Chiral palladium(II) complexes possessing a tridentate N-heterocyclic carbene amidate alkoxide ligand: Access to oxygen-bridging dimer structures

Article abstract of DOI:10.1002/anie.200803793

(Chemical Equation Presented) Catalysts with a bite: Chiral Pd^II complexes were prepared with tridentate N-heterocyclic carbene amidate alkoxide ligands. Dimeric and monomeric forms were mutually convertible by acid or base treatment (see scheme). The catalysts promote asymmetric Heck reactions efficiently, offering high enantioselectivities far superior to those of existing methods.

Full text of DOI:10.1002/anie.200803793

Communications
DOI: 10.1002/anie.200803793
N-Heterocyclic Carbenes
Chiral Palladium(II) Complexes Possessing a Tridentate
N-Heterocyclic Carbene Amidate Alkoxide Ligand:
Access to Oxygen-Bridging Dimer Structures**
Satoshi Sakaguchi, Kyung Soo Yoo, Justin OꢀNeill, Joo Ho Lee, Timothy Stewart, and
Kyung Woon Jung*
N-Heterocyclic carbenes (NHCs) and their palladium com-
plexes have been developed to facilitate the formation of
carbon–carbon and carbon–heteroatom bonds.[1] NHC com-
plexes exhibit unique chemical properties such as strong Pd–
NHC s bonding, which enhances the stabilities of active
organometallic compounds relative to conventional phos-
phane complexes.[2] Moreover, chiral NHC ligands have been
synthesized to promote asymmetric catalysis.[3]
Figure 1. Design of a chiral {Pd(OAc)2} complex (II) for asymmetric
catalysis.
Most of the chiral NHC ligands that have been utilized for
asymmetric PdII catalysis are monodentate, as Lee and
Hartwig demonstrated moderate enantioselectivities (71–
76% ee) in a-arylation.[4] However, monodentate ligands
caused practical difficulties including concomitant formation
of inactive palladium–ligand complexes, such as those with a
trans conformation. Bidentate NHC ligands exhibited better
stabilities and selectivities: Douthwaite reported better
enantioselectivities (up to 92% ee) for asymmetric allylic
alkylation[5a,b] than reactions employing the corresponding
monodentate ligand.[5c]
We report herein the synthesis of chiral tridentate NHC–PdII
complexes and their applications in an asymmetric oxidative
Heck-type reaction as a proof of concept.
The preparation of chiral ligands 4 is shown in Scheme 1.
Hydroxyamide compounds 2 were prepared by reduction of
amino acids 1 and subsequent N-alkylation with bromoacetyl
bromide. Treatment of 2 with benzimidazole in the presence
We envisioned tridentate NHCs would enhance the
stabilities of PdII complexes and enantioselectivities of
various asymmetric reactions. As depicted in Figure 1, we
sought a “chiral {Pd(OAc)2} complex” and designed and
synthesized novel chiral tridentate NHC–PdII complexes (II).
Notably, ligand systems with NHCs, amidates, and oxygen
functionalities (a C,N,O triad) could exert high electron
densities and strong coordination on the PdII complexes to
increase stabilities even in nucleophilic solvents such as water
and alcohols. Therefore, labile ligands such as water, alcohols,
and acetonitrile are likely to be removed easily and thus
enhance the reactivities and efficiencies of NHC–Pd catalysts.
Scheme 1. Synthesis of chiral NHC ligands 4a and 4b. TEA=triethyl-
amine; DCM=dichloromethane.
[*] Dr. K. S. Yoo, J. O’Neill, Dr. J. H. Lee, T. Stewart, Prof. K. W. Jung
Loker Hydrocarbon Research Institute and
Department of Chemistry
University of Southern California, Los Angeles, CA 90089 (USA)
Fax: (+1)213-821-4096
E-mail: kwjung@usc.edu
of KOH in DMF provided compounds 3, which were
subjected to methylation to yield the amido alcohol substi-
tuted benzimidazolium salts 4. The structure was confirmed
by 1H NMR spectroscopic analysis; new peaks assigned to the
NCH3 appeared at d = 4.18 (4a) and 4.15 ppm (4b). Also, the
imidazole H resonances shifted significantly as expected for
iodine salts, appearing at d = 9.55 (4a) and 9.50 ppm (4b).
Because direct coordination of ligands 4 to palladium was
not efficient under numerous conditions, the ligands were
transferred to palladium via silver NHC complexes.[6] As
described in Scheme 2, compounds 4a and 4b were treated
with Ag2O in CH2Cl2 to give silver NHC complexes.
Dr. S. Sakaguchi
Department of Applied Chemistry, Kansai University
Suita, Osaka 564-8680 (Japan)
[**] We acknowledge generous financial support from the National
Institute of General Medical Sciences of the National Institute of
Health (RO1 GM 71495) and the Hydrocarbon Research Founda-
tion. S.S. was supported by Kansai University’s Overseas Research
Program in the year 2006.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200803793.
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Scheme 2. Synthesis of NHC-coordinated PdII complexes.
Figure 2. Solid-state molecular structure of 5a. Hydrogen atoms and
Subsequent treatment of the silver compounds with [PdCl2-
(CH3CN)2] in CH3CN at room temperature provided the
palladium(II)/NHC ligand complexes 5a and 5b in 73 and
75% yields, respectively, for the two steps. Their structures
solvent molecules are omitted for clarity. Selected bond lengths [ꢀ]
and angles [8]: Pd1–C1 1.937(2), Pd1–N3 1.980(2), Pd1–O2
2.1102(18), Pd1–Cl1 2.3031(7), C1-Pd1-N3 88.60(9), C1-Pd1-O2
170.05(9), N3-Pd1-O2 81.67(8), C1-Pd1-Cl1 97.89(7), N3-Pd1-Cl1
172.90(6), O2-Pd1-Cl1 91.94(5).
1
were confirmed with H and 13C NMR spectroscopy by the
complete disappearance of the imidazole protons and by the
observation of the expected change in chemical shifts for the
NCH2CO peaks [d = 5.43/5.35 to 5.82/5.49 ppm for 5a, d =
5.42 (singlet) to 5.74/5.65 ppm for 5b] relative to those of
ligands 4a and 4b; HRMS analysis further confirmed the
assignment by showing molecular ion peaks at m/z 416.0356
([M+H]; calcd for 5a: 416.0357) and m/z 405.0279 ([M+H];
calcd for 5b: 405.0201), respectively.
Dehydrohalogenation of 5a and 5b in the presence of
K2CO3 produced NHC–PdII complexes 6a and 6b in high
yields. Only one isomer of each of the dimeric compounds was
detected in solution by 1H NMR spectroscopic analysis; their
spectra exhibited an upfield shift [d = 5.82/5.49 to 4.99/
4.91 ppm for 6a and d = 5.74/5.65 to 5.05/4.92 ppm for 6b]
of the NCH2CO signals, implying moderate structural dis-
tortion of the square-planar PdII complexes relative to 5.
HRMS spectra (molecular peaks at m/z 759.1105 ([M+H])
for 6a and m/z 828.0789 ([M+H]) for 6b) supported the
assigned dimeric molecular-based structures. We sought
optimal reaction conditions by screening various carbonate
and hydroxide bases. The use of carbonate bases such as
Na2CO3, KHCO3, and NaHCO3 provided the dimeric palla-
dium complex in decent yields (70–52%). However, in the
presence of NaOH, dehydrohalogenation of 5 afforded
dimeric complex 6 in a decreased conversion of 48%.
Figure 3. Solid-state molecular structure of 6a. Hydrogen atoms and
solvent molecules are omitted for clarity. Selected bond lengths [ꢀ]
and angles [8]: Pd1–C1 1.947(3), Pd1–N2 1.978(3), Pd1–O1 2.052(2),
Pd1–O1’ 2.072(2), Pd1···Pd1’ 2.9731(5), C1-Pd1-N2 90.04(12), C1-Pd1-
O1’ 104.01(11), N2-Pd1-O1’ 165.12(11), Pd1-O1-Pd1’ 92.26(10), O1-
Pd1-O1’ 81.94(11).
À
Regarding oxygen and neighboring atoms, the Pd O bond
À
length in a Pd OH bond (anionic bonding) is shorter (0.05–
À
After further purification, complexes 5a and 6a were
crystallized from CH2Cl2/Et2O. The molecular structures of
5a and 6a were established by single-crystal X-ray diffraction
studies (Figures 2 and 3). The solid-state structures of 5a and
6a show that the NHC rings are aligned roughly perpendic-
ular to the square-planar Pd coordination plane. Notably, the
0.15 ꢀ) than the Pd O bond length (dative bonding)
observed for known aqua complexes.[8] In addition, the Pd
À
À
O bond in 6a is slightly shorter than the Pd O bond in 5a,
which is informative evidence that the O1 atom in 6a
contributes to the Pd2O2 bridging through delocalization of
the electrons from the oxygen donors. The dimeric palladium
complex 6a crystallized in the chiral space group C2 with
bridging of the oxygen atom to the palladium atom. The
Pd2O2 core is not planar, but inclined at a dihedral angle of
145.58 about the Pd···Pd axis. The substituents of the alkoxide
oxygen atoms adopt an endo arrangement, which makes the
structure of the dimeric palladium complex unique among
dimeric palladacycles. Conclusively, 5a and 6a are unprece-
dented PdII complexes consisting of a carbene, amidate, and
alkoxide.
À
Pd N bond lengths of both structures are shortened
(1.980(2) ꢀ for 5a and 1.978(3) ꢀ for 6a) relative to other
À
Pd N bonds, such as with protonic amines, azides, and
imines.[7] This peculiar structural feature indicates that the
À
Pd N bonding is anionic coordination. For example, the
geometry about N2 in 6a is approximately trigonal planar as
shown by the torsion angle (10.88) for C3···C12···Pd1···N2 and
the sum of the bond angles (355.808). Therefore, these
torsional parameters highlight the utility of anionic coordi-
nation between nitrogen and palladium, which is distin-
More importantly, the dimeric structure 6a was com-
pletely stable in air and water environments. Both dimeric
À
guished from a lone-pair coordination, such as for Pd NH.
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and monomeric catalysts survived harsh conditions, including
water and protic solvents, unlike other known Pd catalysts.
Thus, these kinds of catalysts can provide opportunities to
transmetallation step between palladium and an aryl boronic
acid (or aryl halide) which can be encountered in palladium-
catalyzed reactions such as Suzuki and boron Heck-type
reactions.
À
effect difficult reactions, including C H activation, which we
will report in due course.
In this context, asymmetric catalytic properties of air- and
water-stable complexes 6 were examined by subjecting these
novel catalysts to oxidative boron Heck couplings between
aryl boronic acids and acyclic olefins.[10] First, we screened
representative oxidants for asymmetric coupling reaction
with methyl tiglate and phenylboronic acid in the presence of
6a. Under an O2 atmosphere (1 atm), the desired product 10
was obtained in 49% yield. In contrast, the reaction under an
air atmosphere resulted in low yield of 10 (11%), and no
reaction occurred by employing CuCl2 as an oxidant. There-
fore, the coupling reactions were carried out in DMF at room
temperature under O2 atmosphere (Table 1). The desired
The isolated dimeric structure itself did not show active
catalytic properties, presumably by reaching a stable resting
stage. However, this structure was easily converted into
various active monomeric Pd–ligand structures. Dimer–mo-
nomer catalyst equilibrium has been reported for a number of
palladium-catalyzed reactions, and prior investigations sup-
port the concept that the dimer can act as a reservoir for the
active monomer.[9] As shown in Scheme 3, PdII–NHC complex
Table 1: Selected results for catalytic oxidative Heck-type reaction of aryl
boronic acids with acyclic alkenes catalyzed by 6a and 6b.[a]
Entry Ar
R1, R
Cat. Product
Conf.[d]
(yield, ee)[b,c]
1
2
3
4
Ph
Me, OMe 6a
Me, OMe 6a
10 (49%, 91% ee)
11 (61%, 92% ee)
12 (31%, 98% ee)
13 (32%, 90% ee)
R
–
R
R
2-naphthyl
Ph
p-MeOC6H4 Me, H
Scheme 3. Conversion of 6a into monomeric PdII complexes by HCl
(with a coordinating anion; A) and HBF4 (with a noncoordinating
anion; B).
Me, H
6a
6b
[a] All reactions were carried out with 1.1 equiv aryl boronic acids and
5 mol% 6. [b] Yields of isolated products. [c] Determined by chiral HPLC
analysis (Daicel Chiracel OD; mobile phase: iPrOH:hexane=5:95 v/v%,
6a was converted into monomeric Pd complex 5a (as
confirmed by 1H NMR spectroscopy) by cleavage of the
Pd2O2 core in the presence of HCl (coordinating anion). In
contrast, the protonated dimeric complex 7 was afforded by
aqueous HBF4 (noncoordinating anion) solution and then
conveniently transformed into cationic PdII complex 8 by
heating.
Using this concept, we monitored the conversion of dimer
6a into monomer in the presence of phenylboronic acid as a
coordinated anion substrate. The transformation reaction was
carried out using dimeric PdII complex 6a (16 mmol) and
phenylboronic acid (32 mmol), in [D6]DMF at room temper-
ature for 16 h (Scheme 4). Arylmetalation of phenylboronic
acid was observed to give phenylpalladium(II) complex 9 in
82% conversion (1H NMR spectroscopy), although the
reaction was very slow in DMF. On the basis of this result,
the observed intermediate structure can provide evidence of a
rate: 1 mLminÀ1
[d] Absolute configuration.
) and NMR analysis with a chiral Eu reagent.
rearrangement products were obtained in modest yields, but
still far higher than the corresponding Heck reactions (less
than 5% yields). However, both dimers 6a and 6b provided
excellent enantioselectivities (greater than 90% ee), and the
absolute configurations of 10, 12, and 13 were confirmed as R-
enriched by transforming the products into the corresponding
phenyl propionic esters and comparing them with authentic
samples.[11] To our knowledge, these examples are the first
cases to demonstrate high enantioselectivities (greater than
90% ee) in intermolecular Heck-type reactions. Above all,
the distinguished degree of asymmetric induction should stem
from tight binding of tridentate ligands to Pd metal during the
entire catalytic processes.
Another interesting feature of Heck-type reactions car-
ried out using dimeric catalysts was the observation of a
nonlinear dependence of reaction rate on the concentration
of Pd. For example, van Leeuwen and co-workers recently
found a half-order dependence on catalyst concentration and
attributed this result to the formation of
a dimeric
[{PdLArX}2] species.[9d] Hence, the oxygen-bridging dimeric
complex behaves chemically as a catalyst precursor.
In summary, we have designed novel PdII catalysts and
developed an efficient synthesis of chiral tridentate amidate/
Scheme 4. Conversion of 6a into monomeric PdII complex 9 by phenyl-
boronic acid.
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alkoxy/carbene PdII complex 6. These catalytic complexes
facilitated an asymmetric oxidative Heck-type reaction
between aryl boronic acids and acyclic alkenes, which offered
high enantioselectivities unprecedented in intermolecular
Heck-type couplings. This ligand architecture can be readily
altered by using different chiral substrates and can then be
expanded for use with various palladium catalyzed coupling
reactions. Currently in progress are further studies focusing
on the preparation of conformationally stable and enantio-
merically pure PdII analogues and their applications toward
asymmetric cross-coupling reactions using various substrates,
as well as investigations to gain mechanistic insights.
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Experimental Section
5a: A suspension of benzimidazolium salt 4a (500 mg, 1.23 mmol)
and silver(I) oxide (150 mg, 0.65 mmol) in CH2Cl2 (52 mL) was stirred
for 2 h in the dark at room temperature. The reaction mixture was
concentrated under reduced pressure to give a dark-red solid.
[PdCl2(CH3CN)2] (260 mg, 1 mmol) was added to a suspension of
the silver complex in CH3CN (50 mL) in the dark at room temper-
ature. Then, the resulting suspension was stirred for 2 h and filtered
through a plug of glass fiber filter paper. The filtrate was evaporated
to dryness in vacuo to afford product 5a (378 mg, 73% yield) as an
1
orange solid; H NMR (CD3OD): d = 7.61 (d, J = 16.0 Hz, 1H), 7.54
[6] a) H. M. J. Wang, I. J. B. Lin, Organometallics 1998, 17, 972;
b) I. J. B. Lin, C. S. Vasam, Coord. Chem. Rev. 2007, 251, 642.
[7] For protonic amine: a) K. I. Gasanov, A. S. Antsyshkina, G. G.
Sadikov, N. A. Ivanova, D. I. Mirzai, I. A. Efimenko, V. S.
Sergienko, Crystallogr. Rep. 2002, 47, 603. For azide: b) W.
Beck, W. P. Fehlhammer, K. Feldl, T. M. Klapotke, G. Kramer, P.
Mayer, H. Piotrowski, P. Pollmann, W. Ponikwar, T. Schutt, E.
Schuierer, M. Vogt, Z. Anorg. Allg. Chem. 2001, 627, 1751. For
imine: c) A. Fernꢅndez, E. Pereira, J. J. Fernandez, M. Lopez-
Torres, A. Suarez, R. Mosteiro, J. M. Vila, Polyhedron 2002, 21,
39.
[8] a) J. Ruiz, F. Florenciano, C. Vincente, M. C. R. de Arellano, G.
Lopez, Inorg. Chem. Commun. 2000, 3, 73; b) C. Bartolome, P.
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Organometallics 2002, 21, 3536; c) J. Vicente, A. Arcas, Coord.
Chem. Rev. 2005, 249, 1135.
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Priermeier, M. Beller, H. Fischer, Angew. Chem. 1995, 107, 1989;
Angew. Chem. Int. Ed. Engl. 1995, 34, 1844; b) T. Rosner, J.
Le Bars, A. Pfaltz, D. G. Blackmond, J. Am. Chem. Soc. 2001,
123, 1848; c) G. Rothenberg, S. C. Cruz, G. P. F. van Strijdonck,
H. C. J. Hoefsloot, Adv. Synth. Catal. 2004, 346, 467; d) G. P. F.
van Strijdonck, M. D. K. Boele, P. C. J. Kamer, J. G. de Vries,
P. W. N. M. van Leeuwen, Eur. J. Inorg. Chem. 1999, 1073.
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(d, J = 16.4 Hz, 1H) 7.37 (m, 2H), 5.82 (d, J = 16.4 Hz, 1H), 5.49 (d,
J = 16.4 Hz, 1H), 4.35 (s, 1H), 3.75 (q, 1H), 3.61–3.51 (ABX, J =
16.4 Hz, 2H), 1.82 (m, 1H), 0.84 (d, J = 6.7 Hz, 3H), 0.77 ppm (d, J =
6.7 Hz, 3H); 13C NMR (CD3OD): d = 168.9, 136.1, 135.9, 135.8, 135.6,
124.9, 124.7, 111.9, 62.9, 58.5, 52.4, 35.1, 29.8, 20.0, 19.0, 18.6,
18.5 ppm; HRMS-ESI (m/z) [M+H+] calcd for C15H21ClN3O2Pd:
416.0357, found: 416.0356.
6a: K2CO3 (207 mg, 1.5 mmol) was added to a solution of 5a
(208 mg, 0.5 mmol) in water (15 mL, HPLC grade). The suspension
was stirred for 8 h at room temperature. Then, CH2Cl2 (75 mL) was
added, and the mixture was stirred for 1 h. The aqueous layer was
washed with CH2Cl2 (2 ꢁ 50 mL), and the organic layers were
combined, dried over anhydrous Na2SO4, and concentrated to give
a yellow solid 6a (154 mg, 81%). Crystals for X-ray diffraction were
obtained by layering solutions of 6a in dichloromethane with Et2O
and allowing slow diffusion at room temperature. 1H NMR (CD3OD):
d = 7.64–7.69 (m, 2H), 7.44–7.46 (m, 2H), 4.99 (d, J = 16.4 Hz, 1H),
4.91 (d, J = 16.4 Hz, 1H), 4.17 (s, 3H), 3.62 (m, 1H), 3.45 (m, 2H),
2.18 (m, 1H), 0.96 (d, J = 6.8 Hz, 3H), 0.75 ppm (d, J = 6.8 Hz, 3H);
13C NMR (CD3OD): d = 166.8, 164.7, 135.4, 134.6, 125.4, 125.2, 112.2,
111.7, 74.4, 70.7, 54.7, 52.4, 33.8, 30.5, 20.4, 19.8 ppm; HRMS-ESI
(m/z) [M+H+] calcd for C30H39N6O4Pd2: 759.1102, found: 759.1105.
Received: August 2, 2008
Published online: October 29, 2008
[11] a) M. Shi, L. H. Chen, C. Q. Li, J. Am. Chem. Soc. 2005, 127,
3790; b) S. Kawahara, A. Nakano, T. Esumi, Y. Iwabuchi, S.
Hatakeyama, Org. Lett. 2003, 5, 3103.
Keywords: asymmetric catalysis · Heck reaction ·
N-heterocyclic carbenes · precatalysts · tridentate ligands
.
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