A neutral, chiral, bis(imidazolidine)-derived NCN-type palladium pincer complex with catalytic activity

Article abstract of DOI:10.1002/chem.201204017

Caught in a pincer: A chiral, imidazolidine-derived NCN-type palladium pincer complex has been prepared using a ligand introduction technique. Single-crystal X-ray diffraction analysis of this complex showed a well-organized asymmetric sphere. The neutral palladium/chloride version exhibited significant catalytic activity for the reaction of nitroalkenes with malononitrile to give products in a highly enantioselective manner (see scheme). Copyright

Full text of DOI:10.1002/chem.201204017

DOI: 10.1002/chem.201204017
A Neutral, Chiral, Bis(imidazolidine)-Derived NCN-Type Palladium Pincer
Complex with Catalytic Activity
Takayoshi Arai,*[a] Ikiyo Oka,[a] Takuma Morihata,[a] Atsuko Awata,[a] and
Hyuma Masu[b]
The function of pincer ligands is typically to chelate tran-
sition metals through the action of three adjacent coplanar
coordination sites, resulting in complexes that are both espe-
cially stable and rigid.[1] Since the first reports by Shaw,[2]
van Koten[3] and Noltes[3] in the 1970s, a variety of pincer
complexes have been designed and synthesized with possible
applications in catalysis and materials science. The stable,
so-called XCX-type palladium pincer complexes, incorporat-
ing a strong carbon–metal s bond and two additional chelat-
ing moieties (X), are particularly useful in promoting cataly-
sis. One example of the successful application of these com-
pounds is the use of the PCP-type palladium catalyst to pro-
mote the Heck and/or Suzuki–Miyaura coupling reactions.[4]
Owing to the unique properties of metal pincer complexes,
recent work has focused on their use in asymmetric catalysis
for the synthesis of optically active compounds. For exam-
ple, a series of chiral oxazoline-derived NCN-type pincer li-
gands (Phebox)[5] have been reported for the metal com-
plexes as an analogue of the well-known coordination com-
plex of pybox-metal catalyst.[6] The use of such chiral metal
pincer complexes in highly enantioselective catalysis has,
however, proved challenging. The meridional orientation of
the pincer ligands in the coordination complex creates an
unconstrained reaction sphere, leading to difficulties in the
control of stereoselective reactions.
which the pyridine and oxazoline rings lie flat on the equa-
torial plane while coordinated with the metal center. Using
this PyBidine–CuACTHNUTRGNEUNG(OTf)2 catalyst, highly endo-selective reac-
tions of iminoesters and nitroalkenes were possible, produc-
ing adducts at up to 99% ee. This previous work inspired us
to the development of new NCN-type metal pincer catalysts
through the use of a similar chiral imidazolidine motif.[8]
We initially planned to synthesize an imidazolidine-de-
rived palladium triflate pincer complex (NCN-Pd-OTf) by
the oxidative addition of Pd0 to the aryl triflate precursor 1.
This method was considered because precursor 1 was easily
synthesized in a single condensation reaction between a 2,6-
formyl aromatic species and the optically active N-benzyl
(R,R)-diphenylethylenediamine (Scheme 1a).
However, the oxidative addition of palladium was strong-
ly suppressed, which was presumably due to the steric hin-
We previously developed a chiral N,N,N-terdentate PyBi-
dine ligand (where PyBidine is an abbreviation of bis(imida-
zolidine)pyridine)[7] as an analogue of the pybox ligand. X-
ray crystallographic analysis of a single crystal of the PyBi-
dine-CuACHTUNGTRENNUNG(OTf)2 complex showed that the two imidazolidine
rings are oriented perpendicular to the equatorial terdentate
coordination plane. The imidazolidine rings therefore act as
“chiral fences” to shield the first and third quadrants of the
(S,S)-diphenylethylenediamine-derived PyBidine-CuACTHNUTRGNEUNG(OTf)2
complex. This is in contrast to the pybox metal complex, in
[a] Prof. Dr. T. Arai, I. Oka, T. Morihata, A. Awata
Department of Chemistry, Graduate School of Science
Chiba University, Inage, Chiba 263-8522 (Japan)
Fax : (+81)43-290-2889
E-mail: tarai@faculty.chiba-u.jp
[b] Prof. Dr. H. Masu
Chemical Analysis Center
Chiba University, Inage, Chiba 263-8522 (Japan)
Scheme 1. Synthesis of a) the imidazolidine-derived pincer palladium tri-
flate complex (NCN-Pd-OTf), b) the imidazolidine-derived pincer palla-
dium chloride complex (NCN-Pd-Cl) and c) anion exchange of the com-
plex.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201204017.
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COMMUNICATION
drance of the 2,6-imidazolidine rings attached to the ben-
zene ring. Among the several alternative approaches we ex-
amined, the synthesis of the chiral imidazolidine-derived
NCN-type palladium pincer complex NCN-Pd-Cl was suc-
cessfully carried out using Uozumiꢁs ligand introduction pro-
cedure.[9] The reaction of trans-(4-tert-butyl-2,6-difolmylphe-
nyl)chlorobis(triphenylphosphine)palladium with N-benzyl
(R,R)-diphenylethylenediamine by reflux in MeCN under
an O2 atmosphere proceeded successfully and resulted in a
white precipitate, which was isolated by filtration using
MeOH (Scheme 1b). ESI-HRMS analysis of the product re-
corded a peak at m/z 863.311 corresponding to NCN-Pd
(M+-Cl: 863.3300).
1
The respective H NMR spectra of the NCN-Pd-Cl com-
plex and of the 2,6-bis(imidazolidine)benzene triflate pre-
cursor 1 are provided in Figure 1. The peaks that are due to
the imidazolidine rings of 1 in the region of d=3.4–5.3 ppm
are shifted downfield (d=3.8–5.6 ppm) in the NCN-Pd-Cl
complex. The broad peak at d=4.7–4.8 ppm results from
the presence of the N-H groups in NCN-Pd-Cl.
Figure 1. 1H NMR spectra of the NCN-Pd-Cl complex and the 2,6-bis-
ACHTUNGTRENNUNG(imidazolidine)benzene triflate precursor (1).
Figure 2. Structure of NCN-Pd-Cl derived from X-ray crystallographic
analysis (ellipsoids set at 50% probability). Top view (a) and front view
À
(b). Coordination bonds (Pd N) are indicated with black dotted lines.
Phenyl rings adjusting to the coordinating nitrogen atoms are colored
blue; hydrogen atoms on nitrogen atoms are colored orange. One disor-
dered tBu group is omitted for clarity.
A colorless single crystal of NCN-Pd-Cl was obtained by
recrystallization from CH2Cl2/toluene, and X-ray crystallo-
graphic analysis confirmed the structure (Figure 2). The
structure was solved in the space group P3121, including dis-
order owing to the tBu group (see the Supporting Informa-
tion). The predicted all-trans-stereochemistry of the two imi-
dazolidine rings, owing to steric repulsion between the sub-
stituents of the chiral diamine precursor, was confirmed.[7]
The two imidazolidine rings in this complex coordinate to
Pd while also maintaining the bonds between the protons
(marked orange) and the coordinating nitrogen atoms. The
positions of these protons were unequivocally determined
from the observed X-ray diffraction patterns. The palladium
atom in the center of the square planer coordination sphere
has an N1-Pd1-N1 angle of 159.40(8)8. The two imidazoli-
dine rings stand to the square coordination plane in the di-
hedral angle of 119.55(5)8, as observed in the PyBidine–Cu-
ing nitrogen atoms such that they form an extended chiral
fence. The adjacent phenyl ring (blue) has the dihedral
angle of 81.36(5)8 to the square coordination plane. There-
fore, the second and fourth quadrants are highly shielded as
a result of incorporating imidazolidine ligands with the
phenyl substituents (Figure 2b).
The catalytic activity of this air-stable imidazolidine-de-
rived NCN-Pd complex was demonstrated using a reaction
capable of being activated by the presence of a Lewis acid.
To allow the use of an NCN-Pd complex as a Lewis acid cat-
alyst, a widely used technique has been the initial formation
of a cationic complex by exchange of the counterion to
obtain a vacant coordination sphere. As a test case, we
therefore examined the use of a cationic palladium pincer
complex in a series of conjugate addition reactions employ-
ing alkyl nitriles. We prepared cationic NCN-Pd-OTf by
ACHTUNGTRENNUNG(OTf)2 complex. In the NCN-Pd-Cl complex, however, the
imidazolidine rings force their attached phenyl rings
(marked blue) to adopt positions relative to the coordinat-
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T. Arai et al.
Table 2. Conjugate addition of malononitrile to nitroalkenes catalyzed
by the imidazolidine-derived complex NCN-Pd-X.
treating the NCN-Pd-Cl complex with AgOTf (Scheme 1c;
for details, see the Supporting Information).
Using either the neutral or the cationic NCN-Pd catalyst,
we were able to study the conjugate addition reaction of
malononitrile to nitroalkenes.[10] This reaction, using the
simple, small malononitrile molecule as the nucleophile, is
potentially useful for producing synthetically important
compounds. However, there have been few examples of the
successful catalytic, asymmetric reaction of malononitrile to
generate nitroalkenes to date. The first reported instance
was by Takemoto using an organocatalyst,[11] followed by
Guoꢁs recently published results on an efficient catalytic
asymmetric reaction.[12,13] In our work, the reaction of malo-
nonitrile with nitrostyrene (3a in Table 1) was catalyzed
well by the cationic NCN-Pd-OTf complex to give the prod-
uct 4a in 75% yield with 77% ee (Table 1, entry 1).
Table 1. Optimization of the conjugate addition of malononitrile to nitro-
alkenes catalyzed by the imidazolidine-derived complex NCN-Pd-X.
Entry
Nitroalkene
X
Yield [%]
ee [%]
1
2
3
3a
3a
3b
3b
3b
OTf
Cl
Cl
Cl
OTf
75
82
60
82
80
77
80
90
87
88
4[a]
5
[a] NaHCO3 (1 equiv) was added.
Surprisingly, the neutral NCN-Pd-Cl complex also exhibit-
ed strong catalytic activity and gave product 4a in 82%
yield with 80% ee (entry 2); these results are actually supe-
rior to those obtained using the cationic form of this cata-
lyst. It should be noted that the NCN-Pd-Cl catalyst was not
degraded or modified during the course of the reaction, as
[a] Conducted for 96 h. [b] NaHCO3 (1 equiv) was added. [c] Conducted
for 63 h.
1
determined by a lack of significant changes in the H NMR
spectra of the crude reaction mixture. The cyclohexyl-substi-
tuted nitroalkene 3b was also converted using the neutral
NCN-Pd-Cl in moderate yield with 90% ee (entry 3). The
addition of NaHCO3 as a base was helpful in improving the
chemical yield of 4b, albeit with slightly reduced enantio-
meric purity (entry 4). For many of the aliphatic nitroal-
kenes (such as 3b), the cationic NCN-Pd-OTf complex also
demonstrated strong catalytic activity (entry 5).
Preliminary results for the imidazolidine-derived NCN-
type palladium pincer-catalyzed conjugate addition of malo-
nonitrile to a variety of nitroalkenes are summarized in
Table 2. Because the catalytic activity varied with the partic-
ular nitroalkene reacted, only generalized conclusions are
possible with regard to which is the most appropriate cata-
lyst. In general, use of the neutral NCN-Pd-Cl complex re-
sulted in products obtained in high enantiomeric purity as
well as moderate to high yields. When working solely with
aliphatic nitroalkenes, either a combination of the neutral
NCN-Pd-Cl with NaHCO3 or NCN-Pd-OTf alone gave
products with up to 92% ee. The reaction using 2-ethylmalo-
nonitrile was catalyzed by the cationic NCN-Pd-OTf com-
plex to give the product having a quaternary carbon center.
The absolute configuration of the product 4a was deter-
mined using a 79% ee material obtained by the reaction
with (R,R)-NCN-Pd-Cl. The oxidative degradation reaction
of this compound using magnesium monoperoxyphthalate[14]
resulted in the corresponding R compound produced at
77% ee (Scheme 2).[15]
In conclusion, a chiral, imidazolidine-derived NCN-type
palladium pincer/chloride (NCN-Pd-Cl) complex has been
prepared and its structure characterized. The well-organized
asymmetric reaction sphere of this complex was applied to
the catalytic asymmetric reaction of various nitroalkenes
with malononitrile. Both the cationic NCN-Pd-OTf version
and the original neutral NCN-Pd-Cl complex exhibited sig-
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Palladium Pincer Complexes
COMMUNICATION
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[5] For recent reviews of bisACTHNUGRTENUNG(oxazolyl)phenyl ligands (Phebox), see:
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Scheme 2. Chemical transformation and determination of the absolute
configuration of 4a. y.=yield.
[6] H. Nishiyama, H. Sakaguchi, T. Nakamura, M. Horihata, M. Kondo,
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[7] T. Arai, A. Mishiro, N. Yokoyama, K. Suzuki, H. Sato, J. Am. Chem.
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nificant catalytic activity. The catalyst activity of the imid-
ACHTUNGTRENNUNGazolidine-derived NCN-Pd-X complex is provided consider-
able assistance by forming a hydrogen-bonding between the
substrate and the proton on nitrogen in the pincer complex
(Figure 2).[7,16,17] Further study is now in progress with the
aim of elucidating the catalytic function of this new com-
plex.
[8] For imidazoline-derived NCN pincer catalysts, see: a) X.-Q. Hao, J.-
F. Gong, C.-X. Du, L.-Y. Wu, Y.-J. Wu, M.-P. Song, Tetrahedron
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Experimental Section
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PhBidine-Pd-Cl: The trans-(4-tert-butyl-2,6-diformylphenyl)chlorobis(tri-
phenylphosphine)palladium complex[9] (269 mg, 0.31 mmol) was added to
a solution of (1R,2R)-N-benzyl-1,2-diphenylethane-1,2-diamine (284 mg,
0.94 mmol) in MeCN (9.52 mL). The mixture was refluxed under an O2
atmosphere for 48 h. After cooling to RT, the precipitate was washed
with MeOH and dried under reduced pressure to give NCN-Pd-Cl
(108.8 mg, 39%).
General procedure for the conjugate addition of malononitrile to aromat-
ic nitroalkenes catalyzed by the imidazolidine-derived NCN-Pd complex:
NCN-Pd-Cl (0.01 mmol) and malononitrile (19.8 mg, 0.3 mmol) were
added to a one-necked round flask containing a stir bar under Ar. THF
(0.8 mL) was added to the flask and the mixture was stirred at 08C. Ni-
troalkene (0.2 mmol) in THF (0.2 mL) was added to the resulting solu-
tion. After being stirred for appropriate time, the reaction mixture was
purified by silica gel column chromatography to afford the product. The
enantiomeric excesses of the products were determined by chiral station-
ary-phase HPLC using a Daicel Chiralcel OD-H, Chiralpak AD-H, or
Chiralpak AS-H column.
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[14] S. Fçrster, O. Tverskoy, G. Helmchen, Synlett 2008, 2803.
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[16] For mechanistic studies on the catalytic Michael addition, see: a) S.-
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology,
Japan.
Keywords: asymmetric catalysis
· conjugate addition ·
imidazolidines · palladium · pincer complexes
[17] In a reaction of the malononitrile with chalcone, the combination
use of NCN-Pd-Cl catalyst and NaHCO3 (1 equiv) gave the product
only 46% yield with 29% ee (72 h). This suggests the nitro function-
ality of the nitroalkenes is efficiently activated by the NCN-Pd-Cl
catalyst.
[1] For reviews on pincer catalysts, see: a) M. Albrecht, G. van Koten,
Angew. Chem. 2001, 113, 3866; Angew. Chem. Int. Ed. 2001, 40,
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Boom, D. Milstein, Chem. Rev. 2003, 103, 1759; d) E. Peris, R. H.
Crabtree, Coord. Chem. Rev. 2004, 248, 2239; e) N. Selander, K.
Szabꢂ, Chem. Rev. 2011, 111, 2048.
Received: November 9, 2012
Published online: January 4, 2013
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