Azaphosphatrane organocatalysts in confined space: Cage effect in CO 2 conversion

Article abstract of DOI:10.1002/chem.201402058

The endohedral functionalization of a molecular cage by an azaphosphatrane unit has allowed for the creation of highly engineered catalytic cavities for efficient conversion of CO₂ into cyclic carbonates. Strong structure/activity/stability correlations have been demonstrated by careful adjustment of the size, shape, and electronic properties of the hemicryptophane host.

Full text of DOI:10.1002/chem.201402058

DOI: 10.1002/chem.201402058
Communication
&
Supramolecular Chemistry
Azaphosphatrane Organocatalysts in Confined Space: Cage Effect
in CO2 Conversion
Bastien Chatelet,[a] Lionel Joucla,[a] Jean-Pierre Dutasta,[a] Alexandre Martinez,*[a] and
Vꢀronique Dufaud*[b]
Abstract: The endohedral functionalization of a molecular
cage by an azaphosphatrane unit has allowed for the cre-
ation of highly engineered catalytic cavities for efficient
conversion of CO2 into cyclic carbonates. Strong structure/
activity/stability correlations have been demonstrated by
careful adjustment of the size, shape, and electronic prop-
erties of the hemicryptophane host.
Scheme 1. Synthesis of cyclic carbonates from epoxides and carbon dioxide,
catalyzed by azaphosphatranes.
The use of carbon dioxide (CO2), a primary greenhouse gas, as
a non-toxic and largely available C1 building block is attracting
growing interest for the development of sustainable and green
chemistry.[1] In particular, the conversion of CO2 into cyclic car-
bonates in the presence of an epoxide is very attractive both
because of the high atom economy of the reaction and for the
many applications of cyclic carbonate compounds as building
blocks or additives.[2] Hence, numerous catalysts have been de-
veloped for this purpose.[3] Many catalytic systems were found
to be very active but, in most cases, they required fairly drastic
reaction conditions and often a co-catalyst to achieve high
conversions. Some systems also have the environmental draw-
back of the use of toxic metals. Therefore, the design of novel
metal-free catalysts with enhanced properties still remains to
be developed as a step towards effective CO2 conversion. In
this context, azaphosphatranes (AZAP), the acidic counterparts
of proazaphosphatrane superbases,[4] proved to be original
and tunable catalysts for the synthesis of cyclic carbonates
from CO2 and epoxides (Scheme 1).[5]
trane molecule. The resulting highly reactive tricyclic phospho-
ryl–carbamate intermediate could also be involved in the deg-
radation process of the catalyst through the opening of the
azaphosphatrane structure. We thus anticipated that the en-
capsulation of the azaphosphatrane catalyst in a molecular
cage should avoid this deactivation pathway. Indeed, the en-
capsulation of an active species in a molecular cavity, as it is
often observed for enzymes, can both: 1) change its reactivity
inducing higher rate constants and/or new selectivities, and
2) improve its stability by protecting the catalyst from degrada-
tion.[6] Among the different structural types of supramolecular
catalysts,[7] the hemicryptophane host appears very promising
as it can combine a recognition site and a catalytic site.[8]
Herein, we investigate how the construction of different mo-
lecular cavities around the PÀH site can change the catalytic
activity and the robustness of azaphosphatranes. Caged aza-
phosphatranes 1a–d were synthesized following a known
strategy,[9,10] and tested in the cycloaddition of CO2 with epox-
ides (Figure 1). For comparison, non-caged azaphosphatrane
models 2a–d were also prepared. As we shall see, the structur-
al changes of the molecular cavity around the PÀH site greatly
influence the catalytic behavior of the encapsulated azaphos-
phatranes.
In particular, we have shown that the substitution pattern
on the catalyst greatly affects its activity and stability. Detailed
kinetic studies allowed us to propose a mechanism involving
unique dual activation of both the epoxide, through hydrogen
bonding, and CO2, through insertion into the PÀN bond (Fig-
ure S1 in the Supporting Information), at a single azaphospha-
To study the effect of confinement on the catalytic activity
of azaphosphatranes, we first compared azaphosphatrane–
hemicryptophane 1a with its open-faced analogue, 2a, which
lacks a cavity (Figure 1). The coupling of styrene oxide with
CO2 was chosen as a benchmark. Typically, the reaction was
carried out over 24 h under mild conditions (1 bar, 1008C) with
a catalyst loading of 1 mol%. Both the model and encaged cat-
alysts gave satisfactory results, with the yields of product
being 73% and 82%, respectively. Thus, the catalytic proper-
ties of azaphosphatranes in the conversion of CO2 to cyclic car-
bonates were not altered by encapsulation, suggesting that
[a] Dr. B. Chatelet, Dr. L. Joucla, Dr. J.-P. Dutasta, Dr. A. Martinez
Laboratoire de Chimie, ꢀcole Normale Supꢁrieure de Lyon
46, Allꢁe d’Italie, F-69364 Lyon (France)
E-mail: alexandre.martinez@ens-lyon.fr
[b] Dr. V. Dufaud
Laboratoire de Chimie, Catalyse, Polymꢂres, Procꢁdꢁs (C2P2), CNRS
Universitꢁ Claude Bernard Lyon 1, CPE Lyon
43 bd du 11 Novembre 1918, F-69616 Villeurbanne (France)
E-mail: veronique.dufaud@univ-lyon1.fr
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402058.
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Figure 2. Effect of confinement on catalytic performances of supramolecular
azaphosphatrane 1a and its model, 2a. Reaction conditions: styrene oxide
(50.0 mmol), catalyst (0.05 mmol), CO2 (1 bar), 1008C. TONs were determined
1
by H NMR spectroscopy by using 2,4-dibromomesitylene (2.0 mmol) as an
internal standard.
through encapsulation. Secondly, a steady decline in activity
was observed for model catalyst 2a over the four-day test,
whereas encaged organocatalyst 1a exhibited higher stability
under these conditions, with no noticeable alteration of activi-
ty over the four-day experiment. Consequently, at the end of
the reaction (96 h), the TON for the azaphosphatrane included
in a hemicryptophane host was about three times higher than
that of the corresponding uncapped model compound. The
constraint induced by the cage structure around the phospho-
rus atom seems to correlate with the catalyst stability, hence
suggesting that the active site is protected from degradation.
These results also support our mechanism involving dual acti-
vation of epoxide and CO2 by a single azaphosphatrane cata-
lyst molecule. Indeed, a strong decrease of activity is expected
if the activation of epoxide and CO2 would occur at two differ-
ent molecules of catalyst because both reactants would be
encaged and activated in two different molecular cavities, thus
greatly limiting their ability to react together.
Deeper insight into the role played by the cage structure
was obtained by tuning the size and shape of the cavity above
the PÀH site. We first examined the catalytic activity of supra-
molecular catalyst 1b, which bears bulky naphtyl linkers, and
compared it to its model compound, 2b (Figure 1). Surprising-
ly, under our initial reaction conditions (1 mol% of catalyst,
24 h, 1008C, 1 bar), model catalyst 2b was far more active
than its encaged counterpart, 1b (77% and 3% yields, respec-
tively). Thus, the confinement imposed by the hemicrypto-
phane structure strongly affects the performance of the AZAP
organocatalyst. To more accurately probe the change of reac-
tivity induced by the cage structure, a series of kinetic studies
was carried out over a longer reaction period (4 days) at
a lower catalyst loading (0.1 mol%; Figure 3a). Model catalyst
2b was found to display behavior that was similar to that of
model catalyst 2a: good initial activity was observed, but after
24 h, the TON dramatically decreased. On the other hand, en-
capsulated organocatalyst 1b showed nearly constant activity
over the four days of the experiment, although its initial activi-
ty was ten times lower than that of parent model 2b. Whereas
Figure 1. Supramolecular azaphosphatranes 1a–d having cavities of differ-
ent size and shape, and the corresponding model compounds, 2a–d (coun-
ter ion: ClÀ).
supramolecular catalyst 1a did not suffer from product inhibi-
tion. A second series of experiments was then performed with
a 1000:1 epoxide-to-catalyst ratio to explore the catalyst stabil-
ity over a longer period (96 h). The progress of the reaction
was monitored by 1H NMR analysis of aliquots taken every
24 h. After each 24 h period, an appropriate amount of styrene
oxide was added to bring the substrate-to-catalyst ratio back
to 1000:1.
Two main differences between the supramolecular catalyst
1a and its model 2a were found (Figure 2). Firstly, regarding
the turnover number (TON) after 24 h, encaged azaphospha-
trane 1a was found to be twice as active as its model counter-
part, thus highlighting an enhancement of the reactivity
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begins with the activation of the epoxide by hydrogen bond-
ing to the PÀH site, an interaction that should be strongly dis-
favored in 1b where the helical arrangement of the naphtyl
groups limits the accessibility to the phosphorus center (see
Figure S3 in the Supporting Information). These results high-
light the size and shape dependence of reactivity for organo-
catalysts based on hemicryptophane cages in the conversion
of CO2 to cyclic carbonates. These results also clearly demon-
strate the crucial role of the PÀH center in the AZAP structure
because limiting its access by the sterically congested naph-
thalene linkers, strongly decreased reactivity.
To further establish the key influence of the catalytic space
above the PÀH center on catalytic performance, we investigat-
ed the catalytic behavior of two additional caged azaphospha-
tranes (1c and 1d, Figure 1): 1c provides further insight into
the role played by the naphtalene unit on reactivity whereas
1d provides information regarding a more open structure,
which should lead to higher activity. Indeed, both supramolec-
ular catalysts, 1c and 1d, exhibited high activity after 24 h of
reaction with 89% and 84% yields, respectively, values that are
close to those of their parent models (yield: 83% for 2c and
75% for 2d). The kinetic profiles of encapsulated catalysts 1c
and 1d and model organocatalysts 2c and 2d (Figure 3b,c)
mirror the behavior described above for 1a and 2a. Encaged
azaphosphatranes 1c and 1d displayed constant catalytic ac-
tivities over the four-day experiments, whereas those of model
parent catalysts 2c and 2d dramatically decreased over the
same period.
These results are in agreement with our hypothesis. Firstly,
they confirm that the change of reactivity induced by the
naphthalene unit is related to change of the available space
around the reactive center and not to specific electronic prop-
erties of the naphthalene moiety. Furthermore, these trends
highlight how the inner-cavity volume and the accessibility to
the PÀH site affect the reactivity of the encaged azaphospha-
trane (the TONs for 1c after 24 h were found to be 1.5 and
23 times higher than those for 1a and 1b, respectively). Thus,
protection of the reactive site by encapsulation allowed TONs
of greater than 700 to be achieved, thus making 1c and 1d re-
markably active and stable supramolecular organocatalysts.
The preorganization of the molecular cage likely reinforces the
ability of the catalytic core to maintain its atrane structure
during the catalytic cycle, thus improving its stability. Indeed,
the loss of catalytic activity observed for all the model com-
pounds may originate from the instability of the phosphoryl–
carbamate intermediate formed after CO2 insertion into the PÀ
N bond.[11] The constraint induced by the cage structure
around the phosphorus atom should favor the regeneration of
the polycyclic structure of the azaphosphatrane unit at the
end of the catalytic cycle (see Figure S1 in the Supporting In-
formation). This behavior underlines the relevance of hemi-
cryptophane hosts for designing efficient and modular supra-
molecular catalysts.[8c] Indeed, most of the known supramolec-
ular catalysts suffer from product inhibition and have to be
used in stoichiometric amounts. On the contrary, hemicrypto-
phane compounds are rather flexible, as previously observed,[9]
allowing for greater lability of the host–guest association, in
Figure 3. Influence of the architecture of the cavity on the catalytic reactivity
of supramolecular azaphosphatranes 1b–d and model analogues 2b–d.
Reaction conditions: styrene oxide (50.0 mmol), catalyst (0.05 mmol), CO2
(1 bar), 1008C. TONs were determined by H NMR spectroscopy by using
2,4-dibromomesitylene (2.0 mmol) as an internal standard.
1
the two model compounds, 2a and 2b, displayed similar cata-
lytic activities during the first 24 h with TONs of around 100,
strong differences were observed between the related caged
derivatives, the TONs for supramolecular azaphosphatrane 1a
being 15 times higher than those for 1b.
We have recently shown that the size and shape of the mo-
lecular cavity in 1a–d was strongly dependent on the nature
of the linker, and examination of the X-ray structural data,
when going from 1a to 1b, showed that the molecular cavity
grew along the pseudo C3 axis of the molecule but also
became narrower (see Figure S2 in the Supporting Informa-
tion).[10] Thus, access to the phosphorus site in 1b is more re-
stricted than in host 1a. Recall that the proposed mechanism
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that may account for the remarkable efficiency for catalytic
CO2 conversion observed here.
In summary, specific tailor-made nanoreactors based on the
hemicryptophane host, each defining a specific confined space
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[(Sup)3Base]).
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Keywords: azaphosphatranes
·
CO2 conversion
·
cyclic
carbonates · green chemistry · organocatalysis
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Received: February 6, 2014
Published online on && &&, 0000
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Communication
COMMUNICATION
&
Supramolecular Chemistry
B. Chatelet, L. Joucla, J.-P. Dutasta,
A. Martinez,* V. Dufaud*
&& – &&
Azaphosphatrane Organocatalysts in
Confined Space: Cage Effect in CO2
Conversion
Combining supramolecular chemistry
with CO2 conversion into cyclic carbo-
nates has led to efficient and robust
encaged organocatalysts. The remark-
able properties of azaphosphatranes
toward this reaction were not only re-
tained but magnified by encapsulation
in a supramolecular hemicryptophane
structure. These results also support the
proposed mechanism involving dual ac-
tivation of both the epoxide and CO2 at
a single azaphosphatrane molecule.
Chem. Eur. J. 2014, 20, 1 – 5
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