mechanistic background and additional electrochemical con-
siderations (see calculations of Gibbs energies for electron
transfer in the Supporting Information), we propose that the
silver ions complexed to the portals (Figure 3) facilitate a
highly exergonic one-electron oxidation of singlet DBH.
Elimination of nitrogen from the resulting azo radical cation
affords the 1,3-cyclopentanediyl radical cation,[23] which
undergoes a rapid 1,2-H shift to give the cyclopentene radical
cation.[22] We presume that the latter is reduced, again in an
exergonic reaction, by the (still portal-associated) silver atom
Table 1: Photoproducts of DBO under different conditions with and
without CB7 and metal ions[a]
Host
Metal ion
HD[b]
BCH[b]
–
–
65
35
CB7
–
–
65
65–75
35
25–35
alkaline (earth) metal ions,
Fe3+, Co2+, Cu2+, Zn2+, Ag+
alkaline (earth) metal ions,
Cr3+, Mn2+, Zn2+, Pb2+
Tl+, Fe3+, Co2+, Ni2+, Cu2+, Ag+
CB7
CB7
65–75
83–90
25–35
10–17
[a] Concentrations: 2 mm DBO, 4 mm CB7, and 10 mm metal ion.
[b] Products correspond to 1,5-hexadiene and bicyclo[2.2.0]hexane, see
Equation (1).
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Communications
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Keywords: cucurbiturils · homogeneous catalysis · host–
guest complexes · photochemistry · supramolecular chemistry
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