Synthesis and characterization of conformationally rigid chiral pyridine-N-heterocyclic carbene-based palladacycles with an unexpected Pd-N bond cleavage

Article abstract of DOI:10.1002/chir.22116

The versatility of a previously developed method for the synthesis of chiral carbene-based palladacycles is demonstrated through the synthesis of two new chiral pyridine-functionalized N-heterocyclic carbene palladacycles with different wingtip groups. The efficiency in their resolution with different counter anions and different chiral amino acid salt auxiliaries has been studied. The absolute stereochemistries of all the chiral compounds were confirmed by single crystal X-ray crystallography. An unexpected Pd-N bond cleavage that resulted in the racemization of the α-carbon center in these complexes has also been investigated. Chirality 25:149-159, 2013. 2013 Wiley Periodicals, Inc. Copyright

Full text of DOI:10.1002/chir.22116

CHIRALITY 25:149–159 (2013)
Synthesis and Characterization of Conformationally Rigid Chiral
Pyridine–N-Heterocyclic Carbene-Based Palladacycles with an
Unexpected Pd–N Bond Cleavage
1
1
1
2
1
*
*
KIM HONG NG, YONGXIN LI, WEI XIAN TAN, MINYI CHIANG, AND SUMOD A. PULLARKAT
1Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore
2School of Chemical and Life Sciences, Singapore Polytechnic, Singapore
ABSTRACT
The versatility of a previously developed method for the synthesis of chiral
carbene-based palladacycles is demonstrated through the synthesis of two new chiral
pyridine-functionalized N-heterocyclic carbene palladacycles with different wingtip groups.
The efficiency in their resolution with different counter anions and different chiral amino
acid salt auxiliaries has been studied. The absolute stereochemistries of all the chiral
compounds were confirmed by single crystal X-ray crystallography. An unexpected Pd–N
bond cleavage that resulted in the racemization of the a-carbon center in these complexes
has also been investigated. Chirality 25:149–159, 2013.
© 2013 Wiley Periodicals, Inc.
KEY WORDS: N-heterocyclic carbene; palladacycle; conformational study/Pd–N cleavage
INTRODUCTION
A thorough conformational analysis of the palladacycles was
also undertaken both in solid state and in solution.
The history of carbene complexes can be traced back to
1964, when Fischer successfully characterized the first
carbene complex that was coordinated to a tungsten metal
center, and approximately 10 years later, Schrock synthesized
another class of carbene complexes exhibiting distinctively
different characteristics to the Fischer carbene.1,2 However,
it was Arduengo who reported the first crystalline form of
a free carbene ligand that fueled the unprecedented
development in carbene chemistry in 1991.3 Compared to
phosphines, N-heterocyclic carbenes (NHCs) are mainly
strong s donors and weak p-accepting ligands.4–9 Due to
the strong metal–NHC bond, NHC-based catalytic systems
typically exhibit a high degree of stability against heat, mois-
ture, and air during the course of their synthetic applica-
tions. Therefore, NHCs have emerged as a popular class of
ligands in organometallic catalysis especially in palladium-
based catalytic systems.10–30 Chelating systems are believed
to be able to provide a more rigid environment in the course
of catalysis, thereby providing more steric control to induce
better selectivity in asymmetric scenario.31 Amino and imino
functionalized NHC palladacycles have displayed remark-
ably enantiomeric excess values of up to 92% in asymmetric
allylic alkylation reaction.32,33 Pyridine-functionalized NHCs
have also attracted recent interest and have demonstrated
good potential in different catalytic scenarios.34–46 Crabtree
et al.47,48 and Hahn et al.49 have previously reported a series
of palladium tridentate NHC complexes and successfully
applied them to the catalysis of the Heck reaction. A quick
literature search revealed that previous efforts in the synthesis
of chiral NHC palladacycles typically involved chiral starting
materials like (S)-(-)-(1,1’-Binaphthalene-2,2’-diyl)bis(diphenyl-
phosphine); BINAP and oxazolines, and to the best of our
knowledge, none of the abovementioned pyridine–NHC
palladacycles exhibited any chirality in the carbon chelate
backbone. We have previously demonstrated an effective
method to synthesize chiral pyridine-functionalized NHC
palladacycles with a chiral carbon chelate backbone; we
hereby extend the efficient and facile synthesis and character-
ization of a series of pyridine–NHC chelating palladacycles.50
RESULTS
The synthesis of palladacycle 1 has been previously
reported.50 The two new palladacycles 2 and 3 were synthe-
sized via a similar methodology starting from the respective
imidazolium substrates as shown in Scheme 1. Similar to palla-
dacycle 1, palladacycles 2 and 3 were insoluble in an array of
organic solvents with the exception of dimethyl sulfoxide
(DMSO) at 60ꢀC. Single crystal X-ray crystallography grade
crystals of the palladacycles were obtained via slow diffusion
of diethyl ether into a MeOH/DMSO solution. The ORTEPs
for the newly synthesized palladacycles are shown in Figures 1
and 2. Racemic palladacycles 2 and 3 were crystallized in a
centrosymmetric space group. This study revealed that the
six-membered chelate rings of the palladacycles are in the boat
confirmation, with the phenyl group on the sp3 carbon of the
ring occupying the axial position. The selected bond lengths
and angles are given in Tables 1, 2, and 3. Both palladacycles
2 and 3 do not exhibit any marked differences in terms of bond
lengths and angles as compared to their analog 1. The single
X-ray crystallography-based analysis of palladacycle 2 further
revealed that Cl(2) being trans to the NHC will experience a
stronger trans effect as compared to Cl(1) which is trans to a
N atom. The trans effect is evident in the elongation of 0.062 Å
in the Pd(1)–Cl(2) bond compared to the Pd(1)–Cl(1) bond.
Additional Supporting Information may be found in the online version of this
article.
Contract grant sponsor: We thank Nanyang Technological University for
support of this research (MOE2009-T2-2-065) and for a research scholarship
to MC..
*Correspondence to: Sumod A. Pullarkat, Division of Chemistry and Biological
Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological
University, Singapore 637371. E-mail: sumod@ntu.edu.sg; Minyi Chiang, School
of Chemical and Life Sciences, Singapore Polytechnic, Singapore. E-mail:
chiang_minyi@sp.edu.sg
Received for publication 28 May 2012; Accepted 09 August 2012
DOI: 10.1002/chir.22116
Published online 18 January 2013 in Wiley Online Library
(wileyonlinelibrary.com).
© 2013 Wiley Periodicals, Inc.

150
NG ET AL.
N
N
N
Pd
Me
Cl
Cl
Palladacycle 1
N
N
N
Me
N
,
,
N
Cl
N
N
MeCN
MeCN
N
N
N
N
Cl
Cl
10
Me
11
1. Ag2O, CH2Cl2
1. Ag2O, CH2Cl2
2. PdCl2(MeCN)2, MeCN
2. PdCl2(MeCN)2, MeCN
N
N
N
N
N
N
Pd
Pd
Me
Cl
Cl
Cl
Cl
Palladacycle 2
Palladacycle 3
Scheme 1. Synthesis of pyridine–NHC palladacycles 2 and 3.
Fig. 2. ORTEP representation of palladacycle 3 (50% probability ellipsoids
shown with selected hydrogen atoms omitted for clarity).
Fig. 1. ORTEP representation of palladacycle 2 (50% probability ellipsoids
shown with selected hydrogen atoms omitted for clarity).
group in the carbene moiety and that of the six-membered
CN chelate are projecting towards the opposite sides of the
square plane. Likewise, for palladacycle 3, the trans effect is
evident in the elongation of 0.068 Å in the Pd(1)–Cl(2) bond
when compared to the Pd(1)–Cl(1) bond. The palladium
The palladium center is in a square planar geometry with a
small tetrahedral distortion angle of 2.55ꢀ between the {N
(3)–Pd(1)–C(2)} and {Cl(1)–Pd(1)–Cl(2)} planes. The NMe
Chirality DOI 10.1002/chir

CHIRAL PYRIDINE–NHC-BASED PALLADACYCLES
151
TABLE 1. Selected bond lengths (Å) and angles (º) for
palladacycle 2
the axial position can be established. In addition, as illus-
trated in Figure 4, if the other isomer with the Ph group in
the equatorial position is indeed present in the solution,
correlations between the H11–H15 protons with both the
Pd(1)–C(2)
Pd(1)–Cl(1)
C(2)–N(1)
C(8)–N(1)
1.952(3) Pd(1)–N(3)
2.307(8) Pd(1)–Cl(2)
1.343(3) C(2)–N(2)
1.394(3) C(3)–N(2)
1.463(4) C(9)–N(2)
85.53(10) C(2)–Pd(1)–Cl(1)
2.051(2)
2.369(7)
1.351(3)
1.394(3)
1.471(3)
91.01(8)
175.88(8)
93.07(3)
119.14(19)
1
H17 and H4 protons should be observable in the 2D H–1H
ROESY NMR spectrum. However, these correlations were
conspicuously absent. Therefore, it can be concluded that in
solution, no rotational conformers were present (at least in
significant amounts so as to be detected by the ROESY exper-
iment), and palladacycle 2 remained locked as it was in solid
state in the boat conformation with its Ph group in the axial
position. Similarly, the conformation of palladacycle 3 in solu-
tion was also determined by 2D 1H–1H ROESY NMR (Fig. 5).
Figure 2 shows the numbering scheme of the protons, with
the protons numbered in accordance to their respective
carbons. The key correlation (A) shows that a strong interac-
tion is present between the H10 and H18 and H10 and H9
protons. This indicated that palladacycle 3 is in a boat
conformation with the phenyl group in the axial position.
As shown in Figure 6, if palladacycle 3 is able to undergo
ring flipping, the presence of the other rotational conformer
with the a-phenyl group in the equatorial position should be
C(1)–N(1)
C(2)–Pd(1)–N(3)
N(3)–Pd(1)–Cl(1)
N(3)–Pd(1)–Cl(2)
N(1)–C(2)–Pd(1)
174.71(6)
90.36(6)
133.7(2)
C(2)–Pd(1)–Cl(2)
Cl(2)–Pd(1)–Cl(1)
N(2)–C(2)–Pd(1)
C(16)–N(3)–Pd(1) 121.09(18) C(20)–N(3)–Pd(1) 118.84(19)
TABLE 2. Selected bond lengths (Å) and angles (º) for
palladacycle 3
Pd(1)–C(7)
Pd(1)–Cl(1)
C(7)–N(2)
C(9)–N(2)
1.963(3) Pd(1)–N(3)
2.287(8) Pd(1)–Cl(2)
1.350(3) C(7)–N(1)
1.371(4) C(8)–N(1)
1.471(4) C(6)–N(1)
86.06(10) C(7)–Pd(1)–Cl(1)
2.052(2)
2.355(8)
1.347(4)
1.396(4)
1.438(4)
91.81(8)
176.05(9)
91.24(3)
119.0(2)
C(10)–N(2)
C(7)–Pd(1)–N(3)
N(3)–Pd(1)–Cl(1)
N(3)–Pd(1)–Cl(2)
N(1)–C(7)–Pd(1)
176.64(7)
90.78(7)
136.1(2)
C(7)–Pd(1)–Cl(2)
Cl(2)–Pd(1)–Cl(1)
N(2)–C(7)–Pd(1)
C(17)–N(3)–Pd(1) 121.12(19) C(21)–N(3)–Pd(1) 120.3(2)
H9
H17,H4
H19
H20
H18
H11-H15
TABLE 3. Comparison of selected bond lengths (Å) and
angles (º)
Palladacycle
1
2
3
Carbene C–Pd/Å
1.951(3)
0.064
90.8(7)
1.952(3)
0.062
91.01(8)
1.963(3)
0.068
91.81(8)
Pd–Cl bond elongation/Å
Carbene carbon–Pd–Cl/ꢀ
(A)
center is in a square planar geometry with minimal tetrahedral
distortion angle of 0.16ꢀ between the {N(3)–Pd(1)–C(7)} and
{Cl(1)–Pd(1)–Cl(2)} planes. Similar to palladacycle 2, the
NPh group in the carbene moiety and the CN chelate pallada-
cycle 3 is also projecting in the opposite side of the
square planar palladium center. Due to the bulkiness of the
Ph group in palladacycle 3, the NPh group is tilted at 42.8ꢀ
away from the plane of the imidazole ring to avoid any
unfavorable steric interaction with the Cl(1).
Fig. 3. 2D 1H–1H ROESY NMR of palladacycle 2.
In the context of potential application of these complexes in
asymmetric catalysis scenarios, it is imperative to confirm
whether the axial orientation adopted by the phenyl group
was indeed retained in solution. The conformation of pallada-
cycle 2 in solution was thus determined by two-dimensional
(2D) Proton–proton rotating-frame Overhauser effect spec-
troscopy nuclear magnetic resonance (1H–1H ROESY NMR)
analysis (Fig. 3). The assignment of proton signals was made
by a combination of correlation spectroscopy, heteronuclear
multiple quantum coherence, and heteronuclear multiple-
bond correlation. Figure 1 shows the numbering scheme of
the protons with the protons numbered in accordance to their
respective carbons. From the key correlation (A) seen in the
ROESY NMR, there is a strong interaction between H9–H17
and H9–H4. Therefore, the presence of the palladacycle 2 in
the boat conformation in solution with the phenyl ring in
Fig. 4. Two possible ring conformations for palladacycle 2.
Chirality DOI 10.1002/chir

152
NG ET AL.
Resolution of the racemic palladacycles (Æ)-2 and (Æ)-3
H18,H9
H10
(similar to palladacycle 150) was performed via screening a
range of amino acid salts in methanol. Equimolar amounts
of sodium (SC)-phenylalanate were able to coordinate to
(Æ)-2, while sodium (SC)-prolinate was added to (Æ)-3. The
formation of the diastereomeric pair can be confirmed by
1H NMR via the two distinct sets of protons peaks. The
diastereomerically pure crystal of (SC,SC)-4 > 99% de (accord-
ing to 1H NMR spectrum) with [a]365 = +202 (c = 0.55, MeOH)
formed from (Æ)-2 was selectively crystallized by slow
diffusion of diethyl ether into an ethanol solution of the diaste-
reomeric mixture. The best diastereomeric ratio was 1:20
with further slow evaporation of the diastereomers mixture
in acetonitrile. From the molecular structure (Fig. 7), the S
absolute configuration of the a-carbon stereocenter can be
confirmed using (SC)-phenylalanate as reference point, as
well as based on the anomalous X-ray scattering method with
the Flack parameter of 0.001(16). Complex (SC,SC)-4 adopted
the trans-(N,N) arrangement, with a boat conformation in the
six-membered ring where the phenyl group is occupying the
axial position (Table 4). Optically active complex (S)-2 was
achieved in 60% yield in the form of yellow powder with [a]
436 = À27.8, (c = 0.5, DMSO) via treatment with 1-M HCl (SC,
SC)-4 (Scheme 2). Subsequently, the diastereomerically pure
complex (SC,SC)-5 formed by reacting (Æ)-3 with sodium
(SC)-prolinate was isolated by slow diffusion of diethyl ether
into a MeOH solution of the diastereomeric mixture (Fig. 8).
It has a diastereomeric purity of >99% de with [a]436 = À167
(c = 0.5, MeOH). Similar to complex (SC,SC)-4, (SC,SC)-5 also
adopted the trans-(N,N) arrangement with the six-membered
ring in boat conformation (Fig. 9). The selected bond lengths
and angles were showed in Table 5.
H20
H21
H19
Ph Protons
Ph Protons
(A)
Fig. 5. 2D 1H–1H ROESY NMR of palladacycle 3.
detected in the 2D H–1H ROESY NMR spectrum. Although
in this instance, the correlation signals of H12–H16 cannot
be assigned conclusively due to overlapping with the H1–H5
protons; however, from the absence of any correlations
between the Ph protons with both H18 and H9 in the 2D
1H–1H ROESY NMR spectrum, conclusion can be drawn that
the other conformation does not exist in solution within the
detection limits of the NMR experiment. Upon changing the
carbene skeletal framework from imidazolium to benzimida-
zolium, no significant differences were observed in the bond
lengths between the carbene carbon and the palladium
center. The degree of elongation of the Pd–Cl bond trans
to the NHC was also comparable. Furthermore, upon the
introduction of bulkier R groups like phenyl, there is a slight
increase of about 0.01 Å in the bond lengths between the
carbene carbon and the palladium centers compared to the
less bulky methyl group. There is also a very slight increase
(0.004 Å) in the elongation of the Pd–Cl bond length that
is trans to the NHC in the case of palladacycle 3 when
compared to palladacycle 1. An increase in the carbene
carbon–Pd–Cl (Cl trans to the pyridine) bond angle is
observed with the increase in the bulkiness of the R group.
This can be attributed to the need for the angle enlargement
to accommodate the sterically bulkier R group. All of the
above observations are summarized in Table 3.
1
Following the same method used in Scheme 2, complex
(SC,SC)-5 was treated with 1-M HCl to achieve the optically
Fig. 6. Two possible conformations of palladacycle 3.
Chirality DOI 10.1002/chir
Fig. 7. Molecular structure of (SC,SC)-4.

CHIRAL PYRIDINE–NHC-BASED PALLADACYCLES
153
TABLE 4. Selected bond lengths (Å) and angles (ꢀ) for complex
(SC,SC)-4
Pd(1)–C(1)
Pd(1)–N(4)
C(1)–Pd(1)–N(4)
1.950(2)
2.013(15) Pd(1)–O(1)
96.73(7) C(1)–Pd(1)–N(3)
Pd(1)–N(3)
2.030(16)
2.047(14)
86.75(7)
N(4)–Pd(1)–N(3) 176.34(7)
C(1)–Pd(1)–O(1)
N(3)–Pd(1)–O(1)
N(1)–C(1)–Pd(1)
172.62(6)
95.91(6)
133.26(15)
N(4)–Pd(1)–O(1)
N(2)–C(1)–Pd(1)
80.77(6)
119.08(14)
C(16)–N(3)–Pd(1) 122.70(12)
C(20)–N(3)–Pd(1) 118.22(14)
Fig. 9. Molecular structure of complex (SC,SC)-5.
TABLE 5. Selected bond lengths (Å) and angles (ꢀ) for complex
(SC,SC)-5
Scheme 2. Removal of chiral auxiliary using 1-M HCl.
Pd(1)–C(1)
Pd(1)–N(4)
C(1)–Pd(1)–N(4)
1.952(2)
2.036(17) Pd(1)–O(1)
97.87(8) C(1)–Pd(1)–N(3)
Pd(1)–N(3)
2.022(18)
2.053(15)
85.97(8)
N(4)–Pd(1)–N(3) 172.97(7)
C(1)–Pd(1)–O(1)
N(3)–Pd(1)–O(1)
N(1)–C(1)–Pd(1)
171.17(8)
93.93(7)
136.04(16)
pure (S)-3. The single crystal X-ray diffraction grade single
crystal of palladacycle (S)-3 (Fig. 10 and Table 6) was
obtained from the slow diffusion of diethyl ether into a
MeOH/DMSO solution. The absolute configuration at the
stereocenter was shown to be S and is supported by Flack
parameter of À0.005(14). Efforts to crystallize out the complexes
(RC,SC)-4, (RC,SC)-5, (S)-2, (R)-2, and (R)-3 had been unsuc-
cessful to date.
It is well known that one of the chloride ligands in the
palladacycles 1–3 can be selectively replaced by stronger
incoming ligands such as triphenylphosphine. Therefore, in
order to improve the solubility of the complex in organic
solvents, one of the chloro ligand on the palladium center
had been changed to triphenylphosphine as shown in
Scheme 3. The introduction of the bulky triphenylphosphine
into the complex is postulated to be able to disrupt the p–p
stacking in the crystal lattice and therefore lead to an increase
in solubility of the complexes. The resolved palladacycles
(R)-1, (S)-1, (S)-2, and (S)-3 were added to 1 equivalent of
triphenylphosphine in dichloromethane and stirred for an
N(4)–Pd(1)–O(1)
N(2)–C(1)–Pd(1)
81.37(6)
118.24(16)
C(17)–N(3)–Pd(1) 121.21(16)
C(21)–N(3)–Pd(1) 119.30(14)
hour to give (R)-6, (S)-6, (S)-7, and (S)-8, respectively. The
progress of the reaction was monitored by phosphorus-31
(31P) NMR, and all the four chiral palladacycles gave a new
single phosphorous peak (summarized in Table 7) indicative
of the fact that a single regioisomer was being formed. X-ray
diffraction grade crystals are obtained through slow diffu-
sion of diethyl ether into the methanol solution of (R)-6,
Fig. 8. Diastereomeric mixture of palladacycle 3 with sodium (SC)-prolinate.
Fig. 10. Molecular structure of (S)-3.
Chirality DOI 10.1002/chir

154
NG ET AL.
TABLE 6. Selected bond lengths (Å) and angles (ꢀ) for complex
Akin to (S)-7, (S)-8 was prepared as per the procedure
illustrated in Scheme 3. A new signal in 31P NMR was
observed at 26.94 ppm, and no other resonance signals were
seen. Since the phosphorous chemical shift of palladacycle
(S)-8 is quite similar to that of palladacycle (S)-7 and (S)-6,
the triphenylphosphine is expected to be coordinated trans
to the Npyridine. Surprisingly, a Pd–N bond cleavage occurred
between the Npyridine atom and the palladium center as seen
from X-ray diffraction studies (Fig. 13) and as illustrated in
Scheme 4. Consequently, complex 9 loses its chirality and be-
came a racemic singly ligated complex. The product was
initially isolated as an off-white solid after 1 h and displayed
optical activity ([a]436 = À233, c = 0.20, MeOH). However,
racemization of the product occurred after 24 h in solution
during the crystallization process, and the crystals of racemic
complex (Æ)-9 were isolated. The product that was stored in
the solid form when analyzed for optical activity after 1 week
of storage continued to display optical activity. Therefore,
racemization of the product only occurred or was accelerated
in solution state.
(S)-3
Pd(1)–C(1)
Pd(1)–Cl(2)
C(1)–Pd(1)–N(3)
N(3)–Pd(1)–Cl(1)
N(3)–Pd(1)–Cl(2)
N(2)–C(1)–Pd(1)
1.948(3) Pd(1)–N(3)
2.376(7) Pd(1)–Cl(1)
2.047(3)
2.301(8)
91.6(9)
176.2(9)
92.0(3)
84.8(11)
175.3(8)
91.5(8)
C(1)–Pd(1)–Cl(1)
C(1)–Pd(1)–Cl(2)
Cl(1)–Pd(1)–Cl(2)
N(1)–C(1)–Pd(1)
121.5(19)
133.5(2)
C(21)–N(3)–Pd(1) 119.5(2)
C(17)–N(1)–Pd(1) 121.5(2)
The unexpected bond cleavage may be attributed to
the bulkiness of the phenyl substituent on the N of the imida-
zolium since the Npyridine–Pd bond cleavage was not observed
in complexes (S)-6 and (S)-7 which have comparatively
less bulky methyl group as the substituent on the wingtip
N (but initial signs of strain are evident in the bond distances
listed in Table 7). Due to the presence of the sterically bulky
moeity, the palladium center might not be able to accom-
modate the triphenylphosphine group while maintaining
the bidentate chelating ligand in its coordination sphere.
Therefore, the weaker Npyridine–Pd bond cleaves in order
to create enough space for the incoming triphenylphosphine
group. The hemilability of pyridine-functionalized NHC has
been observed previously by Lin et al.51 Upon introduction
of triphenylphosphine, an Npyridine–Pd cleavage was also
observed in their NHC palladium system. The hemilability
of this NHC ligand system was further challenged by the
use of a weaker and softer coordinating ligand as compared
to PPh3 and triphenylarsine. Scheme 5 shows the possibility
of the racemic complex 10 adopting either structure. The
X-ray diffraction grade crystal of racemic complex 10 was
obtained, and from the X-ray crystallography study, an
Scheme 3. Replacement of one chloride ion with PPh3.
(S)-6, (S)-7, and (S)-8 shown in Figures 11, 12, and 13, and the
selected bond length and angles are tabulated in Tables 8,
9, 10, and 11. Replacement of one of the chloride ions with
PPh3 therefore improved the solubility tremendously in
dichloromethane (DCM) with retention of the chiral center.
Crystals were obtained easily and ORTEP of (S)-7 is shown
in Figure 12 along with significant bond parameters in
Table 10.
TABLE 7. Comparison of structures and bond angles (ꢀ)
Palladacycle
(S)-6
(S)-7
(S)-8
31P NMR/ppm
28.31
Boat
5.2
28.99
Boat
4.8
26.94
Conformation
–
–
–
C(1)–Pd(1)–P(1)/ꢀ
Distortion of square planar/ꢀ
13.7
6.37
N
pyridine–Pd cleavage was observed again even with a weaker
Fig. 11. Molecular structures of (R)-6 and (S)-6.
Chirality DOI 10.1002/chir

CHIRAL PYRIDINE–NHC-BASED PALLADACYCLES
155
TABLE 9. Selected bond lengths (Å) and angles (ꢀ) for complex
(S)-6
Pd(1)–C(1)
Pd(1)–Cl(1)
C(1)–Pd(1)–N(3)
N(3)–Pd(1)–P(1) 168.5(4)
N(3)–Pd(1)–Cl(1) 92.4(4)
C(17)–P(1)–Pd(1) 116.7(5)
C(23)–P(1)–Pd(1) 113.2(5)
1.977(14) Pd(1)–N(3)
2.115(12)
2.264(4)
97.9(4)
172.1(5)
87.3(14)
109.8(5)
–
2.329(3)
83.7(5)
Pd(1)–P(1)
C(1)–Pd(1)–P(1)
C(1)–Pd(1)–Cl(1)
P(1)–Pd(1)–Cl(1)
C(29)–P(1)–Pd(1)
–
TABLE 10. Selected bond lengths (Å) and angles (ꢀ) for
complex (S)-7
Pd(1)–C(1)
Pd(1)–Cl(1)
C(1)–Pd(1)–N(3)
N(3)–Pd(1)–P(1)
C(1)–Pd(1)–Cl(1)
C(21)–P(1)–Pd(1)
C(27)–P(1)–Pd(1)
1.972(1)
2.327(4)
84.12(5)
173.55(3)
175.26(4)
112.2(5)
114.3(5)
Pd(1)–N(3)
Pd(1)–P(1)
C(1)–Pd(1)–P(1)
Cl(1)–Pd(1)–P(1)
N(3)–Pd(1)–Cl(1)
C(33)–P(1)–Pd(1)
–
2.094(1)
2.274(4)
95.78(4)
88.55(14)
91.80(3)
111.9(5)
–
TABLE 11. Selected bond lengths (Å) and angles (ꢀ) for
racemic complex 9
Fig. 12. Molecular structure of (S)-7.
Pd(1)–C(1)
Pd(1)–Cl(1)
C(1)–Pd(1)–Cl(1)
P(1)–Pd(1)–Cl(2)
Pd(1)–P(1)–C(34)
Pd(1)–P(1)–C(22)
1.979(18) Pd(1)–P(1)
2.263(5)
2.373(5)
85.5(5)
Pd(1)–Cl(2)
2.354(5)
92.7(5)
92.4(19)
114.49(6)
–
C(1)–Pd(1)–P(1)
Cl(1)–Pd(1)–Cl(2)
Pd(1)–P(1)–C(28)
–
89.1(17)
117.16(6)
111.15(6)
PPh3
N
N
DCM
N
N
N
N
Pd
Ph
Pd
Ph
Cl
Cl
PPh3
Cl
Complex 8
(S)-3
PPh3
DCM
N
N
N
Fig. 13. Molecular structure of racemic complex 9.
Cl Pd
Ph
PPh3
Cl
Complex 9
TABLE 8. Selected bond lengths (Å) and angles (ꢀ) for complex
(R)-6
Scheme 4. Removal of one ClÀ ion by PPh3.
Pd(1)–C(1)
Pd(1)–Cl(1)
C(1)–Pd(1)–N(3)
N(3)–Pd(1)–P(1) 168.4(5)
N(3)–Pd(1)–Cl(1) 92.5(5)
C(23)–P(1)–Pd(1) 113.3(6)
C(29)–P(1)–Pd(1) 109.0(6)
1.975(19) Pd(1)–N(3)
2.115(16)
2.263(5)
97.9(6)
172.3(6)
87.2(18)
116.6(6)
–
2.331(4)
83.7(7)
Pd(1)–P(1)
structure of complex 10 is depicted in Figure 14, selected bond
length and angles are given in Table 12.
C(1)–Pd(1)–P(1)
C(1)–Pd(1)–Cl(1)
P(1)–Pd(1)–Cl(1)
C(17)–P(1)–Pd(1)
–
MATERIALS AND METHODS
Reactions involving air-sensitive compounds were performed under a
positive pressure of purified nitrogen using standard Schlenk techniques.
All the commercially available chemicals and solvents were used without
prior drying or purification. PdCl2(NCMe)2 and 1-phenylimidazole53
52
were prepared according to literature methods. 1H and carbon (13C)
NMR spectroscopies were performed on a Bruker Avance (Bruker BioSpin
AG, Fällanden,Switzerland) 300, 400, and 500 NMR spectrometers
arsine ligand in comparison to phosphine. Hence, the Npyridine
Pd bond in racemic complex 3 exhibits the highest hemilability
when compared to complexes 1 and 2. The molecular
–
Chirality DOI 10.1002/chir

156
NG ET AL.
Scheme 5. Analysis of the hemilability of the pyridine group.
radiation (graphite monochromator). SADABS absorption corrections
were applied. All non-hydrogen atoms were refined anisotropically,
while the hydrogen atoms were introduced at calculated positions
and refined riding on their carrier atoms. The absolute configurations
of the chiral complexes were determined unambiguously by using the
Flack parameter. CCDC 841566, 841567, and 875261–875266 contain
the supplementary crystallographic data for complexes 2, 3, and (Sc,
Sc)-4, (Sc-Sc)-5, (S)-3, (R)-6, (S)-6, (S)-7, 9, and 10, respectively. These
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Center via www.ccdc.cam.ac.uk/data_request/cif.
EXPERIMENTAL
1-Methyl-3-(phenyl(pyridin-2-yl)methyl)-1H-benzo[d]imidazol-3-
ium chloride, [10]. Solid 1-methylbenzimidazole (3.24 g, 24.5 mmol)
was added to a stirring solution of compound 5 (5.00 g, 24.5 mmol) in
50 ml of CH3CN. The reaction mixture was heated at refluxing tempera-
ture for 48 h. The reaction mixture was reduced in vacuo, and the result-
ing oil was stirred in diethyl ether. The diethyl ether layer was decanted
away to give an off-white solid, 5.3 g, 64%. 1H NMR (400 MHz, CDCl3):
d = 4.30 (s, 3H, CH3), 7.31–7.34 (m, 1H, aromatic protons), 7.39–7.44
(m, 5H, aromatic protons), 7.46–7.48 (m, 1H, aromatic proton), 7.56–7.61
(m, 2H, aromatic protons), 7.65–7.67 (m, 2H, aromatic protons), 7.76–7.78
(m, 1H, aromatic proton), 7.84 (t, 1H, JH,H = 3.9Hz, aromatic proton), 8.56
(d, 1H, JH,H = 4.2 Hz, aromatic proton), 11.33 (s, 1H, imidazolium proton)
ppm. 13C NMR (100 MHz, CDCl3): d = 33.99(N–CH3), 67.23(N–C–Ph),
112.56, 116.16, 124.27, 124.77, 126.95, 127.07, 128.98, 129.61, 129.72, 131.57,
132.51, 134.87, 138.15, 144.27, 149.97, 154.73, 155.93. HRMS (ESI) m/z:
[M À Cl]+ calcd for C16H16N3 300.1501, found 300.1503.
Fig. 14. Molecular structure of racemic complex 10.
TABLE 12. Selected bond lengths (Å) and angles (ꢀ) for
racemic complex 10
Pd(1)–C(1)
Pd(1)–Cl(1)
N(1)–C(1)
N(1)–C(2)
N(1)–C(10)
C(1)–Pd(1)–Cl(1)
As(1)–Pd(1)–Cl(2)
1.968(2)
2.358(6)
1.353(3)
1.381(3)
1.482(3)
86.5(6)
Pd(1)–As(1)
Pd(1)–Cl(2)
N(2)–C(1)
N(2)–C(3)
N(2)–C(4)
C(1)–Pd(1)–As(1)
Cl(1)–Pd(1)–Cl(2)
2.359(3)
2.357(6)
1.357(3)
1.389(3)
1.436(3)
91.8(6)
1-Phenyl-3-(phenyl(pyridin-2-yl)methyl)-1H-imidazol-3-ium chlo-
ride, [11]. Liquid 1-phenylimidazole (3.24 g, 24.5 mmol) was added to
a stirring solution of compound 5 (5.00 g, 24.5mmol) in 50 ml of CH3CN.
The reaction mixture was heated at refluxing temperature for 48 h. The re-
action mixture was reduced in vacuo, and the resulting oil was stirred in
diethyl ether. The diethyl ether layer was decanted away to give an off-
white solid, 5.3 g, 64%. 1H NMR (400MHz, CDCl3): d = 6.65 (s, 1H,
aromatic proton), 7.28–7.31 (m, 1H, aromatic proton), 7.35–7.37 (m, 3H,
aromatic protons), 7.42–7.52 (m, 3H, aromatic proton), 7.56–7.58 (m, 2H,
aromatic protons), 7.68–7.76 (m, 5H, aromatic protons), 7.92 (s, 1H, aromatic
proton), 8.17 (s, 1H, aromatic proton), 8.59 (d, 1H, JH,H =4.7Hz, aromatic
proton), 11.18 (s, 1H, imidazolium proton) ppm. 13C NMR (100 MHz,
CDCl3): d = 65.97 (N–C–Ph), 116.26, 119.64, 121.78, 123.52, 123.90, 124.87,
129.20, 129.35, 129.51, 130.26, 130.64, 134.58, 136.19, 136.46, 137.80, 149.47,
150.10, 155.06 ppm. HRMS (ESI) m/z: [MÀ Cl]+ calcd for C21H18N3
312.1501, found 312.1501.
87.9(17)
93.9(2)
(Fällanden, Switzerland). Multiplicities were given as s (singlet), b
(broad singlet), d (doublet), t (triplet), q (quartet), dd (doublets of
doublet), m (multiplets) etc. The number of protons (n) for a given
resonance is indicated by nH. Coupling constants are reported as a J
value in Hz. NMR spectra (1H NMR) are reported as s in units of parts
per million (ppm) downfield from SiMe4 (d 0.0), relative to the signal of
chloroform-d (d 77.20, triplet) (13C NMR). Phase-sensitive 1H–1H
ROESY spectra were obtained with a Bruker AMX-500 spectrometer
and were acquired into a 1024 Â 512 matrix with a 250-msec spin lock
time and a spin lock field strength such that gB1/2p = 5000 Hz and then
transformed into 1024 Â 1024 points by using a sine-bell weighting
function in both dimensions. Mass spectra were recorded on a Thermo
Finnigan MAT 95 XP mass spectrometer (Thermo Fisher Scientific Inc.,
Waltham, MA, USA) with electron ionization mode and Waters
quadrupole time-of-flight Premier mass spectrometer (Waters Corpo-
ration, Milford, MA, USA) with electrospray ionization (ESI) mode.
Melting points were determined on SRS-Optimelt MPA-100 apparatus
and were uncorrected. Optical rotations were measured on the
specified solution in 0.1-dm cell at 25 ꢀC with a PerkinElmer model
341 polarimeter (Waltham, MA, USA). Single crystal X-ray diffraction
data were collected on a Bruker X8 CCD diffractometer with Mo Ka
Racemic palladacycle [2]. To a solution of compound 10 (4.50 g,
13.4 mmol) in 30 ml of CH2Cl2, Ag2O (1.70 g, 7.3 mmol) was added in
the dark. The reaction mixture was stirred at room temperature for 12 h
and was filtered through celite. A PdCl2(NCMe)2 suspension (3.48 g,
13.4 mmol in 100 ml of CH3CN) was added to the filtrate in the dark.
The reaction mixture was then stirred overnight at room temperature
and was filtered through a short plug of celite the next day. The filtrate
was reduced in vacuo to approximately 50 ml, and diethyl ether (200 ml)
Chirality DOI 10.1002/chir

CHIRAL PYRIDINE–NHC-BASED PALLADACYCLES
157
was added which resulted in the precipitation of an orange-yellow solid
4.01 g, 63%. mp = 330.0–330.5 ꢀC (dec). 1H NMR (400 MHz, DMSO):
d = 4.20 (s, 3H, CH3), 7.36–7.39 (m, 2H, aromatic protons), 7.41–7.46
(m, 3H, aromatic proton), 7.52 (quintet, 2H, JH,H = 7.0 Hz, aromatic proton),
7.65 (t, 1H, JH,H = 6.3Hz, aromatic proton), 7.80 (d, 1H, JH,H = 7.3 Hz,
aromatic proton), 7.85 (s, 1H, aromatic proton), 8.15–8.18 (m, 2H, aro-
matic proton), 8.23 (t, 1H, JH,H = 7.5 Hz, aromatic proton), 9.14 (s, 1H,
aromatic proton) ppm. 13C NMR (100 MHz, DMSO): d = 35.26 (N–CH3),
63.36 (N–C–Ph), 110.83, 111.98, 124.51, 125.31, 126.41, 126.98, 128.44,
128.94, 132.90, 134.18, 138.06, 140.62, 154.40, 155.19, 163.76 ppm. HRMS
(ESI) m/z: [M À H]+ calcd for C20H16Cl2N3Pd 475.9727, found 475.974.
enriched mother liquor was concentrated to dryness and redissolved in
ethanol.
Diastereomer (SC,SC)-5 1.8 g, 62%, [a]436 = À167 (c = 0.5, MeOH),
mp = 222.4–223.5 ꢀC (dec). 1H NMR (400 MHz, DMSO): d = 0.98–1.04
(m, 1H), 1.15–1.26 (m, 1H), 1.40–1.52 (m, 1H), 1.56–1.66 (m, 1H),
1.86–2.01 (m, 1H), 2.29–2.38 (m, 1H), 3.22 (dd, 1H, JH,H = 8.6 Hz,
JH,H = 2.9 Hz), 7.23 (d, 2H, JH,H = 7.0 Hz, aromatic protons), 7.34 (s, 1H,
aromatic proton), 7.43–7.51 (m, 3H, aromatic protons), 7.62–7.70
(m, 3H, aromatic proton), 7.74–7.79 (m, 2H, aromatic proton), 7.86–7.87
(m, 2H, aromatic proton), 8.10 (d, 1H, JH,H = 2.0 Hz, aromatic protons),
8.13 (d, 1H, JH,H = 7.4 Hz, aromatic protons), 8.32 (td, 1H, JH,H = 7.7 Hz, JH,
H = 1.5Hz, aromatic protons), 8.88 (d, 1H, JH,H = 4.8 Hz, aromatic proton)
ppm. 13C NMR (100MHz, DMSO): d = 23.74, 29.15, 68.19, 69.07, 125.23,
125.63, 127.27, 127.37, 128.28, 130.13, 130.37, 131.46, 139.74, 140.56,
142.87, 154.42, 155.95, 182.17 ppm. HRMS (ESI) m/z: [MÀ Cl]+ calcd for
C26H25N4O1206Pd 531.1012, found 531.1014.
Racemic palladacycle [3]. To a solution of compound 11 (4.50 g,
13.4 mmol) in 30 ml of CH2Cl2, Ag2O (1.70 g, 7.3 mmol) was added in the
dark. The reaction mixture was stirred at room temperature for 12 h and
was filtered through celite.
A PdCl2(NCMe)2 suspension (3.48 g,
13.4 mmol in 100 ml of CH3CN) was added to the filtrate in the dark.
The reaction mixture was then stirred overnight at room temperature
and was filtered through a short plug of celite the next day. The filtrate
was reduced in vacuo to approximately 50 ml, and diethyl ether (200 ml)
was added which resulted in the precipitation of an orange-yellow solid
4.01 g, 63%. mp = 294.8–296.5 ꢀC (dec). 1H NMR (400 MHz, DMSO):
d = 7.36 (s, 1H, aromatic proton), 7.39–7.45 (m, 4H, aromatic protons),
7.47–7.58 (m, 4H, aromatic protons), 7.69 (t, 1H, JH,H = 6.7 Hz, aromatic
proton), 7.83–7.86 (m, 3H, aromatic proton), 8.05–8.08 (m, 2H, aromatic pro-
ton), 8.24 (t, 1H, JH,H = 7.9 Hz, aromatic proton), 9.23 (s, 1H, aromatic
proton) ppm. 13C NMR (100 MHz, DMSO): d = 67.16 (N–C–Ph), 123.15,
123.87, 124.91, 125.21, 127.15, 128.07, 128.45, 128.65, 128.84, 137.81,
139.18, 140.47, 154.17, 155.16 ppm. HRMS (ESI) m/z: [M À H]+ calcd
for C21H16Cl2N3Pd 487.9727, found 487.9719.
Chiral complex (S)-[3]. To a suspension of complex (SC,SC)-5 (0.50 g,
0.88 mmol) in 1 ml of MeOH, 1-M HCl (aq) (8.8 ml, 8.8 mmol) was added.
The reaction mixture was stirred vigorously for approximately 1 h and
was concentrated down to give a pale yellow solid. The solid was washed
three times with copious amount of MeOH to give a pale yellow solid
0.28 g, 65%, [a]436 = À27.8 (c = 0.20, DMSO).
Chiral complex (S)-[7]. To a suspension of complex (S)-2 (0.1 g,
0.21 mmol) in 10 ml of CH2Cl2, triphenylphosphine (0.055 g, 0.21 g) was
added. The solution was stirred for 1 h. After 1 h, the clear solution
was concentrated to dryness. The product was purified through precip-
itation in CH2Cl2 and diethyl ether to give an off-white solid 0.15, 97%,
[a]436 =À37 (c= 0.57, MeOH), mp = 209.0–210.9 ꢀC (dec). 1H NMR
(400 MHz, MeOD): d =3.15 (s, 3H, CH3), 6.51 (s, 1H), 6.97 (t, 2H,
JH,H = 7.8Hz, aromatic proton), 7.11–7.25 (m, 11H, aromatic protons),
7.36–7.42 (m, 6H, aromatic protons), 7.51 (t, 2H, aromatic protons),
7.09–7.33 (m, 11H, aromatic protons), 7.56–7.59 (m, 1H, JH,H = 7.1 Hz,
aromatic proton), 7.65 (t, 2H, JH,H = 6.0 Hz, aromatic proton), 7.72 (s, 1H,
aromatic proton), 8.04 (d, 1H, JH,H = 7.10 Hz, aromatic proton), 8.14
(t, 1H, JH,H = 8.2 Hz, aromatic proton), 8.18 (d, 1H, JH,H = 7.8 Hz, aromatic
proton), 9.23–9.24 (m, 1H, aromatic proton) ppm. 13C NMR (100 MHz,
MeOD): d = 36.17, 65.95,112.06, 112.79, 126.79, 126.68, 127.01, 127.80,
127.82, 128.73, 129.69, 129.80, 130.47, 130.64, 132.90, 135.14, 135.81, 140.
09, 142.48, 151.25, 155.02, 155.11, 174.15ppm. 31P{1H} (161 MHz, MeOD):
d = 28.99ppm. HRMS (ESI) m/z: [M À Cl]+ calcd for C38H32ClN3PPd
704.1061, found 704.1055.
Optical resolution of racemic complexes (À)-[2] and (+)-[2]. Sodium
(SC)-phenylalanate (0.98 g, 5.2 mmol) was added to a suspension of the
racemic complex (Æ)-2 (2.50 g, 5.2 mmol) in 100 ml of MeOH. The reaction
mixture was stirred for 1 h and was concentrated in vacuo. The residue was
redissolved in ethanol, and diethyl ether was allowed to diffuse into the
solution slowly. Diastereomer (SC,SC)-4 which crystallized out as off-white
crystals the next day was isolated and washed with ethanol. Complex (RC,
SC)-4 enriched mother liquor was concentrated to dryness and redissolved
in acetonitrile. Slow evaporation of the acetonitrile solution allowed the
remaining diastereomer (SC,SC)-4 to crystallize out.
Diastereomer (SC,SC)-4 0.9 g, 60%, [a]365 = +202 (c = 0.55, MeOH),
mp = 215.9–216.5 ꢀC (dec). 1H NMR (400 MHz, DMSO): d = 2.82–2.87
(m, 1H), 3.13 (dd, 1H, JH,H = 14.0 Hz, JH,H = 1.7), 3.22–3.24 (m, 1H),
3.95 (s, 3H, CH3), 5.73–5.77 (m, 2H), 7.23 (t, 1H, JH,H = 6.9Hz, aromatic pro-
ton), 7.29–7.36 (m, 4H, aromatic protons), 7.39–7.40 (m, 3H, aromatic
protons), 7.49–7.52 (m, 4H, aromatic protons), 7.73–7.77 (m, 1H, aromatic
protons), 7.82–7.86 (m, 1H, aromatic protons), 8.01 (s, 1H, aromatic proton),
8.13–8.17 (m, 1H, aromatic proton), 8.32–8.39 (m, 2H, aromatic proton), 8.72
(d, 1H, JH,H = 5.4 Hz, aromatic proton) ppm. 13C NMR (100MHz, DMSO):
d = 34.00, 61.46, 62.48, 111.12, 111.82, 124.50, 126.08, 126.40, 126.67,
128.43, 128.53, 128.86, 129.26, 132.76, 134.01, 137.78, 137.91, 141.73,
152.22, 154.85, 164.25, 177.30 ppm. HRMS (ESI) m/z: [M À Cl]+ calcd for
Complex [9]. To a suspension of complex (S)-3 (0.1 g, 0.20 mmol) in
10 ml of CH2Cl2, triphenylphosphine (0.053 g, 0.20 mmol) was added.
The solution was stirred for 1 h. After 1 h, the clear solution was concen-
trated to dryness. The product was purified through precipitation in
DCM and diethyl ether to give an off-white solid 0.148 g, 98%. 1H NMR
(400 MHz, MeOD): d = 6.33 (s, 1H), 7.03 (t, 2H, JH,H = 7.8 Hz, aromatic pro-
ton), 7.17–7.27 (m, 13H, aromatic proton), 7.32–7.35 (m, 4H, aromatic pro-
tons), 7.39 (s, 2H, aromatic protons), 7.41–7.47 (m, 5H, aromatic protons),
7.82 (t, 1H, JH,H = 6.6 Hz, aromatic proton), 8.04 (d, 1H, JH,H = 7.6 Hz,
aromatic proton), 8.13 (s, 1H, aromatic proton), 8.29 (t, 1H, JH,H = 7.7Hz,
aromatic proton), 9.45–9.46 (m, 1H, aromatic proton). 13C NMR
(100 MHz, MeOD): d = 70.17, 125.12, 125.29, 126.25, 127.08. 127.96,
128.58, 129.41, 130.34, 130.40, 130.70, 130.96, 132.46, 136.14, 138.93,
139.36, 142.46, 155.00. 155.23, 161.88 ppm. 31P{1H} (161 MHz, MeOD):
d = 26.94ppm. HRMS (ESI) m/z: [MÀ Cl]+ calcd for C39H32N3ClP108Pd
716.1016, found 716.1068.
C
29H27N4O1206Pd 569.1169, found 569.1183.
Chiral complex (S)-[2]. To a suspension of complex (SC,SC)-4 (0.50 g,
0.83 mmol) in 1 ml of MeOH, 1-M HCl (aq) (8.3 ml, 8.3 mmol) was added.
The reaction mixture was stirred vigorously for approximately 1 h and
was concentrated down to give a pale yellow solid. The solid was washed
three times with copious amount of MeOH to give a pale yellow solid
0.26 g, 66%, [a]365 = +405 (c = 0.21, DMSO).
Complex (Æ)-[10]. To
a
suspension of complex (Æ)-3 (0.1 g,
0.20 mmol) in 10 ml of DCM, triphenylarsine (0.063 g, 0.20 mmol) was
added. The solution was stirred for 1 h. After 1 h, the clear solution was
concentrated to dryness. The product was purified through precipitation
in DCM and diethyl ether to give an off-white solid 0.16 g, 98%. 1H
NMR (400 MHz, MeOD): d = 6.63 (s, 1H), 6.94–6,97 (m, 2H, aromatic pro-
tons), 7.19 (t, 2H, JH,H = 8.0 Hz, aromatic protons), 6#?>7.25–7.37 (m, 14H,
aromatic protons), 7.40 (s, 1H, aromatic proton), 7.49 (t, 3H, JH,H = 8.0 Hz,
aromatic proton), 7.54 (d, 1H, JH,H = 4.0 Hz, aromatic protons), 7.63–7.67 (m,
Optical resolution of racemic complexes (À)-[3] and (+)-[3]. Sodium
(SC)-prolinate (0.70 g, 5.1 mmol) was added to a suspension of the racemic
complex (Æ)-3 (2.50 g, 5.1 mmol) in 100 ml of MeOH. The reaction mixture
was stirred for 1 h and was concentrated in vacuo. The residue was redis-
solved in MeOH, and diethyl ether was allowed to diffuse into the solution
slowly. Diastereomer (SC,SC)-5 which crystallized out as off-white crystals
the next day was isolated and washed with CH2Cl2. The complex (RC,SC)-5
Chirality DOI 10.1002/chir

158
NG ET AL.
13. Caddick S, Cloke FGN, Clentsmith GKB, Hitchcock PB, McKerrecher D,
Titcomb LR, Wiliams MRV. An improved synthesis of bis(1,3-di-N-tert-
butylimidazol-2-ylidene)palladium(0) and its use in C–C and C–N
coupling reactions. J Organomet Chem 2001;617:635–639.
14. Huang J, Nolan SP. Efficient cross-coupling of aryl chlorides with aryl gri-
nard reagents (Kumada reactions) mediated by a palladium/imidazolium
chloride system. J Am Chem Soc 1999;121:9889–9890.
15. Frisch AC, Rataboul F, Zapf A, Beller M. First Kumada reaction of
alkyl chloride using N-heterocyclic carbene/palladium catalyst system.
J Organomet Chem 2003;687:403–409.
1H, aromatic proton), 7.71–7.75 (m, 2H, aromatic protons), 7.84–7.87 (m,
1H, aromatic proton), 8.08 (d, 1H, JH,H = 8.0 Hz, aromatic proton), 8.16 (d,
1H, JH,H = 2.0 Hz, aromatic proton), 8.33 (dt, 1H, JH,H =7.7Hz, JH,H =1.5Hz,
aromatic proton), 9.49 (d, 1H, JH,H = 4.7 Hz aromatic proton) ppm. 13C NMR
(100 MHz, MeOD): d = 70.17, 116.82, 124.87, 124.96, 126.12, 126.26, 127.25,
128.10, 128.56, 129.78, 129.94, 130.13, 130.35, 130.50, 130.95, 131.03, 131.97,
132.46, 134.09, 134.71, 139.01, 139.62, 142.61, 142.61, 154.90, 155.32,
164.02 ppm. HRMS (ESI) m/z: [MH À Cl]+ calcd for C39H33N3ClAs108Pd
761.0618, found 761.0627.
16. Zhou JR, Fu GC. Palladium catalyzed Neigishi cross-coupling reactions of
unactivated alkyl iodide, bromides, chlorides and tosylates. J Am Chem
Soc 2003;125:12527–12530.
17. Hadei N, Kantchev EAB, O’Brien CJ, Organ MG. The first Neigishi cross-
coupling reaction of two alkyl centres utilizing a Pd-N-heterocyclic
carbene (NHC) catalyst. Org Lett 2005;7:3805–3807.
18. Organ MG, Arola S, Dubovyk I, Hadei N, Kantchev EAB, O’Brien CJ,
Valente C. A user-friendly, all-purpose Pd-NHC precatalyst for the Negishi
reaction: a step towards a universal cross-coupling catalyst. Chem Eur J
2006;12:4749–4755.
19. Herrmann WA, Böhm VPW, Gstöttmayr GWK, Grosche M, Resinger C-P,
Weskamp T. Synthesis, structure and catalytic application of palladium(II)
complexes bearing N-heterocyclic carbenes and phosphines. J Organomet
Chem 2001;617:616–628.
CONCLUSION
We have successfully synthesized and comprehensively
characterized two new pyridine-functionalized NHC pallada-
cycles and analyzed their conformational rigidity both in solid
state and in solution via single crystal X-ray diffraction studies
and 2D 1H–1H NMR analysis. It was seen that upon replacing
one of the chloride ions with PPh3 in a regioselective manner,
the solubility of these complexes improved tremendously
with the retention of the chiral center and also led to easier
crystallization. Interestingly, cleavage of the Npyridine–Pd
bond that occurred in complex 9 demonstrated the hemilabil-
ity of the pyridine-functionalized NHC palladacycle and is
indicative of a limitation imposed by steric bulkiness of
the wingtip group. Based on the information obtained from
the conformational rigidity analysis, we are currently
exploring the synthesis of other versions of these catalysts
with a view of exploring their potential in various asym-
metric catalysis scenarios.
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ACKNOWLEDGMENT
We thank Prof. Leung Pak-Hing for fruitful discussions.
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