Palladium catalysed asymmetric alkylation of benzophenone Schiff base glycine esters in ionic liquids

Article abstract of DOI:10.1007/s12039-011-0093-4

Asymmetric alkyl substitution of various benzophenone Schiff base substrates under biphasic conditions proceeded using optically active Palladium(II) complexes. The corresponding products were obtained in high yields but with moderate enantiomeric excess (ee) . Addition of specific ionic liquids to the reaction medium enhanced reactivity and selectivity for phase transfer catalytic (PTC) glycine alkylation. It has been found that there is an anionic influence of the ionic liquids that modify the steric environment around the enolate ion. A computer-assisted molecular design of enantioselective phase-transfer catalysis with the palladium complex and the ionic liquid has been done. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0093-4

c
J. Chem. Sci. Vol. 123, No. 4, July 2011, pp. 467–476. ꢀ Indian Academy of Sciences.
Palladium catalysed asymmetric alkylation of benzophenone Schiff base
glycine esters in ionic liquids
DAE HYUN KIMa, JIN KYU IMa, DAE WON KIMa, MINSERK CHEONGa,
HOON SIK KIMa,∗ and DEB KUMAR MUKHERJEEb,∗
aDepartment of Chemistry and Research institute for Basic Sciences, Kyung Hee University, 1 Hoegi-Dong,
Dongdaemun-Gu, Seoul 130-701, Republic of Korea
bDepartment of Chemistry, Ramsaday College, Amta, Howrah 711401, India
e-mail: debkumarmukherjee@rediffmail.com; khs2004@khu.ac.kr
MS received 1 January 2011; revised 4 March 2011; accepted 3 May 2011
Abstract. Asymmetric alkyl substitution of various benzophenone Schiff base substrates under biphasic con-
ditions proceeded using optically active Palladium(II) complexes. The corresponding products were obtained
in high yields but with moderate enantiomeric excess (ee). Addition of specific ionic liquids to the reaction
medium enhanced reactivity and selectivity for phase transfer catalytic (PTC) glycine alkylation. It has been
found that there is an anionic influence of the ionic liquids that modify the steric environment around the eno-
late ion. A computer-assisted molecular design of enantioselective phase-transfer catalysis with the palladium
complex and the ionic liquid has been done.
Keywords. Asymmetric alkylation; Schiff base; phase-transfer catalysis; chiral ionic liquid.
1. Introduction
quaternary ammonium salts have also been successfully
used in the asymmetric alkylation of a glycine deriva-
tive by various groups.19–25 Recovered polymeric cata-
lysts show high selectivity and can be used again for the
same reaction.
Asymmetric phase transfer catalysis offers a power-
ful method for many reactions including the synthesis
of unnatural amino acids.1–4 The first general synthe-
sis of racemic amino acids by phase transfer catalysis
(PTC) based on the alkylation of glycine ester Schiff
bases was reported in 1978.5 In 1989 chiral catalysts
derived from the cinchona alkaloids afforded optically
active amino acids in a room temperature enantiose-
lective PTC process.6 A second generation of chiral
quaternary ammonium salts, the N,O- dialkylated cin-
chona salts, gave impressive enantioselectivities (79–
80% ee).7,8 A third generation of chiral PTC catalysts
has also been reported independently by Corey and
Lygo groups.9,10 In these reactions a variety of alkyl
halides were used and either enantiomer of the product
could be prepared by selective use of the pseudoenan-
tiomeric cinchonidine11,12 or cinchonine13,14 derived
catalysts. Further modifications of the catalytic sys-
tem include dimeric,15 trimeric16 and other stereogenic
centers17,18 which allow many options for improving
greater reactivity and selectivity. Polymer supported
Although there are successful catalysts for phase
transfer alkylation reaction, formation of C–C bonds
through a direct alkylation using orthopalladated com-
plex was unknown and has not been reported so far.
Only one group,26 as far as our knowledge goes, has
earlier used chiral copper and cobalt salen complexes
as phase-transfer catalysts for asymmetric synthesis of
α–methyl α-amino acids. We have been interested for
some time in the application of phase transfer catalysis
to the preparation of amino acid derivatives. The opti-
cally active orthopalladated phenanthrylamine phase
transfer catalyst has been produced and explored for
asymmetric glycine alkylation by us.27 The sterically
hindered orthopalladated complex provided asymmet-
ric induction in benzophenone Schiff base substrates
under biphasic conditions. Prompted by the successful
results from the phenanthrylamine moiety in PTC, we
focused on different orthopalladated complexes hypoth-
esizing that with the proper alignment of the ammonium
centers, optimum enantioselectivity would be observed.
We have reported28 a set of chiral palladium complexes
which were effective in asymmetric induction of a range
∗For correspondence
467

468
Dae Hyun Kim et al.
of electrophiles. The ee content was however moderate the cyanide displacement of benzyl chloride and alky-
in each case and effort was on to increase it. lation of benzyl cyanide under phase transfer condi-
Screening of different reaction conditions show that tions. Some have even reported simple transformation
low temperature (−20◦C to 0◦C) and dichloromethane of chiral natural anions to liquid medium and their use
or a mixture of toluene:chloroform (7/3,V/V) as sol- to induce chirality.34–36 This prompted us to explore
vents are effective in promoting the displacement reac- the alkylation of N-diphenylmethylene glycine esters in
tions under phase transfer conditions. Recently the chiral ionic liquid medium using optically active pal-
environmentally benign room temperature ionic liquids ladium(II) complexes. We report here the combination
emerged as an alternative reaction media for chemi- of an asymmetric palladium catalyst and a prochiral
cal processes including chemical catalysis.29–31 Several ionic solvent that promotes glycine alkylation under
groups have recently demonstrated32,33 the use of room mild conditions. The strategy adopted could broaden
temperature ionic liquid as a catalyst and solvent for both understanding and applicability.
Pd+2
N
Pd-chiral complex(S)
(10 mol%)
O
O
-
O
(S)
Ph
Ph
N
t-Bu
Ph
Ph
N
H
t-Bu
O
O
Ph
Ph
t-Bu
50% KOH(aq)
PhCH2Br(1.2 equiv.)
CH2Cl2, 20°C, 12h
O
CH2Ph
(Alkylated enantiomer)
2. Experimental
EtOAc, 9:1). The Schiff base was found to be unstable
even in neutral alumina plates. Astonishingly, none of
the recent literature has cited this until we came across
an article published by Martin J O’Donnel and co-
workers.40 Tert-butyl-N-diphenylmethyleneglycinate
(substarte II) was also used for alkylation with methyl
iodide and benzyl bromide as alkylating agents. The
Schiff base derivatives of glycine were chromato-
graphed on grade V basic alumina with ethyl acetate
Analytical grade reagents and freshly distilled solvents
were used throughout our investigation. The palladium
complexes were prepared and characterized as per stan-
dard literature methods with slight modifications done
to suit our experimental conditions. The synthetic pro-
cedure and analytical data of the compounds can be
found in a previous communication by the authors.
1-Butyl-3-methylimidazolium based ionic liquids like
[BMIm]MeHPO3, [BMIm]MeSO4, [BMIm]CH3COO
and [BMIm]Tf2N were prepared by known litera-
1
in hexane as eluant. Vibrational, electronic and H
NMR spectra were taken with Perkin Elmer 883,
Shamadzu MPC-3700 and Bruker 400 MHz instru-
ments, respectively. The enantioselectivity was deter-
mined by chiral HPLC analysis (chiracel OD, hexane:
2-propanol (99.5:0.5), flow rate 1 ml/min, 20◦C, λ =
254 nm). Optical rotation studies wherever necessary
were determined on a Perkin Elmer 241 polarimeter
using 1% solution in CH2Cl2.
ture methods37,38 and the H NMR spectra of the as-
1
synthesized liquids are provided in the supporting doc-
uments accompanying the manuscript. The ionic liquid
(N,N-dimethylephedriniumbis-(trifluoromethanesulfon)
imidate) has been reported39 to be a solid (mp = 54◦C)
but we have actually isolated the liquid at a vacuum of
0.04 mbar and used it in the reaction medium. All these
ionic liquids were vacuum dried at 70◦C prior to use
to free them from moisture contamination. Ionic liq-
uids like [BMIm]Cl, [BMIm]BF4 and [BMIm]PF6 were
however obtained from Aldrich chemicals and used as
received.
The Schiff base Ethyl-N-diphenylmethyleneglycinate
(substrate I) was found to be unstable over the silica
gel slides and always produced two visible spots (visu-
alized under UV light). The spot at Rf = 0.42 has
been assigned to the imine and the other spot at Rf =
0.70 corresponds to Benzophenone (eluent, n-Hexane/
2.1 Experimental procedure for the Pd-catalysed
asymmetric alkylation
Palladium complex (0.05 mmol) was dissolved in
methylene chloride (1 mL). Aqueous KOH solution
(50%, 0.5 mL) was added to a vigorously stirred solu-
tion of the Schiff base (0.2 g, 0.70 mmol), metal com-
plex and benzyl bromide (1.2 eq, 0.1 mL, 0.85 mmol)
in methylene chloride. Chiral ionic liquid (0.5 ml)
was added to the mixture at room temperature almost

Palladium catalysed asymmetric alkylation of benzophenone Schiff base glycine esters in ionic liquids
469
immediately and stirred for several hours. The course based on phenanthrylamine (catalyst I), naphthylamine
of the reaction was followed by TLC (eluent, (catalyst-II) and benzylamine moiety (catalyst-III) as
n-hexane/ethylacetate, 90/10) until the starting mate- shown in scheme 1 and the catalytic studies were made
rial has been consumed. The suspension was diluted under similar conditions.
with diethylether and the combined organic extracts
Highest enantioselectivity was achieved when methyl
were dried over Na2SO4, filtered and concentrated in iodide was used as the electrophile for the alkylation
vacuum. Purification of the residue by flash column of tert-butyl glycinate benzophenone Schiff base using
chromatography on alumina 90 active basic (0.063– catalyst I (40%, table 1, entry 4). Under similar condi-
0.200 mm) afforded the alkylated product as colourless tions and using the same set of catalyst and the Schiff
oil (yield generally >80%).
base, lower enantioselectivity (∼15%) was noticed with
benzyl bromide as electrophile (table 1, entry 18).
Lower enantioselectivities were also observed when the
ethyl ester was used as the substrate for alkylation com-
pared to the tert-butyl glycine esters as evident from
the catalytic runs 2,4 ; 6,7 ; 9,10 and 12,13 (table 1).
Though the difference in ee content is very small, the
trend of increased bulkiness giving better selectivity is
evident both from the viewpoint of two different gylcine
esters and different chiral palladium complexes used in
our studies.
3. Results and discussion
3.1 Asymmetric alkylation of benzophenone imine
glycinate under phase transfer conditions using
optically active palladium complexes
The orthopalladated dimeric complexes (Catalyst-I-III)
and the dimeric R-complex of the benzylamine variety
(catalyst-IV) were prepared by known literature meth-
ods and these were then used as catalyst precursors
for phase transfer alkylation reactions. Though acetato-,
chloro- and bromo-bridged orthopalladated complexes
were prepared and reported in a previous article by us,28
we have used only the chloro-bridged chiral palladium
complexes in the present context. 50% Aqueous potas-
sium hydroxide solution and 1.2 equivalents of the alky-
lating agent was used in most of the runs under biphasic
conditions. All Asymmetric alkylation reactions were
conducted at room temperature (20◦C).
3.2 Asymmetric alkylation of benzophenone imine
glycinate under phase transfer conditions using
optically active palladium complexes and the chiral
ionic liquid
Use of different solvents or mixed solvents (table 1)
did not improve much the rate of reaction or the ee of
the product mixture. We therefore thought of using
the chiral ionic liquid (CIL) in combination with the
optically active orthopalladated complexes and study
their combined effects on product composition. When
we added 1 ml (9 mol %) of the chiral ionic liq-
uid (N,N-dimethylephedriniumbis-(trifluoromethane-
sulfon)imidate) to the same reaction solution that
To examine the effect of the chiral as well as
achiral additives in liquid–liquid phase-transfer alkyla-
tion reactions, we prepared the three set of catalysts
CH3
H3C
H3C
CH3
Pd
H3C
N
CH3
Pd
X
Me
Me
N
Me
N
Pd
X
2
X
2
2
X=C l
X=C l
catalyst- II
X=C l
catalyst- I (S, enantiomer)
catalyst- III (S, enantiomer)
catalyst- IV (R, enantiomer)
Scheme 1. Orthopalladated complexes used as catalysts in enantioselective alkylation reaction.

470
Dae Hyun Kim et al.
Table 1. Alkylation of glycine derivatives under phase transfer conditions using chiral orthopalladated complex.
Entry No
Catalyst used
substrate
Electrophile
solvent
CH2Cl2
PhMe:CHCl3
PhMe:CHCl3
CH2Cl2
*Pdt/Yield (%)a
ee (%)b
1
Complex-I
Complex-I
Complex-I
Complex-I
Complex-II
Complex-II
Complex-II
Complex-III
Complex-III
Complex-III
Complex-III
Complex-IV
Complex-IV
Complex-IV
Complex-III
Complex-II
Complex-I
Complex-I
Complex-I
Complex-I
I
I
I
II
I
I
II
II
I
II
I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
Ia/88
Ia/86
30
33
33
40
26
25
30
25
18
25
20
22
28
12
10
15
17
15
12
17
2
3d
4
IIa / 90
IIa / 90
Ia / 88
Ia / 86
IIa / 88
IIa / 90
Ia / 85
IIa / 85
Ia / 88
Ia / 84
IIa / 86
IIb / 78
IIb / 74
IIb / 75
IIb / 78
IIb / 88
IIb / 85
IIb / 74
5
6
7
8
CH2Cl2
PhMe:CHCl3
PhMe:CHCl3
CH2Cl2
9
PhMe:CHCl3
PhMe:CHCl3
PhMe:CHCl3
PhMe:CHCl3
PhMe:CHCl3
PhMe:CHCl3
PhMe:CHCl3
PhMe:CHCl3
PhMe:CHCl3
CH2Cl2
10
11d
12
13
14
15
16
17
18
19c
20d
I
II
II
II
II
II
II
II
II
CH2Cl2
CH2Cl2
Alkylating agent: benzyl bromide/methyl iodide, t = 20◦C, time = 12 h
∗
Absolute configuration of products was determined to be (S) from literature data for catalysts 1-III and (R) for catalyst IV
a: isolated crude oil before column chromatography
b: determined by 1H-NMR, chiral HPLC and optical rotation studies
c: 5 eq of the electrophile used
d: a lower temperature of −10◦C was employed
yielded 30% enantiomeric excess (entry 1, table 1) and
The enantiomeric R-complex of palladium (complex-
stirred the reaction vigorously for 12 hours, we noticed IV) was also studied as the catalyst in the enan-
a further increase in enantioselectivity. With chloro- tioselective alkylation reaction of tert-butyl glyci-
bridged phenanthrylamine orthopalladated complex as nate under similar optimised conditions to find the
catalyst (10 mol%) and methyl iodide as the alkylating match–mismatch effect. There was the mismatch effect
agent, ethyl-N-diphenylmethyleneglycinate (substrate- observed (R-enantiomer major in this case) although
I) yielded (S)-Ethyl-N-diphenyl methylene alaninate similar increment in ee (∼60%) was noticed (entry 8,
as the major isomer (table 2). The enantiomer excess table 2) when the chiral ionic liquid was added to the
improved to 42% when chiral ionic liquid (CIL) was catalyst system. The ee was a mere 22% (entry 12,
used in addition to CH2Cl2 (1 mL) and 50% aqueous table 1) with no chiral ionic liquid added to the system.
KOH solution as base. Even 0.5 mL of the chiral ionic Even though the chiral ionic liquid alone cannot induce
liquid produced the same result under similar condi- enantioselectivity under biphasic conditions (entry 19,
tions. With tert-butyl-N-diphenyl methyleneglycinate table 2) it acts as a chiral booster to increase the ee
as substrate, the ee also increased to 48% keeping when used along with the orthopalladated complexes.
all other reagents and reaction conditions unchanged Even with a weaker base like K2CO3 and addition of
(entry 3, table 2). The same trend of ee increment 18-crown-6 to encapsulate the potassium ion, no asym-
was also noticed when benzyl bromide was used as metric induction could be achieved with the ionic liquid
the electrophile. With benzyl bromide as electrophile, alone. The charge distribution over the nitrogen atom
tert-butyl-N-diphenylmethyleneglycinate (substrate-II) in the chiral ionic liquid (preparation and structure pro-
produced (S)-tert-butyl-N-diphenylmethylene-L-phe- vided as electronic Supplementary information) is so
nylalaninate as the major isomer (ee 28%, entry 14, diffused that it fails to replace the potassium ion bound
table 2). Here too incorporation of the chiral ionic to the enolate and form an ion pair with the enolate ion.
liquid improved the asymmetric induction by over 60% This is the first instance as far as literature survey says
from the previous value (17%, entry 17, table 1).
where a chiral ionic liquid acts as a chiral improver in

Palladium catalysed asymmetric alkylation of benzophenone Schiff base glycine esters in ionic liquids
471
Table 2. Alkylation of glycine derivatives under phase transfer conditions using chiral orthopalladated complex and chiral
ionic liquid(CIL) at RT.
Entry No
Catalyst used
substrate
electrophile
Solventc
CH2Cl2
CIL
CIL
[Bmim]PF6
[Bmim]BF4
CIL
CIL
CIL
[Bmim]PF6
CIL
[Emim][Tf2N]
CIL
[Emim][Tf2N]
CIL
CIL
CIL
[Emim][Tf2N]
CIL
Yield (%)a
ee (%)b
1
2
3
4
5
6
7
8
Complex-I
Complex-I
Complex-I
Complex-I
Complex-I
Complex-II
Complex-III
Complex-IV
Complex-III
Complex-III
Complex III
Complex-IV
Complex-IV
Complex-I
Complex II
Complex-III
Complex-III
Complex-IV
–
I
I
II
I
I
I
I
I
II
II
II
II
II
II
II
II
II
II
II
II
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
CH3I
88
88
92
86
88
88
92
84
85
88
82
85
88
90
88
88
85
85
70
74
30
42
48
24
26
35
30
34
24
35
37
35
37
28
25
18
20
9
10
11
12
13
14
15
16
17
18
19
20
CH3I
C6H5CH2Br
C6H5CH2Br
C6H5CH2Br
C6H5CH2Br
C6H5CH2Br
C6H5CH2Br
C6H5CH2Br
20
CIL
Racemic
Racemic
–
CILd
a: isolated yield after column chromatography on basic alumina
b: determined by 1H NMR and chiral HPLC analysis
c: ionic liquids were always used in association with dichloromethane and 50% aq KOH solution
d: 18-crown-6 (10%) was used along with 10 mol% of CIL
asymmetric alkylation reactions. By changing the sol- simultaneous computer calculations to understand the
vent composition with chiral ionic liquid and even by nature of interactions and influence of counter-ion
incorporation of room temperature ionic liquids like involved in such phase-transfer alkylation reactions.
[Bmim]PF6 (1-butyl-3-methyl imidazolium hexafluoro-
Dramatic counter anion effects were observed in
phosphate) and [Bmim]BF4 (1-butyl-3-methyl imidazo- phase transfer catalysis in Michael addition system by
lium tetrafluoroborate), there was however no improve- Shibasaki et al.41 making it possible to further improve
ment on the product purity (entry 4 and 5, table 2). reactivity and selectivity. Since the (+) variety of the
The slight decrease in these cases may be attributed to ephedrinium chiral ionic liquid could not be prepared
the high viscous nature of the ionic liquids affecting employing the same procedure nor the desired ionic
the diffusion phenomenon in phase-transfer alkylation liquids with ephedrinium could be prepared by chang-
reactions.
ing the anionic part, we examined the asymmetric alky-
We almost invoked the idea that it is the chirality of lation reaction under phase-transfer conditions using
the chiral ionic liquid employed that led to enhance- the following ionic liquids as shown in table 3. Some
ment of asymmetric induction until before we thought of these ionic liquids were prepared and characterized
of using an ionic liquid having the same counter- by known literature methods and others were obtained
ion as the N,N-dimethylephedrinium salt. Fortunately, from commercial sources. The conversion yield and the
we could use the [Emim][Tf2N] ionic liquid (Solvent- ee percentage change with and without the ionic liquids
Innovation, Germany, 99% pure) as a substitute to the are presented here. For the sake of comparison we have
chiral ionic liquid. Contrary to what we observed in used the same catalyst, same alkylating agent and same
case of [Bmim]PF6, we found almost similar incre- substrate under similar experimental conditions.
ment in ee as noticed in case of the chiral ionic liquid
We tried to investigate what physicochemical prop-
(entries 10,11 and 16,17, table 2). The thought that chi- erty if not chirality of the ionic liquid could lead to
rality of the chiral ionic liquid would be the factor for almost 50% increment in asymmetric induction. Param-
the rise in ee content soon subsided. We focused our eters like density, viscosity, conductivity and solubility
work on more studies with different ionic liquids and of the ionic liquids were therefore considered that could

472
Dae Hyun Kim et al.
Table 3. Anionic effect of imidazolium based ionic liquids in catalytic asymmetric PT alkylationa promoted by palladium
catalyst.b
Entry
Ionic liquid used (5 mol%)
Time (h)
Yield (%)c
Ee (%)
Ee changed
1
2
3
4
5
6
7
8
9
10
[BMIm]Cl
[BMIm]BF4
[BMIm]PF6
[BMIm]PF6
12
12
12
06
24
12
12
12
24
12
84
78
74
40
78
80
86
88
90
88
28
22
20
12
22
24
28
30
30
36
+12%
−12%
−20%
−52%
−12%
−4%
[BMIm]PF6
[BMIm]MeHPO3
[BMIm]MeSO4
[BMIm]CH3COO
[BMIm]CH3COO
[BMIm]Tf2N
+12%
+20%
+20%
+44%
a: alkylating agent: CH3I; substrate: tert-butylglycine Schiff base ester; T = 20◦C; base: 50% aq KOH
b: catalyst = 10 mol % orthopalladated benzylamine complex(S-enantiomer)
c: isolated yield before column chromatography over basic alumina
d: compared with the run involving catalyst only under similar PT conditions (entry 10, table 1)
throw some light in this regard. There appears to be no a greater chance to affect the stereo-geometry around
overall correlation between density, viscosity and con- the enolate ion formed at the interface of the aqueous
ductivity of the ionic liquids studied as revealed in lit- and the organic layer. The electrophile would prefer-
eratures.42,43 The usual density and viscosity order of ably approach the enolate ion-bound palladium com-
ionic liquids and other physicochemical parameters are plex from the −site which is sterica−lly less hindered.
given separately as supplementary information.
Anions like BF4 , CH3COO−, MeSO4 and Cl− because
Although (CF3SO2)2N− has the highest density of their high solubility in the aqueous phase will have
because of its high molecular mass, its viscos- minimal effect in asymmetric induction process as wit-
ity is quite low indicating very weak attraction nessed by low ee increment (4–12%, table 3) using
with the imidazolium cation. The high viscosity of these anions under phase-transfer alkylation conditions.
[BMIm]PF6 is attributed to strong C(2)–H–F (imida- Low viscosity of the ionic liquid and low solubility
zolium cation–anion) interaction as molecular structure in the aqueous phase seems to be the right combina-
of the ionic liquid shows much shorter C–H–F dis- tion that works in favour of [BMIm]Tf2N in influencing
tances (2.3 Å) compared to the H–F Van der Waals dis- enantioselectivity under present circumstances.
tance of 2.7 Å.42 The weak interaction of Tf2N− (bis-
Computer studies have been made to examine
trifluoromethanesulphonimidate anion) with the imida- the complexes formed and the nature of interactions
zolium cation will lead to greater Van der Waals attrac- between the chiral phase transfer catalyst and enolates
tion with the palladium complex in the organic layer. that are known to be alkylated enantioselectively. A
The steric congestion around the enolate ion would similar molecular recognition technique and computa-
therefore lead to enhanced enantioselectivity. Though tional tool have been employed by Lipkowitz et al.44
we expected the acetate and the chloride anions to inter- although their catalysts, used as asymmetric templates,
act with the palladium complex better because of their were derived from the cinchona alkaloid family.
more localized charges, their increased solubility in the
In the mechanistic model (scheme 2), contact ion
aqueous phase seems to nullify this advantage. Regard- pairing takes place between the anionic oxygen of the
ing solubility of ionic liquids in water at 20◦C,−for th−e enolate and just one of the tetrahedral faces of the
same [BMIm]+ cation, BF4−, CF3SO3−, CH3CO2 , NO3
cationic nitrogen of the alkaloid species. In case of the
and Cl− all display complete solubilities with water. chiral palladium complexes, the bridged dimer species
[BMIm]PF6 and [BMIm]Tf2N, on the other hand, show spontaneously dissociates into the monomer solvent
very low solubility with water at room temperature. adduct and immediately combines with the Z-enolate
Since the solubility of [BMIm]Tf2N in water is quite to form a stable square planar species. This mode of
low (1.4 mass%),37 it will form a rich organic phase bonding actually prevents the enolate component to be
layer with CH2Cl2 in which the palladium catalyst is solvated or racemized in strongly basic media. The eno-
eventually dissolved. The anion would therefore have late with the catalyst is successfully transferred to the

Palladium catalysed asymmetric alkylation of benzophenone Schiff base glycine esters in ionic liquids
473
Scheme 2. General phase-transfer mechanism for asymmetric alkylation of active methylene compounds.
organic layer where it is lined up in the sterically most been taken as the reference substrate in all model
favourable geometry with the alkylating agent. Only the computational studies with benzylamine orthopalla-
appropriate re face or the si face of the α-carbon of the dated complex as the catalyst. The electrophile is not
enolate is available for electrophilic attack leading to accounted for in the modelling study and it is assumed
the observed R and S products respectively. The nitro- that the low energy structures derived from the model
gen atom of the chiral ionic liquid fails to dislodge the are the ones leading to product.
potassium or sodium ion bound to the enolate oxygen
The palladium catalyst with S-ligand (complex III)
(scheme 2) and therefore only racemic products have coordinates to Z-enolate in a square planar fashion.
been identified when N,N-dimethylephedriniumbis- The complex with si face exposed to give S-enantiomer
(trifluoromethanesulfon)imidate has been employed in is calculated to be more stable than one with re face
the reaction medium without the palladium complexes exposed to give R-enantiomer by 3.5 kJ/mol. Palladium
as catalyst.
catalyst with R-ligand (complex IV) also coordinates
to Z-enolate in a square planar fashion. In this case,
the complex with re face exposed to give R-enantiomer
(figure 1b) is calculated to be more stable than one
with si face exposed to give S-enantiomer (figure 1a) by
almost 3.5 kJ/mol.
3.3 Computational studies and analysis based on
findings
The interactions between the Z-enolate form of
glycine derivative and palladium chiral catalysts were
theoretically investigated using a Gaussian 03 pro-
gram.45 tert-butyl-N-diphenylmethyleneglycinate has
With the incorporation of the ionic liquids having
trifluoromethane suphonyl imide anions to complex 3
favouring the S-enantiomer, coulombic and Van der
Waals attraction of the palladium complex and the ionic
(a)
(b)
Figure 1. Chiral palladium benzyl complex coordinated to Z-enolate. (a) S-enantiomer; (b) R-enantiomer.

474
Dae Hyun Kim et al.
(a)
(b)
Figure 2. (a) Side view with anion coordination. (b) Top view with anion coordination.
liquid lead to a stereogenic center that favours the incre- Supplementary information
ment in ee (figure 2). The oxygen atoms bound to sul-
Synthesis, 1H NMR spectra and physicochemical prop-
phur in the sulphonyl imide anion has been found in
the model to interact with the CH3 groups of the palla-
dium complex. 1H NMR studies of the recovered ionic
liquid phase after product extraction however did not
reveal any changes in peak positions and so no coor-
dination could be established through spectral stud-
ies. Both the side view (figure 2a) and the top view
(figure 2b) of the coordinated anion of the ionic liq-
uid with the palladium bound enolate however shows
considerable steric congestion on the re face. There-
fore forces the electrophile to approach from the much
exposed si face leading to increased percentage of the
S-enantiomer. BF4− and PF−6 are not good coordinat-
ing anions42 that can stabilize a geometry for increased
asymmetric induction and therefore no ee increase is
noted on employing either [Bmim]BF4 or [Bmim]PF6
as chiral improvers.
erties of ionic liquids are provided as supplementary
material (see www.ias.ac.in/chemsci).
Acknowledgements
Part of this project was supported by Science and Tech-
nology Department, Ministry of Korean Government
and part by the University Grants Commission (UGC),
Eastern Regional Office, India.
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