Synthesis of palladacycles employing iminoisoindolines as monoanionic bidentate ligands

Article abstract of DOI:10.1039/b806544f

A series of air- and moisture-stable iminoisoindoline-based palladacycles have been prepared in two operationally simple steps from commercially available reagents. para-Substituted N,N′-diphenyliminoisoindoline ligands are easily synthesized from phthalaldehyde and para-substituted anilines and further reaction of the iminoisoindoline ligands with Pd(OAc)₂ in dichloromethane at room temperature results in formation of six-membered [C,N] dinuclear cyclopalladated complexes with the general formula [(iminoisoindoline)Pd(μ-OAc)]₂. The resulting palladacyclic complexes were tested as precatalysts in Heck and Suzuki coupling reactions.

Full text of DOI:10.1039/b806544f

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Synthesis of palladacycles employing iminoisoindolines as monoanionic
bidentate ligands†
Jackson M. Chitanda,a Demyan E. Prokopchuk,a J. Wilson Quailb and Stephen R. Foley*a
Received 2nd May 2008, Accepted 29th July 2008
First published as an Advance Article on the web 22nd September 2008
DOI: 10.1039/b806544f
A series of air- and moisture-stable iminoisoindoline-based palladacycles have been prepared in two
operationally simple steps from commercially available reagents. para-Substituted
N,N¢-diphenyliminoisoindoline ligands are easily synthesized from phthalaldehyde and
para-substituted anilines and further reaction of the iminoisoindoline ligands with Pd(OAc)2 in
dichloromethane at room temperature results in formation of six-membered [C,N] dinuclear
cyclopalladated complexes with the general formula [(iminoisoindoline)Pd(m-OAc)]2. The resulting
palladacyclic complexes were tested as precatalysts in Heck and Suzuki coupling reactions.
phthalaldehyde and para-substituted anilines (Fig. 1). The ligands
Introduction
precipitate from the reaction mixture as analytically pure solids.
Palladacycles represent an increasingly important class of
Palladacyclic complex formation is also facile, simply involving
organometallic compounds, where their influence is especially
reaction of the iminoisoindoline ligand with Pd(OAc)2 resulting
dominant in the field of coupling reactions for organic
in precipitation of the desired palladacyclic species as air- and
transformations.1,2 This is reflected in the diversity of the pal-
moisture-stable orange or green solids. Here we present a simple
ladacycles that have been reported in literature, the most com-
two step procedure for the synthesis of four iminoisoindoline-
mon of which are palladacycles incorporating [C,P] and [C,N]
based palladacycles from commercially available starting materi-
metallacycle formations.3 Many palladium-mediated coupling
als. The catalytic activities of this new family of palladacycles were
reactions are thought to involve palladacyclic intermediates4 and
several palladacycles are also reported to be biologically active
compounds for cancer therapy.5 The majority of palladacycles
tested in standard Heck and Suzuki coupling reactions.
2
3
contain one s(M–Csp ) or s(M–Csp ) bond in a chelating bidentate
monoanionic ligand environment, with five- or six-membered N-
or P-containing ring systems.3
We previously reported the synthesis of a g-diimine ligand in
which intramolecular cyclization could be induced to form the
corresponding iminoisoindoline.6 Upon reaction of the g-diimine
with Pd(OAc)2, a five-membered palladacycle was synthesized.
With this in mind, we thought that iminoisoindoline ligands could
represent a convenient and facile route into the formation of rare
[C,N] imine-based six-membered palladacycles. Iminoisoindolines
could coordinate to palladium through the imine functionality,
followed by C–H activation of the N-bound aryl group and
subsequent ortho-palladation. There are several examples of
tridentate [N,N,N] and [C,N,N] iminoisoindolines as ligands
in pincer-type complexes,7 however we describe here the first
synthesis and characterization of a palladacyclic species derived
from monoanionic bidentate [C,N] iminoisoindoline ligands.
A wide variety of para-substituted iminoisoindoline ligands can
be prepared in a one pot procedure from commercially available
starting materials involving simple condensation reactions of
Fig. 1 Iminoisoindoline ligands.
Results and discussion
Iminoisoindoline ligands 1–5 were prepared by the reaction of
phthalaldehyde with 2 equiv. of the corresponding arylamine
under dinitrogen in high yield according to Scheme 1. The
particular ligands were chosen in order to investigate electronic
and steric effects in the para positions of the N-aryl substituents
(R = H (1), Me (2), iPr (3), COMe (4), NO2 (5) (Scheme 1)). The
iminoisoindoline ligands precipitate from solution as analytically-
pure white or yellow solids. Except for 3, the iminoisoindolines
have all been previously reported, however their potential as
ligands has never before been investigated.8
It has been previously proposed that in situ formation of a
g-diimine followed by rapid intramolecular cyclization results in
formation of the corresponding iminoisoindoline.8,9 We have re-
cently reported that a g-diimine can be isolated, provided sufficient
steric bulk is introduced in the ortho positions of the aryl-N
aUniversity of Saskatchewan, Department of Chemistry, 110 Science Place,
S7N 5C9, Saskatoon, Saskatchewan, Canada. E-mail: stephen.foley@
usask.ca
bSaskatchewan Structural Sciences Centre, 110 Science Place, S7N 5C9,
Saskatoon, Saskatchewan, Canada
† CCDC reference numbers 687003–687006 (6·CH2Cl2, 7·CHCl3,
8·CO(CH3)2 and 9·CH2Cl2). For crystallographic data in CIF or other
electronic format see DOI: 10.1039/b806544f
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Fig. 2 Isomers of [(iminoisoindoline)Pd(m-OAc)]2 (6–9).
each pair of methylene protons constitute an AX system for both
isomers, two doublets would be expected for the syn-isomer as well,
however the methylene protons of the syn-isomer are coincident,
appearing as a singlet shifted slightly downfield (~0.1 ppm) relative
to that of the free ligand. Upon cooling to -40 ◦C in CDCl3, only
a slight broadening of the methylene resonances in the syn-isomer
is observed. Due to steric effects, the anti-isomer is favored over
the syn-isomer with anti/syn ratios increasing as the steric bulk
in the ortho position of the iminoisoindoline ring increases. Thus,
anti/syn isomers were observed in ratios from 8 : 1 for 9 (R =
COMe) to 3 : 1 for 6 (R = H). The mass spectra of complexes 6–9
all showed a distinct signal which was assigned to their respective
molecular cation [M - OAc]+.
Scheme 1 Preparation of iminoisoindoline ligands and their corre-
sponding palladacycles. (i) Diethyl ether, 12 h, rt; (ii) dichloromethane,
12 h, rt.
substituent to retard cyclization. Even then, the g-diimine was
observed to undergo slow cyclization in the presence of catalytic
amounts of H+.6
The crystal structures of palladacycles 6–9 were determined.
All four structures co-crystallized with one molecule of the
solvent they were grown from. Complexes 6 and 9 co-crystallized
with one molecule of dichloromethane, while 7 co-crystallized
with one molecule of chloroform and 8 co-crystallized with one
molecule of acetone. All four complexes crystallized exclusively
as the anti-isomer, unambiguously confirming the presence of
a six-membered [C,N] palladacycle. The anti-configuration is
also observed in the crystal structures of previously reported
acetato-bridged dinuclear palladacycles,10 with the exception of
one report showing the exclusive crystallization of a syn-isomer.11
The two palladium atoms in 6–9 are bridged by two acetate
ligands and each palladium center has a chelating [C,N]-bound
iminoisoindoline ligand forming the palladacycle. The dinuclear
acetato-bridged complexes adopt a characteristic closed-book
conformation where the two [C,N]-bound iminoisoindoline lig-
ands stack on top of one another. As expected, the coordination
geometry about the palladium atoms in all four structures is
approximately square planar with the sum of the angles around
the palladium atoms for all three complexes being 360 1◦. The
Synthesis of [(iminoisoindoline)Pd(l-OAc)]2 palladacycles
Reaction of Pd(OAc)2 with one equiv. of the respective imi-
noisoindoline 1–4 in dichloromethane at ambient temperature
yielded the desired palladacycles 6–9 of the general formula
[(iminoisoindoline)Pd(m-OAc)]2, as analytically pure precipitates
(Scheme 1). Interestingly, no reaction was observed with NO2-
substituted iminoisoindoline 5 and Pd(OAc)2. This is likely due
to the electron-withdrawing/deactivating effects of the nitro sub-
stituent inhibiting both imine coordination and ortho-palladation.
Complexes 6–9 are air- and moisture-stable complexes that decom-
pose above 200 ◦C. No coordination complexes were observed
prior to cyclopalladation. Palladacycles 6–9 were characterized
by IR and NMR spectroscopy, mass spectrometry and elemental
analysis. Crystal structures were obtained for complexes 6–9.
The IR data confirmed the presence of the Pd–N bond in
the cyclopalladated complexes. In the spectra of complexes 6–
=
9, the signals for the C N bond vibrations were shifted to a
lower wavenumber compared to those of the free iminoisoindoline
(Dl ~ 35 cm-1).
˚
˚
Dinuclear palladacycles in which the two palladium centers
are linked by two bridging acetato groups can exist as anti- or
syn-isomers (Fig. 2).10 In this case, NMR data allows for easy
differentiation between the anti- and syn-conformations where the
anti-isomer exhibits overall C2 symmetry and the syn-isomer is
Cs symmetric. A characteristic indication of cyclopalladation in
Pd–Pd distance was found to be 2.9975(4) A for 6, 3.0049(3) A for
˚
7, 3.1130(3) for 8 and 2.9685(6) A for 9 which is consistent with
previously reported acetato-bridged dinuclear palladacycles.10 The
Pd–C and Pd–N bond lengths of complexes 6–9 were all essentially
˚
˚
identical (within esd) at 1.97(1) A and 2.01(1) A respectively. The
˚
Pd–O distances of the two acetate ligands differ by about 0.10 A
1
˚
complexes 6–9 is the observed H NMR resonance for the CH2
for 6–9 (for example, in 6, Pd(1)–O(1) is 2.157 A while Pd(1)–O(3)
˚
protons of the iminoisoindoline ring. The ligands (1–5) show a sin-
glet corresponding to the two methylene protons at ~5 ppm. Upon
cyclopalladation, these methylene protons become diastereotopic
in the anti-isomer resulting in formation of two doublets at ~4.6
and ~3.5 ppm, each corresponding to one proton per ligand. As
is 2.053 A), indicative of the stronger trans-influence of the aryl
carbon compared to that of the imine nitrogen.
ORTEP plots for 6–9 shown in Fig. 3 through 6. Crystallo-
graphic data is summarized in Table 1. Selected bond distances
and angles are provided in Table 2.
6024 | Dalton Trans., 2008, 6023–6029
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Table 1 Crystal data and refinement parameters for complexes 6–9
6·CH2Cl2
7·CHCl3
8·CO(CH3)2
9·CH2Cl2
Formula
Formula wt
Color
C45H38Cl2N4O4Pd2
982.49
Green
C49H45Cl3N4O4 Pd2
1073.04
Orange
C59H66N4O5Pd2
1123.96
Yellow
C53H46Cl2N4O8Pd2
1150.64
Orange
Crystal system
Space group
Monoclinic
P21/c
Monoclinic
P21/c
23.1864(3)
Monoclinic
P21/c
Monoclinic
P21/c
˚
a/A
12.5421(2)
16.7665(3)
18.9026(4)
91.3617(13)
4
13.7107(2)
19.1758(3)
21.3745(3)
106.8883(1)
4
18.6888(8)
13.9845(11)
21.6903(11)
124.159(3)
4
˚
b/A
9.6437(1)
˚
c/A
20.2415(2)
105.026(1)
4
1.630
173(2)
b/◦
Z
r
calc/Mg m-3
1.642
173(2)
1.388
173(2)
1.629
173(2)
Temp./K
F(000)
1976
57 938/8109
0.0866
2.47 to 26.37
R1 = 0.0384, wR2 = 0.0830
R1 = 0.0556, wR2 = 0.0924
2168
77 979/11 273
0.0734
2.35 to 28.71
R1 = 0.0403, wR2 = 0.0809
R1 = 0.0615, wR2 = 0.0889
2320
77 135/12 313
0.1066
2.26 to 27.47
R1 = 0.0426, wR2 = 0.0878
R1 = 0.0696, wR2 = 0.1004
2328
55 029/8577
0.0984
2.63 to 25.35
R1 = 0.506, wR2 = 0.1144
R1 = 0.695, wR2 = 0.1247
Reflns collected/unique
Rint
q range/◦
final R1(I >2sI)
R1(all data)
◦
˚
Table 2 Selected bond distances (A) and angles ( ) for complexes 6–9
6
7
8
9
˚
Bond distances/A
Pd(1)–C(10)
Pd(1)–N(2)
Pd(1)–O(3)
Pd(1)–O(1)
Pd(1)–Pd(2)
1.972(3)
2.004(3)
2.053(3)
2.157(2)
2.9975(4)
1.969(3)
2.016(3)
2.159(2)
2.083(2)
3.0049(3)
1.960(3)
2.004(3)
2.139(2)
2.055(2)
3.1130(3)
1.975(5)
2.008(4)
2.064(4)
2.147(4)
2.9685(6)
Bond angles/◦
C(10)–Pd(1)–N(2)
C(10)–Pd(1)–O(1)
N(2)–Pd(1)–O(3)
O(3)–Pd(1)–O(1)
90.40(13)
91.70(13)
95.31(10)
82.46(10)
90.00(11)
91.77(11)
93.85(9)
84.22(9)
88.62(12)
89.63(11)
93.95(10)
87.84(9)
90.7(2)
92.70(19)
94.02(16)
82.65(15)
Fig. 4 ORTEP plot of 7 at the 50% probability level. The hydrogen atoms
have been omitted for clarity.
Catalysis
While palladacycles have been around since 1965,12 the first
examples of palladacycles as precatalysts in the Heck and Suzuki
reaction were not published until 1995.13 Palladacyclic compounds
currently rank among the best precatalysts for a variety of C–C
coupling reactions.1,3,13 Several palladacycles are now commer-
cially available from chemical companies such as Aldrich and
Strem and most notably include the imine-based Na´jera catalyst14,
the amine-based Indolese catalyst15 and Bedford’s phosphite-
based catalyst.16
The catalytic activity of palladacyclic complexes 6 and 9 was
tested in the standard Suzuki coupling reaction of aryl halides
with phenylboronic acid, using Cs2CO3 as a base, 1% precatalyst
loading and dioxane as solvent at 80 ◦C. As shown in Table 3,
Fig. 3 ORTEP plot of 6 at the 50% probability level. The hydrogen atoms
have been omitted for clarity.
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Table 3 Suzuki cross-coupling of aryl halides with phenylboronic acida
Entry
R
X
Time/h
Catalyst
Conversionb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
H
H
Me
COMe
CN
COMe
Me
CN
COMe
OMe
OMe
Me
COMe
CN
I
3
3
3
3
3
18
24
24
24
24
96
24
24
24
6
6
6
6
6
6
9
9
9
9
9
9
9
9
> 99
94
92
75
80
43
94
> 99
> 99
90
18
27
> 99
> 99
Br
Br
Br
Br
Cl
Br
Br
Br
Br
Cl
Cl
Cl
Cl
a Reaction conditions: 1 mmol of aryl halides, 1.5 mmol phenyl boronic
acid, 2 mmol Cs2CO3, 1 mmol% Pd precatalyst, 3 mL of dioxane.
b Determined by 1H NMR in reference to the residue aryl-halide.15,16
Fig. 5 ORTEP plot of 8 at the 30% probability level. The hydrogen atoms
have been omitted for clarity.
a fairly good conversion of 60% and 53% respectively, while p-
acetochlorobenzene resulted in only 16% conversion (entry 11).
Under the same conditions, coupling of deactivated aryl chlorides
was unsuccessful.
Conclusion
We have synthesized and studied a series of air- and moisture-
stable iminoisoindoline-based palladacycles. These complexes are
easily prepared in two operationally simple steps from com-
mercially available reagents. Complexes 6 and 9 were found to
be active precatalysts for the Suzuki and Heck C–C coupling
reactions with precatalyst 9 (R = COMe) exhibiting significantly
higher activity than 6 (R = H). If highly electron-withdrawing
groups are employed on the diphenyliminoisoindoline ligands
(i.e. iminoisoindoline 5, R = NO2), palladacyclic formation is
completely inhibited. Further investigations on the reactivity and
catalytic activity of this family of palladacycles are underway and
this work will be reported at a later date.
Fig. 6 ORTEP plot of 9 at the 50% probability level. The hydrogen atoms
have been omitted for clarity.
good to excellent yields of biphenyls were obtained in the
Suzuki coupling reaction for both activated and deactivated aryl
bromides. Interestingly, for activated aryl chlorides, 6 gave only a
43% yield (entry 6), while 9 resulted in quantitative yields (entries
13 and 14). With deactivated chlorides however, low conversions
were obtained.
We further investigated the activity of palladacyclic complexes
6 and 9 in the standard Heck reaction of activated and deactivated
aryl halides with butyl acrylate. The results are shown in Table 4.
Quantitative yields were obtained when employing bromoanisole
and bromobenzaldehyde in the presence of 0.01 and 0.1 mol%
of 9 respectively (entries 5 and 6), even at lower temperature
(100 ◦C, entry 7). A decrease in activity was observed when
deactivated aryl bromides such as p-bromotoluene (61%) and
p-bromoanisole (56%) were used. Among the activated aryl
chlorides only chlorobenzaldehyde and bromobenzonitrile gave
Experimental
General Information
Unless otherwise stated, all reactions were performed under N2
using standard Schlenk techniques or in a N2-filled drybox.
All reaction temperatures for catalytic reactions refer to the
temperature of pre-equilibrated oil or sand baths. All melting
points were recorded on a Gallenkamp melting point apparatus
1
and are uncorrected. 1H and 13C{ H} NMR spectra were recorded
on a Bruker 500 MHz Avance spectrometer. Chemical shifts for
1H and 13C NMR are reported in ppm in reference to the residual
1H and 13C resonances of CDCl3 (1H: d 7.24; 13C: d 77.23) and
DMSO-d6 (1H: d 2.50; 13C: d 39.51). Coupling constants are given
in Hz. Elemental analyses were performed on a Perkin-Elmer
6026 | Dalton Trans., 2008, 6023–6029
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Table 4 Heck cross-coupling of aryl halides with butyl acrylatea
Entry
R
X
Time/h
Catalyst (mol%)
Conversionb (%)
TONc
1
2
H
H
H
CN
COMe
COH
COH
Me
OMe
COH
COMe
CN
I
3
3
12
3
3
3
24
3
3
3
24
24
6 (0.001)
6 (1)
> 99
71
0
96
> 99
> 99
> 99
61
56
60
100 000
71
Br
Cl
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
3d
4
6 (3)
0
96
10 000
1000
100
61
9 (1)
5d
6
9 (0.01)
9 (0.1)
9 (1)
7e
8
9 (1)
9
9 (1)
56
60
16
53
10
11d
12
9 (1)
9 (1)
16
53
9 (1)
◦
1
a Reaction conditions: aryl halide (1.0 mmol), acrylate (2.0 mmol), base (2.0 mmol), Pd precatalyst, solvent (DMA, 3 ml), 145 C. b Determined by H
NMR based on residual aryl halide.15,16 c TON = turnover number (mol product per mol catalyst). d CsOAc used as base. e Performed at 100 ◦C.
-1
=
2400 CHN elemental analyzer. IR data was collected by Diffuse
Reflectance Spectroscopy. Pd(OAc)2 was purchased from PMO
Pty Ltd, Australia. Aniline, p-methylaniline, p-isopropylaniline,
p-acetoaniline, p-nitroaniline and phthalaldehyde were purchased
from the Sigma-Aldrich Chemical Company and used as received.
The syntheses of iminoisoindolines 1, 2, 4 and 5 have been reported
in the literature, however spectral data for these compounds has
not been communicated and is thus included here.8
N 8.69. FT-IR (KBr, cm ): 1650 (C N), 1633, 1615, 1615, 1609.
ESI-MS m/z calcd for C22H20N2: 312.16; found: 313.16 [M + H]+.
1-p-Isopropylphenylimino-2-p-isopropylphenylisoindoline
(3).
(98% yield, white powder.) 1H NMR (CDCl3): d 7.88 (d, J = 7.9,
2H, Ar), 7.42 (d, J = 7.3, 1H, Ar), 7.35 (m, 1H, Ar), 7.24 (d,
J = 7.5, 2H, Ar), 7.17 (d, J = 7.5, 2H, Ar), 7.05 (m, 1H, Ar),
6.91 (d, J = 7.5, 2H, Ar), 6.70 (d, J = 7.5, 1H, Ar), 4.91 (s, 2H,
CH2), 2.89 (m, 2H, CH(CH3)2), 1.28 (d, J = 6.7, 6H, CH(CH3)2),
1.25. (d, J = 6.7, 6H, CH(CH3)2). 13C NMR (CDCl3, ppm): d
153.56 (C=N), 148.58, 143.71, 143.00, 140.62, 139.56, 139.54,
131.81, 130.22, 127.38, 127.17, 126.96, 126.64, 122.85, 121.16,
120.20, 53.13 (CH2), 33.74 (CH(CH3)2), 24.52 (CH(CH3)2), 24.25
(CH(CH3)2). Anal. calcd (%) for C24H20N2O2: C 78.24, H 5.47, N
7.60; found: C 78.45, H 5.17, N 7.38. FT-IR (KBr, cm-1): 1648
General synthesis for iminoisoindolines 1–5
Phthalaldehyde (17.2 mmol), arylamine (36.1 mmol, 2.1 equiv.),
formic acid (0.05 mL) and ether (30 mL) were combined in a
100 mL Schlenk flask equipped with a stir bar. The solution
was stirred for 12 h at ambient temperature under dinitrogen.
The resulting precipitate was filtered and washed with ether (3 ¥
20 mL), then dried under vacuum to obtain white or yellow solids.
=
(C N), 1642, 1606. EI-MS m/z calcd for C26H28N2: 368.22; found:
368.22.
1-p-Acetophenylimino-2-p-acetophenylisoindoline (4). Metha-
1-Phenylimino-2-phenylisoindoline (1). (75.0% yield, white
nol was used in place of ether to obtain a higher yield (72% yield,
◦
1
◦
powder, mp = 127.8–129.5 C.) H NMR (CDCl3, ppm): d 8.01
(d, J = 6.0, 2H, Ar), 7.44 (d, J = 7.5, 1H, Ar), 7.38 (m, 3H, Ar),
7.31 (m, 2H, Ar), 7.04 (m, 3H, Ar), 6.99 (d, J = 6.7, 2H, Ar), 6.66
(d, J = 7.1, 1H, Ar), 4.94 (s, 2H, CH2). 13C NMR (CDCl3, ppm):
d 153.52, 150.87, 141.81, 140.59, 130.48, 129.34, 129.12, 127.53,
126.70, 123.33, 122.92, 122.44, 121.44, 120.18, 53.18 (CH2). Anal.
1
yellow powder, mp: 170.5–171.8 C.) HNMR (CDCl3, ppm): d
8.10 (d, J = 8.4, 2H, Ar), 8.00 (d, J = 8.9, 2H, Ar), 7.99 (d, J = 8.4,
2H, Ar), 7.50 (d, J = 7.5, 1H, Ar), 7.43 (m, 1H, Ar), 7.09 (m, 1H,
Ar), 7.04 (d, J = 8.4, 2H, Ar), 6.76 (d, J = 7.3, 1H, Ar), 5.00 (s,
2H, CH2), 2.62 (s, 3H, COCH3), 2.58 (s, 3H, COCH3). 13C NMR
(CDCl3, ppm): d 197.3 (COCH3), 196.9 (COCH3), 154.8 (C=N),
152.7, 145.2, 140.0, 132.1, 131.9, 131.7, 131.2, 130.8, 130.2, 129.7,
126.3, 123.0, 120.8, 117.4, 99.9, 52.9 (CH2), 25.5 (COCH3). Anal.
calcd (%) for C20H16N2: C 84.48, H 5.67, N 9.85; found: C 84.57, H
-1
=
5.62, N 9.60. FT-IR (KBr, cm ): 1646 (C N), 1590, 1498. ESI-MS
m/z calcd for C20H16N2: 284.1313; found: 285.1392 [M + H]+.
calcd (%) for C24H20N2O2: C 78.24, H 5.47, N 7.60; found: C 78.45,
-1
=
H 5.17, N 7.38. FT-IR (KBr, cm ): 1662 (C N), 1589. ESI-MS
1-p-Methylphenylimino-2-p-methylphenylisoindoline (2). (51%
yield, white powder.) 1H NMR (CDCl3, ppm): d 7.83 (d, J = 7.8,
2H, Ar), 7.41 (d, J = 7.6, 1H, Ar), 7.35 (m, 1H, Ar), 7.18 (d, J =
7.8, 2H, Ar), 7.11 (d, J = 7.4, 2H, Ar), 7.05 (m, 1H, Ar), 6.87 (d,
J = 7.4, 2H, Ar), 6.71 (d, J = 7.6, 1H, Ar), 4.89 (s, 2H, CH2),
2.36 (s, 3H, CH3), 2.32 (s, 3H, CH3). 13C NMR (CDCl3, ppm):
d 153.67 (C=N), 148.37, 140.67, 139.29, 130.27, 129.89, 129.67,
129.38, 127.39, 126.70, 124.30, 122.87, 121.04, 121.44, 120.47,
53.27 (CH2), 21.14 (Ar-CH3), 21.03 (Ar-CH3). Anal. calcd (%)
for C22H20N2: C 84.58, H 6.45, N 8.97; found: C 84.30, H 7.57,
m/z calcd for C24H20N2O2: 368.15; found: 369.16 [M + H]+.
1-p-Nitrophenylimino-2-p-nitrophenylisoindoline
(5). (80%
1
yield, yellow powder.) H NMR (CDCl3): d 8.27 (m, 4H, Ar),
8.17 (d, J = 9.3, 2H, Ar), 7.52 (m, 2H, Ar), 7.16 (m, 1H, Ar),
7.07 (d, J = 8.84, 2H, Ar), 6.78 (d, J = 7.90, 1H, Ar), 5.05 (s, 2H,
13
=
CH2). C NMR (CDCl3): d 156.4 (C N), 152.9, 146.6, 142.6,
142.0, 141.2, 132.1, 129.7, 128.0, 125.7, 125.5, 124.9, 124.0, 121.5,
119.4, 53.2 (CH2). Anal. calcd. for C20H14N4O4: C 64.48, H 3.77,
N 14.97; found: C 64.38, H 3.61, N 15.24.
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General synthesis for palladacycles 6–9
1.18 (d, J = 6.9, 12H, CH(CH3)2); syn-isomer d 7.51 (d, J =
8.0, 2H, Ar), 7.34 (m, 4H, Ar), 7.31 (d, J = 7.9, 2H, Ar), 7.24
(m, 4H, Ar), 7.20 (d, J = 7.9, 2H, Ar), 7.00 (m, 2H, Ar), 7.10
(d, J = 7.9, 2H, Ar), 6.90 (d, J = 7.9, 2H, Ar), 5.83 (m, 2H,
Ar), 5.05 (s, 4H, CH2), 2.98 (m, 4H, CH(CH3)2)), 1.98 (s, 6H,
CH3COO), 1.30 (d, J = 6.9, 6H, CH(CH3)2), 1.25 (d, J = 6.9, 6H,
CH(CH3)2), 1.20 (d, J = 6.9, 12H, CH(CH3)2). 13C NMR (CDCl3):
anti-isomer d 179.0 (CH3COO), 151.5 (C=N), 146.5, 144.2, 142.3,
140.9, 134.4, 134.3, 131.1, 130.7, 128.0, 127.5, 127.3, 126.8, 125.7,
125.2, 124.9, 122.9, 122.0, 111.6, 52.8 (CH2), 34.0 (CH(CH3)2),
33.8 (CH(CH3)2), 24.59 (CH3COO), 24.57 (CH(CH3)2), 24.5
(CH(CH3)2), 24.3 (CH(CH3)2), 24.1 (CH(CH3)2). Anal. calcd (%)
Iminoisoindoline (1.765 mmol) and Pd(OAc)2 (1.765 mmol,
1.0 equiv.) were dissolved in dichloromethane (30 mL) in an oven
dried 100 mL Schlenk flask equipped with a stir bar. After 12 h
of stirring at ambient temperature under dinitrogen, the reaction
mixture was filtered to remove palladium black. The filtrate
was then concentrated and ether (30 mL) added to precipitate
the desired palladacycle. The resulting precipitate was filtered,
washed with cold ether (3 ¥ 10 mL) then dried under vacuum.
Crystals suitable for X-ray diffraction studies were obtained by
slow evaporation from a 50 : 50 dichloromethane–hexane solution
for 6 and 9. Crystals of 7 were obtained from CHCl3 and crystals of
8 were grown from a 50 : 50 acetone–hexane solution all at ambient
temperature.
for C56H62N4O4Pd2: C 63.10, H 5.67, N 5.26; found: C 62.96, H
-1
=
5.68, N 5.32. FT-IR (KBr, cm ): 1615.4 (C N), 1578.9, 1552.1,
1504.2, 1415.1. ESI-MS m/z calcd for C56H60N4O4Pd2: 1067.2841
[M], 1005.26 [M - OAc]+; found: 1005.26 [M - OAc]+.
Bis(l-acetato)bis(1-phenylimino-2-phenylisoindoline)dipallad-
ium(II) (6). (42% yield, green powder, mp = 222.5–224.8 ◦C
Bis(l-acetato)bis(1-p-acetophenylimino-2-p-acetophenylisoindo-
line)di◦palladium(II) (9). (40% yield, orange powder, mp = 242.5–
244.5 C (decomp.).) 1H NMR (CDCl3, ppm): anti : syn = ca. 8 : 1;
anti-isomer d 8.26 (s, 2H, Ar), 7.85 (d, J = 8.0, 2H, Ar), 7.53 (m,
4H, Ar), 7.38 (m, 4H, Ar), 7.10 (d, J = 8.2, 2H, Ar), 7.04 (m,
2H, Ar), 6.36 (d, J = 8.5, 2H, Ar), 5.95 (d, J = 8.0, 2H, Ar),
5.77 (d, J = 8.1, 2H, Ar), 4.76 (d, J = 16.8, 2H, CH2), 3.82 (d,
J = 16.8, 2H, CH2), 2.58 (s, 6H, COCH3), 2.56 (s, 6H, COCH3),
1.66 (s, 6H, CH3COO); syn-isomer 8.10 (d, J = 7.9, 4H, Ar), 7.90
(m, 6H, Ar), 7.56–7.02 (m, 8H, Ar), 5.95 (d, J = 7.9, 4H, Ar),
5.17 (s, 4H, CH2), 2.67 (s, 6H, COCH3), 2.65 (s, 6H, COCH3),
1.96 (s, 6H, CH3COO). 13C NMR (DMSO, ppm): anti-isomer
d 197.07 (COCH3), 196.64 (COCH3), 178.60 (CH3COO), 151.37
(C=N), 150.01, 141.42, 138.73, 135.66, 134.47, 131.92, 130.13,
129.90, 128.97, 127.76, 126.94, 126.59, 126.11, 125.26, 123.18,
122.71, 112.79, 53.49 (CH2), 26.68 (COCH3), 26.23 (COCH3),
24.41 (CH3COO). Anal. calcd (%) for C52H44N4O4Pd2: C 58.60, H
4.16, N 5.26; found: C 58.38, H 4.01, N 5.13. FT-IR (KBr, cm-1):
1
(decomp.).) H NMR (CDCl3, ppm): anti : syn = ca. 3 : 1; anti-
isomer d 7.67 (d, J = 7.6, 2H, Ar), 7.44–6.88 (m, 20H, Ar),
6.24 (d, J = 7.6, 2H, Ar), 5.68 (d, J = 8.1, 2H, Ar), 4.62 (d,
J = 16.8, 2H, CH2), 3.61 (d, J = 16.8, 2H, CH2), 1.62 (s,
6H, CH3COO); syn-isomer d 7.44–6.88 (m, 20H, Ar), 5.94 (m,
6H, Ar), 5.09 (s, 4H, CH2), 1.96 (s, 6H, CH3COO). 13C NMR
(CDCl3, ppm): anti-isomer d 179.33 (CH3COO), 151.63 (C=N),
146.37, 140.72, 136.67, 136.04, 131.01, 130.91, 129.01, 128.09,
127.67, 127.44, 127.21, 125.98, 125.90, 124.85, 124.56, 122.04,
121.97, 111.83, 52.93 (CH2), 24.45 (CH3COO). Anal. calcd (%)
for C44H36N4O4Pd2: C 58.87, H 4.04, N 6.24; found: C 59.70, H
-1
=
4.23, N 6.10. FT-IR (KBr, cm ): 1614 (C N), 1603, 1585. EI-MS
m/z calcd for C44H36N4O4Pd2: 896.08 [M], 897.08 [M + H]+; found
897.0878 [M + H]+.
Bis(l-acetato)bis(1-p-methylphenylimino-2-p-methylphenyliso-
indoline)dipalladium(II) (7). (46% yield, orange powder.) 1H
NMR (CDCl3): anti : syn = ca. 3 : 1); anti-isomer d 7.47–6.96 (m,
12H, Ar), 6.85 (m, 4H, Ar) 6.57 (d, J = 7.9, 2H, Ar), 6.17 (d, J =
8.0, 2H, Ar), 5.74 (d, J = 8.0, 2H, Ar), 4.60 (d, J = 16.8, 2H,
CH2), 3.77 (d, J = 16.8, 2H, CH2), 2.30 (s, 6H, Ar–CH3), 2.20
(s, 6H, Ar–CH3), 1.64 (s, 6H, CH3COO); syn-isomer d 7.47–6.96
(m, 16H, Ar), (d, J = 7.9, 2H, Ar), 6.00 (d, J = 7.9, 4H, Ar),
5.04 (s, 4H, CH2), 2.42 (s, 6H, Ar–CH3), 2.22 (s, 6H, Ar–CH3),
1.98 (s, 6H, CH3COO). 13C NMR (CDCl3): anti-isomer d 179.3
(CH3COO), 151.1 (C=N), 144.0, 140.7, 137.0, 135.4, 133.8, 131.1,
130.9, 130.7, 129.7, 127.9, 127.8, 127.4, 127.0, 125.9, 125.4, 124.1,
121.9, 111.4, 53.1 (CH2), 24.6 (CH3COO), 21.3 (Ar–CH3), 20.9
(Ar–CH3). Anal. calcd (%) for C48H44N4O4Pd2: C 60.38, H 4.75,
N 5.87; found: C 60.43, H 4.64, N 6.95. FT-IR (KBr, cm-1): 1619
=
1667 (C N), 1623, 1484. ESI-MS m/z calcd for C52H44N4O8Pd2:
1064.1 [M], 1005.1 [M - OAc]+; found 1005.2 [M - OAc]+.
General procedure for Heck coupling reactions
In a typical run, an oven-dried 25 mL two-necked flask equipped
with a stir bar was charged with a known mol% catalyst and
base (2.0 mmol). Under nitrogen, N,N-dimethylacetamide (DMA)
(3 mL), arylhalide (1.0 mmol) and n-butylacrylate (2.0 mmol) were
added via syringe. The flask was then placed in a pre-heated sand
bath at 145 ◦C. After the specified time the flask was removed from
the sand bath and water (20 mL) was added followed by extraction
with dichloromethane (4 ¥ 10 mL). The combined organic layers
were washed with water (3 ¥ 10 mL), dried over anhydrous MgSO4,
and filtered. Solvent was removed under vacuum. The residue was
dissolved in CDCl3 and analyzed by 1H NMR. Percent conversions
were determined against the remaining aryl halide.16,17
=
(C N), 1615, 1508. ESI-MS m/z calcd for C48H44N4O4Pd2: 952.14
[M], 893.13 [M - OAc]+; found 893.1554 [M - OAc]+.
Bis(l-acetato)bis(1-p-isopropylphenylimino-2-p-isopropylphe-
nylisoindoline)dipalladium(II) (8). (30% yield, yellow powder.) 1H
NMR (CDCl3): anti : = ca. 5 : 1; anti-isomer d 7.54 (s, 2H, Ar),
7.41 (m, 2H, Ar), 7.24 (d, J = 7.9, 2H, Ar), 7.00 (m, 4H, Ar),
6.83 (d, J = 7.9, 2H, Ar), 6.80 (d, J = 8.2, 2H, Ar), 6.65 (d,
J = 8.2, 2H, Ar), 6.16 (d, J = 8.2, 2H, Ar), 5.83 (d, J = 8.2,
2H, Ar), 5.74 (d, J = 8.2, 2H, Ar), 4.53 (d, J = 16.9, 2H, CH2),
3.30 (d, J = 16.9, 2H, CH2), 2.91 (sept, J = 6.9, 2H, CH(CH3)2),
2.81 (sept, J = 6.9, 2H, CH(CH3)2), 1.64 (s, 6H, CH3COO), 1.32
(d, J = 6.9, 6H, CH(CH3)2), 1.28 (d, J = 6.9, 6H, CH(CH3)2),
General procedure for Suzuki coupling reactions
In a typical run, an oven dried 25 mL two-necked flask equipped
with a stir bar was charged with a known mol% catalyst, base
(2.0 mmol) and phenylboronic acid (1.5 mmol). Under nitrogen,
DMA (3 mL) and aryl halide (1.0 mmol) were added via syringe.
The flask was placed in pre-heated sand bath at 80 ◦C. After the
6028 | Dalton Trans., 2008, 6023–6029
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specified time the flask was removed from the sand bath and water
(20 mL) was added followed by extraction with dichloromethane
(3 ¥ 10 mL). The combined organic layers were washed with water
(3 ¥ 10 mL), dried over anhydrous MgSO4, and filtered. Solvent
was removed under vacuum. The residue was dissolved in CDCl3
and analyzed by 1H NMR. Percent conversions were determined
against the remaining aryl halide.16,17
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Data was collected at -100 ◦C on a Nonius Kappa CCD diffrac-
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data reductions used the programs DENZO and SCALEPACK.19
SIR9720 was used to solve the structures and SHELXL9721 was
used to refine the structures. ORTEP-3 for Windows22 was used for
molecular graphics and PLATON23 was used to prepare material
for publication. H atoms were placed in calculated positions with
´
2004, 13, 2716–2722; (f) E. Balogh-Hergovich, G. Speier, M. Re´glier,
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U
iso constrained to be 1.5 times Ueq of the carrier atom for methyl
protons and 1.2 times Ueq of the carrier atom for all other hydrogen
atoms. For complex 9 there are four acetyl groups in the molecule,
attached on atoms C12, C18, C42 and C48. The acetyl group on
C48 is badly disordered and would not refine to reasonable bond
angles and bond lengths. To avoid putting meaningless values into
the CSD, the average of the bond lengths and bond angles of the
other three acetyl groups was used to form a rigid acetyl group on
C48. The thermal ellipsoids on C52 and O51 were restrained using
the ISOR command in SHELXL. The resulting displacements
for these atoms were much larger than for the equivalent groups.
Consequently, C52 (and the attached H atoms) and O51 had very
large Ueq.
9 (a) I. Takahashi, M. Tsuzuki, H. Yokota, H. Kitajima and K. Isa,
Heterocycles, 1994, 37, 933–942; (b) I. Takahashi and M. Hatanaka,
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11 A. Ferna´ndez, D. Va´zquez-Garc´ıa, J. J. Ferna´ndez, M. Lo´pez-Torres,
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Acknowledgements
12 A. C. Cope and R. W. Siekman, J. Am. Chem. Soc., 1965, 87, 3272–3273.
13 (a) W. A. Herrmann, C. Brossmer, K. Ofele, C.-P. Reisinger, T.
Priermeier, M. Beller and H. Fischer, Angew. Chem., Int. Ed. Engl.,
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We gratefully thank NSERC for financial support and the
Canadian Government through the Commonwealth Scholarship
fund for J.M.C.’s doctoral fellowship.
14 (a) D. A. Alonso, L. Botella, C. Na´jera and C. Pacheco, Synthesis, 2004,
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Dalton Trans., 2008, 6023–6029 | 6029
©