Palladium complexes of planar chiral ferrocenyl phosphine-NHC ligands: New catalysts for the asymmetric suzuki-miyaura reaction

Article abstract of DOI:10.1021/om100125k

Air-stable neutral and cationic palladium complexes bearing chiral phosphine-N-heterocyclic carbene ligands with planar chirality only have been prepared in moderate to good yields and characterized by NMR and X-ray diffraction studies. They are shown to

Full text of DOI:10.1021/om100125k

Organometallics 2010, 29, 1879–1882 1879
DOI: 10.1021/om100125k
Palladium Complexes of Planar Chiral Ferrocenyl Phosphine-NHC
Ligands: New Catalysts for the Asymmetric Suzuki-Miyaura Reaction
Nathalie Debono,†,‡ Agnes Labande,*,†,‡ Eric Manoury,†,‡ Jean-Claude Daran,†,‡ and
ꢀ
Rinaldo Poli†,‡,§
†CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse, France,
‡
§
Universite de Toulouse, UPS, INPT, LCC, F-31077 Toulouse, France, and Institut Universitaire de France,
103, bd Saint-Michel, 75005 Paris, France
ꢁ
Received February 16, 2010
Scheme 1. Synthesis of Racemic and Enantiopure Ferrocenyl
Phosphine-Imidazolium Salts 1a,b
Summary: Air-stable neutral andcationic palladium complexes
bearing chiral phosphine-N-heterocyclic carbene ligands with
planar chirality only have been prepared in moderate to good
yields and characterized by NMR and X-ray diffraction
studies. They are shown to catalyze the asymmetric coupling
of aryl bromides with arylboronic acids in good yields and
moderate enantioselectivities (up to 42% ee) with low catalyst
loadings (0.1-0.5 mol %).
N-heterocyclic carbenes (NHCs) have received a great deal
of attention recently and are now considered as ligands of
choice for various catalytic reactions,1 among which are
Suzuki-Miyaura reactions using aryl bromides and less
reactive aryl chlorides.2 They have several advantages over
phosphines, such as air and thermal stability of the resulting
complexes. We have focused our attention on the synthesis of
functionalized NHC ligands, with the aim to produce robust
and yet highly active catalysts.3 The combination of a
phosphine and a NHC allows access to stable chelate com-
plexes with interesting electronic properties that have been
successfully used in catalysis.4 Among C-C cross-coupling
reactions, the Suzuki-Miyaura reaction has become one of
the most appealing, due to its tolerance to functional groups
and the low toxicity of its byproducts.5 Although axially
chiral biaryls are present in numerous natural products and
constitute an important class of ligands for asymmetric
catalysis, there are few reports to date of asymmetric Suzuki-
Miyaura reactions.6 One of the challenges remains to find
catalysts that are able to induce high levels of enantioselecti-
vities at low loadings. Surprisingly, NHC ligands have never
been used so far in the asymmetric version of the Suzuki-
Miyaura reaction. We report here the first example, using a
chiral palladium-NHC complex with planar chirality only.
We presented recently the synthesis of achiral and racemic
ferrocenyl phosphine-NHC ligands and showed their effici-
ency in the rhodium-catalyzed hydrosilylation of ketones.3c,d
Here we describe for the first time the synthesis of such
ligands in their enantiopure form, as well as their palladium
complexes. Building on our experience in the preparation of
enantiopure ferrocenyl ligands,7 we obtained enantiopure
(R)- and (S)-ferrocenyl phosphine-imidazolium salts 1a,b in
*To whom correspondence should be addressed. E-mail: agnes.labande@
lcc-toulouse.fr.
(1) (a) Nolan, S. P. N-Heterocyclic Carbenes in Synthesis; Wiley-VCH:
Weinheim, Germany, 2006. (b) Glorius, F. N-Heterocyclic Carbenes in
Transition Metal Catalysis; Springer-Verlag: Heidelberg, Germany, 2007.
(c) Bourissou, D.; Guerret, O.; Gabbaï, F. P.; Bertrand, G. Chem. Rev. 2000,
100, 39–91. (d) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290–
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(f) Díez-Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612–
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Herdtweck, E.; Grosche, M.; Herrmann, W. A. Angew. Chem., Int. Ed.
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Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.; Nolan, S. P. J. Am. Chem.
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(4) Selected publications: (a) Tsoureas, N.; Danopoulos, A. A.;
Tulloch, A. A. D.; Light, M. E. Organometallics 2003, 22, 4750–4758.
(b) Focken, T.; Raabe, G.; Bolm, C. Tetrahedron: Asymmetry 2004, 15,
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Organometallics 2005, 24, 4241–4250. (d) Shi, J.-C.; Yang, P.-Y.; Tong, Q.;
Wu, Y.; Peng, Y. J. Mol. Catal. A: Chem. 2006, 259, 7–10. (e) Hahn, F. E.;
Jahnke, M. C.; Pape, T. Organometallics 2006, 25, 5927–5936. (f) Lee,
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3746–3754.
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r
2010 American Chemical Society
Published on Web 03/25/2010
pubs.acs.org/Organometallics

1880 Organometallics, Vol. 29, No. 8, 2010
Debono et al.
Figure 1. ORTEP representations of complexes 2a-rac (left) and 2a-(R) (right). Ellipsoids are shown at the 30% level. All hydrogens
˚
are omitted for clarity. Selected bond distances (A) and angles (deg) are as follows. 2a-rac: C(22)-Pd(1) = 1.991(3), P(1)-Pd(1) =
2.2444(8), Cl(1)-Pd(1) = 2.3614(9), Cl(2)-Pd(1) = 2.3397(8); C(22)-Pd(1)-P(1) = 84.95(9), C(22)-Pd(1)-Cl(1) = 88.24(9), P(1)-
Pd(1)-Cl(2) = 95.06(3). 2a-(R): C(23)-Pd(1) = 1.976(3), P(1)-Pd(1) = 2.2472(10), Cl(1)-Pd(1) = 2.3665(9), Cl(2)-Pd(1) =
2.3481(9); C(23)-Pd(1)-P(1) = 86.61(10), C(23)-Pd(1)-Cl(1) = 83.61(10), P(1)-Pd(1)-Cl(2) = 98.97(3).
NMR data of the allylic compounds indicated the presence
of two species in a 55:45 (3a) or 75:25 (3b) ratio, which we can
attribute to exo and endo configurational isomers. This
refers to the position of the allyl group relative to the fer-
rocene, as described by Togni et al. for similar complexes.4g
Unfortunately, the NMR data did not allow us to determine
the configuration of the major isomer. The structures of
complexes 2a-rac, 2a-(R), 3a-rac, and 3b-rac were confirmed
by crystallographic methods (Figures 1 and 2). The struc-
tures of both 3a-rac and 3b-rac display the endo isomer, with
the central C-H of the allyl group pointing toward the
ferrocenyl moiety. The allyl group of complex 3a is dis-
ordered, which is not uncommon for this type of complex.4g,8
The bond lengths and angles are all within the expected
range, either for neutral or for cationic complexes, with a
square-planar or slightly distorted square-planar geometry.
Pd-CNHC and Pd-P distances are longer in the cationic
complexes 3. In the neutral complex 2a, surprisingly, the
Pd-Cl bond trans to the NHC is slightly but significantly
shorter than the Pd-Cl bond trans to the phosphine. We
would have expected the opposite, since the NHC should be
more donating and exert a higher trans influence. However,
this has already been observed for a similar complex.9
Finally, a noticeable difference is observed in the bond angles
between allyl complexes 3a and 3b. Indeed, the CNHC-Pd-P
angle is 88.52(11)° in 3a, which bears a methyl substituent on
the imidazol-2-ylidene part, whereas it reaches 102.06(8)° in
the case of 3b, possessing a bulkier mesityl group.
Scheme 2. Synthesis of Neutral and Cationic Palladium(II)
Complexes
good yields (Scheme 1). Both racemic and enantiopure
imidazolium salts were prepared by reaction of the racemic
and enantiopure ferrocenyl alcohol, respectively, with HBF4,
immediately followed by the N-substituted imidazole. The phos-
phine was then cleanly deprotected with an excess of Raney nickel
in MeCN.
Two different precursors were used to prepare palladium
complexes: PdCl2(MeCN)2 led to the neutral complexes 2a-rac,
2a-(R), and 2a-(S), while [Pd(allyl)Cl]2 gave the cationic com-
plexes 3a,b-rac and 3a,b-(S) in moderate to good yields
(Scheme 2). Oddly enough, all our attempts to synthesize the
neutral complex bearing a bulky mesityl group on the NHC
unit (2b) failed. PdCl2(PhCN)2 was tested under similar con-
ditions but also failed to give the expected product. We finally
treated the allyl complex 3b-rac in CH2Cl2 with a solution of
aqueous HCl and obtained again an intractable mixture. All
complexes, even those possessing an allyl moiety, are air-stable
and can be purified by column chromatography on silica gel.
Preliminary catalytic tests were carried out with racemic
complexes, in order to evaluate their activity in the Suzuki-
Miyaura coupling reaction between aryl bromides and phe-
nylboronic acid (Table 1).
(8) (a) Danopoulos, A. A.; Tsoureas, N.; Macgregor, S. A.; Smith, C.
Organometallics 2007, 26, 253–263. (b) Normand, A. T.; Stasch, A.; Ooi,
L.-L.; Cavell, K. J. Organometallics 2008, 27, 6507–6520.
(9) Yang, W.-H.; Lee, C.-S.; Pal, S.; Chen, Y.-N.; Hwang, W.-S.; Lin,
I. J. B.; Wang, J.-C. J. Organomet. Chem. 2008, 693, 3729–3740.

Communication
Organometallics, Vol. 29, No. 8, 2010 1881
Figure 2. ORTEP representations of cations in complexes 3a-rac (left) and 3b-rac (right). Ellipsoids are shown at the 30% level. All
˚
hydrogens are omitted for clarity. Selected bond distances (A) and angles (deg) are as follows. 3a-rac: C(22)-Pd(1) = 2.050(4),
P(1)-Pd(1) = 2.2964(11), C(31)-Pd(1) = 2.173(5), C(32)-Pd(1) = 2.173(6), C(33)-Pd(1) = 2.186(5), C(31)-C(32) = 1.320(8),
C(32)-C(33)=1.408(8); C(22)-Pd(1)-P(1)=88.52(11), C(22)-Pd(1)-C(33)=99.98(18), P(1)-Pd(1)-C(31)=102.99(16). 3b-rac:
C(11)-Pd(1) = 2.054(3), P(1)-Pd(1) = 2.3128(7), C(31)-Pd(1) = 2.157(2), C(32)-Pd(1) = 2.167(2), C(33)-Pd(1) = 2.1744(17),
C(31)-C(32) = 1.394(5), C(32)-C(33) = 1.375(5); C(11)-Pd(1)-P(1) = 102.06(8), C(11)-Pd(1)-C(33) = 97.48(9), P(1)-Pd(1)-
C(31)=92.32(7).
Table 1. Suzuki-Miyaura Reaction between Aryl Bromides and
Table 2. Asymmetric Suzuki-Miyaura Reaction between
Phenylboronic Acida
Naphthyl Bromides and Naphthylboronic Acidsa
entry
cat.
Rn
yield (%)b
1
2
3
4
5
2a-rac
3a-rac
3b-rac
2a-rac
2a-rac
4-OMe
4-OMe
4-OMe
2-Me
83
51
42
87
40
entry Pd cat. (mol %)
R1
R2 T (°C) yield (%)b ee (%)c
1
2
3
4
5
6
7
8
2a-(R) (0.1)
2a-(R) (0.1)
2a-(R) (0.1)
2a-(R) (0.5)
2a-(R) (0.5)
2a-(R) (0.5)
2a-(R) (0.5)
2a-(S) (0.5)
2a-(S) (0.5)
2a-(S) (0.5)
2a-(S) (0.5)
3a-(S) (0.5)
3a-(S) (0.5)
3a-(S) (0.5)
3b-(S) (0.5)
3b-(S) (0.5)
3b-(S) (0.5)
Me
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
70
70
70
40
40
40
40
40
40
40
40
40
40
40
40
40
40
89
86
89
88
57d
93
92
88
95
95
0
38
33
30
42
39d
33
24
40
35
23
OMe
OEt
Me
2,4,6-Me3
a Reagents and conditions: aryl bromide (1.0 equiv), phenylboronic
acid (1.2 equiv), Pd cat. (0.1 mol %), K2CO3 (2.4 equiv), toluene, 70 °C,
1 h. b GC yield.
Me
OMe
OEt
Me
OMe
OEt
H
After optimization of the reaction conditions with 4-
bromoanisole, toluene and K2CO3 were chosen respectively
as the best solvent and base. Complex 2a-rac was found to
give the best results, with 83% yield (entry 1) after 1 h at 70 °C
and a low catalyst loading (0.1 mol %). The cationic allyl
complexes 3a-rac and 3b-rac were less active, giving respec-
tively 51% and 42% of product (entries 2 and 3) under the
same conditions. The introduction of an ortho substituent
did not lower the yield with 2a-rac: 87% was obtained with 2-
bromotoluene (entry 4). Finally, sterically crowded 2-bro-
momesitylene was successfully coupled to phenylboronic
acid under these conditions (entry 5), which prompted us
to turn to naphthyl derivatives (Table 2).
9
10
11
12
13
14
15
16
17
Me
0
OMe
OEt
Me
OMe
OEt
30
14
86
82
0
28
10
19
<2
a Reagents and conditions: naphthyl bromide (1.0 equiv), boronic
acid (1.2 equiv), Pd cat., K2CO3 (2.4 equiv), toluene, 24 h. b Isolated
yield. c Determined by HPLC with a Chiracel-OJ column. d Reaction
stopped after 8 h.
any substantial improvement when the temperature was
lowered (Table 2, entries 1-3 and 4-7). Reducing the tem-
perature to 40 °C allowed us to reach a 42% ee for R1 = Me
(entry 4). The same level of enantioselectivity was observed
when the reaction was stopped after 8 h instead of 24 h (entry 5),
Complex 2a-(R) successfully catalyzed the coupling of
naphthyl bromides to naphthylboronic acid under these
conditions. Reaction times were not optimized and were
extended to 24 h to maximize conversions. Enantioselecti-
vities obtained initially were modest, and we did not observe

1882 Organometallics, Vol. 29, No. 8, 2010
Debono et al.
which means we probably have the same catalytic species
throughout the reaction. As expected, similar levels of ena-
ntioselectivities were observed with the opposite enantiomer
2a-(S) (entries 8-10). However, no product was obtained
when the methyl substituent was introduced ortho to the
boronic acid instead of to the bromide (entry 11). The allyl
palladium complexes 3a-(S) and 3b-(S) gave surprising
results. Indeed, complex 3a-(S), bearing a methyl substituent
on the nitrogen atom of the imidazol-2-ylidene, gave the
expected binaphthyls in very low yields (entries 12-14), no
product being observed in the case of methyl-substituted
naphthyl bromide (entry 12). The catalyst seemed to decom-
pose in the course of the reaction, giving a black precipitate in
the reaction medium. Complex 3b-(S), bearing a bulkier
mesityl substituent on nitrogen, reacted with methyl- and
methoxy-substituted naphthyl bromides (entries 15 and 16)
but again decomposed in the course of the reaction in the
presence of ethoxy-substituted naphthyl bromide (entry 17).
Moreover, ee’s observed with this catalyst are very low. Our
first hypothesis was that steric crowding near the palladium
was probably too important in the case of 3b and became
detrimental to the reaction. However, X-ray structures in-
dicated important variations in the CNHC-Pd-P angles
between 3b-rac (102.06(8)°) and other complexes (84.95(9)°
for 2a-rac to 88.52(11)° for 3a-rac) that could account for the
differences in reactivity.
In conclusion, new palladium(II) complexes bearing planar
chiral ferrocenyl phosphine-NHC ligands showed very good
activities in the Suzuki-Miyaura reaction of aryl bromi-
des with arylboronic acids. Although enantioselectivities are
moderate, this is the first example of asymmetric Suzuki-
Miyaura reactions with complexes bearing N-heterocyclic
carbene ligands. Future studiesincludetheuseof otherplanar
chiral NHC ligands in order to improve enantioselectivities.
Acknowledgment. We thank the CNRS and the Agence
Nationale de la Recherche (ANR-07-JCJC-0041, postdoc-
toral grant to N.D.) for financial support of this work.
Supporting Information Available: A scheme summarizing the
preparation of racemic and enantiopure 1,2-disubstituted ferro-
cenyl alcohols, text and figures giving full experimental details
and spectroscopic data for the preparation of all new com-
pounds, figures giving NMR spectra, and CIF files giving
crystallographic information. This material is available free of
charge via the Internet at http://pubs.acs.org.