Competition versus Cooperation in Catalytic Hydrogelators for anti-Selective Mannich Reaction

Article abstract of DOI:10.1002/chem.201701724

Chemical systems find similarities in different sociological and biological processes, in which the entities compete or cooperate for a favorable outcome. The structural and functional adaptations leading to emergent properties, especially in catalysis, are based on factors such as abundance of substrates, stability of the transition state, and structural/functional attributes of catalysts. Proline and acid groups appended to catalytic fibers of two self-sorting hydrogelators compete for the Mannich reaction between aniline, benzaldehyde, and cyclohexanone to give low overall selectivity (anti/syn 77:23). In a sol–gel system of the same molecules, on the other hand, the soluble acid appended molecules tend to cooperate with the fibers of proline-appended catalyst to give improved selectivity (anti/syn 95:5). The available options for the catalytic molecules are to carry out the reaction independently or in cooperation. However, these options are chosen based on the efficiency, selectivity, and mobility of catalysts as a result of their abilities to self-assemble.

Full text of DOI:10.1002/chem.201701724

A Journal of
Accepted Article
Title: Competition vs Cooperation in Catalytic Hydrogelators for anti-
selective Mannich Reaction
Authors: Nishant Singh and Beatriu Escuder
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To be cited as: Chem. Eur. J. 10.1002/chem.201701724
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Competition vs Cooperation in Catalytic Hydrogelators for anti-
selective Mannich Reaction.
Nishant Singh [a] and Beatriu Escuder*[a]
Abstract: Chemical systems find similarities in different sociological
and biological processes where the entities compete or cooperate
for a favourable outcome. The structural and functional adaptations
leading to emergent properties, especially in catalysis are based on
factors like abundance of substrates, stability of transition state and
structural/functional attributes of catalysts. Here we show how
proline and acid groups appended catalytic fibres of two self-sorting
hydrogelators compete for Mannich reaction between aniline,
benzaldehyde and cyclohexanone to give low overall selectivity
incompatible groups catalysis in solution is largely challenged.
The mutual neutralization of such incompatible groups becomes
inevitable making it harder to achieve high efficacy using
cooperation amongst different groups in solution. On the other
hand, the bottom up approach can allow to construct catalysts
with different catalytic centers in the same pot without the need
of complex synthetic procedures.[12] It is because the information
about the self-assembly leading to secondary structures lies in
the molecular structure, which usually are molecules which can
interact based on non-covalent forces such as hydrogen bonds,
ionic interactions and Van der Waals forces. Intelligent design
and use of different molecular structures can allow to have self-
assembled systems with compatible or incompatible functional
groups, which can be spatially separated or placed nearby
depending on the requirements.[12-20] Self-assembly of
amphiphilic molecules with covalently appended catalytic
moieties may result in the formation of hydrophobic pockets
which makes the recognition and approach of hydrophobic
substrates easier in the vicinity of the active sites. It also allows
better cooperation and increased local concentration of the
functional groups along with added advantages like easier
product separation and recyclability of the self-assembled
catalyst.[21-26] Owing to these properties, self-assembling catalytic
hydrogelators have previously been reported to carry out
transformations such as Henry reaction,[25] Aldol reaction,[12, 21-22,
24] ester hydrolysis[26-29] and oxygen activation[30] with enzyme like
(anti/syn-77/23). Whereas, in
a sol-gel system of the same
molecules, the soluble acid appended molecules tend to cooperate
with the fibres of proline appended catalyst to give improved
selectivity (anti/syn-95/5). The available options for the catalytic
molecules here are to carry out the reaction independently or in
cooperation. However, these options are chosen based on the
efficiency, selectivity and mobility of catalysts finding origin in their
abilities to self-assemble.
Introduction
Enzymes consisting of different catalytic domains demonstrate
cooperation while working individually or together to carry out
reactions efficiently in an enantioselective manner.[1, 2] However
synthetically having more than one catalyst similar in structure,
function or both, in the same pot to carry out asymmetric
transformations can be very hard to control or predict. Such
catalysts have an intrinsic tendency to compete for the same
reactions or interfere with the catalytic cycle of the other,
consequently bringing down the overall selectivity of the final
outcome. Schreiner et al.,[3, 4] Jacobsen et al.[5] and others[6] have
successfully demonstrated the use of Brønsted acids with
structurally different co-catalysts having similar attributes to
carry out enantioselective transformations. It becomes even
more challenging with a set of chiral and achiral catalysts to
carry out enantioselective transformations. Snapper et al.[7] with
an achiral Lewis base and a chiral Brønsted base and Seidel et
al.[8] using a chiral Brønsted acid with an achiral nucleophile,
against the odds of decrease in the stereoselectivity have
demonstrated enantioselective transformations. A combination
of co-catalysts to work in concert though highly difficult, can be
used to perform asymmetric reactions with greater efficiency and
selectivity which is usually not possible with single catalytic
systems. In this context, use of different catalytic hydrogelators
together can be very interesting to carry enantioselective
asymmetric reactions.[9-11] Specially while dealing with mutually
efficacy. However, their application using
a combinatorial
approach in complex multicomponent reactions for enantio- and
diastereoselective transformations still remains to be tested. C-C
bond forming direct three component Mannich reactions are
important candidates in this category. The obtained products are
used to prepare β-amino carbonyl synthons[31-33] with
applications in polymers, natural product and pharmaceuticals
[34]
among others.
However, amongst wide range of applied
catalysts[31, 34-39] those able to give enantioselective anti-product
in major are seldom reported.
[33, 35-37, 40]
Specially in case of
chiral organocatalysts such as proline or pyrrolidine derivatives,
the bulky carboxylic acid groups at α position orients the
enamine while donating proton to imine, giving enantioselective
41]
syn-product in majority.[40,
Thus catalysts which can afford
anti-selective Mannich reaction in an asymmetric or even non-
asymmetric fashion[40-42] are of great interest. Thus, a system
satisfying any or all of the mentioned points as summarized
below will be of importance in the fields of catalysis and self-
assembly, (a) combination of chiral and achiral catalysts for
asymmetric transformations, (b) individual and concerted use of
catalytic
hydrogelators
for
complex
multicomponent
transformations and, (c) anti-selective catalysts to afford
Mannich type reactions via enamine pathway.
[a]
Dr. N. Singh, Dr. B. Escuder*
Department de Química Inorgànica i Orgànica
Universitat Jaume I
Av Sos Baynat, 12071
E-mail: escuder@uji.es
For this purpose, we chose three catalytic hydrogelators-
ProValDoc, ProVal8 and SucVal8. These hydrogelators have
covalently appended proline (ProVal8 and ProValDoc) and
carboxylic acid (SucVal8) as their catalytic groups making them
as potential candidates to carry out direct three component
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Mannich reactions. (Scheme 1a and 1b) Owing to the difference Results and Discussion
in their molecular structures, ProValDoc and SucVal8 fibers
ProValDoc is an amphiphilic molecule with proline as catalytic
moiety forming hydrogels at minimum gel concentration of 5.7
mM whereas SucVal8 is a bolaamphiphilic hydrogelator with an
acidic group at each end being able to form gels around 6 mM.
Gels to perform Mannich reactions between benzaldehyde,
aniline and cyclohexanone were prepared by heating 6 mM of
compounds in milliQ water to obtain a clear solution, followed by
sonication for a minute and left for 24 hours at room temperature.
Mixed gels of ProValDoc, ProVal8 and SucVal8 were prepared
with desired amount of individual compounds following the same
procedure. To test the catalytic ability of the gels for direct one
pot Mannich reaction, aniline (96 µmol), aldehyde (96 µmol) and
cyclohexanone (1.5 mmol) were added to gels prepared in 4mL
of milliQ water and vortexed for ten seconds. The reaction
mixtures at desired time were extracted twice in CDCl3 and dried
over MgSO4. Final products were obtained after purification over
column chromatography to determine the yields. 1H NMR
spectroscopy was used to know the diastereoselectivities and
the enantiomeric ratios were determined by chiral HPLC
chromatography. The experiments were done in triplicates.
Experiments were performed in unbuffered media and the pH
values before and after addition of reagents, as well as at the
end of reaction were measured (SI Fig 3). Slight variations of the
initial values were observed that could be related to changes in
polarity as well as to the heterogeneity of the samples.
In systems able to self-assemble, a major percentage of
molecules are involved in the formation of 1D aggregates.
However a small of amount of molecules are present in the
solution which are in equilibrium with these self-assembled
structures. The concentration of molecules present in the
solution can be determined by 1H NMR spectroscopy as the
larger phase separated aggregates tend to be NMR silent. By
determining the amount of molecules in the solution we can
compare their catalytic activity if any, to that of the gels. This
allows us to know if the catalysis is taking place only by the
Scheme 1. (a) Molecular structures of different hydrogelators. (b)
Schematic of Mannich reaction between aniline, cyclohexanone and
benzaldehyde and, (c) cartoon representation of different catalytic
systems.
virtue of molecules present in solution or the self-assembled
[21-25, 43]
fibers are catalytically active as well.
All the individual
gelator molecules have been reported before and the amount of
molecules present in solution was determined by 1H NMR by
self-sort independently without mutual neutralization or
adversely affecting the catalytic activity of each other.[12] The
self-sorted networks have thus been used before to carry out a
tandem reaction of deacetalisation of benzaldehyde
dimethylacetal by SucVal8 and subsequent aldol reaction with
cyclohexanone by ProValDoc in the same pot. [12] However, this
was not possible with ProVal8 and SucVal8, as both being
bolaamphiphilic molecules tend to co-assemble and form a salt
bridge between their mutually incompatible catalytic groups.
Here we present the use of self-assembling properties of these
catalytic hydrogelators and their combination in different ratios to
obtain an array of different self-sorted, co-assembled or sol-gel
catalytic systems. (Scheme 1c) Here we show how the catalytic
performances of these systems are dictated by their self-
assembling circumstances, depending on which their various
components can work in concert or competition to perform anti-
selective asymmetric Mannich reaction.
comparing with an internal standard (hydroquinone) of known
[12, 21-25]
concentration.
The solubility of ProValDoc was below
the detection limit of 1H NMR (0. 2 mM, 500 MHz) so it was
assumed that majority of the molecules (>97%) were
incorporated in the fibers and were responsible for catalysis. The
determined solubility of ProVal8 was 1.5 mM and that of
SucVal8 was around 1mM. The catalytic performance of the
molecules in solution was tested keeping the same ratio of
substrate to catalyst as in the case of gels.
The proline based hydrogelator ProValDoc was able to carry
out the direct Mannich reaction in high yield (90%) and excellent
diastereoselectivity for the anti-product (anti/syn: 90/10).
However, the enantiomers of the anti-isomer were present as a
racemic mixture. (Entry 1, Table 1) It is common for proline
catalysed asymmetric Mannich reaction to yield syn-product in
majority with high enantiomeric ratio. This has been explained in
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previous reports as the result of presence of the carboxylic acid
at the 2- position as a steric and proton donating group. [40-41]
The diastereoslectivity is mainly controlled due to the orientation
of the enamine while the
Scheme 2. Mechanistic models for different catalytic systems, (a) syn-selective (high e.r.) catalysis by L-proline in solution,[40-41] (b) anti-selective (low e.r.)
catalysis by ProValDoc gel and, (c) anti-selective (high e.r.) catalysis by sol-gel. (ProValDoc gel + SucVal8 solution.)
enantioselectivity depends on the electrophilicity of the imine. In
case of proline the bulky carboxylic acid dictates the orientation
of the enamine and imine. The s-trans conformation of the
enamine takes part in C-C bond formation with its Re face
attacking the Si face of the E-imine. The free carboxylic acid as
a proton transfer agent increases the electrophilicity of the imine
giving highly enantioselective syn- products. (Scheme 2a) In the
case of ProValDoc the electron transferring carboxylic acid is
capped by amide bond formation which alters the steric factor
while also being an ineffective proton donor. The change in the
steric influence in the immediate vicinity of the nitrogen of the
pyrrolidine ring must be favoring the orientation of enamine to
give anti- isomer as a major product. In the absence of efficient
proton transfer agent the imine cannot be preferentially
stabilized in the transition state which should result in the
obtained racemic mixture. (Scheme 2b) SucVal8 on the other
hand carried out the reactions in good yield (80%) but with poor
diastereoselectivity (d.r: 62/38) and enantiomeric ratio (anti, e.r:
54/46). (Entry 2, Table 1) The reaction in this case would take
place via attack of enol on the imine. [44] Hydrogen transfer to the
nitrogen of the imine by the acid groups of SucVal8 could
stabilise the transition state.
However, the enol can attack the imine from both the sides
being the reason for poor stereoselectivity. ProVal8-another
bolamphiphilic molecule structurally similar to SucVal8 but with
proline groups was also tested for the reaction. Self-assembled
ProVal8 (9 mM) alone could catalyze the reaction with moderate
yield and poor selectivity showing again a slight preference for
anti-select product (Yield: 75%, d.r: 65/35, e.r: 60/40). (Entry 9,
Table 1)
SucVal8 at 1 mM (Yield: 20%, d.r: 60/40, e.r: 51/49) and
ProVal8 at 1.5 mM (Yield: 40%, d.r: 62/38, e.r: 50/50), in the
absence of catalytic fibers showed no selectivity and lower yield
when compared to the catalysis by the gels. (Entries 3,
10, Table 1) This difference in yields and stereoselectivities of
the final products could be attributed to the formation of
hydrophobic pockets and cooperation due to the increased local
concentration of catalytic groups upon self-assembly. The rate of
conversion of the final product by the three individual
Figure 2. NMR spectra of 1 mM SucVal8 (red) and 1 mM SucVal8 + 6 mM
ProValDoc (green) (D2O, 500 MHz).
hydrogelators was also determined by seeing the conversion of
the final product over time using 1H NMR. (Figure 1) Kobs for
ProValDoc, SucVal8 and ProVal8 were 0.4×10-4±1.2×10-6 s-1,
0.27×10-4±1.8×10-6 s-1 and 0.21×10-4±2.4×10-6 s-1 respectively.
Figure 1. Conversion of Mannich product with respect to time in presence of
different catalytic hydrogelators as seen 1H NMR.
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ProValDoc being the most effective of the three catalysts, with
highest reaction rate and selectivity. (Note: ProValDoc presents
one catalytic group per molecule whereas SucVal8 and ProVal8
bear 2 equivalent of catalyst per molecule; however not all the
catalytic sites would be accessible within the fibers. For the sake
of simplicity, Kobs were calculated using the theoretical amount of
catalytic sites.) After testing the catalytic efficiencies of the
individual hydrogels, they were next tested as mixed systems to
carry out the reactions. The structural difference of the two
hydrogelators-SucVal8 and ProValDoc allows them to form
self-sorted networks which has been described before in detail
elsewhere. [12] We thus wanted to see the effect on the reaction
performance when self-sorted networks of both the gelators
were present in the same pot. ProValDoc and SucVal8 were
implied in different ratios of 1:1 (6 mM: 6 mM), 1:2 (6 mM: 12
mM) and 2:1 (12 mM: 6 mM). (Entries 4, 6 and 7, Table 1) The
presence of both the networks did not improve the
stereoselectivity of the final obtained product when compared to
ProValDoc alone (the better of the two catalysts). Moreover, the
spatially separated fiber networks happen to be competing for
the reaction independently following their respective reaction
pathways. The stereoselectivities depended on the SucVal8:
ProValDoc ratio, higher amount of SucVal8 resulted in poorer
overall stereoselectivity. The spatially separated fiber networks
would not be flexible and dynamic enough to interact with each
other. This would prevent any kind of cooperation or interference
Table 1. Mannich reaction between aniline, benzaldehyde and cyclohexanone as carried out by different catalytic systems.
Entry
SucVal8
ProValDoc
[mM]
ProVal8
[mM]
-
Yield%[a]
d.r.(anti)[b]
e.r [c]
[mM]
1
2
-
6(f)
90
80
12
92
94
96
95
95
75
40
75
60
90/10
62/48
60/40
77/23
95/5
50/50
54/46
51/49
68/32
85/15
63/37
66/34
58/42
60/40
50/50
53/47
52/48
6(f)
1(s)
6(f)
1(s)
12(f)
6(f)
6(f)
-
-
-
-
3
-
4
6(f)
6(f)
6(f)
12(f)
1(s)
-
-
5
-
-
6
74/26
78/22
71/29
65/35
62/38
71/29
69/31
7
-
8
-
9
9(f)
1.5(s)
9(f)
9(f)
10
11
12
-
-
1(s)
6(f)
-
-
13
14
3(f)
6(f)
-
-
9(f)
62
65
69/31
68/32
51/49
52/48
1.5(s)
[a]
[b]
Isolated yields after column chromatography,
determined by 1H NMR, [c] determined by chiral HPLC for anti product (enantiomers unassigned).*(s)-for
molecules in solution, (f)-for self-assembled fibres. See supporting information for details.
amongst them, thus leading them to follow their separate
reaction pathways while competing for the resources.
However, SucVal8 when unable to self-assemble at 1 mM was
SucVal8 was present at 1 mM. (Figure 2) It is possible that the
hydrophobic patches of SucVal8 could be accommodated in the
hydrophobic pockets of the ProValDoc fibers near the proline
catalytic sites. This catalytic system with both the functional
groups in close proximity can result in enantioselective anti-
major product, where the close vicinity of the carboxylic acid
bearing SucVal8 molecules to the formed enamine between
cyclohexanone and ProValDoc can stabilize the imine by proton
sharing in the transition state, giving an improved enantiomeric
ratio. (Scheme 2c) This was not possible when molecules of
SucVal8 were able to form their independent networks and
used with
6 mM ProValDoc gel, the obtained anti/syn-
diastereomeric ratio was 95/5. Interestingly the enantiomeric
ratio (e.r.-anti) was improved significantly to 85:15 from 50:50 for
1
ProValDoc and 54:46 for SucVal8. (Entry 5, Table 1) From H
NMR using the same concentration of hydroquinone as a
reference, the detected amount of SucVal8 molecules in the
mixed system of SucVal8 (1 mM)+ProValDoc (6 mM) was
found to be 1/3 of the amount of detected molecules when only
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would work in cooperation with each other but in competition
with ProValDoc assemblies to carry out the Mannich
transformation. Interestingly on reversing the quantities and
implying 1 mM of ProValDoc with 6 mM SucVal8 no significant
improvement in the stereoselectivity was observed with d.r:
71/29 and e.r: 58/42. (Entry 8, Table 1) It can be deduced that
the major catalysts should show clear dominance and
preference with regard to the rate and selectivity to make the
minor catalysts cooperate and act as promoter. This might to
some extent resemble a model proposed by Bradford et al.
catalytic pathways. Consequently, the final stereoselectivity was
lower than that of the more selective ProValDoc catalyst.
However, in a sol-gel system of SucVal8 present in solution
while ProValDoc present as aggregated catalytic fibers, the free
to move molecules of SucVal8 in solution being catalytic
inefficient when compared to ProValDoc fibers opt to cooperate
as promotors by stabilizing the transition state. The proton
sharing by SucVal8 molecules to the imine in the transition state
results in a drastic improvement in the enantiomeric ratio. This
was a result of the inability of SucVal8 to carry out the reaction
efficiently or selectively when present in solution making them to
organize in the vicinity of the active centers of ProValDoc to
give a mutually favorable catalytic outcome. In the case of co-
assembly of structurally similar bolaamphiphilic ProVal8 and
SucVal8, the proximity of the functional groups failed to improve
the selectivity or the efficiency in the final outcome. As both the
catalytic hydrogelators in this case were poorly selective and
with comparable efficiency the final selectivity or efficiency could
not be improved even when they were implied in different
proportions. In conclusion, we can say that in the presence of
major catalyst which shows a clear preference for a kind of
product, another minor not so efficient catalyst would prefer to
act as promoter in order to attain a mutually favorable outcome.
Several phenomena in chemistry such as homochirality or chiral
concerning chemical organization of different soluble catalysts
[45]
for their preference of a consistent outcome.
They propose
that similar to Darwinian evolution in biology, different catalysts
or reactions can organize themselves by simple physio-chemical
drives to compete or cooperate by indulging in search and
selection processes for
a consistent outcome following a
¨Stochastic Innovation¨ mechanism.
To further test this, we used structurally similar ProVal8 and
SucVal8 hydrogelators together. [12] In the co-assembled system
of ProVal8 and SucVal8, the close proximity of the incompatible
acid and proline groups in the same fibers results in formation of
salt bridges. [12] In general the stereoselectivities were improved
slightly using co-assembled systems of SucVal8 and ProVal8 in
different ratios. A deficit in yields was observed when the
gelators were used in comparable proportions, which could be a
direct result of neutralization of the incompatible catalytic
functional groups. (Entries 12, 13, Table 1) To minimize the
mutual neutralization, one of the gelators (minor) was used in
lower proportion than the other (major). (Entries 11, 14, Table
1) Moreover we expected the sporadic presence of the minor
gelator co-assembling with the major gelator to form a co-
catalytic active site via salt bridge formation and work in concert
to improve the overall selectivity. But no considerable
improvement in the overall stereoselectivity was observed.
(Entries 11, 14, Table 1) We know from before that both these
self-assembled systems have comparable catalytic efficiencies
to carry out the reaction with poor selectivities. This again
alludes that it is essential to have the major catalyst with a clear
preference for a particular product, as having a co-catalyst with
similar attributes is not suffice to afford the reaction in a
stereoselective way.
[46]
[47]
symmetry breaking,
prebiotic/nucleotide chemistry,
chemical reaction systems and catalysis both by simple
molecules and enzymes[48-52] can be explained by deriving
analogies
from
processes
of
search,
selection,
reproduction/replication and emergence of new properties as
described in Darwinian theory of evolution. The established way
for enzymes to perform reaction with precise control in a specific
and efficient manner is by association of different catalytic
domains. One of the many examples is the synthesis of fatty
acid in animal cells which is carried out by a mammalian fatty
acid synthase with several catalytic domains. [53] The process of
search, selection and reproduction is performed by different
parts where acyl transferase is responsible for finding and
selecting new building blocks while ketosynthase is responsible
for using it in chain elongation. The selectivity is determined by
the spatial placements of different catalytic sites on the enzyme
and the linker joining them. In catalysis by simpler synthetic
catalysts, the processes of search, selection or reproduction
need specific interpretations where collisions of molecules can
be termed as chance/search and the kinetic and
thermodynamics factors determine the process of selection and
reproduction. Thus, use of viable designs and different catalysts
by applying combinatorial approach can result in relevant
emergent properties because of their organization and combined
actions. This could be beneficial through an industrial point of
view and would also help understand the not so clear underlying
principles of complex working of enzymes.
Conclusions
In conclusion, here we have shown how three different
hydrogelators - ProValDoc, ProVal8 and SucVal8 are able to
perform anti-select Mannich reaction while ProValDoc being the
most selective and efficient catalysts of all. ProValDoc and
SucVal8 can self-sort due to the difference in their molecular
structures keeping their catalytic abilities intact in different
spatial domains but in the same pot. In the self-sorted system
when the two catalytic fibers were implied in different proportion,
the spatially separate arrangement of the two fiber networks did
not allow any kind of cooperation or interference among them.
Owing to this the two comparably efficient fiber networks
competed for the same resources following their separate
Acknowledgements
We thank the EU (Marie Curie ITN–Smartnet, PITN-GA-2012-
316656) and the Ministry of Economy and Competitiveness of
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[25] F. Rodríguez-Llansola, B. Escuder, J. F. Miravet, J. Am. Chem. Soc.
2009, 131, 11478-11484.
Spain (Grant CTQ2016-76287-R) for funding. N. S. thanks EU
for a Marie Curie ESR contract.
[26] C. Zhang, X. Xue, Q. Luo, Y. Li, K. Yang, X. Zhuang, Y. Jiang, J. Zhang, J.
Liu, G. Zou, X-J. Liang, ACS Nano 2014, 8, 11715-11723.
[27] M. O. Guler, S. I. Stupp, J. Am. Chem. Soc. 2007, 129, 12082-12083.
[28] N. Singh, M. P. Conte, R. V. Ulijn, J. F. Miravet, B. Escuder, Chem.
Commun. 2015, 51, 13213-13216.
Keywords: molecular gels • self-assembly • asymmetric
catalysis • catalytic hydrogels • self-sorting • systems chemistry
[29] C. M. Rufo, Y. S. Moroz, O. M. Moroz, J. Stohr, T. A. Smith, Z. Hu, W. F.
DeGrado, I. V. Korendovych, Nat Chem. 2014, 6, 303-309.
[30] O.V. Makhlynets, P.M. Gosavi, I. V. Korendovych, Angew. Chem. Int. Ed.
2016, 55, 9017-9020.
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This article is protected by copyright. All rights reserved.

10.1002/chem.201701724
Chemistry - A European Journal
FULL PAPER
FULL PAPER
Nishant Singh and Beatriu Escuder*
Competition vs Cooperation in
Catalytic Hydrogelators for anti-
selelctive Mannich Reaction.
Bottom up approach can be used to construct functional architectures using various non-covalent
interactions between the self-assembling molecules. Such systems like self-sorted, co-assembled and
sol-gel though constructed using the same building blocks can have different emergent properties which
depend on the relative positioning of the molecules and the final self-assembled structures. Owing to
this, these systems find applications in different fields like material chemistry and drug delivery and can
be potentially implied in catalysis to carry out enantioselective asymmetric transformations.
This article is protected by copyright. All rights reserved.