Catalytic enantioselective addition of cyclic β-keto esters with activated olefins and N-boc imines using chiral C 2-symmetric cationic Pd2+ N-heterocyclic carbene (NHC) diaqua complexes

Article abstract of DOI:10.1021/om100331z

The asymmetric addition of cyclic β-keto esters to activated olefins and N-Boc imines was realized by using chiral cationic C₂-symmetric N-heterocyclic carbene (NHC) Pd²⁺ diaqua complexes 1a,b as the catalysts, producing the correspo

Full text of DOI:10.1021/om100331z

Organometallics 2010, 29, 2831–2834 2831
DOI: 10.1021/om100331z
Catalytic Enantioselective Addition of Cyclic β-Keto Esters with
Activated Olefins and N-Boc Imines Using Chiral C2-Symmetric Cationic
Pd2þ N-Heterocyclic Carbene (NHC) Diaqua Complexes
Zhen Liu and Min Shi*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, People’s Republic of China
Received April 22, 2010
Summary: The asymmetric addition of cyclic β-keto esters to
activated olefins and N-Boc imines was realized by using
chiral cationic C2-symmetric N-heterocyclic carbene (NHC)
Pd2þ diaqua complexes 1a,b as the catalysts, producing the
corresponding adducts in moderate to high yields (up to 95%)
and with good to high enantioselectivities (up to 96% ee).
Nevertheless, the most significant observation is that when
the (R)-NHC Pd2þ diaqua complex was used in these reac-
tions, different absolute configurations were observed in
comparison to those obtained with catalysts obtained from
(R)-phosphane ligands.
transformations have opened up the possibility of the develop-
ment of enantioselective catalysis.4-6
Michael- or Mannich-type addition reactions of acidic
carbon nucleophiles to a variety of activated olefins or
imines are some of the most important and practically useful
carbon-carbon bond-forming reactions in organic synthesis.7
In these reactions, the use of readily enolizable compounds
such as β-keto esters as nucleophiles for the construction of
chiral tertiary carbon centers have especially attracted much
attention.8 Thus far, a number of Pd enolates of ketones have
been successfully applied to the above reactions, affording
the corresponding adducts in high yields and good enantio-
meric excesses under mild conditions.9 For example, Sodeoka
and co-workers originally reported that Pd (R)-phosphane
ligand diaqua complexes reacted with 1,3-dicarbonyl com-
pounds, such asβ-keto esters, to give chiral Pdenolates. Using
this novel Pd enolate chemistry, efficient catalytic enantiose-
lective addition reactions with various electrophiles have been
achieved.10 On the other hand, we previously reported the
synthesis of a series of the chiral cationic Pd2þ NHC diaqua
complexes and their application in the catalytic enantioselec-
tive arylation of N-tosylarylimines with arylboronic acids.11b
Recently, N-heterocyclic carbenes (NHCs) have become a
very important class of ligands in organometallic chemistry
and catalysis.1 On the basis of recent achievements in this
field, N-heterocyclic carbenes (NHCs) clearly are not just
“phosphane mimics”, as they are sometimes called in the
literature, since NHCs as ligands or catalysts showed several
advantages over their phosphine counterparts. The NHCs
have the general advantage of being better σ donors and
weaker π acceptors than phosphine ligands, and these
ligands are also air and moisture stable. These advantages
have attracted several research groups to search for new
catalytic systems using NHCs as ancillary ligands for many
catalytic reactions.2 Recently, NHC-Pd complexes have sig-
nificantly emerged as effective catalysts for a variety of coupling
reactions.3 However, to the best of our knowledge, the promise
of a highly active and enantioselective NHC-Pd catalyst
has not been fulfilled, even though many palladium-mediated
(6) (a) Sato, Y.; Imakuni, N.; Mori, M. Adv. Synth. Catal. 2003, 345,
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Pergamon: New York, 1991; Vol. 4, pp 1-67. (c) Arend, M.; Westermann,
B.; Risch, N. Angew. Chem., Int. Ed. 1998, 37, 1044.
(8) For selected examples of catalysts: (a) Watanabe, M.; Ikagawa,
A.; Wang, H.; Murata, K.; Ikariya, T. J. Am. Chem. Soc. 2004, 126,
11148and references cited therein. (b) Sasai, H.; Arai, T.; Satow, Y.; Houk,
K. N.; Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194. (c) Corey, E. J.;
Noe, M. C.; Xu, F. Tetrahedron Lett. 1998, 39, 5347. (d) Hagiwara, E.; Fujii,
A.; Sodeoka, M. J. Am. Chem. Soc. 1998, 120, 2474.
(9) For representative examples which involve putative palladium
enolates: (a) Ito, Y.; Aoyama, H.; Hirao, T.; Mochizuki, A.; Saegusa, T.
J. Am. Chem. Soc. 1979, 101, 494. (b) Palucki, M.; Buckwald, S. L. J. Am.
Chem. Soc. 1997, 119, 11108. (c) Hamann, B. C.; Hartwig, J. F. J. Am.
Chem. Soc. 1997, 119, 12382. (d) Satoh, T.; Kawamura, Y.; Miura, M.;
Nomura, M. Angew. Chem., Int. Ed. 1997, 36, 1740. For an excellent
textbook: (e) Tsuji, J. Palladium Reagents and Catalysts: New Perspective
for the 21st Century; Wiley: Chichester, U.K., 2004.
(10) (a) Sodeoka, M.; Ohrai, K.; Shibasaki, M. J. Org. Chem. 1995,
60, 2648. (b) Hagiwara, E.; Fujii, A.; Sodeoka, M. J. Am. Chem. Soc. 1998,
120, 2474. (c) Fujii, A.; Hagiwara, E.; Sodeoka, M. J. Am. Chem. Soc. 1999,
121, 5450. (d) Hamashima, Y.; Hotta, D.; Sodeoka, M. J. Am. Chem. Soc.
2002, 124, 11240. (e) Hamashima, Y.; Yagi, K.; Takano, H.; Tamas, L.;
Sodeoka, M. J. Am. Chem. Soc. 2002, 124, 14530. (f) Hamashima, Y.;
Sodeoka, M. Chem. Rec. 2004, 4, 231. (g) Hamashima, Y.; Hotta, D.;
Umebayashi, N.; Tsuchiya, Y.; Suzuki, T.; Sodeoka, M. Adv. Synth. Catal.
2005, 347, 1576. (h) Hamashima, Y.; Sasamoto, N.; Hotta, D.; Somei, H.;
Umebayashi, N.; Sodeoka, M. Angew. Chem., Int. Ed. 2005, 44, 1525.
*Fax: 86-21-64166128. Mshi@mail.sioc.ac.cn.
(1) (a) Bourisou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. Chem.
Rev. 2000, 100, 39. (b) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41,
1290. (c) Radiusa, U.; Bickelhaupt, F. M. Coord. Chem. Rev. 2009, 253, 678.
(2) (a) Choi, T. -L.; Grubbs, R. H. Angew. Chem., Int. Ed. 2003, 42,
1743. (b) Navarro, O.; Kelly, R. A., III; Nolan, S. P. J. Am. Chem. Soc. 2003,
125, 16194. (c) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.;
Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101. (d) Albrecht, M.;
Miecznikowski, J. R.; Samuel, A.; Faller, J. W.; Crabtree, R. H. Organome-
tallics 2002, 21, 3596.
(3) (a) Herrmann, W. A.; Elison, M.; Fisher, J.; Koecher, C.; Artus,
G. R. J. Angew. Chem., Int. Ed. 1995, 34, 2371. (b) Albert, K.; Gisdakis, P.;
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C. J.; Organ, M. G. Angew. Chem., Int. Ed. 2007, 46, 2768.
(4) (a) Glorius, F.; Altenhoff, G.; Goddard, R.; Lehmann, C. Chem.
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2010 American Chemical Society
Published on Web 06/01/2010
pubs.acs.org/Organometallics

2832 Organometallics, Vol. 29, No. 12, 2010
Liu and Shi
Figure 1. Chiral cationic Pd2þ NHC diaqua complexes 1a,b.
Table 1. Catalytic Enantioselective Michael Addition of Cyclic
β-Keto Ester 2a
at room temperature to afford 3a in 98% yield and 71% ee
with S configuration for the major enantiomer (Table 1,
entry 1). It should also be noted that the Pd2þ (R)-Tol-BINAP
diaqua catalyst produces product 3a with an R configuration
as the predominant species.10g In contrast to the Pd2þ (R)-
NHC diaqua catalyst 1a, catalyst 1b was found to be less
reactive in this reaction, giving 3a in 86% yield and 38% ee
under the standard conditions, presumably due to thefact that
the sterically hindered N-benzyl group did not favor this
reaction (Table 1, entry 2). Adding 5 mol % of 4-NO2C6H4-
CO2H as the additive in the combination with catalyst 1a
produced 3a in 96% yield and 40% ee (Table 1, entry 3). The
examination of the solvent effects revealed that CH2Cl2 is the
best choice if 1a is used as the catalyst. Other solvents such as
tetrahydrofuran (THF), toluene, 1,2-dichloroethane (DCE),
and dioxane generally gave poor results in this reaction
(Table 1, entries 4-7). Unfortunately, lowering or elevating
the temperature resulted in poorer results (Table 1, entries 8
and 9). Therefore, the best reaction conditions involve carry-
ing out the reaction in CH2Cl2 at room temperature (20 °C)
using the Pd2þ (R)-NHC diaqua catalyst 1a in the presence of
entry
solvent
electrophile
time (h)
yield (%)a
ee (%)b
1
CH2Cl2
CH2Cl2
CH2Cl2
THF
toluene
DCE
dioxane
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MVK
MVK
MVK
MVK
MVK
MVK
MVK
MVK
MVK
EVK
24
24
24
24
24
24
24
24
24
72
48
48
98 (3a)
86 (3a)
96 (3a)
80 (3a)
90 (3a)
89 (3a)
76 (3a)
69 (3a)
98 (3a)
91 (3b)
93 (3c)
90 (3d)
71 (S)c
38 (S)
40 (S)
53 (S)
39 (S)
63 (S)
38 (S)
70 (S)
63 (S)
19(-)
2d
3e
4
5
6
7
8f
9g
10
11
12
PVK
nitroethene
0
38(-)
a Isolated yields. b Determined by chiral HPLC. c Determined by com-
parison of the sign of optical rotation with the literature value.10g
d Complex 1b was used. e 5 mol % of 4-NO2C6H4CO2H was added.
f The reaction was carried out at -10 °C. g The reaction was carried out
at 35 °C.
˚
molecular sieves 4 A. Other Michael acceptors have also been
tested under the optimized reaction conditions using catalyst
1a. In addition to methyl vinyl ketone (MVK), ethyl vinyl
ketone (EVK) and phenyl vinyl ketone (PVK) were also
examined and we found that increasing the steric bulkiness
resulted in a decrease in the enantioselectivity (entries 10 and
11). The asymmetric addition of cyclic β-keto ester 2a to
nitroethene also proceeded smoothly to give the correspond-
ing adduct 3d in 90% yield and 38% ee (entry 12).
Herein, we have turned our attention to the investigation of
the catalytic activity of these chiral cationic Pd2þ NHC diaqua
complexes in enantioselective addition reactions of cyclic β-keto
esters with several electrophiles such as activated olefins and
N-Boc imines. It was found that the corresponding adducts
could be obtained in moderate to high yields (up to 95%) and
with good to high enantioselectivities (up to 97% ee) under mild
conditions. In this paper, we wish to report the details of these
findings.
Catalytic Diastereo- and Enantioselective Addition of
β-Keto Esters to N-Boc Imines. The above success led us to
investigate the diastereoselective addition of β-keto esters
to N-Boc imines using Pd2þ (R)-NHC diaqua catalyst 1a.
Initially, we also examined the solvent and temperature
effects in this reaction using phenyl-substituted N-Boc imine
as the substrate and the results of these experiments are
summarized in Table 2. It was found that the corresponding
product 4a was obtained in 91% yield along with 80% ee
(anti:syn, dr = 3.5:1) when the reaction was carried out in
CH2Cl2 at room temperature (20 °C) using catalyst 1a
(Table 2, entry 1). Interestingly, when the Pd2þ (R)-NHC
diaqua complex was used for this asymmetric addition
reaction, a different major diastereomer and absolute con-
figuration were also observed in comparison to the product
obtained with Pd2þ (R)-BINAP diaqua catalyst.10h Other
solvents such as tetrahydrofuran (THF), toluene, and 1,2-
dichloroethane (DCE) generally gave lower dr or ee values
in this reaction (Table 2, entries 2-4). Furthermore, it was
found that lowering the temperature could reduce the
dr value of the product, leaving the ee value unchanged
(Table 2, entry 5). Thus, we established the optimized reaction
Results and Discussion
Synthesis of Chiral Cationic C2-Symmetric Pd2þ N-Hetero-
cyclic Carbene (NHC) Diaqua Complexes 1a,b. The chiral
cationic Pd2þ NHC diaquacomplexes1a,b, showninFigure 1,
were designed and synthesized in a six-step pathway starting
from optically active binaphthyl-2,20-diamine (BINAM) ac-
cording to our previously reported procedure.11
Catalytic Enantioselective Michael Addition of Cyclic
β-Keto Ester 2a. An initial experiment was carried out by
reacting cyclic β-keto ester 2a with methyl vinyl ketone
(MVK) in the presence of the Pd2þ (R)-NHC diaqua catalyst
˚
1a (5 mol %) together with 4 A molecular sieves at room
temperature (20 °C). The reaction was conducted in CH2Cl2
(11) (a) Chen, T.; Jiang, J. J.; Xu, Q.; Shi, M. Org. Lett. 2007, 9, 865.
(b) Ma, G. N.; Zhang, T.; Shi, M. Org. Lett. 2009, 11, 875. (c) Zhang, T.;
Shi, M. Chem. Eur. J. 2008, 14, 3759.

Note
Organometallics, Vol. 29, No. 12, 2010 2833
Table 2. Optimization of the Reaction Conditions for Catalytic
Enantioselective Addition of β-Keto Ester 2a to N-Boc Imines
Table 3. Catalytic Diastereo- and Enantioselective Addition of
β-Keto Esters 2 with N-Boc Imines
R1
time (h) yield (%)a drb
ee (%)c
73
entry solvent
temp
time (h) yield (%)a drb
ee (%)c
entry
n
1
2
3
4
5
CH2Cl2 room temp
THF room temp
toluene room temp
DCE room temp
CH2Cl2 -10 °C
72
48
48
48
96
91
87
86
90
85
3.5:1 80 (S,S)
1.5:1 71 (S,S)
3:1
2:1
2:1
1
2
3
4
5
6
7
8
1 (2a) 2-ClC6H4
1 (2a) 3-ClC6H4
1 (2a) 3-CF3C6H4
1 (2a) 4-ClC6H4
1 (2a) 4-CF3C6H4
1 (2a) 4-FC6H4
1 (2a) 4-BrC6H4
1 (2a) 4-CH3C6H4
1 (2a) cyclohexyl
2 (2b) 3-CF3C6H4
2 (2b) 4-CF3C6H4
48
48
24
48
24
36
48
36
24
48
48
80 (4b)
95 (4c)
90 (4d)
91 (4e)
90 (4f)
92 (4g)
89 (4h)
91 (4i)
92 (4j)
85 (4k)
79 (4l)
1:5
1:20 91
1:20 94
2:1
1:10 95
2:1
2:1
2:1
d
69 (S,S)
76 (S,S)
80 (S,S)
90 (S,S)
a Isolated yields. b dr (anti:syn); determined by 1H NMR spectro-
scopic analysis of the crude products. c ee (anti); determined by chiral
HPLC.
83 (S,S)
70 (S,S)
80 (S,S)
96
9
10
11
1:10 88
1:5 80
conditions for this reaction: using 5 mol % complex 1a as the
catalyst and CH2Cl2 as the solvent to perform the reaction at
room temperature.
a Isolated yields. b dr (anti:syn); determined by 1H NMR spectro-
scopic analysis of the crude products. c ee (major); determined by chiral
HPLC. d Only one diastereoisomer was isolated.
Next, the asymmetric additions of cyclic β-keto esters 2a,b
with a variety of N-Boc imines were evaluated under the
optimal conditions. The results are summarized in Table 3.
The corresponding adducts 4b-i were generated in high yields
(up to 95%) and good to excellent enantiomeric excesses (up
to 95% ee) regardless of whether they have electron-donating
or electron-withdrawing substituents on their benzene rings
(Table 3, entries 1-8). Furthermore, the position of these
substituents on the benzene rings is not restrictive for obtain-
ing high enantioselectivities (Table 3, entries 1-5). To our
delight, by using teh cationic Pd2þ diaquo complex 1a as the
catalyst, the N-Boc aliphatic imine substrate also efficiently
gave the corresponding product 4j in 92% yield and 96% ee as
a single diastereomer (Table 3, entry 9). Moreover, this system
was also applicable to the six-membered cyclic β-keto ester 2b,
affording the corresponding Mannich adducts 4k,l in good
yields along with high enantioselectivities (Table 3, entries 10
and 11). Interestingly, we found that, as for those N-Boc
imines having an electron-withdrawing substituent on the
ortho or meta position of their benzene rings, the diastereos-
electivities of the products were different from those having
substituents on the para position of their benzene rings under
identical conditions on the basis of NMR spectroscopic data
(Table 3, entries 1-3 and 10 vs entries 4 and 6-8). In these
cases, the syn products were obtained as the major diastereo-
mers, presumably due to steric effects and the electronic
properties of the substrates. As for the p-CF3-substituted
imine, the syn product was formed as the major species,
suggesting strong electronic effects on the diastereoselectivity
in this asymmetric addition reaction (Table 3, entries 5 and
11). The corresponding adducts 4 were obtained with medium
diastereoselectivity when they have para substituents on the
benzene rings (Table 3, entries 4, and 6-8, except for the
strongly electron withdrawing p-CF3-substituted imine).
Moreover, it was found that adducts 4 were produced in good
to excellent diastereoselectivity when they have ortho or meta
substituents on their benzene rings (Table 3, entries 1-3 and
10), presumably due to the fact that the sterically more bulky
and strongly electron withdrawing substituents favor high
diastereoselectivities in this asymmetric catalytic process.
To determine the absolute configuration of 4, the structure of
the major asymmetric addition product of 1-[(4-bromophenyl)-
tert-butoxycarbonylaminomethyl]-2-oxocyclopentanecarboxylic
acid tert-butyl ester (4h) was unequivocally determined by a
single-crystal X-ray structural analysis. Its ORTEP drawing and
its CIF data are presented in the Supporting Information.12 The
stereochemistry of the major product of 4h was deduced as the
S,S configuration at both the quaternary carbon and tertiary
carbon centers.
A plausible catalytic cycle is outlined in Scheme SI-1 in
the Supporting Information on the basis of Sodeoka’s
suggestion.10g,h First, the chiral bis(NHC)2PdOH species A
is generated from the palladium diaqua complex during
the reaction along with the generation of a Brønsted acid
(TfOH) and water. The chiral palladium species A reacts
with the β-keto ester to give the chiral palladium enolate B,
which undergoes the addition reaction with the electrophiles
(E, activated olefins or N-Boc imines) to give intermediate D
via intermediate C. Finally, tautomerization followed by ligand
exchange with water gives the addition product and regenerates
palladium species A (see the Supporting Information).
The generally accepted stable palladium enolate might be
used to explain the observed absolute configuration of the
products (Figure 2).10g,h Since the bis(NHC) ligand is less
sterically hindered in comparison with the Pd2þ (R)-phos-
phane ligand diaqua catalyst, in which each phosphorus
atom has two phenyl groups, the bulky ester (tBu) can locate
at the same side of the NHC ligand in the enolate face. Thus,
the Re face of the palladium enolate is blocked preferentially,
and the incoming electrophiles would react with palladium
enolate at the Si face in a highly enantioselective manner. On
the other hand, the relativestereochemistryis derivedfrom the
face selection of the imines to the palladium enolate. The
imines might react with the Pd enolate from the Si face with
the aryl groups directed to the more advantageous space in the
chiral environment according to their different steric bulks
and the electronic properties through an open transition-state
(12) The crystal data of 4h have been deposited with the CCDC with
file number 741415. Crystal data: empirical formula C22H30BrNO5,
formula weight 468.38, crystal size 0.279 ꢀ 0.256 ꢀ 0.245 mm3, colorless,
prismatic habit, crystal system monoclinic, lattice type primitive, lattice
˚
˚
˚
parameters a = 9.9053(17) A, b = 11.2911(18) A, c = 11.0981(19) A,
o
3
˚
R = 90°, β = 109.586(3) , γ = 90°, and V = 1169.4(3) A , space group
P21, Z = 2, Dcalcd = 1.330 g/cm3, F000 = 488, R1 = 0.0671, wR2 =
0.1623, diffractometer Rigaku AFC7R.

2834 Organometallics, Vol. 29, No. 12, 2010
Liu and Shi
(50 mg) were dissolved in the solvent (0.5 mL) under an argon
atmosphere. The solution was stirred at the appointed tempera-
ture. After the reaction was complete (monitored by TLC), the
solvent was removed under vacuum and the residue was purified
by flash column chromatography on silica gel with ethyl acetate/
petroleum ether (1:20, v/v) as eluent to afford the products.
General Procedure for the Catalytic Enantioselective Addition
of β-Keto Esters to N-Boc Imines Using C2-Symmetric Cationic
Pd2þ N-Heterocyclic Carbene (NHC) Diaqua Complexes. In a
dried Schlenk tube, catalyst (0.01 mmol; 1a, 9.6 mg; 1b, 11 mg),
N-Boc imines (0.4 mmol, 82-109 mg), and β-keto esters (0.2 mmol;
2a, 37 mg; 2b, 40 mg) were dissolved in CH2Cl2 (1.0 mL) under an
argon atmosphere. The solution was stirred at room temperature.
After the reaction was complete (monitored by TLC), the solvent
was removed under vacuum and the residue was purified by flash
column chromatography on silica gel with ethyl acetate/petroleum
ether (1:20, v/v) as eluent to afford the products.
Figure 2. Proposed transition-state model.
model as suggested by Sodeoka.10g,h,13 Thus, it seems to us
that our enantioselective addition reaction occurs with the
proposed geometry as depicted in Figure 2 in accord with the
observed absolute and relative stereochemistry.
(S)-2-Oxo-1-(3-oxobutyl)cyclopentanecarboxylic Acid tert-
Butyl Ester (3a). This is a known compound.10g 1H NMR
(CDCl3, 400 MHz, TMS): δ 1.44 (9H, s), 1.81-2.07 (5H, m),
2.14 (3H, s), 2.22-2.30 (1H, m), 2.35-2.50 (3H, m), 2.69-2.77
(1H, m). 13C NMR (CDCl3, 100 MHz, TMS): δ 19.5, 26.9, 27.8,
29.8, 34.5, 37.9, 38.8, 59.4, 81.9, 170.6, 208.0, 215.2. HPLC
(Daicel AS column, 95:5 hexanes/iPrOH, 0.7 mL/min, λ 230 nm,
In conclusion, we have successfully established a series of
new, efficient, chiralC2-symmetriccationic Pd2þ NHC diaqua
complex catalyzed systems for the asymmetric addition of
cyclic β-keto esters to activated olefins and N-Bocimines. This
system provides easy access to the corresponding adducts in
moderate to high yields (up to 95%) and with good to high
enantioselectivities (up to 96% ee). Interestingly, the most
significant observationis thatwhenthe Pd2þ (R)-NHC diaqua
complex was used for these reactions different absolute con-
figurations were observed compared to those obtained with
Pd2þ (R)-phosphane ligand diaqua catalysts.
t
(c 0.92, CHCl3). Yield: 98%.
major = 17.0 min, tminor = 15.1 min): 71% ee. [R]20D = -5.2°
Acknowledgment. Financial support from the Shanghai
Municipal Committee of Science and Technology (Nos.
06XD14005 and 08dj1400100-2), the National Basic Re-
search Program of China (No. 973-2010CB833302), and
the National Natural Science Foundation of China (Nos.
20902019, 20872162, 20672127, 20821002, 20732008, and
20702059) is greatly acknowledged, and we also thank
Mr. Jie Sun for performing X-ray diffraction studies.
Experimental Section
General Procedure for the Catalytic Enantioselective Addition
of β-Keto Ester 2a to Activated Olefins Using C2-Symmetric
Cationic Pd2þ N-Heterocyclic Carbene (NHC) Diaqua Com-
plexes. In a dried Schlenk tube, catalyst (0.01 mmol; 1a,
9.6 mg; 1b, 11 mg), activated olefins (0.4 mmol, 28-53 mg),
β-keto ester 2a (0.2 mmol, 37 mg), and 4A molecular sieves
Supporting Information Available: Text, figures, tables, and a
CIF file giving procedures for the synthesis of catalysts, experi-
mental details and characterization data, a plausible reaction
mechanism, chiral HPLC traces, and X-ray crystallographic
data for 4h. This material is available free of charge via the
Internet at http://pubs.acs.org.
(13) An open transition state was proposed as an important candi-
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