An enantiomerically pure pyridine NC-palladacycle derived from [2.2]paracyclophane

Article abstract of DOI:10.1071/CH13440

An enantiomerically pure planar chiral pyridine-based palladacycle was prepared from [2.2]paracyclophane in just four steps. The palladacycle shows potential in catalysis, mediating the Suzuki coupling of an aryl chloride. It also permits the ortho bromination of [2.2]paracyclophane, a reaction that can be hard to achieve selectively. CSIRO 2014.

Full text of DOI:10.1071/CH13440

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem. 2014, 67, 374–380
Full Paper
http://dx.doi.org/10.1071/CH13440
An Enantiomerically Pure Pyridine NC-Palladacycle
Derived from [2.2]Paracyclophane
A
A
A B
,
Jean E. Glover, Paul G. Plieger, and Gareth J. Rowlands
A
Institute of Fundamental Sciences, Massey University, Private Bag 11 222,
Palmerston North, New Zealand.
B
Corresponding author. Email: g.j.rowlands@massey.ac.nz
An enantiomerically pure planar chiral pyridine-based palladacycle was prepared from [2.2]paracyclophane in just four
steps. The palladacycle shows potential in catalysis, mediating the Suzuki coupling of an aryl chloride. It also permits the
ortho bromination of [2.2]paracyclophane, a reaction that can be hard to achieve selectively.
Manuscript received: 23 August 2013.
Manuscript accepted: 21 October 2013.
Published online: 19 November 2013.
Introduction
Cyclopalladated complexes (CPCs) have found extensive
use as pre-catalysts, catalysts,[20,21] and intermediates in several
ligand transformations where the Pd–C bond is functiona-
lised.[22,23] Chiral CPCs have been successfully employed as
mild Lewis acids for asymmetric variants of the Overman
rearrangement of allylic trichloroacetamides[24] and the hydro-
phosphination of methylidenemalonates[25] as well as in an
example of an asymmetric Suzuki coupling.[26] The current
interest in CPCs centres around their intermediacy in directed
C–H activation chemistries. Either isolated CPCs or proposed
CPC intermediates are readily transformed into a variety of
C–O, C–X, C–P, and C–C bonds. Such reactions provide a mild
and powerful method for the ortho functionalisation of aryl
systems.[22]
[2.2]Paracyclophane (1; R ¼ H; Fig. 1) is a robust molecule that
comprises two aryl rings held in close proximity by two ethyl
bridges. Its rigid structure has the potential to create well defined
chiral scaffolds for use in asymmetric catalysis, medicinal
chemistry, and materials science.[1–6] Yet [2.2]paracyclophane
has only seen limited use in these areas. Two challenges curtail
its exploitation, the resolution of planar chiral enantiomers and
the functionalisation of substituted derivatives.[7–10] At present
there are no enantioselective syntheses and all routes to [2.2]
paracyclophane derivatives require a resolution step. Access to
enantiopure forms of the common starting materials, such as
mono- and dibromo[2.2]paracyclophane, are not trivial. The
chemistry of [2.2]paracyclophane is littered with idiosyncrasies
and itisnotalways possible to transfer simple aromaticchemistry
to [2.2]paracyclophane without encountering unusual reactivity.
One challenging example is the ortho-functionalisation of
4-substituted [2.2]paracyclophanes; a range of selectivity
issues have been observed including reaction at the bridgehead
(C2), at the para-position (C7), and at the ‘directing’ group
itself.[11,12]
Our initial goal was to develop a method that permitted the
resolution of pyridyl [2.2]paracyclophanes and would allow us
to modify the core of these molecules to form improved Lewis
base catalysts[19] and sterically congested planar chiral mono-
phosphanes for comparison with our planar chiral heterocyclic
7
8
We are interested in developing methodology that
permits the facile formation of enantiopure polysubstituted
[2.2]paracylcophane derivatives. Previously we have used sulf-
oxides as traceless chiral auxiliaries for the formation of
enantiopure monosubstituted [2.2]paracyclophane deriva-
tives.[9,13–15] Frustratingly, our methodology was not compa-
tible with our implementation of Fagnou’s C–H activation
chemistry,[16–18] which we had employed in the synthesis of
planar chiral Lewis base catalysts.[19] In those studies we had to
resolve dibromo[2.2]paracyclophane before arylation. As the
formation of the pyridine N-oxide derivatives proceeded with
only moderate yield precious resolved materials were wasted.
We believed it would be advantageous to resolve the planar
chiral pyridine-substituted [2.2]paracyclophanes themselves.
As with our sulfoxide chemistry we were interested in achieving
the resolution in a manner that would permit further functiona-
lisation of the [2.2]paracyclophane framework.
H
H
2a
2s
9
N
Pd
Cl
5
4
R
16
15
H
H
1a
1s
10
PPh3
12 13
3
1
N
Pd
Cl
Ph3P
2
Fig. 1. [2.2]Paracyclophane (R ¼ H; 1) and cyclopalladated complexes
2 and 3.
Journal compilation Ó CSIRO 2014
www.publish.csiro.au/journals/ajc

[2.2]Paracyclophane-Derived Palladacycles
375
phosphanes.[27,28] Several [2.2]paracyclophane-based CPCs
have previously been prepared: Dunina has reported the syn-
thesis and resolution of both C,P-[29] and C,N-palladacycles
2.[26,30] Richards demonstrated the elegant kinetic resolution of
4-N,N-dimethylaminomethyl[2.2]paracyclophane that pro-
ceeded by the selective formation of a CPC.[31] Bolm has
highlighted the utility of CPCs to allow the problematic ortho
(C5) functionalisation of [2.2]paracyclophanes first through the
reaction of isolated C,N-CPC with potassium diphenylpho-
sphide[11] and later through a catalytic process that permitted
directed acetoxylations.[32]
been formed,[11] analysis of the reaction mixture suggests that
only the ortho-palladated molecule was prepared and the loss
of material was a result of decomposition and not the formation
of isomers.
1
The H NMR spectrum indicates that the ortho-palladated
CPC was isolated as a single isomer with the phosphane trans to
the pyridine as expected. There are six discrete aromatic protons
for the [2.2]paracyclophane backbone ranging from 6.90 to
5.66 ppm. Theses signals are distinct from the phenyl or pyridine
aromatic protons’ resonances, which range from 9.67 to
7.27 ppm. There are six well defined signals for ethylene protons
and one multiplet with an integral of two protons confirming that
no insertion into the bridging ethylene C–H bonds had occurred.
Interpretation of the NOESY spectrum for the CPC 6 permits
identification of all the protons of the [2.2]paracyclophane
backbone (Fig. 2).[34] The assignment was based on the strong
interaction between H-9s and H-18, the proton ortho to the
pyridine–[2.2]paracyclophane biaryl bond. A smaller interac-
tion can be observed between H-10s and H-18. Each benzylic
proton shows a strong interaction with the adjacent aromatic
proton allowing simple interpretation. H-12, the proton pseudo-
gem to the pyridine ring, displays a more shielded resonance
than the analogous proton in the imine-based palladacycle[30]
2 (5.66 vs 6.49 ppm). Presumably this is the result of the
anisotropic effect of the pyridine ring. The ring current of
the pyridine ring can also be invoked to explain the deshielded
resonance observed for H-9s that is at 3.89 ppm compared with
3.21–2.06 ppm for the other ethylene protons (and 3.07 ppm for
[2.2]paracyclophane).
The trans (P,N)-geometry of the phosphane and the pyridine
ligand was determined by NOE cross peaks between the ortho
phenyl protons of the phosphane and both H-2s and H-1s of the
PCP skeleton along with a weak interaction with H-2a. In
addition, it is clear that H-2a is in a highly shielded environment
with a resonance at 2.06 ppm compared with the other bridge-
head protons that range between 2.58–3.89 ppm and H-2s,
which is a multiplet between 2.91ꢀ2.98 ppm. A similar effect
has been observed in the 1H NMR spectra of the imine analogue
and results from the proximity of the proton with the aromatic
ring of the phosphane. For 6 the increased shielding for H-2a
over H-2s is explained by the shorter distance of H-2a (on C2)
In this paper, we report the synthesis of a CPC derived
from 2-([2.2]paracyclophan-4-yl)pyridine, its resolution, and
demonstrate its potential for the functionalisation of [2.2]para-
cyclophane and as a catalyst.
Results and Discussion
Racemic 2-([2.2]paracyclophan-4-yl)pyridine 4 was readily
prepared from [2.2]paracyclophane
1
in three steps
(Scheme 1):[33] bromination was followed by the direct arylation
of pyridine N-oxide employing the chemistry of Fagnou.[16–18]
The heterocyclic derivative was subjected to trichlorosilane-
mediated reduction to furnish the pyridine 4. This material can
be obtained in 40–50 % yield after three steps and only one
purification process, chromatographic separation of the N-oxide.
Formation of CPC 5 was achieved by heating a mixture of the
pyridine 4 and palladium(II) acetate to 708C overnight followed
by ligand substitution with lithium chloride to give a yellow
amorphous powder. It is assumed that the powder was a mixture
of racemic and meso chloride-bridged diastereoisomers. No
useful spectroscopic data could be obtained on this material
except the high-resolution mass spectrum. This in conjunction
with subsequent reactions implied that the desired CPC had been
prepared.
In order to remove the issue of diastereoisomers and allow
better characterisation of the CPC, the dimer was cleaved by
treatment with triphenylphosphane. The resulting monomeric
phosphane 6 was isolated in moderate yield (60–70 %). While it
is possible that a regioisomeric mixture of CPCs containing both
the ortho-palladated (aromatic C–H insertion) and the bridge-
head-palladated (benzylic C–H insertion) species could have
1. Br2, Fe
2. C5H5NO, Pd(OAc)2,
·
tBu3P HBF4, K2CO3
1. Pd(OAc)2
2. LiCl
3. Cl3SiH, Et3N
N
40–50 % (3 steps)
ꢀ
Pd
95 %
Cl
2
1
4
5
Br2
NaOAc
70 %
Phenylalanine, NaHCO3
Ph3P
60–70 %
ꢀ
80 – 95 %
N
N
N
Pd
N
Pd
H2N
O
O
H2N
Pd
Br
Cl
Ph3P
O
O
H
H
Ph
Ph
6
(pS,S)-7
(pR,S)-7
8
Scheme 1. Synthesis of pyridine-derived cyclopalladated complexes.

376
J. E. Glover, P. G. Plieger, and G. J. Rowlands
˚
from the centroid of the nearest phenyl ring (2.97 A) as com-
˚
pared with H-2s which is further away at 3.45 A (Fig. 3). This
between the analogous protons and the centroid were 2.81 and
˚
3.34 A for H-2a and H-2s, respectively.
correlation is comparable to the imine derivative in which the
chemical shifts were 1.93 and 2.79 ppm and the distance
Both the ortho-palladation and the relative orientations of the
chloro and phosphane substituents were confirmed by X-ray
crystallography (Fig. 3). The pyridine CPC is structurally
similar to the previously reported imine-based CPC[30] and
displays similar distortion of the palladium centre in com-
parison to the achiral phenyl derivative 3 (Fig. 1).[35] The key
differences between the [2.2]paracyclophane-based CPC and
the simple phenyl analogue 3 include the distortion of the
geometry of the palladium and the elongation of the bonds to
palladium. The achiral phenyl analogue 3 contains a planar
palladium centre with an interplanar angle between the planes
derived from the C–Pd–N and P–Pd–Cl atoms of 2.58. The
phosphane [2.2]paracyclophane complex 6 shows far greater
distortion from the ideal planar system with the analogous
interplanar angle of 22.08. The imine-based CPC 2 displays a
smaller distortion (16.98) possibly reflecting a higher degree of
conformational freedom for the imine substituent.
Ha
Ha
Hs
Hs
Hs
Hs
N
N
Pd
Pd
H
O
Cl
Ph
Hs
Hs
Ha
H2N
Hs
P
Ha
Ph
Hs
O
H
Ph
6
(pS,S)-7
Bond lengths suggest a minimisation of steric interaction
between the palladium substituents and the [2.2]paracyclophane
˚
backbone. The Pd–P bond length is longer in 6 (2.296(2) A) than
Hs
Hs
in either the imine-derivative (2.2703(7) A)[30]or the achiral
phenyl derivative (2.2510(5) A) 3 (Fig. 1).[35] A similar elonga-
˚
˚
˚
tion of the Pd–Cl bond is also observed for 6 (2.427 (1) A) when
compared with the analogous bond lengths for the imine and
˚
pyridine examples (2.3713(6) and 2.3707(7) A, respectively).
N
Pd
H
O
H2N
Hs
The key step was the resolution of the racemic CPC and this
was achieved by reacting the bridged chloro dimer 5 with the
sodium salt of phenylalanine (Scheme 1). The reaction cleanly
produces two complexes that were readily separated by column
chromatography (SiO2) and the structure, including absolute
stereochemistry, of the first eluted material was determined by
NMR spectroscopy and X-ray diffraction studies. It proved
impossible to grow X-ray quality crystals of the second eluted
molecule because of its reduced solubility and propensity for
Hs
O
H
Ph
(pR,S)-7
Fig. 2. Important NOESY interactions in the cyclopalladated complexes 6,
(pS,S)-7, and (pR,S)-7. Plain arrows indicate a strong NOESY interaction
and dashed arrows a weak interaction.
C(1)
C(2)
C(3)
C(4)
P(1)
Pd(1)
N(1)
Cl(1)
Fig. 3. X-ray structure of 6. Solvent molecules and hydrogen atoms have been removed for clarity (except for H-2a
and H-2s). The dashed line indicates the proximity of H-2a to the aryl ring of the phosphane. Ellipsoids are drawn at
the 50 % probability level.[36]

[2.2]Paracyclophane-Derived Palladacycles
377
5 (0.5 mol-%),
B(OH)2
Cl
·
K3PO4 H2O (2 equiv.),
toluene, 70ꢁC
C(1)
C(2)
26 %
C(3)
C(4)
9
11
10
Scheme 2. Cyclopalladated complex-mediated Suzuki coupling of
p-chlorotoluene.
Pd(1)
N(2)
N(22)
C(32)
paracyclophane backbone reducing any steric interaction that
would distort the palladium centre.
O(2)
We had three goals when we initially formed the CPCs,
having shown that they could be used to resolve the planar
chirality we then turned our attention to proving their compe-
tency as (pre)catalysts for coupling reactions and investigated
the functionalisation of the ortho-position of the [2.2]paracy-
clophane ring. Our preliminary results, coupled with recent
publications from other groups,[11,26,32] suggest that these
palladacycles are useful materials. We only attempted the chal-
lenging coupling of an aryl chloride as it is clear that virtually all
CPCs couple simple aryl bromides and iodides.[20] We were
pleased to see that the simple chloride-bridged dimer 5 promot-
ed the coupling of phenylboronic acid 9 and para-chlorotoluene
10 when the mixture was heated to 708C in toluene to give the
biaryl 11 in 26 % yield (Scheme 2). The yield is low but it shows
that CPC 5 matches the efficiency of our best heterocyclic
monophosphane while displaying the added advantage of being
considerably easier to synthesise.[27] It should be noted that we
cannot rule out the possibility that the dimer simply acts as
a reservoir of active Pd0 but the coupling of a chloride at a
relatively low temperature (708C) combined with the results of
Dunina and co-workers for the analogous imine derivative[26] is
encouraging.
O(1)
Fig. 4. X-ray structure of (pS,S)-7. Solvent molecules and hydrogen atoms
have been removed for clarity (except for H32). Ellipsoids are drawn at the
50 % probability level.[37]
forming amorphous powders. Similarities in the 1H NMR
spectra, in conjunction with the mass balance for the reaction,
indicate that the two complexes are diastereomeric, only differ-
ing by their planar chirality of the [2.2]paracyclophane back-
bone rather than geometry at the palladium centre.
1
The H NMR spectrum of the reaction mixture indicates
the formation of the expected 1 : 1 mixture of diastereomers.[34]
The two complexes are very similar, only the resonances for
the paracyclophane aromatic protons are differentiated in the two
complexes; the alkyl protons of both [2.2]paracyclophane
and phenylalanine occur between 3.95 and 2.53 ppm while
the aromatic protons superimposed upon each other occur
between 8.81 and 7.07 ppm. There are limited NOE interactions
between the phenylalanine residue and the [2.2]paracyclophane
backbone (Fig. 2). In both complexes the strongest of these
interactions is found between H-2s and the axial and equatorial
amine signals. This indicates that both isomers have the same
geometry at the palladium centre with the amine trans to the
pyridine. In the first complex eluted from the column there is a
weak NOE interaction between the ortho-aromatic protons of
the phenylalanine residue and H-2s. This suggests that this
diastereomer has the phenylalanine ‘inside’ the [2.2]paracyclo-
phane and determines that it is the (pS) diastereomer. This was
confirmed by X-ray diffraction studies.
CPC 5 also permits the ortho-functionalisation of the [2.2]
paracyclophane backbone. Simple treatment with bromine gave
the bromide 8 in excellent yield (Scheme 1) and we have no
doubt that this material will be a useful precursor for the
formation of functionalised planar chiral pyridine molecules.
Based on the chemistry of Bolm and co-workers,[32] it is clear
that the [2.2]paracyclophane-based palladacycles offer the
opportunity to incorporate many different functional groups.
Conclusion
The 1H NMR resonances for the bridgehead protons H-2s and
H-2a for (pS,S)-7 and (pR,S)-7 are markedly different to those
in the phosphane derivative. In the amino acid derivatives, H-2s
is more shielded than H-2a, with a resonance of 2.54 and
2.53 ppm compared with 2.98–2.72 and 2.98–2.76 ppm. In the
phosphane the pattern is reversed and H-2a has a lower reso-
nance, 2.06 ppm compared with H-2s, which is 2.98–2.91 ppm.
This dramatic change is a result of the anisotropic effect of the
phenyl rings of the phosphane, which are orientated over the
bridgehead. In the phenylalanine derivative neither H-2 proton
is in close proximity to the phenyl ring.
This paper describes the rapid preparation and resolution of a
planar chiral palladacycle. The enantiomerically pure complex
can be formed in just four steps from readily available [2.2]
paracyclophane. The resulting complex shows potential in
catalysis and is a suitable precursor for the further functionali-
sation of the notoriously problematic ortho-position of [2.2]
paracyclophane. We are currently investigating the use of these
complexes in the synthesis of new monophosphanes analogous
to the successful (2-diphenylphosphino-1-naphthyl)isoquino-
line (QUINAP) ligand[38–40] and research in this area will be
published in due course.
The X-ray crystal structure of the first diastereomer eluted is
shown in Fig. 4. It confirms the assignment of the (pS) stereo-
chemistry of the [2.2]paracyclophane backbone and indicates
Experimental
All starting compounds and solvents were used as received
from commercial sources without further purification unless
otherwise noted. 4-Bromo[2.2]paracyclophane was synthesised
according a modification of the Cram and Day procedure
˚
that the ortho-hydrogen atoms of the phenyl ring are 3.156 A
from H-2s and could give rise to a weak NOE signal. The
phenylalanine residue is free to rotate away from the [2.2]

378
J. E. Glover, P. G. Plieger, and G. J. Rowlands
(Br2/Fe in CH2Cl2); we have found that heating is unneces-
sary.[41] Column chromatography was carried out on silica gel
(grade 60, mesh size 230–400, Scharlau). Visualisation techni-
ques employed included using ultraviolet light (254 nm),
potassium permanganate, ethanolic phosphomolybdic acid, or
ninhydrin when applicable. NMR spectra were recorded at room
temperature on Bruker-400 and Bruker-500 Avance instru-
ments, with the use of the solvent proton as an internal standard.
Melting points were recorded on a Gallenkamp melting point
apparatus and are uncorrected. Mass spectra and high resolution
mass spectrometry was performed at the Waikato Mass Spec-
trometry Facility, The University of Waikato, New Zealand.
H-13, H-15, H-16), 3.74–3.66 (1H, m, H-2), 3.24–3.15
(2H, m, 2 ꢂ CHH), 3.12–3.05 (2H, m, 2 ꢂ CHH), 3.03–2.91
(2H, m, 2 ꢂ CHH), 2.71–2.63 (1H, m, CHH). dC (125 MHz,
CDCl3) 159.1, 149.6, 140.6, 139.8, 139.6, 139.4, 138.2, 136.3,
136.2, 133.2, 132.9, 132.7, 132.6, 132.4, 130.7, 124.2, 121.4,
35.5, 35.3, 35.2, 34.5. m/z (HRMS ESI) 286.1591; C21H20N
([M þ H]þ) requires 286.1590.
Racemic Di-m-chlorobis{5-(pyridin-2-yl)[2.2]
paracyclophan-4-yl-C,N}dipalladium(II) (ꢃ)-5
A suspension of 2-([2.2]paracyclophan-4-yl)pyridine 4 (0.47 g,
1.64 mmol, 1.0 equiv.) and palladium(II) acetate (0.39 g,
1.72 mmol, 1.05 equiv.) in toluene (16.4 mL) was heated to 708C
overnight. The solvent was removed and the residue dissolved in
acetone (16.4 mL). To this was added lithium chloride (0.14 g,
3.28 mmol, 2.0 equiv.) and the resulting suspension was stirred
at room temperature for 3 h. The solid was removed by filtration
and washed with water to give 5 as an amorphous yellow powder
(0.39 g). A second crop of 5 was obtained by adding water to the
acetone filtrate and filtering the resulting precipitate, which was
washed with water to give 5 (0.30 g; combined yield was
2-([2.2]Paracyclophan-4-yl)pyridine N-Oxide
Asuspensionof4-bromo[2.2]paracyclophane (1.50 g,5.23 mmol,
1 equiv.), pyridine N-oxide (1.99 g, 20.91 mmol, 4.0equiv.),
K2CO3 (1.44 g, 10.45mmol, 2.0equiv.), t-Bu3P ꢁ HBF4 (0.23 g,
0.78 mmol, 0.15 equiv.), and Pd(OAc)2 (0.06 g, 0.26 mmol,
0.05 equiv.) in toluene (17.4mL) was heated to reflux overnight.
The reaction was cooled to room temperature and filtered
through celite, washing with CH2Cl2/MeOH (1 : 1, 100 mL) and
acetone/MeOH (1 : 1, 100 mL). The filtrate was concentrated
and purified by gradient column chromatography (CH2Cl2/
MeOH, 98 : 2-95 : 5-90 : 10). The resulting solid was placed
on a sintered funnel and washed with Et2O to remove the last
traces of pyridine N-oxide and ligand by-products to give
2-([2.2]paracyclophan-4-yl)pyridine N-oxide (0.94 g, 66 %) as a
white crystalline solid. mp 181–1838C. nmax /cmꢀ1 3047, 2930,
1474, 1256, 1035, 765. dH (400 MHz, CDCl3) 8.33 (1H, d, J 6.4,
H-6pyr), 7.66 (1H, dd, J 7.8, 1.8, H-3pyr), 7.41 (1H, t, J 7.8,
H-4pyr), 7.31–7.25 (1H, m, H-5pyr), 6.67 (1H, d, J 7.7, H-15/
H-16), 6.64 (1H, d, J 8.4, H-16/H-15), 6.61 (2H, s, H-7, H-8),
6.57 (1H, s, H-5), 6.52 (2H, dd, J 12.0, 8.4 H-12, H-13),
3.35–3.04 (5H, m, CH2), 2.99–2.92 (2H, m, CH2), 2.85–2.79
(1H, m, CH2). dC (125 MHz, CDCl3) 150.9, 141.5, 140.3, 140.0,
139.6, 139.0, 135.1, 134.8, 133.6, 132.6, 132.4, 131.9, 130.9,
129.3, 128.1, 125.1, 124.4, 35.5, 35.4 (ꢂ 2), 35.0.m/z (HRMS
EI) 324.1359; C21H19NONa ([M þ Na]þ) requires 324.1360.
0.69 g; . 95 %). m/z (HRMS ESI) 815.0665; Anal. Calc. for
C42H ClN2Pd2 815.0631. m/z (HRMS ESI) 390.0496; Anal.
35
36
Calc. for C21H18NPd ([0.5M – Cl]þ) 390.0469. m/z 817, 535,
390, 284.
Racemic Chloro{5-(pyridin-2-yl)[2.2]paracyclophan-
4-yl-C,N}(triphenylphosphane-P)palladium(II) (ꢃ)-6
To a yellow suspension of racemic di-m-chlorobis{5-(pyridin-
2-yl)[2.2]paracyclophan-4-yl-C,N}dipalladium(II) (ꢃ)-5 (0.11 g,
0.13 mmol, 1.0 equiv.) in toluene (5 mL) was added triphenyl-
phosphane (0.06 g, 0.25 mmol, 2.0 equiv.). The suspension was
stirred at room temperature for 2.5 h. The volume of toluene was
reduced to ,2 mL and hexane was added until no more pre-
cipitate formed. The solid was filtered off and the crude material
purified by recrystallisation (CH2Cl2/Et2O) to give 6 (0.05 g;
60 %). Mp 194–1958C (dec.). nmax /cmꢀ1 3052, 2925, 2856,
1600, 1566, 1530, 1481, 1464, 1446, 1265, 1097, 739.
dH (400 MHz, CDCl3) 9.67 (1H, t, J 3.7, H-21), 7.96–7.89
(2H, m, H-18, H-19), 7.68–7.63 (6H, m, 6 ꢂ Ar-Hm), 7.40–7.36
(3H, m, 3 ꢂ Ar-Hp), 7.31–7.27 (7H, m, H-20, 6 ꢂ Ar-Ho), 6.90
(1H, dd, J 7.7, 1.6, H-13), 6.47 (1H, dd, J 7.8, 1.5, H-16), 6.39
(1H, dd, J 7.9, 1.6, H-15), 6.13 (1H, d, J 7.7, H-7), 5.71
(1H, d, J 7.0, H-8), 5.66 (1H, dd, J 7.7, 1.7, H-12), 3.89 (1H, dd,
J 14.3, 8.2, H-9s), 3.21 (1H, ddd, J 13.1, 10.5, 4.3, H-1s), 3.03
(1H, dd, J 12.6, 9.5, H-10a), 2.98–2.91 (1H, m, H-2s), 2.86–2.74
(2H, m, H-1a, H-9a), 2.58 (1H, ddd, J 12.9, 8.7, 8.6, H-10s), 2.06
(1H, ddd, J 13.8, 10.6, 4.4, H-2a). dC (100 MHz, CDCl3) 167.7,
167.6, 166.4, 166.3, 150.7, 147.2, 146.11, 146.1, 139.7, 138.2,
138.1, 135.9, 135.6, 135.3, 134.2, 133.0, 132.9, 132.6, 132.0,
131.9, 131.8, 131.5, 130.3, 130.2, 129.7, 127.8, 127.7, 122.9,
120.5, 120.5, 41.6, 36.4, 35.9, 33.6. dP (162 MHz, CDCl3) 31.5.
m/z (HRMS ESI) 652.1394; Anal. Calc. for C39H33NPPd
652.1380. m/z 652, 390, 339, 284.
2-([2.2]Paracyclophan-4-yl)pyridine 4
To a solution of 2-([2.2]paracyclophan-4-yl)pyridine N-oxide
(0.94 g, 3.13 mmol, 1.0 equiv.) in CH2Cl2 (31.3 mL) at room
temperature was added Cl3SiH (4.74 mL, 46.89 mmol,
15.0 equiv.) and Et3N (4.35 mL, 31.26 mmol, 10.0 equiv.)
sequentially. The initial addition of Cl3SiH causes considerable
precipitate to form, hindering stirring of the suspension; addition
of Et3N results in a finer suspension that stirs more readily. The
suspension was heated to reflux for 3 h and then cooled to 08C
and diluted with CH2Cl2 (20 mL). NaOH(aq) (1 M, 20 mL) was
added cautiously. Further CH2Cl2 (20 mL) and NaOH(aq)
(1 M, 20 mL) was added and the suspension stirred at room
temperature until effervescence had ceased and most solid had
dissolved (,2 h). The layers were separated and the aqueous
layer extracted with CH2Cl2 (3 ꢂ 20 mL). The combined
organic layers were dried (MgSO4) and concentrated to give a
residue that was purified by column chromatography (elution
EtOAc/hexane, 3 : 2) followed by recrystallisation from hot
CH2Cl2 to give 2-([2.2]paracyclophan-4-yl)pyridine 4 (0.71 g,
80 %). Mp 136–1378C. nmax /cmꢀ1 3046, 2982, 2934, 2894,
2855, 1584, 1566, 1500, 1467, 1424, 1266, 1146. dH (400 MHz,
CDCl3) 8.77 (1H, d, J 4.8, H-6pyr), 7.79 (1H, td, J 7.7, 1.9,
H-4pyr), 7.53 (1H, d, J 7.9, H-3pyr), 7.26–7.23 (1H, m, H-5pyr),
6.84 (1H, d, J 1.6, H-5), 6.64–6.55 (6H, m, H-7, H-8, H-12,
(pS,S)-{5-(Pyridin-2-yl)[2.2]paracyclophan-4-yl-C,N}
(phenylalaninato-N,O)palladium(II) (pS,S)-7 and (pR,S)-
{5-(Pyridin-2-yl)[2.2]paracyclophan-4-yl-C,N}
(phenylalaninato-N,O)palladium(II) (pR,S)-7
To a yellow suspension of racemic di-m-chlorobis{5-(pyridin-
2-yl)[2.2]paracyclophan-4-yl-C,N}dipalladium(II) (ꢃ)-5 (0.18 g,
0.21 mmol, 1.0 equiv.) in MeOH (21 mL) was added (S)-
phenylalanine (0.07 g, 0.42 mmol, 2.0 equiv.) and NaHCO3

[2.2]Paracyclophane-Derived Palladacycles
379
(0.04 g, 0.42 mmol, 2.0 equiv.). The suspension was stirred at
room temperature overnight. After 2 h a clear brown solution
had formed. The solvent was removed under reduced pressure
and the residue diluted with CH2Cl2 (3 mL). The solid was
removed by filtration and the filtrate concentrated. The crude
material was purified by column chromatography (acetone/
CH2Cl2, 9 : 1). First eluted was (pS,S)-{5-(pyridin-2-yl)[2.2]
paracyclophan-4-yl-C,N}(phenylalaninato-N,O)palladium(II)
(pS,S)-7 as a yellow powder (0.06 g; 55 % assuming racemic
starting material). Mp 219–2218C (dec.). [a]D ꢀ88.0 (c 0.85,
CHCl3). nmax /cmꢀ1 3332, 3222, 3029, 2923, 2853, 1622, 1599,
1532, 1482, 1385, 1265, 1154, 1078, 935, 724. dH (400 MHz,
CDCl3) 8.79 (1H, s, H-21), 7.81 (2H, d, J 4.7, H-18, H-19),
7.45–7.31 (5H, m, Ar-H), 7.07 (1H, d, J 4.0, H-20), 6.80 (1H,
d, J 6.8, H-13), 6.59 (1H, d, J 7.7, H-16), 6.54 (1H, d, J 7.7,
H-15), 6.23–6.22 (1H, m, H-7), 6.13–6.11 (1H, m, H-8), 5.93
(1H, d, J 6.7, H-12), 3.98–3.89 (1H, m, H-23), 3.87–3.78 (1H, m,
H-9s), 3.54 (1H, dd, J 14.6, 3.0, H-24), 3.38 (1H, br s, NH), 3.25
(1H, dd, J 14.0, 10.0, H-24), 3.18–3.03 (3H, m, H-1s, H-10s,
NH), 2.98–2.72 (4H, m, H-1a, H-2a, H-9a, H-10a), 2.54 (1H,
ddd, J 13.6, 8.9, 4.9, H-2s). dC (100 MHz, CDCl3) 178.0, 165.8,
158.4, 150.3, 145.9, 144.4, 138.9, 138.7, 138.4, 136.7, 135.9,
134.3, 133.2, 132.6, 132.3, 131.7, 130.4, 129.3, 127.5, 122.1,
120.9, 60.9, 40.6, 36.6, 36.5, 35.9, 33.7. m/z (HRMS ESI)
577.1088; Anal. Calc. for C30H28N2NaO2Pd 577.1078. m/z 577,
473, 381, 353, 284.
1.1), 7.16 (1H, d, J 7.7), 6.86 (1H, d, J 7.7), 6.83–6.76 (3H, m),
6.49 (1H, d, J 7.8), 3.60 (1H, ddd, J 13.5, 8.1, 4.8), 3.35 (1H, dd,
J 11.2, 10.0), 3.27–3.16 (1H, m), 3.13–3.06 (1H, m), 2.97–2.88
(1H, m), 2.86–2.82 (2H, m), 2.33–2.25 (1H, m). dC (100 MHz,
CDCl3) 159.4, 155.1, 145.2, 140.3, 139.5, 139.3, 137.5, 137.1,
136.6, 135.3, 134.0, 132.2, 129.2, 128.6, 127.5, 125.3, 123.2,
37.2, 36.3, 35.5, 33.4. m/z (HRMS ESI) 364.0695; Anal. Calc.
79
for C21H BrN 364.0695.
19
2-Methyl-1,10-biphenyl
A suspension of phenylboronic acid 9 (0.20 g, 1.64 mmol,
1.5 equiv.), p-chlorotoluene 10 (0.13 mL, 1.09 mmol,
1.0 equiv.), K3PO4 ꢁ H2O (0.51 g, 2.20 mmol, 2.0 equiv.), and
CPC 5 (0.005 g, 0.005 mmol, 0.005 equiv. (1 mol % Pd)) in
toluene (5.5 mL) was heated to 708C for 12 h. The solvent was
removed and the crude material purified by column chroma-
tography (hexane/EtOAc) to give 11 (0.05 g, 26 %). Two sub-
sequent repeats produced similar results (21 and 29 %). All data
were in agreement with the literature.[42]
X-Ray Crystallography
X-Ray data of the compounds 6 and 7 were recorded at low
temperature with a Rigaku-Spider X-ray diffractometer, com-
prising a Rigaku MM007 microfocus copper rotating-anode
generator, high-flux Osmic monochromating and focussing
Second eluted was (pR,S)-{5-(pyridin-2-yl)[2.2]paracyclo-
phan-4-yl-C,N}(phenylalaninato-N,O)palladium(II) (pR,S)-7
as a yellow powder (0.05 g; 45 % assuming racemic starting
material). Mp 206–2098C (dec.). [a]D þ91.7 (c 1.31, CHCl3).
dH (400 MHz, CDCl3) 8.81 (1H, d, J 5.4, H-21), 7.86–7.83 (2H,
m, H-18, H-19), 7.28–7.21 (3H, m, 2 ꢂ H-27, H-28), 7.19–7.16
(2H, m, 2 ꢂ H-26), 7.10 (1H, dd, J 9.0, 5.4, H-20), 6.90 (1H, dd,
J 7.8, 1.4, H-13), 6.62 (1H, dd, J 7.9, 1.5, H-16), 6.57 (1H,
dd, J 7.9, 1.6, H-15), 6.31 (1H, d, J 7.8, H-7), 6.22 (1H, d, J 7.8,
H-8), 6.01 (1H, dd, J 7.8, 1.8, H-12), 3.95–3.83 (2H, m, H-9s,
H-23), 3.69–3.62 (1H, m, NH), 3.49 (1H, dd, J 13.9, 3.2, H-24),
3.28 (1H, dd, J 13.9, 11.2, H-24), 3.20–3.12 (2H, m, H-1s,
H-10a), 2.98–2.76 (5H, m, H-1a, H-2a, H-9a, H-10s, NH), 2.53
(1H, ddd, J 13.8, 9.7, 5.1, H-2s). dC (100 MHz, CDCl3) 178.8,
165.9, 158.0, 151.3, 144.3, 138.9, 138.8, 138.4, 136.6, 135.8,
134.3, 133.3, 132.6, 132.4, 131.7, 130.6, 129.2, 129.2, 127.4,
122.1, 120.9, 62.4, 40.3, 36.6, 36.5, 35.9, 33.8. m/z (HRMS ESI)
577.1089; Anal. Calc. for C30H28N2NaO2Pd 577.1078. m/z 577,
473, 390, 284.
˚
multilayer mirror optics (CuKa radiation, l 1.5418 A), and a
curved image-plate detector. CrystalClear[43] was utilised for
data collection and FSProcess in PROCESS-AUTO[44] for cell
refinement and data reduction. All structures were solved
employing direct methods and expanded by Fourier techni-
ques.[45] Non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were placed in calculated positions and refined
using a riding model with fixed isotropic U values. For com-
pound 6 two of the chlorine atoms in the dichloromethane
solvent molecule are positionally disordered in the ratio of
(0.75 : 0.25 for Cl11 and Cl12 respectively).
Crystal data for 6: C39H33ClNPPd ꢁ CH2Cl2, M 771.39, T 153
˚
(1) K, l 1.5418 A, monoclinic, space group P21/n, a 18.1862(3),
3
˚
˚
b 9.9971(2), c 19.6312(14) A, b 108.832(8)8, V 3378.1(3) A ,
Z 4, Dc 1.517 mgmꢀ3, m(CuKa) 7.293mmꢀ1, F(000) 1568, crystal
size 0.02 ꢂ 0.07 ꢂ 0.09 mm3. 33 359 reflections measured, 5966
independent reflections (Rint 0.071), the final R was 0.0546
[I . 2s(I)], and wR(F2) was 0.1420 (all data).
Crystal data for (pS,S)-7: C30H28N2O2Pd ꢁ CH2Cl2,
˚
M 639.87, T 153(2) K, l 1.5418 A, monoclinic, space group
˚
P21, a 11.7563(4), b 9.3095(4), c 13.8116(10) A, b 113.256(8)8,
Racemic 4-Bromo-5-(pyridin-2-yl)[2.2]
paracyclophane (ꢃ)-8
V 1388.80(15) A , Z 2, Dc 1.530 mgmꢀ3, m(CuKa) 7.408 mmꢀ1
,
3
˚
F(000) 652, crystal size 0.1 ꢂ 0.2 ꢂ 0.2 mm3. 15212 reflections
measured, 4562 independent reflections (Rint 0.041), the final R
was 0.0397 [I . 2s(I)], and wR(F2) was 0.0855 (all data).
A suspension of Br2 (0.015 mL, 0.29 mmol, 2.10 equiv.) and
NaOAc (0.02 g, 0.27 mmol, 1.95 equiv.) in CCl4 (3 mL) was
added dropwise over 30 min to a yellow/green suspension of
palladacycle 5 (0.12 g, 0.14 mmol, 1.00 equiv.) in CH2Cl2
(3.5 mL) at room temperature. As the Br2 was added the sus-
pension of palladacycle cleared to give a deep red solution. The
solution was stirred at room temperature for 1 h and then poured
into aqueous sat. Na2S2O3 (10 mL). The layers were separated
and the aqueous phase was extracted with CH2Cl2 (3 ꢂ 10 mL).
The combined organic layers were dried (MgSO4) and con-
centrated to give an orange solid. The crude material was puri-
fied by column chromatography (1 % EtOAc/CH2Cl2) to give 8
as a pale yellow powder (0.071 g; 70 %). dH (400 MHz, CDCl3)
7.72 (1H, td, J 7.8, 1.5), 7.59 (1H, d, J 7.1), 7.19 (1H, dd, J 5.7,
Supplementary Material
1H, 13C, and 31P NMR spectra for all new compounds are
available on the Journal’s website.
Acknowledgements
The authors thank Massey University for financial support (GJR & PGP)
and a University Technicians Award (JEG). They also thank KISCO
Ltd for the donation of [2.2]paracyclophane and David Martin for
preliminary results.

380
J. E. Glover, P. G. Plieger, and G. J. Rowlands
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