L-Proline-Derived Basic Catalyst
A R T I C L E S
Scheme 1
Scheme 2
associated with the cooperation among catalytic units or with
conformational restrictions. Supramolecular gels can be con-
sidered as heterogeneous catalysts that present interesting
properties such as self-reparation capabilities, which are absent
in conventional heterogeneous catalytic systems.
It has been reported that supramolecular gels with reactive
groups can participate in chemical reactions with reagents in
solution or in photochemical processes.8 The use of supramo-
lecular gels in catalysis constitutes an almost unexplored field
and only a few examples of catalysis carried out with supramo-
lecular gels or fibrilar aggregates have been reported. The results
described in this area include organocatalysis9 to invoke
hydrocyanation or a hydrolysis reaction, metallocatalysis,10 and
the use of supramolecular gels as phase transfer catalysts.11
With these ideas in mind, we decided to study gelators
containing L-proline moieties as catalysts. The gelator used in
this study (1, Scheme 1) contains terminal L-proline moieties
attached to a L-valine-based gelator scaffold that we have used
in previous studies on supramolecular gels.12 The gelation
properties of 1 in acetonitrile have been reported recently.13
Additionally, we have found that the aggregation of 1 in self-
assembled fibrillar networks inhibits the catalytic activity of the
L-proline moiety in enamine-based aldol reactions and results
in a remarkable increase of its basicity.14 This property could
be ascribed to the cooperation of vicinal L-proline goups in the
gel fibers in the proton abstraction process. The aim of this work
is to demonstrate how supramolecular gelation can be used to
develop systems that present catalytic properties that are absent
in solution (see Scheme 2) and, in particular, to explore the use
of supramolecular gels as basic catalysts in the nitroaldol Henry
reaction.
Scheme 3
for the Henry reaction is to avoid side processes such as
dehydration (see Scheme 3) and to achieve enantioselective
catalysis.15 Heterogenous basic catalyst for the Henry reaction
have been described in the literature with the use, for example,
of alumina, hydrotalcite, silica and with functionalized meso-
porous silica materials.16 It has to be mentioned that L-proline
is not found among the wide variety of bases which have been
described to promote the Henry reaction because its low basicity.
Results and Discussion
The nitroaldol Henry reaction was chosen for these purposes
because it is advantageous for several reasons. It is an example
of a base-catalyzed reaction which has been extensively studied
and the mechanisms of the main reaction and of possible side
reactions are well understood. Additionally, typical substrates
for this reaction such as nitroethane and nitromethane are
appropriate solvents for supramolecular gel formation by
molecule 1. A challenge in the development of new promoters
Compound 1 has been shown to form gels in acetonitrile.13
We have found that this compound also forms gels in ni-
tromethane and nitroethane, the solvents used in the catalytic
studies that will be discussed later. Gel formation can be
explained by the formation of aggregates through multiple
H-bonding interactions.12,17 A schematic model proposed for
such interactions, based on those reported for related molecules,
is shown in Scheme 4.
(8) (a) Miravet, J. F.; Escuder, B. Org. Lett. 2005, 7, 4791–4794. (b) Love,
C. S.; Chechik, V.; Smith, D. K.; Ashworth, I.; Brennan, C. Chem.
Commun. 2005, 5647–5649. (c) Miravet, J. F.; Escuder, B. Tetrahedron
2007, 63, 7321–7325. (d) Dawn, A.; Fujita, N.; Haraguchi, S.; Sada,
K.; Shinkai, S. Chem. Commun. 2009, 2100–2102.
The mininum concentration of 1 for gel formation at 20 °C
in nitromethane and nitroethane was found to be 3 mM and 18
mM, respectively. The thermal stability of these gels was studied
using the vial inversion methodology, and the results are shown
in Figure 1. The onset temperature for the gel disassembly (Tgel)
presents a typical dependence with concentration showing a
plateau above certain concentrations (see Figure 1). This can
be explained having in mind the exponential relationship
(9) (a) Tanaka, K.; Mori, A.; Inoue, S. J. Org. Chem. 1990, 55, 181–185.
(b) Guler, M. O.; Stupp, S. I. J. Am. Chem. Soc. 2007, 129, 12082–
12083.
(10) (a) Xing, B.; Choi, M.-F.; Xu, B. Chem.sEur. J. 2002, 8, 5028–5032.
(b) Miravet, J. F.; Escuder, B. Chem. Commun. 2005, 5796–5798. (c)
Tu, T.; Assenmacher, W.; Peterlik, H.; Weisbarth, R.; Nieger, M.;
Do¨tz, K. H. Angew. Chem., Int. Ed. 2007, 46, 6368–6371.
(11) Tu, T.; Assenmacher, W.; Peterlik, H.; Schnakenburg, G.; Do¨tz, K. H.
Angew. Chem., Int. Ed. 2008, 47, 7127–7131.
(15) Luzzio, F. A. Tetrahedron 2001, 57, 915–945.
(16) (a) Akutu, K.; Kabashima, H.; Seki, T.; Hattori, H. Appl. Catal., A
2003, 247, 65–74. (b) Hoffmann, F.; Cornelius, M.; Morell, J.; Fro¨ba,
M. Angew. Chem., Int. Ed. 2006, 45, 3216–3251.
(12) (a) Escuder, B.; Marti, S.; Miravet, J. F. Langmuir 2005, 21, 6776–
6787.
(13) Rodr´ıguez-Llansola, F.; Miravet, J. F.; Escuder, B. Chem. Commun.
2009, 209–211.
(17) (a) Hanabusa, K.; Tanaka, R.; Suzuki, M.; Kimura, M.; Shirai, H.
AdV. Mater. 1997, 9, 1095–1097. (b) Doi, M.; Asano, A.; Yoshida,
H.; Inouguchi, M.; Iwanaga, K.; Sasaki, M.; Katsuya, Y.; Taniguchi,
T.; Yamamoto, D. J. Pept. Res. 2005, 66, 181–189.
(14) Rodr´ıguez-Llansola, F.; Miravet, J. F.; Escuder, B. Org. Biomol. Chem.
2009, DOI: 10.1039/b904523f.
9
J. AM. CHEM. SOC. VOL. 131, NO. 32, 2009 11479