Chiral dendrigraft polymer for asymmetric synthesis of isoquinuclidines

Article abstract of DOI:10.1039/c6ra15548k

The synthesis of multi-arm star dendrigraft amidoamine polymer with pentaerythritol initiated polyepichlorohydrin as the core, PEN-G₂, on a solid resin support has been demonstrated. We have functionalized a Merrifield resin support with polyepichlorohydrin, and dendrons are grown on it up to second generation using a graft from approach. The estimation of amine functionality was done and found to be 25 mmol g^-1 which was 70% of the theoretical value. Photolytic cleavage of the dendrigraft polymer from the support resulted in a brown water-soluble viscous liquid. The molecular weight of 3966 shows that out of the 9 G₁ dendritic substituents, 5 of them were converted to generation G₂. The TEM image of the G₂ polymer shows an inhomogeneous polygon-like appearance. The chiral modification of the dendrigraft polymer, PEN-G₂, has been done. The copper complex of chiral modified PEN-G₂ dendrigraft polymer was synthesized and characterized. The copper complex of PEN-G₂ dendrigraft polymer was found to be an excellent catalyst for the synthesis of isoquinuclidines via aza Diels-Alder reaction between cyclohexenone and imines. The catalyst exhibited superior enantioselectivity. The reusability of the catalyst was studied for five reaction cycles.

Full text of DOI:10.1039/c6ra15548k

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Chiral dendrigraft polymer for asymmetric synthesis of
isoquinuclidines
Received 00th January 20xx,
Accepted 00th January 20xx
G. Smitha, K. Sreekumar*
DOI: 10.1039/x0xx00000x
Synthesis of Multi-arm Star Dendrigraft amidoamine polymer with pentaerythritol initiated polyepichlorohydrin as core,
PEN-G2 has been demonstrated on a solid resin support. We have functionalized Merrifield resin support with
polyepichlorohydrin and dendrons are grown on it up to second generation using a “graft from” approach. The estimation
of amine functionality was done and found to be 25 mmolg-1 which was 70 % of the theoretical value. Photolytic cleavage
of dendrigraft polymer from the support resulted in brown water soluble viscous liquid. The molecular weight of 3966
shows that out of the 9 G1 dendritic substituents, 5 of them got converted to generation G2. TEM image of G2 polymer
shows inhomogeneous polygon like appearance. The chiral modification of dendrigraft polymer, PEN-G2 has been done.
The copper complex of chiral modified PEN-G2 dendrigraft polymer was synthesized and characterized. The copper
complex of PEN-G2 dendrigraft polymer was found to be an excellent catalyst for the synthesis of isoquinuclidines via Aza
Diels-Alder reaction between cyclohexenone and imines. The catalyst exhibited superior enantioselectivity. Reusability of
the catalyst was studied for five reaction cycles.
www.rsc.org/
Purification of intermediates is easy in solid phase synthesis,
which is the most difficult and time-consuming process in
solution phase synthesis of dendritic polymers. In addition, the
solid resins on which the dendritic polymer is synthesized can
be used as highly functionalized heterogeneous catalyst3 and
also as highly loaded resin for combinatorial library synthesis,
with particular emphasis on one bead one compound
approach.4
1. Introduction
The term Dendronized or Dendrigraft polymer has
emerged as a new concept in macromolecular design and
materials science due to the unique structures which are
seldom achieved by dendrimers and linear polymers.1 The
term dendronized polymer is assigned to polymers having
linear type core while the term dendrigraft polymer is
applicable to branched core polymers. Reactive oligomers or
polymers are used to produce dendrigrafts or dendronized
polymers, instead of using monomers, as if in constructing
dendrimers. The lengthy purification procedure for the
synthesis of these dendritic polymers directs us to use “solid
phase strategy”. Solid phase synthesis is really a challenge,
because of the large number of reactions that take place
simultaneously during the building up of each generation and
the number increases exponentially with increase in
generation. Conversely, solid phase synthesis provides some
inherent advantages over orthodox solution synthesis.2
Synthesis of dendritic polymers need large excess of reagents
for obtaining high purity and defect free products and solid
phase synthesis usually use large excess of reagents.
Recently, we reported solid phase synthesis of PAMAM
dendrigraft
polymer
having
glycerol
initiated
polyepichlorohydrin core, which was the first dendrigraft
polymer on insoluble support.3 In 1997, Bradley and co-
workers introduced the solid phase synthesis of PAMAM
dendrimers on organic polymer support.5 Initially, the
dendrons were prepared on TentagelR up to the fourth
generation. The assembly of the dendrons followed the
divergent synthetic strategy developed by Tomalia et al. for
PAMAM dendrimers in solution.6 It was based on alternating
steps of double Michael addition of terminal primary amines
to methyl acrylate and aminolysis of the terminal esters
formed with 1,2-alkanediamines. Later, the approach was
extended to PAMAM dendrons on polystyrene beads equipped
with a short PEG spacer.7 The reaction proceeded smoothly for
the synthesis of first and second generation dendrimers. Third
and fourth generation dendrimers showed defect structures as
Department of Applied Chemistry, Cochin University of Science and Technoogy,
Kochi- 22, Kerala, India. E-mail: kskpolymer.cusat@gmail.com, Tel: +91-484- observed from ESI MS data. These dendritic resins were used
as high load resins for the synthesis of various molecules.8 The
present approach to synthesize dendrigraft polymers includes
similar strategy of Michael addition and amination, but follows
2575804 (Off), +91-9447121530, +91-9447053021.
Electronic Supplementary Information (ESI) available: [GPC profile, IR, NMR, Solid
state 13C NMR, EDX and MALDI spectrum. SEM, TEM, AFM images. Experimental
procedure, Spectral data of products.
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fewer steps and more number of branches compared to Brassard’s diene with aldimines has been developed, giving the
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DOI: 10.1039/C6RA15548K
α,β-unsaturated δ-lactam derivatives in
conventional PAMAM dendrimer. To the best of our corresponding
knowledge, this is one of the few attempts to synthesize moderate yields with good enantioselectivities under mild
Dendrigraft polymers having branched polymeric core on a conditions. Isolation of the reaction intermediate indicates
resin support other than the one reported earlier.3 Most of the that this asymmetric aza Diels
–
Alder reaction proceeds
stepwise Mannich-type pathway.19 Catalytic
Diels–Alder reaction of α-amino-o-
reports were about single core high generation dendritic through
a
systems.9 So far, no report has appeared on the synthesis of asymmetric
amidoamine polymer on a polymeric core. Our aim was to quinodimethane with α,β-unsaturated aldehydes was achieved
synthesize dendritic systems having large amount of with high diastereo- and enantioselectivities in the presence
functionality even in the low generation level and we have of L-proline, which acts as a promoter to generate the
adopted a ‘graft from strategy’ to synthesize these systems quinodimethane from the corresponding precursor as well as a
using polymeric core on Merrifield resin.
chiral catalyst.20
The amine capacity of Merrifield resin supported PAMAM
To date, there have been only a few reports regarding
dendrimers reported earlier, was found to be between 1 and 2 direct aza hetero-Diels- Alder reaction of cyclohexenone with
mmols g-1 for G0 to G3 generations.9n So here, we have tried to aromatic aldimines. The amino acid catalyzed asymmetric aza
increase the amine capacity even at the low generation level Diels–Alder reaction between aqueous formaldehyde,
by incorporating an oligomeric core. For this purpose, we have unsaturated cyclic ketones, and aromatic amines furnished the
selected pentaerythritol initiated polyepichlorohydrin (PECH) desired azabicyclic ketones (24-48h) with >99% ee.21 A chiral
as core, coupled to the Merrifield resin and amidoamine phosphoric acid, derived from 3,3-di(4-chlorophenyl)-H8-binol,
dendrons were made to grow on it. As a result large number of exhibited superior enantioselectivity, affording fairly good
amidoamine groups can be incorporated in a single step as yields for the reaction of a range of aromatic aldimines with
well as in low generation. After the facile synthesis, photolytic cyclohexenone within 6 days.22 Co(III) anionic complexes of
cleavage of the resin gives a broad understanding of the Schiff bases obtained from salicylaldehydes and
structure of the synthesised polymer.
Asymmetric reactions using chiral catalysts provide the Bronsted acid to catalyse aza Diels
most promising method for construction of chiral molecules.10
Polymer-supported Lewis acids are known to catalyze
enantiomerically pure amino acids act as a novel chiral
–
Alder reaction in CCl4.23
Catalytic aza Diels-Alder reaction is one of the useful methods cycloadditions and polymer-loaded or dendrimer-loaded
for the synthesis of chiral nitrogen containing heterocycles.11 copper catalysts have been reported to be promoters of Diels-
Using aza Diels-Alder reaction, we can synthesize Alder reactions.24 Menger et al. described the synthesis of
isoquinuclidines (azabicyclo [2.2.2] octanes) having N-bicyclic polystyrene-based metallo-polymers containing copper and
structures. They are the structural elements of numerous their use as catalysts in Diels Alder reaction.25 Results suggest
naturally occurring alkaloids with interesting biological that metallo-polymers give better yields than the respective
properties.12 A number of chiral Lewis acids and chiral metal complex. Chow et al. reported the synthesis of dendritic
Brønsted acids, as organocatalysts were reported for the bis(oxazoline)/Cu(II) complexes and their use as catalysts in the
activation of imine functional groups.13 In particular, chiral Diels-Alder reaction.26 The size of the dendrimers had a strong
phosphoric acid based organocatalyst was used for the influence on the kinetics of the reaction with a possible
activation of imine functional group which resulted in a folding-back of the dendritic sectors towards the metallic site
number of asymmetric additions of various nucleophiles to for higher-order dendrimers. Fujita et al. reported the use of
imines.14 In 1996, Kobayashi et al. reported the first examples dendritic bipyridines Dn as ligands for Cu(OTf)2 in the Diels-
of catalytic asymmetric aza Diels-Alder reaction using a chiral Alder reaction of various dienes and dienophiles.27
ytterbium catalyst.15 Later, they reported13d,13f,16 that in the
While, rather fruitful results have been reported in
presence of 1-5 mol % of Merrifield resin supported chiral catalytic asymmetric Diels-Alder reactions,10-11,23,28 successful
BINOL zirconium catalyst, aza Diels-Alder reaction proceeded results are limited in asymmetric aza Diels-Alder reactions
smoothly to afford the corresponding piperidine derivatives in using dendritic systems. Amino acid derivatives were well-
high yields with high enantioselectivities.13e Silane Lewis acid is known for enantioselective Diels–Alder reaction.13m,29 These
effective for the enantioselective promotion of aza Diels–Alder results30 have led us to investigate whether an amino acid-
reaction of acylhydrazones with Danishefsky’s diene, adding to metal complex of dendritic system could be able to mediate
the versatility of the family of silicon Lewis acids.17 An efficient the classical aza Diels–Alder reaction through a catalytic
synthesis of hexahydropyrrolo[3,2-c]quinolin-2-ones and enamine mechanism. Herein, we report the direct catalytic aza
hexahydropyridino[3,2-c]quinolin-2-ones has been developed Diels–Alder reaction of cyclohexenone with aldimines,
in moderate to high yields by one-pot two-step aza Diels–Alder achieved with good diastereo and enantioselectivities in the
reaction. The hexahydropyrrolo[3,2-c]quinolin-2-ones were presence of a copper complex of proline modified dendrigraft
formed as a single exo-stereoisomer in most cases and polymer supported on Merrifield resin.
hexahydropyridino[3,2-c]quinolin-2-ones were formed as a
mixture of exo- and endo-isomers favoring the endo-
diastereomer.18 The chiral N,N
′
-dioxide
–
Yb(OTf)3 complex-
2. Results and discussion
catalyzed enantio- selective aza Diels–Alder reaction of
2.1 Characterization of PEN-G2 polymer
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The resin supported dendrigraft azide polymer was showed a band at 1107 cm-1 and a broad band at 3430 cm-1
View Article Online
synthesized using the schematic procedure (Scheme 1).
which corresponded to C-O-C stretchingDoOfI:e10th.1e0r39l/iCn6kRaAg1e55a4n8dK
due to the hydroxyl group of polyepichlorohydrin. In solid
state CP MAS 13C NMR spectrum, broad signal around 50-85
ppm
includes
CH2-OH,
CH-O-CH2
carbons
of
polyepichlorohydrin, the signal around 125 to 150 ppm is due
to carbons of polystyrene support and 0-50 ppm includes
carbons due to alkyl part of both support and PECH (Figure 1).
Figure 1 Solid State CP MAS 13C NMR Spectrum of PECH attached Merrifield Resin
Scheme 1 Synthesis of resin supported azide polymer
In the TG curve of PECH attached resin, two mass loss steps
were observed. The first decomposition corresponded to
nearly 54 % mass loss in the temperature around 323 OC. The
second stage was completed around 413 OC. The first step of
mass loss in TG could be attributed to elimination of
chlorinated compounds. The mass loss above 400 OC was due
to the breakdown of the polymer backbone (Figure 2).34
The branched hydroxyl terminated PECH (polyepichlorohydrin)
was prepared by the ring opening polymerization of the
oxirane group in ECH (epichlorohydrin) in the presence of
pentaerythritol by activated monomer mechanism (AMM).31 It
was a light yellow viscous liquid. From GPC, the molecular
weight of PECH was found to be 1037 with polydispersity index
of 1.27. The 1H NMR spectrum indicated that the hydroxyl
groups at the terminal ends were secondary in nature.
Merrifield resin (1% cross-linked with DVB) was gifted from
Thermax India Ltd. Its chlorine capacity was found to be 5.2
mmols g-1. It was made photoactive by the introduction of a
nitro group at the ortho position of chloromethyl group.32 The
PECH was coupled to the resin using sodium hydride and
tetrabutyl ammonium bromide.33 After coupling, chlorine
capacity was found to be 7.2 mmols g-1 by Volhards method.
From the scanning electron micrographs of nitrated Merrifield
Resin and PECH attached Merrifield Resin, it was found that,
after modification with PECH, beads with low extent of grafting
were spherical with an appearance similar to the precursor
resin particles. SEM EDAX showed that 18 atom% of chlorine
was present in the sample.
The IR spectral data of nitrated Merrifield resin at 1596 cm-
1 and 1360 cm-1 correspond to the stretching vibrations due to
NO2 group. The IR spectrum of PECH coupled Merrifield resin
Figure 2 TG-DTG plot of PECH loaded Merrifield Resin
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These observations give clear evidence for the attachment the presence of amine functionality (FiguVrieew A3rti)c.le OTnlhinee
of PECH to the Merrifield resin. The hydroxyl groups of PECH quantitative estimation showed the presDeOnIc:e10o.1f0399./1C265RAm15m54o8lKs
loaded resin was estimated quantitatively. The amount of of amine per gram of the resin. This high amine capacity
hydroxyl groups was found to be 1.86 mmolg-1 of the polymer. compared with previously reported polyamines could happen
The hydroxyl group of the polymer was reacted with p-toluene only if the resin was loaded with PECH.
sulphonyl chloride (TsCl) in pyridine.35 After tosylation,
percentage of sulphur was found to be 2.44 % from CHNS data
(C-68.39%, H-5.66%, S-2.44% and N-1.55%). The disappearance
of broad deep peak around 3500 cm-1 in the IR spectrum of
tosylated PECH indicated the alteration of hydroxyl group to
tosyl group. During tosylation, it was observed that the yield
was decreased to half by keeping the reaction for more time.
This was due to the cleavage of the ether linkages in the
polymer by the reaction with TsCl.36 The situation was same
when 4% cross-linked Merrifield resin was used. The reaction
was also monitored with p-toluene sulphonyl chloride in
triethylamine. But there was no great noticeable change with
respect to the yield of the product. The azidation of tosylated
PECH was carried out using sodium azide in
dimethylformamide at 85-90 OC.37 An intense peak at 2100 cm-
1
in IR spectrum indicated the presence of azide functionality.
In the solid state CP MAS 13C NMR spectrum, due to the
conversion of CH2-Cl of PECH to CH2-N3, the signal at 43.5 ppm
was shifted to 38.5 ppm. The colour of the resin was changed
Figure 3 IR spectra of PEN-G0, PEN-G0.5, PEN-G1, PEN-G1.5, PEN-G2
to brown. The polyazide on reduction with lithium aluminium
hydride in THF got converted to –CH2NH2 (Scheme 2).38
Quantification of the number of amino groups from DTG
result was very close to the value obtained by analytical
methods (Figure 4).39 In the TG trace of G0 polymer, the first
mass loss of about 20 % at 186 OC was due to the elimination
of amine as molecular nitrogen. The second mass loss of about
40 % at 404 OC was due to the degradation of polyether chains.
The Michael addition of the G0 polyamine with methyl acrylate
in methanol showed a peak at 1738 cm-1 in the IR spectrum of
G0.5 (Figure 3).6 Even though IR spectrum showed vibration
bands in the region around 3400 cm-1, negative Kaiser
ninhydrin test result confirmed the absence of free amino
groups.
Scheme 2 Synthesis of G 0.5 dendrigraft polymer
Figure 4 TG-DTG plot of PEN-G0
In the IR spectrum of G0 polymer, the peak at 2100 cm-1
had completely disappeared and a peak at 3451 cm-1 showed
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In the solid state CP MAS 13C NMR spectrum of G0.5,
appearance of a peak at 169 ppm confirmed the incorporation
of ester functionality. The G 0.5 polymer on amination with
ethylene diamine got converted to amidoamine G1 polymer
(Scheme 3).40
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DOI: 10.1039/C6RA15548K
Figure 5 TG-DTG plot of PEN-G1
The synthesis procedure was repeated to get G2 DP
(Dendrigraft polymer). Michael addition of G1 polymer
resulted in the conversion of G1 to G1.5 Dendrigraft Polymer.
The peak at 1641cm-1 in the IR spectrum due to carbonyl
stretching of amide -C=O of PEN-G1 got converted to 1740cm-1
after Michael addition with methyl acrylate (Figure 3). In the
solid state CP MAS 13C NMR spectrum of PEN-G1.5, the signal
at 169.4 ppm corresponds to ester carbon (Figure 6).
Scheme 3 Synthesis of G1 and G2.0 dendrigraft polymer
In the IR spectrum of G1 polymer, bands at 1641 and 3466
cm-1 are due to the amide carbonyl and amine moiety of the
polymer (Figure 3). Both Michael addition and amination
reaction took prolonged time for completion because of the
poor swelling of resin loaded polymer in methanol. The amine
capacity of G1 polymer was found to be 18.75 mmols g-1. In
the TG curve of G1 resin; two mass loss steps were observed.
The first decomposition corresponded to nearly 26 % mass loss
in the temperature around 200 OC. The second stage mass loss
of 30 % was observed around 383 OC (Figure 5). The first step
of mass loss in TG can be attributed to elimination of
molecular nitrogen form the amino groups. The mass loss near
400 OC was due to the thermal degradation of the polymer
backbone leading to the formation of hydrogen, carbon
monoxide, carbon dioxide, methane, ammonia, hydrogen
cyanide gas and other higher hydrocarbons.34
Figure 6 Solid state CP MAS 13C NMR spectrum of PEN G1.5 polymer
The above G1.5 polymer on amination with ethylene
diamine was converted to G2 polymer. The IR spectrum of
PEN-G2 polymer showed vibration band at 1662 cm-1 due to
carbonyl stretching of amide carbonyl and the band at 1740
cm-1 in the G1.5 due to ester functionality was disappeared
(Figure 3). TG plot of PEN-G2 polymer showed similar
decomposition pathway as that of G1 polymer, but a total
O
mass loss of 36 % at 194.7 and 272.4 C, and a 25 % mass loss
at 407 OC had occurred (Figure 7).
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pentaerythritol initiated polyepichlorohydrin, the VoienweArrteicpleoOrntleinde
DOI: 10.1039/C6RA15548K
here.
2.2 Characterization of Photolytically Cleaved PEN-G2
Dendrigraft Polymer
Under photolytic conditions, the G0, G1 and G2 dendrigraft
polymer undergo cleavage from the support. On photolytic
cleavage, the nitro group on polystyrene resin was converted
to nitroso group with the elimination of dendritic polymer
(Scheme 4).41
Scheme 4 Mechanism of Photolytic Cleavage
Figure 7 TG-DTG plot of PEN-G2
The resultant G0 polymer was a brown viscous liquid,
soluble in DMSO and methanol. The Chem Bio 3D image of G0
polymer cleaved from the support is shown in the Figure 9.
Scanning electron micrograph of G2 DP shows irregular
agglomerates of different shapes (Figure 8). The loss of
spherical nature was due to the crushing of the supported
Dendrigraft polymer due to prolonged stirring or may be due
to the umbrella effect (to stretch to maximum extent) of the
resin supported dendritic polymer.
Figure 9 Chem Bio 3D image of G0 Dendrigraft Polymer
1
The H NMR spectrum shows that the polymeric arms are
somewhat similar. The appearance of peaks in the range 3.2-
1
3.9 ppm in the H NMR spectrum is due to the CH2-O, CH-O
Figure 8 SEM image of PEN-G2
and NH2 protons of the polymer. The observed behaviour
suggests that growth is regulated by a feedback mechanism
due to confinement imposed by the support.42 From MALDI
TOF MS analysis, the molecular weight of the polymer was
found to be 884, which was agreeable with the theoretical
value (Figure 10).
The amine capacity of G2 polymer was found to be 25
mmols g-1 which was not in good agreement with the
theoretical value. This discrepancy is probably due to defective
growth of the dendrons as a result of steric crowding and also
due to hydrogen bonding which results in the lack of
availability of free amine functionality for carrying out the
Michael addition and subsequent reactions and also to a small
extent of interpenetration of branches to one another. The
amount of amino group in the G0, G1 and G2 serious was
found to be higher for GLR-Gn polymer than PEN-Gn polymer.3
This may be due to the monodispersity and high molecular
weight of glycerol initiated polyepichlorohydrin compared to
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can arise through incomplete reactions brought about by steric
congestion at the periphery or backfolding of flexible dendritic
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DOI: 10.1039/C6RA15548K
884
branches, which hides their functional groups. The highest
molecular weight of the PEN-G2 polymer from MALDI MS
analysis was found to be 3966.02 with a base peak at 1225.41
and another major peak at 1662.72. The molecular weight at
3966.02 shows that out of the 9 G1 dendritic substituents, 5 of
them got converted to G2.
The peak at 1662.72 corresponds to the formation of one
G2 dendron unit. The peak at 1225.41 is due to cleavage of G2
dendritic unit from the polymeric backbone. The highest mass
of 3966 shows that only 30% of dendron substituents are
incorporated. The low experimental mass compared to
theoretical mass can be due to missing branches. The
difference in experimental and theoretical masses can partially
be attributed to structural defects, because, errors can also be
due to the polydisperse nature of the polymer. Also, the lower
mass may be due to the thermal decomposition of the high
generation polymer in comparison with lower generation
dendrigraft polymers.48 For a comparison we tried to find out
the mass of the glycerol based dendrigraft GLR-G2 polymer.49
Merrifield resin carrying the GLR-G2 polymer was cleaved
photolytically. The molecular weight obtained from MALDI
analysis was 2927, which corresponded to 9 dendritic units on
the polyether backbone.
Molecular simulation of the PAMAM dendrimers have
indicated that the early full generations (G = 1-2) are
characterized by asymmetric disk like shapes. These
correspond to open structures that can be readily penetrated
by solvent. Higher generations possess a nearly spherical
shape, which corresponds to closed, densely packed surface
structures.50 In contrast to dendrimers, dendrigraft polymers
show more closed or spherical nature at low generation, but at
higher generations, polymeric arms are more stretched and
have rod like appearance.51
The shape of the polymer in the case of PEN-G2 was
analyzed by atomic force microscopy (AFM) as in the case of
PEN-G1. In AFM, the film uniformity is mostly determined by
the concentration of the dendritic solution regardless of
generation.52 The AFM image of the G2 polymer from lower
concentration (0.01 wt%) at a scan width of 15 µm around 10
nm shows a small elongated worm or string like appearance.
Since polyether backbone is only having approximately 10-13
units, the length of the worm that we observed is agreeable
with the length of the polyether oligomer. Despite the
approximate nature owing to uncertainties associated with the
AFM technique (tip convolution), it was clear that the average
worm length corresponds to the length of the parent
polyether, whereas the height of the polymer chain depends
upon the dendron generation.53
1000 980
960
940
920
900
880
860
840
820
800
m/z
Figure 10 MALDI MS Spectrum of PEN-G0 Polymer
Resin loaded G1 polymer on photolytic cleavage gives a
brown viscous liquid. One issue that needs to be addressed is
the solubility of Dendronized polymers (DP). It has been known
that, in general, DPs containing large number of free
peripheral amine groups have low solubility in most commonly
used solvents.43 The lower solubility of the branched chains
was attributed to their high propensity to crystallization.1l
1
Inspection of the HNMR spectrum of the G1 DP cleaved from
the resin clearly indicates the appearance of amide proton at
8.1 ppm which was absent in G0 DP. To determine the exact
number of dendritic substituents introduced, MALDI-TOF MS
analysis was performed (matrix: dihydroxybenzoic acid) with
the dendronized PEN-G1 polymer. But polymers with
polydispersity index greater than 1.2 are difficult to be
characterized with MALDI MS due to the signal intensity
discrimination against higher mass oligomers.44 The MALDI-
TOF MS of PEN-G1 exhibited several peaks. Focus may be given
to two major peaks. The peak at 2857.55 Da is derived from
nine dendritic substituents on a pentaerythritol initiated
polyether chain. The base peak at 1664.39 Da is derived from
four dendritic substituents on a pentaerythritol initiated
polyether chain. These results indicate that the G0 polymer
was modified to ~70 % with dendron substituents on the
polyether backbone. Generally, in order to minimize defects or
cyclisation and to ensure complete reaction, as we go from
lower to higher generation, large molar excess of the reagents
have to be taken.45
To confirm the introduction of dendritic substituents onto
polyether, dendronized G1 polymer was analyzed by atomic
force microscopy (AFM).46 Samples for AFM analysis were
prepared by spin coating methanolic solution of the
dendronized polymer on a glass plate and AFM analysis was
performed in the tapping mode. The AFM image of the film of
G1 polymer deposited from higher concentration (0.1 % w/w)
at a scan width of 75 µm shows spherical aggregates of
different sizes.
The 1H NMR spectrum of PEN-G2 Dendronized polymer
shows broadening of peaks in comparison with PEN-G1 DP.
The occurrence of structural defects and dendritic aggregation
due to the interdigitation of dendritic arms are commonly
encountered during the synthesis of high generation dendritic
polymers.47 In this regard, defects in the dendritic structure
The TEM micrograph of the PEN-G2 polymer shows
polygon shape with low molecular weight polymers aggregate
inside the polygon (Figure 11). The polygon shape with
longest-extension diameter of up to 13.7 nm may be due to
the clustering of polymeric arms in solution. Reports regarding
dendrigraft polymers say that they are elongated due to linear
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polymeric core with dendritic arms. But in solution they
remain as spherical.54
View Article Online
DOI: 10.1039/C6RA15548K
Figure 11 TEM image of PEN-G2 polymer
2.3 Characterization of Chiral modified dendrigraft PEN-G2 metal
complex
The synthesis of the resin supported chiral modified
dendrigraft PEN-Gn copper complex was achieved by adopting
a three-step methodology, as shown in Scheme 5. Chiral
modification of PEN-G2 polymer was done using Boc-L-proline
followed by deprotection using trifluroacetic acid. After chiral
modification, amount of proline was found to be 12.54 and
20.63 mmolg-1 for G1 and G2 respectively. Chiral modified
dendrigraft PEN-G2 polymer was complexed with copper using
copper acetate in methanol at a temperature of about 50 OC.
Chiral PEN-Gn-Cu was found to be non-hygroscopic, stable and
can be stored for a prolonged period of time without any
change in its catalytic efficiency. The copper coordinated
dendritic polymer appeared as light green powder.
Scheme 5 Chiral modification and Metal complexation of PEN-G2 polymer
2.3.1 ICP-AES Analysis
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The copper capacity of PEN-G1-Cu and PEN-G2-Cu, based
on ICP-AES analysis and confirmed by EDX analysis, were found
to be 20.40, 32.36 % of the polymer, respectively (Table 1). It is
therefore assumed that an average of 2.03 ligands was bound
to Cu2+ ions in chiral PEN-G2 complex. Acetate ions were
completely replaced by the dendritic ligands. The room
temperature magnetic moment of the copper (II) PEN-G2
complex was found to be 2.1B.M. The Cu compounds were
paramagnetic in nature, as was evident from the magnetic
susceptibility measurement, which was consistent with the
presence of Cu centers in their +2 oxidation state.
View Article Online
DOI: 10.1039/C6RA15548K
Table 1 Analytical data for chiral PEN-Gn and chiral PEN-Gn-Cu
Polymer
Proline
NH
Copper
(%)
Copper
(mmol/g)
ICP-AES
Copper
(%)
Figure 12 Scanning electron micrograph of Chiral PEN-G2-Cu
capacity
(mmol/g)
ICP-
AES
EDX
2.3.3 IR Spectral Studies
The IR spectra showed characteristic differences between
the spectral pattern originating from the dendrigraft PEN-G2
polymer, proline modified dendrigraft PEN-G2 polymer and
the corresponding copper complex. The IR spectra are
presented in Figure 13. Dendrigraft PEN G2 polymer on Boc-
proline modification showed bands at 1740 cm-1 due to ester
carbonyl stretching of Boc carbonyl group. On deprotection,
the peak at 1740 cm-1 got disappeared and showed only the
peak due to amide at 1692 cm-1.
Chiral
PEN-G1-
(Cu)
12.54
20.63
20.40
32.36
3.21
5.09
19.23
30.27
Chiral
PEN-G2-
(Cu)
2.3.2 SEM and Energy Dispersive X-ray (EDX) Analysis
The SEM micrographs of chiral PEN-G2-Cu polymer shows
disordered aggregates and aggregated particles look flattened
and show metallic lustre (Figure.12). EDX spectrum confirmed
the presence of Cu, C, N and O as the constituents of the
polymer. The results presented in Table 6.1 are the average of
the data from scanned regions. The data obtained on the
composition of the compounds from the energy dispersive X-
ray spectroscopy, were consistent with the elemental analysis
values (Table .1).
Figure 13 IR Spectra comparison for chiral modification
Proline modified polymer on complexation with copper
showed a distinct shift towards lower frequency region.
Stretching due to proline NH was lowered around 64 cm-1 and
that of amide carbonyl stretching was lowered from 1692 cm-1
to 1625 cm-1. The peak at 1508 cm-1 is due to stretching
vibrations of secondary amine. Bending vibrations due to
primary amine at 1610 cm-1 in the PEN-G2 polymer got
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modified by the secondary NH vibrations in chiral PEN-G2
Journal Name
Figure 14 presents the Cu (2p) XPS spectra of the PEN-G2
View Article Online
polymer. The peak at 1200 cm-1 is due to the CH2 wagging of Cu catalyst. The catalyst displayed characDteOrIi:s1t0ic.10C3u92/Cp63/R2As1i5n5g4l8eKt
cyclopentane ring. After chiral modification, the peak at 1007 with peak located at 934.6 eV. Strong satellite peaks were
cm-1 in PEN-G2 due to the ethereal C-O stretching got merged observed at 942.7, 954.7 and 962.6 eV. The noted binding
with nearby peaks and shifted towards higher frequency energy values are in good agreement with the available
region. The narrow peak at 700 cm-1 can be assigned to Cu-N literature data for Cu ions in the 2+ oxidation state.57 The
stretching.
presence of Cu (II) in supported dendritic polymer has thus
been confirmed from the results of XPS analysis.
2.3.4 Electronic Spectral Studies (UV-Vis DRS)
UV-Vis DRS spectrum of Cu complex of proline modified
PEN-G2 shows two peaks with maximum intensity at 671 nm
and 839 nm. The peak at 839 nm relates to a distorted
octahedral geometry and the peak at 671 nm to a square
pyramidal geometry characteristic of five coordinated
species.55 But on compilation of other characteristic data, the
square pyramidal geometry may be assigned to chiral PEN-G2-
Cu complex. The peak at 671 nm and 839 nm may be ascribed
to the absorption due to overlapping of allowed d-d transitions
in copper after coordination with dendritic ligands.
2.3.5 EPR Spectral Studies
EPR Spectral studies of Cu complex of proline modified
PEN-G2 show typical axial spectra with four hyperfine lines,
which is characteristic of monomeric copper (II) complexes.
The g and A values are obtained from the simulated spectrum
given in Table 2. In all the cases gll was found to be greater
than g┴. This predicts a square pyramidal geometry to five
coordinated complex rather than a trigonal bipyramidal
structure which would be expected to have g┴ greater than
gII.56 Thus the chiral PEN-G2-Cu comprises of coordination of
copper to two proline nitrogens, two amide nitrogens and one
tertiary nitrogen of amidoamine unit.
Figure 14 deconvoluted XPS spectra of Cu (2p3/2) of PEN-G2-Cu
2.3.8 TG-DTG Analysis
A comparative evaluation of the thermogravimetric data of
the PEN-G2 functionalized resins and the corresponding Cu
loaded PEN-G2 dendrigraft polymer is shown in the figure
(Figure 7 & 15). An intense decomposition is observed in the
thermogram of both PEN-G2 and PEN-G2-Cu at temperatures
above 400 OC owing to the degradation of the polymeric
backbone.58
Table 2 Splitting parameters g and A
Polymer
PEN-
gII
g┴
gav
AII
A┴
Aav
2.28 2.07 2.14 195 12.8 69.8
3
G2-Cu
2.3.6 X-ray Diffraction Studies
The room-temperature X-ray diffraction patterns of the
pentaerythritol initiated dendrigraft polymer, PEN-G2 and the
Copper complex of the chiral dendrigraft polymer PEN-G2-Cu
on Merrifield resins are overlayed. After chiral modification
and complexation, the peaks corresponding to various 2 theta
values in PEN-G2 have disappeared indicating the loss of
crystalline nature of the polymer complex. This observation
confirms that the copper has been anchored to the polymer
matrix to yield the polymer supported dendritic copper
catalyst PEN-G2-Cu.
Figure 15. TG-DTG plot of PEN-G2-Cu
Apart from this, in the case of PEN-G2-Cu, a decomposition
step with a weight loss of 25% occurs in the temperature range
2.3.7 X-ray Photoelectron Spectroscopy
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of 150–250 OC. The thermal decomposition of PEN-G2 shows a
weight loss of 30 % which occurs in the temperature range of
120-320 OC. From the reports regarding polyepichlorohydrin
and Merrifield resin,59 this decomposition is ascribed to the
release of amines as nitrogen, carbonyls as CO or CO2 and the
degradation of the polymeric backbone to be left with a
residue containing copper oxide or hydroxide. The first step of
decomposition in chiral PEN-G2-Cu is attributable to the loss of
non-coordinated water, occurring in the temperature range of
65-105 OC. The TG-DTG analysis data for the dendrigraft
polymers are thus in agreement with the percentage
composition.
Table 3 Optimization of solventa
View Article Online
DOI: 10.1039/C6RA15548K
Entry Solvent
Yield
(%)b
(endo/exo)c
ee
(%)d
1
2
3
4
5
6
7
DMSO
CCl4
60
82
78
72
82
78
82
82/18
92/08
76/24
50/50
60/40
55/45
75/25
80
90
74
64
75
78
74
Ethanol
Hexane
Toluene
THF
2.4 Catalytic activity of supported chiral dendrigraft PEN-Gn-Cu
complex
CH3CN
aReaction Conditions: Cyclohexenone (1 mmol),
benzaldehyde (1 mmol), aniline (1 mmol). RT, PEN-G2-
Cu: 20 mg, b Isolated yield of endo and exo, c Determined
by 1H NMR, d Enantiomeric excess of the major product
was determined by chiral HPLC analysis (Chiralpak IB-3
chiral stationary phase, iPrOH/hexane (1:9), 254 nm).
2.4.1 Synthesis of Isoquinuclidines
In a survey of catalytic activity, chiral dendrigraft PEN-G1
and G2 copper complexes were employed in the synthesis of
Isoquinuclidines (Scheme 6).
As shown in Table 4, there was no appreciable change in the
enantiomeric excess of the major product while decreasing the
catalyst loading from .01 to .005 mol %. However, the best
yield and % ee were achieved at .0051 mol % of the catalyst.
We have also checked the influence of the amount of solvent
of the reaction mixture on the catalyst efficiency. A dilution led
to a decrease of the yield but the best % ee of the product was
achieved with 3 mL of carbon tetrachloride.
Scheme 6 Aza Diels-Alder reaction of cyclohexenone with aldimines
It was found that chiral PEN-G2-Cu catalyst was more
efficient than chiral PEN-G1-Cu catalyst. A variety of aldehydes
as substrates has been tried. The effects of various reaction
parameters, such as type of solvent, reaction temperature,
catalyst concentration, etc., were evaluated using
benzaldehyde, aniline and cyclohexenone as model substrates
and chiral PEN-G2-Cu as the catalyst. Optimization studies of
solvent and catalyst concentration are shown in Table 3 and 4.
The reaction of cyclohexenone with imine was carried out
in several solvents at an ambient temperature of 30 oC for 5h.
The results are summarized in Table 3. As shown in the table,
selected solvents provide the product in reasonable yield with
enantiomeric excess greater than 70 %. CCl4 was chosen as the
preferred solvent for further studies, because the best
endo/exo ratio of the product was observed in this solvent.
The efficiency of the catalyst was tested by varying the catalyst
concentration.
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Table 4 Optimization of Amount of Catalysta
After optimizing the reaction conditions, scope of different
substrates was evaluated (Table 6). All the substrates selected
View Article Online
DOI: 10.1039/C6RA15548K
were studied for 3 h. Most of the reactions of cyclohexenone
with imines resulted in good diastereo and enantioselectivity
irrespective of the functional group on the aromatic ring. H
NMR and GC-MS spectra of few diastereomers are shown in
supplementary information. The distereomeric ratio can be
found out from proton NMR spectrum as well as from the GC-
MS. In GC-MS, splitting pattern corresponding to endo and exo
will be different which helps to predict diastereomeric ratio.
Catalyst
Amount
(mg)
Catalyst
Amount
(mol %)
TON,
TOF
(h-1)
Yield
(%)b
(endo
/exo)c
1
ee (%)d
2.0
7.0
.0010
.0036
.0051
.0076
.0102
53
65
82
82
82
53,10.6 60/40
18, 3.6 75/25
16, 3.2 92/08
11, 2.2 88/12
72
74
90
78
90
10.0
15.0
20.0
8, 1.6
90/10
a Reaction Conditions: Cyclohexenone (1mmol), benzaldehyde
(1mmol), aniline (1mmol). CCl4-3mL, RT, b Isolated yield of
endo and exo,c Determined by 1H NMR, d Enantiomeric excess
of the major product was determined by chiral HPLC analysis
(Chiralpak IB-3 chiral stationary phase, iPrOH/hexane (1:9),
254 nm).
Having established the optimum reaction conditions, effect
of generation of the dendrigraft PEN-Gn-Cu was studied (Table
5). A positive dendritic effect was observed as the % ee
increased with generation of the polymer. Indeed, first
generation resulted in endo/exo ratio of 75/25, the second
generation furnished endo/exo product ratio with 92/08 with
90% ee.
Table 5. Effect of Generation of the Dendrigraft PEN-G2-Cua
Polymer Yield
(%)b
TON,
TOF (h-1)
(endo/exo)c ee (%)d
PEN-G1-
Cu
80
25, 5.0
16, 3.2
75/25
85
PEN-G2-
Cu
82
92/08
90
aReaction
Conditions:
Cyclohexenone
(1mmol),
benzaldehyde (1mmol), aniline (1mmol). CCl4-3mL, RT,
b
c
Catalyst amount: 10mg Isolated yield of endo and exo,
Determined by 1H NMR, d Enantiomeric excess of the major
product was determined by chiral HPLC analysis (Chiralpak
IB-3 chiral stationary phase, iPrOH/hexane (1:9), 254 nm).
12 | J. Name., 2012, 00, 1-3
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View Article Online
DOI: 10.1039/C6RA15548K
Table 6 Scope of substrates
Aza Diels-Alder product
Optimized structure
Yield (%)b
endo/exoc
92/08
ee (%)d
82
90
6a
-864.53
82
84
88/12
87/13
84
86
6b
6c
-1068.95
-3435.51
62
84/16
78
6d
6e
-1528.53
-979.69
82
88/12
88
84
80/20
88
6f
-1324.78
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DOI: 10.1039/C6RA15548K
85
88/12
90/10
90
6g
-979.69
76
86
6h
-3550.67
89
90/10
90
6i
6j
-1324.79
68
60/40
88
-1069.64
In order to find whether the yield of the Aza Diels Alder After completion of the reaction, the solution was filtered,
product depends on its ground state energy, structure of the washed with ethyl acetate (3-10 mL), acetone and vacuum
products were optimized using B3LYP exchange correlation dried at 50 OC for about 5h. The catalyst recovered was
functional and 6-31G basis set.60 The optimized energy ie. weighed and reused without loss of significant catalytic
lowest energy of the compound to be in the stable state, is activity. Details regarding catalyst recovery with percentage
depicted in the table (Table 6). As per the energy values, the yield are depicted in Table .7. Successive runs were carried out
compound 6a has maximum energy; so we expect it to have in order to examine the recyclability of the catalyst. After fifth
low yield (endo product) compared with others. But cycle, 87.8 % of catalyst was recovered and reused with 74%
experimental results show endo/exo ratio of 92:08. In some ee.
other cases, the experimental values are agreeable with the
theoretical value. For example, compound 6h have least
energy value (-3550.67) which shows yield of about 90:10.
These results show that formation of Aza Diels-Alder product
cannot be predicted by ground state energy values alone, but
other factors (kinetic and thermodynamic factors) have to be
considered in order to predict the formation of the product
theoretically.
2.4.2 Recyclability of the Catalyst
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Table 7. Recycling of chiral PEN-G2-Cu catalysta
View Article Online
DOI: 10.1039/C6RA15548K
No. of
Cycles
Catalyst
weight
(mg)
Catalyst
recovered
(mg)
Recovery Product Endo/exoc
ee
(%) d
(%)
yield
(%)b
1
2
3
4
5
10
9.2
8.4
7.8
7.4
9.2
8.4
7.8
7.4
6.5
92.0
91.3
92.9
94.9
87.8
82
78
74
65
65
92/08
82/18
78/22
75/25
74/26
90
82
78
74
74
2.4.3 The Proposed Mechanism
Resin (500 mg) was suspended in methanol (50 mL) in the
It is well known that a carbonyl compound possessing α- reaction chamber of an immersion type photo reactor. The
hydrogens will enolize under acidic conditions and the formed suspension was degassed for 1h with dry nitrogen and
enolate will attack imines formed from aldehydes and amines.
irradiated with Philips HP 125W medium pressure Hg lamp at
340-350 nm for 24 h with constant stirring. A solution of CuSO4
was circulated through the outer jacket of the reactor to filter
off light waves below 320 nm. After photolysis, resin beads
were filtered and washed with methanol. Combined filtrate
and washings were evaporated under vacuum.
G0 After photolytic cleavage: 1H NMR (400 MHz, DMSO-d6) δ:
3.9(26 NH proton), 3.2-3.8(48 CH2 & 10 CH) ppm. 13C NMR (100
MHz, DMSO-d6): 78, 77.7, 70.2, 68.8, 68.6, 53.4, 51.6, 51 ppm;
MALDI MS: 884.
G1 After photolytic cleavage: 1H NMR (400 MHz, DMSO-d6) δ:
8.2 (18 amide proton), 3.5-4 (44 NH proton), 3.1-3.4(192 CH2 &
10 CH) ppm; 13C NMR (100 MHz, DMSO-d6): 164.6, 56.3, 48.5,
41.2, 39.7, 39.1, 38.9, 38.6, 38.3, 37.2, 36.9, 14.1 ppm; MALDI
MS: 2857.55.
G2 After photolytic clevage: 1H NMR (400 MHz, DMSO-d6): 8.1
(26 amide proton), 3.5-4.5 (50 NH proton), 2.8-3.5 (258 CH2
&10 CH) ppm; 13C NMR (100 MHz, DMSO-d6): 168.8, 167.7,
164.6, 55, 43.4, 41.1, 40.6, 39, 38.6, 38.3, 37.2, 35.5, 28.3,
21.8, 17.5 ppm; MALDI MS: 3966.02.
3.2 Modification of Dendrigraft PEN-G2 Polymer with Boc
Proline
Active ester of amino acid was prepared by adding 2.5 meq
of HOBt (1.69 g) and 2.5 meq of DCC (2.58 g) to a solution of
Boc-L-Proline (2.69 g) in NMP. This was stirred for 5 min. and
the HOBt ester of amino acid was added to the amino resin,
PEN-G2 (0.5 g). The mixture was shaken for 48 h until the
disappearance of blue colour with ninhydrin. DMSO was added
to the mixture and shaken for 15min. At the end of 15 min.
DIEA was added. The unreacted reagents and byproducts were
filtered off. The resin was washed with dichloromethane:
methanol (66:33 v/v), dichloromethane, NMP and dried under
vacuum at 50 OC.
Scheme 7 Possible mechanism for Aza Diels Alder reaction of cyclohexenone
with aldimines
The (4+2) diene-dienophile cycloaddition of enolate with
aldimine generates intermediate I and II. Finally catalyst leaves
the system to form the product, endo and exo (Scheme 7).
3. Experimental
Amount of Boc-proline: 0.021 molg-1; Yield: 0.58 g.
IR (cm-1): 3460, 2934, 1740, 1652, 1539, 1366, 1103, 725.
3.1 Photolytic cleavage
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Solid state 13C NMR (100 MHz): 172, 168.2, 167.8, 167.2, 152, dendrigraft G0, G1 and G2 amine polyVmieewrArtichleaOvnilninge
DOI: 10.1039/C6RA15548K
144.3, 122.2, 79.5, 76, 73, 61, 60.3, 47, 43, 38.8, 34, 29, 27, 23, pentaerythritol initiated polyepichlorohydrin as core have
20.9 ppm.
been synthesized and characterized. Characterization of
dendrigraft amidoamine polymer has been done after
photolytic cleavage of the same from the support. We have
3.3 Deprotection of Boc from Dendrigraft PEN-G2 Polymer
The resin (0.5 g) was treated with 30
% TFA in developed a highly efficient chiral dendritic copper catalyzed
dichloromethane for 5h. The reaction was monitored using method for the cycloaddition of cyclohexenone with aldimines.
ninhydrin test and IR spectrum. The TFA solution was filtered The developed copper complexes of chiral PEN-G1 and PEN-G2
and the resin was washed with dichloromethane. This was dendrigraft polymer were characterized. We found that
treated with 5 % DIEA in dichloromethane (5min) & 5 % DIEA copper complexes can catalyze Aza Diels-Alder reaction like
in NMP: dichloromethane mixture (1:1 v/v) to get the desired Diels-Alder reaction. The reaction occurs more efficiently with
product. Finally, proline modified PEN-G2 polymer was dried at high generation dendrigraft polymer in comparison with low
50 OC.
generation G1 dendrigraft polymer. After optimizing the
reaction conditions, a detailed study of aza Diels-Alder
reaction was done with chiral PEN-G2 copper catalyst. The
Proline NH capacity: 0.021 mol/g; Yield: 0.46 g;
IR (cm-1): 3460, 2982, 1692, 1525, 1454, 1250, 1117, 750.
Solid state 13C NMR (100 MHz): 168, 167.5, 167, 142.3, 122.4, main features of the synthesis are: only small amount of
79.9, 73, 64, 62.3, 49, 42, 37, 35, 30, 25, 20.2 ppm.
catalyst was needed to drive the reaction and all the reactions
were performed at room temperature. The catalyst performs
3.4 Synthesis of Copper Complex of Proline Modified well with good diastereoselectivity and good enantiomeric
Dendrigraft PEN-G2 Polymer excess. Procedural simplicity, simple recovery and reusability
A 50 mL round bottom flask was charged with 250 mg of of catalysts meet the requirements of benign chemistry. Thus
Merrifield resin supported proline modified PEN-G2 polymer the present catalyst will be of wide practical application in
having 20.63 mmols/g of amine capacity. It was allowed to similar reactions. Further investigation on the application of
swell in DMF for 2 h. Quantitative amount of anhydrous this catalyst for other organic reactions is in progress.
copper acetate (0.021 mol, 0.94 g) in 10 mL methanol was
added to the reaction flask. The reaction mixture was stirred at
50 C for about two days (48h). The polymer was filtered and
O
Acknowledgements
washed with water. The filtrate and washings were collected
together and concentrated. This concentrated solution was
used for the estimation of metal ions by standard methods.
The polymer-supported metal complex was washed with
methanol (20 mL x 3), dioxane (20 mL x 3) and acetone (20 mL
x 3) followed by drying at 50 OC for 3 h.
We would like to thank SAIF, CUSAT for assistance with
various analysis. One of the authors (G.S) thank the CSIR, Govt.
of India for financial assistance in the form of fellowship. The
authors thank PSRT, CUSAT for GPC analysis, NCL, Pune for
Solid state 13C NMR analysis, RGCB and NIIST, Trivandrum for
MALDI analysis. Finally we thank Thermax, India for providing
the gift sample of Merrifield resin.
Dark green powder; Copper loading: 0.005 molg-1; Yield:0.32 g.
3.5 General Procedure for Aza Diels Alder Reaction
A 25 mL RB flask was charged with a magnetic stirrer and
CCl4 (3.0 mL). Cyclohexenone (1.0 mmol), and the catalyst PEN-
G2-Cu (.0051 mol%, 10 mg) were added to the flask. To the
resulting solution after 2 min of stirring, the Schiff base of
aniline and benzaldehyde (1mmol) was added. The reaction
mixture was stirred at room temperature for 3h. After the
completion of the reaction (TLC and GC determination), the
resulting solution was filtered, washed with ethyl acetate,
methanol and acetone, and concentrated by a rotary vacuum
evaporator. The product was separated by passing through a
silica column using the eluent, hexane : ethyl acetate (9:1). The
References
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yield and diastereomer ratio were determined from H NMR
spectrum. Product purification and diastereomer separation
were made by column chromatography on SiO2 column
(hexane/EtOAc/Et3N 40:10:1). The enantiomeric purity was
determined by chiral HPLC analysis (Chiralpak IB-3 chiral
stationary phase, iPrOH/hexane (1:9), 254 nm).
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DOI: 10.1039/C6RA15548K
Chiral dendrigraft polymer for asymmetric synthesis of isoquinuclidines
G. Smitha, K. Sreekumar*
Synthesis of copper complex of chiral modified dendrigraft amidoamine polymer with
pentaerythritol initiated polyepichlorohydrin core, PEN-G2 has been demonstrated on a solid resin
support for the synthesis of isoquinuclidines via Aza Diels-Alder reaction between cyclohexenone
and imines.