A modular approach to trans-chelating, N-heterocyclic carbene ligand complexes

Article abstract of DOI:10.1016/S0957-4166(02)00535-9

The N-methyl bis-imidazolium salts 3 were converted to the silver carbenes 7, then reacted to give palladium(II) complexes 4 with trans-chelating, bidentate bis-imidazolylidine ligands. The similar salts 8, that do not have N-methyl substituents, gave the

Full text of DOI:10.1016/S0957-4166(02)00535-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1969–1972
A modular approach to trans-chelating, N-heterocyclic carbene
ligand complexes
Marc C. Perry, Xiuhua Cui and Kevin Burgess*
Department of Chemistry, Box 30012, Texas A & M University, College Station, TX 77841-3012, USA
Received 28 August 2002; accepted 30 August 2002
Abstract—The N-methyl bis-imidazolium salts 3 were converted to the silver carbenes 7, then reacted to give palladium(II)
complexes 4 with trans-chelating, bidentate bis-imidazolylidine ligands. The similar salts 8, that do not have N-methyl
substituents, gave the tetradentate complexes 9 in direct reactions with palladium chloride. The potential of these complexes for
asymmetric catalysis is discussed. © 2002 Published by Elsevier Science Ltd.
Syntheses of chiral ligands via combinations of suitable
chirons with other building blocks can be a powerful
strategy in the discovery and optimization of asymmet-
ric catalysts. Modular approaches such as this allow the
construction of diverse ligand families from readily
available starting materials. Herein, we describe how
the diamide chiron 1 was combined with a series of
N-substituted imidazoles 2 to give the chiral N-hetero-
cyclic carbene ligand precursors 3, and subsequently,
the corresponding trans-chelated palladium complexes
Syntheses of the ligands began with resolution of trans-
1,2-diaminocyclohexane. The resolution was completed
8
following the Organic Synthesis procedure, but deter-
mination of the enantiomeric purity of the product was
performed differently. The published procedure
describes conversion of the amine functionalities into
4-methylbenzoyl amides, then separation of the enan-
tiomers on a Pirkle HPLC column. In our work, the
diamine was converted into the mono (4-methylben-
zene)sulfonamide 5, then analyzed by chiral capillary
1
–7
9
4.
electrophoresis (CE). The CE method requires much
less sample, and gives baseline resolution of the two
enantiomers in about half the separation time (i.e. 6
min). Fig. 1 shows CE traces for racemic and
diastereomerically pure samples of 5.
Preparation of the bis-imidazolium ligand precursors 3
followed the sequence shown in Scheme 1. The tartaric
acid salt of diastereomerically pure trans-1,2-
diaminocyclohexane was converted to the correspond-
ing bis-ethyl carbonate, then reduced to the
1
0
N,N%-dimethyl amine 6 via a known procedure. N-
Substituted imidazoles were then reacted with the
dichloride 1 to give the imidazolium salts. We were
unable to find good recrystallization solvents for these
salts, but NMR analyses of the crude materials isolated
simply after removal of the DMF solvent indicated they
were of high purity and were formed in near quantita-
*
Corresponding author.
0
957-4166/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0957-4166(02)00535-9

1
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M. C. Perry et al. / Tetrahedron: Asymmetry 13 (2002) 1969–1972
Figure 1. CE traces of racemic and enantiomerically pure 5.
tive yields. Additionally, the formation of organometal-
lic derivatives from these samples proceeded without
difficulty.
Scheme 2. Preparations of the imidazolium salts 4.
Scheme 1. Preparations of the imidazolium salts 3.
crude precipitate was much enriched in the desired
product (Fig. 2b).
Scheme 2 shows how the target palladium complexes 4
were prepared from the imidazolium salts 3. Reaction
of the imidazolium salts with silver oxide at room
1
1–13
temperature,
filtration, and removal of solvent gave
the silver carbene intermediates 7. Without further
purification, these samples, were reacted with bis(ace-
tonitrile)dichloropalladium(II); the desired complexes
4
c–e formed after about 1 h, and were precipitated
from the reaction medium directly by concentrating the
dichloromethane solvent and adding diethyl ether. The
tert-butyl substituted complex 4b took longer to form;
in this case the reaction was allowed to proceed for 16
h.
Formation of the palladium complex 4a did not occur
at 25°C; presumably, this particular syntheses was unfa-
vorable due to the size of the 2,6-di-iso-propylphenyl
1
4
substituent. Preparation of complex 4f at room tem-
perature was also problematic. Fig. 2a shows part of
1
the H NMR for the crude precipitate of 4f, formed via
reaction with the silver carbene at 25°C for 18 h; several
of the peaks that are not characteristic of the product.
However, when the synthesis was repeated using a
microwave reactor set at 100°C for 20 min then the
1
Figure 2. H NMR spectra in CDCl of the crude precipitates
3
formed in the preparation of complex 4f, (a) 25°C for 18 h;
and (b) 100°C microwave for 20 min.

M. C. Perry et al. / Tetrahedron: Asymmetry 13 (2002) 1969–1972
1971
X-Ray quality crystals of complex 4d were obtained.
nated. Second, complex 9b has a CO stretch at 1644
15
−1
The solid structure (Fig. 3) is a near perfect square
cm which is close to that of the imidazolium salt 8b
carbene
−1
−1
planar palladium complex where the ClꢀPdꢀC
(1658 cm ) and to that of the complex 4b (1651 cm ;
thin film on NaCl plates).
bond angles show less than 2° deviation from the ideal
90° (88.1 and 91.2° were measured). The carbenes form
a trans-chelate with the imidazolylidenes twisted such
that their cyclohexyl substituents are directed to oppo-
site faces of the complex. The planes between the
imidazolylidenes lie at an angle of 64° to one another,
and the bisector between these two planes is perpendic-
ular to the ClꢀPdꢀCl bonds.
(1)
Attempts to use complexes 4b–f as catalysts for
intramolecular Heck reactions gave very poor chemical
yields and enantioselectivities. In retrospect, this is
unsurprising given that the trans-geometry of the
chelating N-heterocyclic carbene seems to be the pre-
ferred coordination geometry: catalysis involving reduc-
tive elimination is therefore disfavored because this
requires cis-oriented coordination sites. Moreover, car-
bene ligands are less likely to dissociate than the corre-
20
18
sponding phosphine or bis-pyridine systems, so
catalysis via less saturated intermediates is also
disfavored.
The work reported here may indicate future research
strategies that should be valuable. The ligands 3 are
much more likely to be useful in asymmetric catalysis
involving metals that can form 5- and/or 6-coordinate
intermediates than with the palladium systems reported
here. The current emphasis of our work is on the use of
these ligands to form such complexes with other metals
for which trans-coordination is unlikely to impede
catalysis and may be advantageous.
Figure 3. Chem3D representation of complex 4d generated
from a single crystal X-ray diffraction analysis.
Acknowledgements
trans-Chelating ligands in palladium complexes are well
known, two representative examples being the phosphi-
16
nes based on the xanthene framework (Xantphos), or
on two ferrocene units linked at the cyclopentadienyl
Financial support for this work was provided by The
Robert Welch Foundation and Johnson Matthey plc.
We thank CEM Corporation for the microwave
apparatus used in this study. Help and advice from Dr.
Shane Stichy of the TAMU/LBMS-Applications Labo-
ratory is also acknowledged. We thank Dr. Joe H.
Reibenspies for the X-ray structure determination, and
Dr. Gyula Vigh/Mr. M. Brent Busby for analyzing
compound 5 by CE.
1
7
unit (TRAP).
In addition, bis-pyridine ligands
designed to be trans-chelating have recently been
1
8
reported. A chiral, chelating bis-imidazolylidene lig-
and that forms trans-chelates has also been reported;
19
this is based on the 1,1-binapthyl framework.
Two bis-imidazolium salts, 8a and 8b, without N-
methyl substituents, were also prepared via routes
analogous to the ones outlined above. Complexes with
molecular masses corresponding to structure 9 were
formed when these salts were treated with potassium
tert-butoxide and palladium chloride in DMSO
overnight (Reaction (1)). We assign the coordination
mode of the ligand as amide-N-bonded on the basis of
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