Development of chiral pincer palladium complexes bearing a pyrroloimidazolone unit. Catalytic use for asymmetric Michael addition

Article abstract of DOI:10.1021/ol0494515

Matrix presented. Novel pincer palladium complexes having chiral hexahydro-1H-pyrrolo[1,2-c]imidazolone groups were designed and prepared. Catalytic asymmetric Michael addition of isopropyl 2-cyanopropionate to ethyl vinyl ketone was catalyzed by the chiral pincer palladium complex to give isopropyl 2-cyano-2-methyl-5-oxoheptanoate with high enantioselectivity (up to 83% ee).

Full text of DOI:10.1021/ol0494515

ORGANIC
LETTERS
2004
Vol. 6, No. 11
1833-1835
Development of Chiral Pincer Palladium
Complexes Bearing a
Pyrroloimidazolone Unit. Catalytic Use
for Asymmetric Michael Addition
Kazuhiro Takenaka and Yasuhiro Uozumi*
Institute for Molecular Science (IMS), Myodaiji, Okazaki 444-8787, Japan
uo@ims.ac.jp
Received March 23, 2004
ABSTRACT
Novel pincer palladium complexes having chiral hexahydro-1H-pyrrolo[1,2-c]imidazolone groups were designed and prepared. Catalytic asymmetric
Michael addition of isopropyl 2-cyanopropionate to ethyl vinyl ketone was catalyzed by the chiral pincer palladium complex to give isopropyl
2-cyano-2-methyl-5-oxoheptanoate with high enantioselectivity (up to 83% ee).
Organometallic complexes containing terdentate monoanionic
ligands composed of anionic aryl carbon atoms and two
mutually trans-chelating donor sites at the 2,6-positions of
the aromatic ring (the so-called pincer complexes) have been
recognized as a novel class of functional materials, and in
particular, those having platinum group metals have found
widespread utility as catalysts for several organic transforma-
tions.1,2 We have recently found that hexahydro-1H-pyrrolo-
[1,2-c]imidazolone serves as an effective chiral auxiliary.3
These results prompted us to prepare chiral pincer complexes
having pyrroloimidazolone coordinating groups and to
examine their catalytic use in asymmetrtic synthetic reactions.
Here we report the preparation of novel chiral pincer
palladium complexes having pyrroloimidazolone moieties,
which exhibited high catalytic activity and high stereo-
selectivity in the asymmetric Michael reaction (up to 83%
ee).4
(3) (a) Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001, 123, 2919.
(b) Uozumi, Y.; Yasoshima, K.; Miyachi, T.; Nagai, S. Tetrahedron Lett.
2001, 42, 411. (c) Shibatomi, K.; Uozumi, Y. Tetrahedron: Asymmetry
2002, 13, 1769. (d) Uozumi, Y.; Tanaka, H.; Shibatomi, K. Org. Lett. 2004,
6, 281.
(4) For recent catalytic synthetic applications with palladium pincer
complexes, see: (a) Jung, I. G.; Son, S. U.; Park, K. H.; Chung, K.-C.;
Lee, J. W.; Chung, Y. K. Organometallics 2003, 22, 4715. (b) D´ıez-Barra,
E.; Guerra, J.; Hornillos, V.; Merino, S.; Tejeda, J. Organometallics 2003,
22, 4610. (c) Miyazaki, F.; Yamaguchi, K.; Shibasaki, M. Tetrahedron Lett.
1999, 40, 7379. (d) Morales-Morales, D.; Redo´n, R.; Yung, C.; Jensen, C.
M. Chem. Commun. 2000, 1619. (e) Ohff, M.; Ohff. A.; van der Boom, M.
E.; Milstein, D. J. Am. Chem. Soc. 1997, 119, 11687. (f) Bergbreiter, D.
E.; Osburn, P. L.; Liu, Y.-S. J. Am. Chem. Soc. 1999, 121, 9531. (g) Gruber,
A. S.; Zim, D.; Ebeling, G.; Monteiro, A. L.; Dupont, J. Org. Lett. 2000,
2, 1287. (h) Sjo¨vall, S.; Wendt, O. F.; Andersson, C. J. Chem. Soc., Dalton
Trans. 2002, 1396.
(1) For reviews on pincer complexes, see: (a) Albrecht, M.; van Koten,
G. Angew. Chem., Int. Ed. 2001, 40, 3750. (b) van der Boom, M. E.;
Milstein, D. Chem. ReV. 2003, 103, 1759. (c) Singleton, J. T. Tetrahedron
2003, 59, 1837.
(2) For reviews on palladacycle complexes, see: (a) Herrmann, W. A.;
Bo¨hm, V. P. W.; Reisinger, C.-P. J. Organomet. Chem. 1999, 576, 23. (b)
Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem. 2001, 1917. (c)
Bedford, R. B. Chem. Commun. 2003, 1787.
10.1021/ol0494515 CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/05/2004

The pincer palladium complexes 1-4 were prepared by
the introduction of pyrroloimidazolones to the aromatic ring
of an arylpalladium complex (ligand-introduction route)
(Scheme 1). Thus, trans-chloro(4-tert-butyl-2,6-diformyl-
from 2-Cl in 76% and 83% yields, respectively, via etheri-
fication followed by the treatment with silver triflate.
The X-ray structure of 1-Cl unambiguously establishes that
the product is the expected pincer complex in which the two
nitrogen atoms (N1 and N3) of the pyrroloimidazolone
moieties coordinate to Pd atom attached to aromatic carbon
(Figure 2).5 The structures of the pincer complexes 2-4
Scheme 1
Figure 2. ORTEP drawing of the pincer Pd complex 1-Cl (50%
probability). All hydrogen atoms and solvated toluene molecules
were omitted for clarity.
phenyl)bis(triphenylphosphine)palladium (5) was treated with
5 equiv of the proline anilide 6 in refluxing acetonitrile under
an oxygen atmosphere to give 98% yield of the pincer
palladium complex 1-Cl (Figure 1) via condensation of the
which have functional groups on their pyrrole rings could
not be determined by X-ray analysis because of the difficulty
in obtaining adequate single crystals suitable for X-ray
diffraction. Molecular modeling study of the functionalized
pincer complexes indicates that the functional substituents
on the pyrrole rings would play an essential role in the
asymmetric induction. Thus, as can be seen from the
schematic structure of a pyrrole-substituted pincer complex
shown in Figure 3, the substituents on the pyrrole rings (R
Figure 1. Pincer Pd complexes having pyrroloimidazolone units.
2,6-formyl groups with 6 and subsequent ligand exchange
by the resulting pyrroloimidazolone forming the Pd-N
bonds. Similarly, the complex 2-Cl was obtained in 87%
yield by the reaction of 5 with the anilide 7 derived from
trans-4-hydroxy-L-proline. Since the corresponding pincer
ligands showed little reactivity to palladium (metal-introduc-
tion route), presumably due to the steric bulkiness of the
pyrroloimidazolone groups, the ligand-introduction route
would provide an alternative synthetic protocol for pincer
complexes having sterically demanding groups. The chloride
ligands of 1 and 2 were replaced by the more labile triflate
ligand by treatment with silver triflate to give 1-OTf and
2-OTf in 95% and 94% yields, respectively. The pincer
palladium complexes 3-OTf and 4-OTf having methoxy and
silyloxy groups on their pyrrole rings were also prepared
Figure 3. Schematic structure of a pyrrole-substituted pincer
complex (e.g., compound 2). The aromatic ligand moiety in the
pincer ligand is omitted for clarity.
in Figure 3) are situated in close proximity to the metal
species in the regions of the second and fourth quadrants
(from the viewpoint of metal side) to provide effective chiral
surroundings.
1834
Org. Lett., Vol. 6, No. 11, 2004

To explore the enantiocontrolling potential of the chiral
pincer palladium complexes, we elected to study the catalytic
asymmetric Michael reaction of vinyl ketones and R-cyano-
carboxylates as nucleophiles6 which has attracted increasing
attention since the products bear a quaternary carbon center
with various functionalities.7 It has been reported that the
Michael addition of cyanocarboxylates is catalyzed by chiral
phosphine-rhodium complexes with high enantioselectivity.
Rather surprisingly, only scattered attention has been paid
to the use of palladium catalysts for the Michael addition,
despite their frequent use for various catalytic asymmetric
carbon-carbon forming reactions.8 The reaction of methyl
vinyl ketone (8) with methyl 2-cyanopropionate (9a) was
performed in benzene at 25 °C in the presence of 0.5 mol %
of the chiral pincer palladium complex and 0.1 equiv of
diisopropylethylamine (Scheme 2) to give the desired
Table 1. Asymmetric Michael Addition of R-Cyanoesters to
Vinyl Ketones Using Chiral Pincer Complexesa
run substrate catalyst time (h) product yieldb (%) % eec
1
2
3
4
5
6
7d
8
8/9a
8/9a
8/9a
8/9a
8/9a
8/9b
8/9c
11/9b
1-OTf
2-OTf
3-OTf
4-OTf
2-Cl
2-OTf
2-OTf
2-OTf
3
4
3
4
144
4
10a
10a
10a
10a
10a
10b
10c
12
95
89
93
97
<2
90
93
91
8
81
6
9
80
80
83
24
4
a All reactions were carried out in the presence of 0.5 mol % of pincer
palladium complexes and 0.1 equiv of i-Pr2EtN at 25 °C in benzene or
toluene unless otherwise noted. b Isolated yield. c Determined by GC analysis
(Cyclodex CB). d 1.0 mol % of 2-OTf was used.
The pincer complexes 1-OTf, 3-OTf, and 4-OTf, which
lacked hydroxyl groups, were much less stereoselective and
only gave 8% ee, 6% ee, and 9% ee of 10a, respectively
(runs 1, 3, and 4). It is also interesting to note that the
chemical yield of the product 10a is strongly affected by
the anionic ligand of the pincer complexes. Thus, the Michael
addition did not take place with complex 2-Cl even after a
reaction time of 144 h (run 5), whereas with 2-OTf the
reaction gave a high yield of the product in 4 h. Isopropyl
ester 9b and diisopropylmethyl ester 9c underwent the
Michael addition under similar conditions to give 80% ee
(S) of both 10b and 10c in 90% and 93% yields, respectively
(runs 6 and 7). The highest stereoselectivity was obtained
when the reaction was carried out with ethyl vinyl ketone
(11) and isopropyl cyanopropionate (9b) in the presence of
the chiral pincer catalyst 2-OTf to give 91% yield of the
heptanoate (S)-12 with 83% enantiomeric purity (run 8).
In summary, new chiral pincer complexes bearing pyrro-
loimidazolone groups were designed and prepared via ligand
introduction protocol. The asymmetric Michael addtion of
R-cyanocarboxylates to vinyl ketones was catalyzed by the
pyrroloimidazolone palladium pincer complexes with high
enantioselectivity.
Scheme 2
Michael adduct 10a which was readily isolated by Kugelrohr
distillation. The enantiomeric purity and the absolute con-
figuration of 10a were determined by GC analysis with a
chiral stationary phase column (Cyclodex CB) and measure-
ment of specific rotation value, respectively. The representa-
tive results are summarized in Table 1. Among the chiral
pincer catalysts 1-4, 2-OTf bearing hydroxyl groups on the
pyrrole rings turned out to be the best catalyst, giving 10a
with high enantioselectivity. Thus, the asymmetric Michael
addition catalyzed by 2-OTf afforded 81% ee (S) of the
adduct ethyl 2-cyano-2-methyl-5-oxohexanoate (10a) in 89%
yield (run 2). This selectivity is comparable to that of the
best chiral pincer complexes known for this reaction.7d
Acknowledgment. This work was supported by the
CREST program sponsored by JST. We also thank the JSPS
(Creative Scientific Research, No. 13GS0024; Grant-in-Aid
for Scientific Research, No.15205015) and the MEXT
(Scientific Research on Priority Areas, Nos. 412 and 420)
for partial financial support of this work.
(5) Crystal data of 1-Cl‚toluene: C41H45ClN4O2Pd, orthorhombic,
P212121 (No. 19), a ) 12.2613(5) Å, b ) 12.4185(5) Å, c ) 23.9133(11)
Å, V ) 3641.2(3) Å3, Z ) 4, R1 ) 0.023, wR2 ) 0.060, GOF ) 0.94.
(6) Naota, T.; Taki, H.; Mizuno, M.; Murahashi, S.-I. J. Am. Chem. Soc.
1989, 111, 5954.
(7) For asymmetric Michael addition of R-cyanoesters with chiral
transition metal catalysts, see: Rh complexes: (a) Sawamura, M.; Ha-
mashima, H.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 8295. (b) Sawamura,
M.; Hamashima, H.; Ito, Y. Tetrahedron 1994, 50, 4439. (c) Inagaki, K.;
Nozaki, K.; Takaya, H. Synlett 1997, 119. (d) Motoyama, Y.; Koga, Y.;
Kobayashi, K.; Aoki, K.; Nishiyama, H. Chem. Eur. J. 2002, 8, 2968. Pt
complexes: (e) Blacker, A. J.; Clarke, M. L.; Loft, M. S.; Mahon, M. F.;
Williams, J. M. J. Organometallics 1999, 18, 2867. Pd complexes: (f) Stark,
M. A.; Jones, G.; Richards, C. J. Organometallics 2000, 19, 1282.
(8) See: Handbook of Organopalladium Chemistry; Negishi, E., Ed.;
Wiley: New York, 2002.
Supporting Information Available: Characterization and
experimental procedures for compounds 1-5. Experimental
procedure for the asymmetric Michael addition. X-ray data
for 1-Cl (CIF). This material is available free of charge via
the Internet at http://pubs.acs.org.
OL0494515
Org. Lett., Vol. 6, No. 11, 2004
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