Chiral CNN pincer palladium(II) complexes with 2-aryl-6-(oxazolinyl) pyridine ligands: Synthesis, characterization, and application to enantioselective allylation of isatins and suzuki-miyaura coupling reaction

Article abstract of DOI:10.1021/om400945d

A series of chiral 2-aryl-6-(oxazolinyl)pyridine (aryl = phenyl or 1-naphthyl) ligands 2a-f were conveniently prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a-f with PdCl₂ in toluene in the presence of

Full text of DOI:10.1021/om400945d

Article
pubs.acs.org/Organometallics
Chiral CNN Pincer Palladium(II) Complexes with 2‑Aryl-6-
(oxazolinyl)pyridine Ligands: Synthesis, Characterization, and
Application to Enantioselective Allylation of Isatins and Suzuki−
Miyaura Coupling Reaction
Tao Wang, Xin-Qi Hao, Juan-Juan Huang, Kai Wang, Jun-Fang Gong,* and Mao-Ping Song*
College of Chemistry and Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Zhengzhou
University, Zhengzhou 450001, People’s Republic of China
S
* Supporting Information
ABSTRACT: A series of chiral 2-aryl-6-(oxazolinyl)pyridine (aryl = phenyl or 1-naphthyl) ligands 2a−f were conveniently
prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a−f with PdCl2 in toluene in the
presence of sodium bicarbonate afforded the corresponding CNN pincer Pd(II) complexes 3a−f via aryl C−H bond activation of
1
the related ligands. All of the new compounds have been fully characterized by elemental analysis (MS for ligands), H and 13
C
NMR, and IR spectra. In addition, the molecular structures of Pd(II) complexes 3c−f have been determined by X-ray single-
crystal diffraction. The obtained chiral pincer catalysts were successfully used in the asymmetric allylation of isatins with
allyltributyltin, giving the corresponding 3-allyl-3-hydroxyoxindoles in high yields with enantioselectivities of up to 86% ee. These
pincers could also catalyze the asymmetric Suzuki−Miyaura coupling reaction to provide the axially chiral biaryl products in good
yields with good stereoselectivities (up to 68% ee).
to 85% ee) as well as condensation of sulfonimines and
isocyanoacetate (up to 86% ee).2 The bis(phosphine) PCP
pincer Pd complexes bearing stereogenic benzylic methylene
centers readily catalyzed the enantioselective hydrophosphina-
tion of several kinds of electron-deficient alkenes with
diarylphosphines, giving the chiral phosphine derivatives with
excellent enantioselectivities.3 The pyrroloimidazolone-based
NCN pincer Pd complexes showed high levels of enantiose-
lectivities (up to 83% ee) in the Michael reaction between vinyl
ketones and α-cyanocarboxylates.4 The preliminary attempts
using the bis(imidazolinyl)phenyl (Phebim) NCN pincer
Pd(II) complexes, which were first reported by us, as the
catalysts for the asymmetric addition of diphenylphosphine to
chalcone afforded the expected adduct with up to 85% ee.5
During our study, Nakamura and co-workers6 also explored the
applications of similar Pd-Phebim complexes in several catalytic
INTRODUCTION
■
Palladium-catalyzed reactions have played key roles for the
synthesis of useful organic compounds in both academia and
industry. An important and fascinating subclass of palladium
catalysts are pincer palladium complexes, in which the
terdentate ligand coordinates to the Pd(II) center in a
meridional fashion through sigma and/or dative bonds to
form two stable five- or six-membered palladacycles. These
complexes have been found to be effective catalysts for
numerous catalytic reactions such as aldol reaction, Michael
addition, allylation of aldehydes and imines, and cross-coupling
reactions including Heck, Suzuki, and Sonogashira reactions.1
Further, the applications of chiral pincer Pd(II) complexes in
asymmetric catalytic reactions have attracted increasing
attention in recent years, and good to excellent stereocontrol
has been achieved. For example, the axially chiral 1,1′-bi-2-
naphthol- and 1,1′-biphenanthrol-based bis(phosphite) PCP
pincer Pd complexes displayed good stereoselectivities in
allylation of aldehydes (up to 62% ee) and sulfonimines (up
Received: September 22, 2013
Published: December 11, 2013
© 2013 American Chemical Society
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Scheme 1. Synthesis of Chiral CNN Pincer Pd(II) Complexes 3a−f with 2-Aryl-6-(oxazolinyl)pyridines
Figure 1. Molecular structures of the pincer Pd(II) complexes 3c (left) and 3d (right). Hydrogen atoms are omitted for clarity.
asymmetric reactions, providing excellent enantioselectivities in
all cases. In addition, Arai and co-workers demonstrated that
the related bis(imidazolidine) NCN pincer Pd complexes were
highly enantioselective catalysts for the reaction of nitroalkenes
with malononitriles (up to 93% ee).7 Besides symmetrical PCP
and NCN pincer Pd complexes, the unsymmetrical chiral PCN
pincer Pd complexes also exhibited high stereocontrol in
asymmetric catalysis. We recently developed a facile “one-pot
phosphorylation/metalation” method for the preparation of a
variety of achiral and chiral PCN pincer Pd(II) and Ni(II)
complexes.5b,8 It was found that the chiral PCN Pd pincers
containing aryl-based aminophosphine-imidazoline ligands
could catalyze the asymmetric addition of diphenylphosphine
to β-aryl enones, giving the corresponding phosphine
derivatives in high yields and enantioselectivities (up to 94%
ee).5b Despite the impressive progress made so far in the pincer
Pd-catalyzed enantioselective reactions, actually, much less
research has been done on chiral pincer Pd catalysts compared
with that on achiral ones. The development of new chiral
pincer Pd complexes with high catalytic activities and
stereoselectivities will still be important contributions to the
field of pincer chemistry. In a previous work, we reported the
achiral CNN pincer Pd complexes with N-substituted-2-
aminomethyl-6-phenylpyridine ligands, which were easily
synthesized from commercially available 6-bromo-2-picolinal-
dehyde in two steps. The Pd complexes were used as effective
catalysts for allylation of aldehydes as well as three-component
allylation of aldehydes, arylamines, and allyltributyltin.9 In order
to extend the chiral pincer Pd chemistry, and also in
continuation of our investigations on the pincer metal
complexes,10 herein we would like to describe the chiral
CNN pincer Pd(II) complexes based on 2-aryl-6-(oxazolinyl)-
pyridine ligands (aryl = phenyl or 1-naphthyl), which can also
be conveniently prepared by using 6-bromo-2-picolinaldehyde
as the starting material (Scheme 1). The synthesis and
characterization of the new chiral CNN pincer Pd catalysts as
well as their potential in the asymmetric allylation of isatins and
the Suzuki−Miyaura coupling reaction are presented below.
RESULTS AND DISCUSSION
■
Synthesis of 2-Aryl-6-(oxazolinyl)pyridines and the
Chiral CNN Pincer Pd(II) Complexes. The synthesis of the
required chiral ligands 2a−f was easily done in a two-step
sequence from commercially available 6-bromo-2-picolinalde-
hyde as shown in Scheme 1. First, the Suzuki coupling reaction
of 6-bromo-2-picolinaldehyde with phenylboronic acid or 1-
naphthylboronic acid in the presence of Pd(PPh3)4 in toluene
readily gave 6-aryl-2-picolinaldehyde 1. Then the aldehyde
group in compound 1 was directly converted to oxazolines by
reaction with various chiral amino alcohols including L-valinol,
L-tert-leucinol, L-phenylalaninol, L-phenylglycinol, and (1R,2S)-
2-amino-1,2-diphenylethanol, respectively, according to a
published procedure.11 The expected 2-aryl-6-(oxazolinyl)-
pyridines 2a−f were isolated in good yields (45−76%) after
purification. With the ligands in hand, the palladation was
carried out by refluxing the ligands 2a−f and PdCl2 in toluene
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Figure 2. Molecular structures of the pincer Pd(II) complexes 3e (left) and 3f (right). Hydrogen atoms and solvent molecules are omitted for clarity.
Table 1. Selected Bond Lengths (Å) and Angles (deg) for Complexes 3c−f
3c
3d
3e·(n-hexane)
(2 × 3f)·CH2Cl2
Pd(1)−C(1)
Pd(1)−N(1)
Pd(1)−N(2)
Pd(1)−Cl(1)
N(1)−Pd(1)−C(1)
N(1)−Pd(1)−N(2)
C(1)−Pd(1)−N(2)
N(1)−Pd(1)−Cl(1)
C(1)−Pd(1)−Cl(1)
N(2)−Pd(1)−Cl(1)
1.995(3)
1.975(3)
2.184(2)
2.3004(9)
81.28(11)
78.57(10)
159.84(11)
174.36(8)
97.84(9)
102.27(8)
2.004(7)
1.999(6)
2.202(5)
2.316(2)
81.2(3)
1.995(6)
1.981(6)
2.215(4)
2.292(2)
81.7(3)
1.981(4)
2.039(4)
2.110(3)
2.3218(15)
92.99(19)
81.37(15)
172.6(2)
77.5(2)
77.7(2)
158.5(3)
176.80(16)
97.3(2)
159.3(2)
177.85(18)
96.6(2)
167.24(11)
96.86(17)
89.44(12)
104.14(16)
104.05(15)
in the presence of sodium bicarbonate to afford the air- and
moisture-stable pincer complexes 3a−f in good yields (41−
55%).
(around 77°) are small, which are in accordance with pincers
consisting of two fused five-membered-ring palladacycles and
reflect a relative steric strain of the system. In contrast to
complexes 3c−e, complex 3f possesses one five-membered and
one six-membered palladacycle. It was interesting to find that
for ligand 2f the C-palladation occurred on the 8-position of
naphthyl instead of the 2-position to afford complex 3f. If the
palladation occurred on the 2-position, two fused five-
membered palladacycles would be formed. The reason for the
outcome was possibly due to the higher electron density of the
8-position. In comparison with 3c−e, complex 3f has obviously
different bond angles around the Pd(II) center (Table 1). The
significantly bigger C(1)−Pd(1)−N(2) (around 173° vs 159°)
angle in complex 3f suggests that introduction of a larger
metallacycle decreases the steric strain of the resultant complex.
Similarly to the related CNN Pd complexes,9,12 the Pd−N(2)
bond length in complexes 3c−f is also longer than that of Pd−
N(1), which can be attributed to the higher trans influence of
the metalated carbanion compared to the chloride ligand.
Allylation of Isatins. Enantioenriched 3-substituted 3-
hydroxyoxindoles are important structural motifs for a large
number of natural products and drug candidates.13 In
particular, 3-allyl-3-hydroxyoxindoles are very useful because
the double bond in the allyl group provides a functional handle
for further transformations.14 As a consequence, development
of practical methods for their preparation is of much interest.
Several strategies including asymmetric hydroxylation of 3-allyl-
2-oxindoles15 and asymmetric allylation of isatins16 have been
reported in the literature. Although the metal-catalyzed
allylation of isatins is the most direct method, only a few
metal catalysts have afforded high to excellent enantioselecti-
vities.16f,h−j For example, the highest ee value was only 71%
when chiral palladium-phosphoramidite complexes were used
as the catalysts for the allylation of isatins with allylboron,
which was generated in situ from allylic alcohol and excess
triethylborane.16e In the present study, we found that the
All of the chiral CNN pincer Pd complexes were fully
1
characterized by elemental analysis, H NMR, 13C NMR, and
1
IR spectra. In comparison with the H NMR spectra of the
corresponding ligands 2a−f, one of the resonances in the
downfield region (around 7−9 ppm) due to the aromatic
protons in the Pd complexes 3a−f is absent, indicating the
occurrence of C-palladation of the phenyl or naphthyl ring, and
the signals of the oxazoline protons obviously shift downfield
due to coordination of oxazoline-N to the Pd center. The 13C
NMR spectra also show some evidence for the formation of
pincer complexes. For example, four carbon signals are found
for the 2-phenyl group in the ligands 2a−e, while six carbon
signals correspond to the 2-phenyl group in the pincer Pd
complexes 3a−e. Further, a new quarternary C-signal appears
at around 153 ppm, which is assigned to the orthometalated
carbon atom.
Molecular Structures of the Chiral CNN Pincer Pd(II)
Complexes. The molecular structures of pincer Pd complexes
3c−f were unambiguously determined by X-ray single-crystal
analysis. The molecules are illustrated in Figures 1 and 2,
respectively. Selected bond lengths and bond angles are listed
in Table 1. The Pd(II) center in each complex adopts a
distorted-square-planar configuration with the pincer ligand
coordinated to the metal via the pendant phenyl- or naphthyl-
C, pyridine-N, and oxazoline-N in a terdentate manner and the
chloride ligand occupying the fourth coordination site. In the
Pd complexes 3c−e the two formed palladacycles are both five-
membered rings, which are approximately coplanar with the
central pyridine ring. All of the bond lengths and angles around
the Pd(II) center in the three complexes are similar. The values
of bond lengths and angles are comparable to those in the
related achiral CNN Pd complexes.9,12 The N(1)−Pd(1)−
C(1) angles (around 81°) and N(1)−Pd(1)−N(2) angles
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obtained chiral CNN pincer Pd complexes could exhibit high
enantioselectivities in the enantioselective allylation of isatins
with allyltributyltin as the nucleophilic allyl source. The
experiments began with allylation of N-benzylisatin (4a) as
the model reaction, which was carried out in the presence of 5
mol % of Pd complex in ClCH2CH2Cl (DCE) at room
temperature for 2 h. Under the stated conditions, all of the six
complexes 3a−f produced the expected 3-allyl-3-hydroxyox-
indole 6a in excellent yields. However, the enantioselectivities
of 6a were found to be only moderate in all cases (Table 2,
with decreased reaction temperature, and excellent yields were
still achieved after 12 h (entries 7−9). For example, a 96% yield
with 58% ee was obtained using complex 3b as the catalyst at
−20 °C (entry 9). When the temperature was further lowered
to −40 °C, a decrease in the enantioselectivitity was observed
(45% ee, entry 10). The possible reason for the outcome was
that the DCE solvent solidified at this temperature. Pleasingly, a
95% yield with 71% ee was achieved when the solvent was
changed to CH2Cl2, which has a much lower freezing point
than DCE (entry 11). Then several other solvents including
CHCl3, CH3CN, and THF were also tested at −40 °C, and
none of them gave better enantioselectivities than CH2Cl2
(entry 12−14). With CH2Cl2 as the solvent, the temperature
was further lowered to −60 °C and the ee value could be
improved to 78% without loss of activity (entry 15). When the
reaction was conducted at −70 °C, the enantioselectivity was
not enhanced further (entry 16), and a reduction in the catalyst
loading from 5 mol % to 3 mol % led to decreased yield and
enantioselectivity (entry 17). Allylation of N-benzylisatin (4a)
with allyltrimethyl- or allyltrimethoxysilane as the allyl source
was also tried. No reaction occurred at −60 °C or even at room
temperature in CH2Cl2 with 5 mol % of complex 3b as the
catalyst (data not shown in Table 2). In the presence of one
equivalent of AgF6d as an additive, reaction of 4a with
allyltrimethylsilane at room temperature could afford the
product in a 50% yield wth only 15% ee (entry 18). A 46%
yield wth 59% ee was obtained when the same reaction was
conducted at −60 °C (entry 19). Another additive such as
AgOAc, AgOTf, or AgBF4 was found to be ineffective for the
reaction at this temperature (data not shown), and changing
the solvent from CH2Cl2 to THF gave a racemic product (entry
20). The use of allyltrimethoxysilane as the allyl source did not
provide better enantioselectivites either (entries 21 and 22).
Thus, the optimized conditions for the allylation of isatin
include using 5 mol % of complex 3b as the catalyst and
allyltributyltin as the allyl source in CH2Cl2 at −60 °C for 12 h
(entry 15). In addition, the allylation of a ketimine derived from
4a under similar reaction conditions was briefly investigated.
The reaction proceeded much more slowly than that of 4a, and
the best ee value achieved was 72% (Scheme 2, more results on
this reaction are given in the Supporting Information).
Table 2. Optimization of Reaction Conditions for the
Asymmetric Allylation of N-Benzylisatin Catalyzed by the
a
Chiral CNN Pincer Pd(II) Complexes 3
b
cd
,
entry cat. allyl source
solvent
temp (°C) yield (%) ee (%)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
5b
5b
5c
5c
DCE
RT
96
98
93
97
95
91
97
95
96
92
95
98
87
97
94
91
88
50
46
40
82
80
32
35
30
29
36
24
50
51
58
45
71
63
42
44
78
77
68
15
59
0
DCE
RT
DCE
RT
DCE
RT
DCE
RT
DCE
RT
e
e
e
3b
3e
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
DCE
0
DCE
0
DCE
−20
−40
−40
−40
−40
−40
−60
−70
−70
RT
e
e
e
e
e
e
e
10
11
12
13
14
15
16
17
18
19
20
21
22
DCE
CH2Cl2
CHCl3
CH3CN
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
ef
,
eg
,
eg
,
−60
−60
−60
−60
eg
,
eg
,
CH2Cl2
THF
10
24
With the optimal conditions established, allylation of other
isatins was investigated (Table 3). In all cases, the
corresponding 3-allyl-3-hydroxyoxindole products were isolated
in high yields (89−95%). The enantioselectivities of the
products were generally good and found to be influenced by
the N-protecting group and substituent on the isatins. For
example, N-(p-methylbenzyl)- and N-(o-methylbenzyl)isatin
afforded comparable enantioselectivities (6b and 6c) to that of
N-benzylisatin, and a slightly increased enantioselectivity was
obtained for N-methylisatin (82% ee, 6e). However, when 1-
naphthylmethyl and particularly trityl (Tr) were used as the N-
protecting group, the ee values decreased (6f and 6g). The
eg
,
a
Reaction conditions: 4a (0.20 mmol), 5 (0.30 mmol), cat. 3 (5 mol
b
c
%), solvent (1 mL), 2 h. Isolated yields. Determined by chiral
HPLC. The absolute configuration of the product was assigned to be
S by comparison of the optical rotation with that in ref 16f. 12 h. cat.
3b (3 mol %). In the presence of AgF (0.20 mmol) as an additive.
d
e
f
g
entries 1−6). Among them, complex 3b, with (4S)-tert-butyl,
and 3e, with (4S,5R)-4,5-diphenyl substituents, gave relatively
higher enantioselectivities (35% and 36% ee, respectively,
entries 2 and 5). The enantioselectivities could be improved
Scheme 2. Asymmetric Allylation of a Ketimine Derived from N-Benzylisatin Catalyzed by the Chiral CNN Pincer Pd(II)
Complex 3e
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a
Table 3. Substrate Scope for the Asymmetric Allylation of Isatins Catalyzed by the Chiral CNN Pincer Pd(II) Complex 3b
a
Reaction conditions: 4 (0.20 mmol), allyltributyltin (0.30 mmol), cat. 3b (5 mol %), CH2Cl2 (1 mL), −60 °C, 12 h. Yields are isolated yields, and
the ee values were determined by chiral HPLC. The absolute configurations of the known products were assigned to be S by comparison of optical
rotations with those in refs 16f and i, and the configurations of the new products were assigned by analogy.
isatin without an N-protecting group also gave a reduced ee
value of 60% (6d). In this case, allylation at nitrogen was not
observed, which was in contrast to the chiral palladium-
phosphoramidite catalyst.16e In comparison with the related N-
protected unsubstituted isatins (78−82% ee, 6a, 6b, and 6e), an
electron-donating group such as 5-Me on isatin showed some
beneficial effect on the enantioselectivities of the catalysis
products (83−86% ee, 6j, 6k, and 6l), while an electron-
withdrawing group such as 6-Br displayed slightly inferior
stereocontrol (6r and 6s). Other substituent such as 4-Br, 5-
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MeO, 5-F, 5-Cl, 5-Br, and 7-Br gave comparable results (6h, 6i,
6m−6q, 6t, and 6u).
isolated in a 85% yield with 43% ee after 24 h (entry 1). When
K2CO3 as the base was used, the yield drastically decreased
while the enantioselectivity improved (47% yield with 52% ee,
entry 2). Other bases afforded rather low ee values or trace
amounts of product (entries 3−5). Lowering the reaction
temperature from 80 °C to 50 °C could not give better
enantioselectivity (entry 6 vs entry 1). Since K2CO3 produced a
relatively higher ee, it was selected as the base in the following
experiments. By prolonging the reaction time to 48 h the
product 9a was obtained in a 71% yield with 50% ee (entry 7 vs
entry 2). Then the other five pincer Pd complexes 3a,b and
3d−f were examined, and all of them gave inferior
enantioselectivities (31−48% ee, entries 8−12). Therefore,
the optimized conditions include using complex 3c as the
catalyst with K2CO3 base at 80 °C for 48 h (entry 7). We next
explored the substrate scope. As shown in Table 5, the coupling
reaction of 1-iodo-2-ethoxynaphthalene and 1-iodo-2-benzylox-
ynaphthalene provided comparable results to that of 1-iodo-2-
methoxynaphthalene with 1-naphthaleneboronic acid (9a−9c),
and the coupling of these iodides with 2-methyl or 2-
phenylbenzeneboronic acid gave only low enantioselectivities
(21−29% ee) although excellent yields could be achieved (9d−
9g). When 1-pyreneboronic acid was used as the coupling
partner, moderate enantioselectivities were obtained (9h and
9i, 39% and 43% ee, respectively). Finally, the coupling of 9-
phenanthreneboronic acid with the aforementioned iodides
afforded good enantioselectivities (62−68% ee, 9j−9l).
Asymmetric Suzuki−Miyaura Coupling Reaction. The
cross-coupling of organic halides and organoboron reagents,
known as the Suzuki−Miyaura coupling, is one of the most
efficient methods to create carbon−carbon bonds and thus has
found widespread applications in organic synthesis.17 Although
the reaction has been widely utilized for the synthesis of achiral
biaryl compounds, there are relatively few reports to date
dealing with asymmetric biaryl synthesis involving Suzuki−
Miyaura cross-coupling reactions. Among them, most of the
examples concern the use of chiral palladium-phosphine
complexes as catalysts, giving axially chiral biaryl compounds
with enantioselectivities from moderate to high.18 Recently, C2-
symmetric bis-hydrazones19 and ADCs (acyclic diaminocar-
benes)20 appear as new, phosphine-free chiral ligands for this
reaction, and the first palladium-diene-catalyzed asymmetric
Suzuki−Miyaura coupling reaction has been achieved by the
research group of Lin.21 In addition, the chiral pincer Pd(II)
complexes including the NCN complexes with bis(oxazolinyl)-
phenyl (Phebox) ligands22 and PCN complexes with
(imidazolinyl)aryl phosphinite ligands8c have also been used
as catalysts for the coupling. Overall, the obtained enantiomeric
excesses by the above pincer catalysts are rather modest (<49%
ee). Thus, we wonder whether the present CNN pincer Pd
complexes can behave better in the reaction. In the beginning
the coupling of 1-iodo-2-methoxynaphthalene with 1-naph-
thaleneboronic acid was chosen as a model to optimize the
reaction conditions. The results are shown in Table 4. It was
found that in the presence of 5 mol % of complex 3c with
K3PO4 as the base the corresponding biaryl product 9a was
CONCLUSION
■
In summary, six new chiral CNN pincer Pd(II) complexes
based on 2-aryl-6-(oxazolinyl)pyridine ligands have been
conveniently synthesized and well characterized. These
complexes have been utilized as the catalysts for the
enantioselective allylation of various isatins with allyltributyltin,
producing the corresponding 3-allyl-3-hydroxyoxindoles in high
yields with enantioselectivities of up to 86% ee. In addition,
they are also found to be effective catalysts for the asymmetric
Suzuki−Miyaura reaction of 1-iodo-2-alkoxynaphthalenes with
several kinds of arylboronic acids, giving the axially chiral biaryl
products in good yields with good enantioselectivities (up to
68% ee).
Table 4. Optimization of Reaction Conditions for
Asymmetric Suzuki−Miyaura Reaction of 1-Iodo-2-
methoxynaphthalene with 1-Naphthaleneboronic Acid
a
Catalyzed by the Chiral CNN Pincer Pd(II) Complexes 3
EXPERIMENTAL SECTION
■
General Procedures. Solvents were dried with standard methods
and freshly distilled prior to use if needed. 1-Iodo-2-methoxynaph-
thalene, 1-iodo-2-ethoxynaphthalene, and 1-iodo-2-benzyloxynaphtha-
lene,23 arylboronic acid,24 and isatins16d were prepared according to
the literature methods. All other chemicals were used as purchased.
Melting points were measured on an XT4A melting point apparatus
and are uncorrected. IR spectra were collected on a Bruker
VECTOR22 spectrophotometer in KBr pellets. 1H and 13C NMR
spectra were recorded on a Bruker DPX 400 instrument using TMS as
an internal standard. Mass spectra were performed on an 1100 LC/
MSD Trap XCT System ESI spectrometer. HRMS were determined
on a Waters Q-Tof Micro MS/MS System ESI spectrometer.
Elemental analyses were measured on a Thermo Flash EA 1112
elemental analyzer. Optical rotations were recorded on a Perkin-Elmer
341 polarimeter.
b
cd
,
entry
cat.
base
yield (%)
ee (%)
1
2
3
4
5
3c
3c
3c
3c
3c
3c
3c
3a
3b
3d
3e
3f
K3PO4
K2CO3
Cs2CO3
Na2CO3
KOAc
85
43
52
7
47
27
e
trace
trace
30
n.d.
n.d.
e
f
6
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
41
g
7
71
50
45
32
31
48
44
g
8
g
69
9
76
g
10
73
g
11
78
g
12
72
Synthesis of 6-Aryl-2-Picolinaldehyde 1. The compounds 1
were prepared according to the procedure reported previously by us.9
The analytical data of the new compound 1b are given as follows.
6-(Naphthalen-1-yl)-2-picolinaldehyde (1b). Orange oil (205.3
mg, 88%). IR (KBr): ν 3053, 2827, 1709, 1582, 1509, 1450, 1394,
a
Reaction conditions: 7a (0.30 mmol), 8a (0.20 mmol), base (1.0
b
mmol), cat. 3 (5 mol %), DCE (2 mL), 80 °C, 24 h. Isolated yields.
c
d
Determined by chiral HPLC. The absolute configuration of the
product was assigned to be S by comparison of the optical rotation
e
f
g
1
with that in refs 8c and 19. Not determined. At 50 °C. Reaction
1211, 1156, 985, 880, 792, 737, 715, 635, 564, 504 cm−1. H NMR
time: 48 h.
(400 MHz, CDCl3): δ 10.18 (s, 1H, CHO), 8.05−7.92 (m, 5H, ArH),
199
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Table 5. Substrate Scope for the Catalytic Asymmetric Suzuki−Miyaura Reaction Using the Chiral CNN Pincer Pd(II) Complex
a
3c as the Catalyst
a
Reaction conditions: 7 (0.30 mmol), 8 (0.20 mmol), K2CO3 (1.0 mmol), cat. 3c (5 mol %), DCE (2 mL), 80 °C, 48 h. Yields are isolated yields,
and the ee values were determined by chiral HPLC. The absolute configurations of the known products 9a−d were assigned to be S and that of 9g
was assigned to be R by comparison of optical rotations with those in refs 8c and 19. The absolute configurations of the new products were assigned
by analogy.
7.80 (dd, J = 1.7, 7.1 Hz, 1H, ArH), 7.64 (dd, J = 1.2, 7.0 Hz, 1H,
ArH), 7.60−7.56 (m, 1H, ArH), 7.55−7.47 (m, 2H, ArH). 13C NMR
(100 MHz, CDCl3): δ 193.8, 160.0, 152.7, 137.5, 137.2, 134.0, 131.0,
129.6, 129.3, 128.6, 127.8, 126.8, 126.2, 125.4, 125.2, 119.9. MS
(positive ESI; m/z): 255.2 [M + Na]+.
147.0, 138.8, 137.2, 129.2, 128.7, 127.2, 122.5, 122.3, 72.9, 70.8, 32.8,
19.1, 18.2. MS (positive ESI; m/z): 267.7 [M + H]+, 289.6 [M + Na]+,
305.5 [M + K]+.
(S)-4-(tert-Butyl)-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole
(2b). White solid (199.1 mg, 71%). Mp: 81−83 °C. [α]20D = −0.085 (c
0.120, CH2Cl2). IR (KBr): ν 2954, 2902, 2867, 1640, 1589, 1577,
1566, 1476, 1459, 1449, 1360, 1345, 1267, 1244, 1114, 1090, 1058,
1026, 991, 959, 919, 829, 772, 747, 724, 695, 673 cm−1. 1H NMR (400
MHz, CDCl3): δ 8.08 (dd, J = 2.4, 6.4 Hz, 1H, ArH), 8.05−8.03 (m,
2H, ArH), 7.85−7.80 (m, 2H, ArH), 7.49−7.45 (m, 2H, ArH), 7.43−
7.40 (m, 1H, ArH), 4.49 (dd, J = 8.8, 10.2 Hz, 1H, OxH), 4.35 (app t,
J = 8.4 Hz, 1H, OxH), 4.14 (dd, J = 8.3, 10.2 Hz, 1H, OxH), 0.99 (s,
9H, C(CH3)3). 13C NMR (100 MHz, CDCl3): δ 162.9, 157.5, 147.0,
138.8, 137.2, 129.2, 128.8, 127.2, 122.6, 122.3, 76.4, 69.4, 34.0, 26.0.
MS (positive ESI; m/z): 281.1 [M + H]+, 303.1 [M + Na]+.
(S)-4-Phenyl-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole (2c).
General Procedure for the Synthesis of 2-Aryl-6-
(oxazolinyl)pyridines 2a−f. To a solution of 1a (183.1 mg, 1.0
mmol) [or 1b (233.1 mg, 1.0 mmol)] in t-BuOH (15 mL) was added
the corresponding chiral amino alcohol (1.1 mmol). The mixture was
stirred at room temperature under a N2 atmosphere for 2 h, and
K2CO3 (414.6 mg, 3.0 mmol) and I2 (507.6 mg, 2.0 mmol) were
added to the mixture and stirred at 70 °C. After 16 h, the mixture was
quenched with saturated aqueous Na2SO3 until the color of iodine
almost disappeared and was extracted with CH2Cl2. The organic layer
was washed with brine, dried over Na2SO4, filtered, and evaporated.
The residue was purified by preparative TLC on silica gel plates to
afford the corresponding ligands 2a−f.
White solid (204.2 mg, 68%). Mp: 95−97 °C. [α]20 = −0.175 (c
D
(S)-4-Isopropyl-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole (2a).
0.140, CH2Cl2). IR (KBr): ν 3028, 2912, 1634, 1590, 1580, 1566,
White solid (194.4 mg, 73%). Mp: 84−86 °C. [α]20 = −0.094 (c
1475, 1460, 1449, 1368, 1323, 1245, 1116, 1084, 1065, 1027, 958, 908,
D
1
0.130, CH2Cl2). IR (KBr): ν 2975, 2956, 1635, 1588, 1470, 1457,
767, 737, 703, 686, 672, 623, 616, 547 cm−1. H NMR (400 MHz,
1371, 1360, 1266, 1245, 1110, 1064, 1045, 963, 923, 833, 770, 750,
CDCl3): δ 8.15−8.12 (m, 1H, ArH), 8.11−8.07 (m, 2H, ArH), 7.84−
7.82 (m, 2H, ArH), 7.49−7.41 (m, 3H, ArH), 7.38−7.33 (m, 4H,
ArH), 7.31−7.26 (m, 1H, ArH), 5.46 (dd, J = 8.6, 10.2 Hz, 1H, OxH),
4.91 (dd, J = 8.6, 10.2 Hz, 1H, OxH), 4.40 (app t, J = 8.5 Hz, 1H,
OxH). 13C NMR (100 MHz, CDCl3): δ 164.1, 157.5, 146.6, 141.9,
138.6, 137.3, 129.2, 128.7, 127.6, 127.1, 126.8, 122.6, 122.5, 75.3, 70.2.
MS (positive ESI; m/z): 301.1 [M + H]+.
1
743, 723, 698, 673, 624 cm−1. H NMR (400 MHz, CDCl3): δ 8.03−
8.00 (m, 3H, ArH), 7.81−7.77 (m, 2H, ArH), 7.47−7.37 (m, 3H,
ArH), 4.52 (dd, J = 8.2, 9.4 Hz, 1H, OxH), 4.23 (app t, J = 8.2 Hz, 1H,
OxH), 4.17 (dd, J = 6.2, 9.3 Hz, 1H, OxH), 1.94−1.86 (m, 1H,
CH(CH3)2), 1.06 (d, J = 6.8 Hz, 3H, CH3CHCH3), 0.94 (d, J = 6.8
Hz, 3H, CH3CHCH3). 13C NMR (100 MHz, CDCl3): δ 162.9, 157.5,
200
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(S)-4-Benzyl-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole (2d).
124.9, 124.0, 120.8, 120.2, 73.1, 72.7, 34.6, 26.2. Anal. Calcd for
C18H19ClN2OPd (421.23): C, 51.32; H, 4.55; N, 6.65. Found: C,
51.44; H, 4.50; N, 6.49.
White solid (238.9 mg, 76%). Mp: 105−107 °C. [α]20 = −0.051 (c
D
0.110, CH2Cl2). IR (KBr): ν 3029, 2930, 2893, 1645, 1577, 1567,
1472, 1461, 1451, 1434, 1369, 1245, 1162, 1116, 1088, 1069, 1023,
962, 865, 787, 777, 744, 719, 701, 671, 619, 502 cm−1. 1H NMR (400
MHz, CDCl3): δ 8.05−8.01 (m, 3H, ArH), 7.82−7.81 (m, 2H, ArH),
7.48−7.41 (m, 3H, ArH), 7.35−7.29 (m, 2H, ArH), 7.27−7.21 (m,
3H, ArH), 4.71−4.63 (m, 1H, OxH), 4.45 (app t, J = 9.0 Hz, 1H,
OxH), 4.26 (app t, J = 8.0 Hz, 1H, OxH), 3.32 (dd, J = 5.0, 13.7 Hz,
1H, CHHPh), 2.77 (dd, J = 9.2, 13.7 Hz, 1H, CHHPh). 13C NMR
(100 MHz, CDCl3): δ 163.5, 157.6, 146.8, 138.7, 137.9, 137.4, 129.3,
128.8, 128.6, 127.2, 126.6, 122.49, 122.45, 72.5, 68.2, 41.8. MS
(positive ESI; m/z): 315.1 [M + H]+, 337.1 [M + Na]+.
[(S)-4-Phenyl-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole]-
palladium(II) Chloride (3c). Orange solid (45.9 mg, 52%). Mp: 297−
299 °C. [α]20 = +0.457 (c 0.130, CH2Cl2). IR (KBr): ν 3036, 1584,
D
1466, 1454, 1422, 1385, 1355, 1327, 1277, 1247, 1235, 1190, 1156,
1069, 1025, 1002, 936, 925, 820, 770, 750, 728, 697, 617, 553, 453
1
cm−1. H NMR (400 MHz, d6-DMSO): δ 8.21−8.14 (m, 2H, ArH),
7.72 (dd, J = 1.5, 7.0 Hz, 1H, ArH), 7.66 (dd, J = 1.8, 7.4 Hz, 1H,
ArH), 7.51−7.48 (m, 3H, ArH), 7.43−7.39 (m, 2H, ArH), 7.37−7.32
(m, 1H, ArH), 7.14−7.06 (m, 2H, ArH), 5.49 (dd, J = 6.6, 10.2 Hz,
1H, OxH), 5.23 (dd, J = 8.9, 10.2 Hz, 1H, OxH), 4.77 (dd, J = 6.7, 8.8
Hz, 1H, OxH). 13C NMR (100 MHz, d6-DMSO): δ 167.8, 164.4,
152.6, 146.0, 143.0, 140.5, 139.7, 135.7, 129.9, 128.5, 127.8, 127.1,
124.84, 124.78, 122.1, 121.5, 78.2, 65.8. Anal. Calcd for
C20H15ClN2OPd (441.22): C, 54.44; H, 3.43; N, 6.35. Found: C,
54.44; H, 3.32; N, 6.15.
(4S,5R)-4,5-Diphenyl-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole
(2e). White solid (169.4 mg, 45%). Mp: 128−131 °C. [α]20D = −0.225
(c 0.110, CH2Cl2). IR (KBr): ν 3353, 3029, 2930, 1649, 1582, 1565,
1525, 1497, 1448, 1383, 1238, 1167, 1022, 827, 751, 701, 688, 627,
1
618, 566, 529 cm−1. H NMR (400 MHz, CDCl3): δ 8.22−8.18 (m,
1H, ArH), 8.14−8.12 (m, 2H, ArH), 7.94−7.89 (m, 2H, ArH), 7.50−
7.41 (m, 3H, ArH), 7.08−7.01 (m, 8H, ArH), 6.99−6.96 (m, 2H,
ArH), 6.14 (d, J = 10.2 Hz, 1H, OxH), 5.84 (d, J = 10.2 Hz, 1H, OxH).
13C NMR (100 MHz, CDCl3): δ 164.6, 157.7, 146.7, 138.6, 137.5,
[(S)-4-Benzyl-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole]-
palladium(II) Chloride (3d). Orange solid (50.0 mg, 55%). Mp: 233−
234 °C. [α]20 = +0.241 (c 0.100, CH2Cl2). IR (KBr): ν 3023, 2942,
D
1636, 1586, 1497, 1463, 1455, 1436, 1422, 1385, 1312, 1269, 1242,
1190, 1151, 1117, 1068, 1024, 942, 869, 808, 763, 733, 724, 696, 638,
137.4, 136.4, 129.4, 128.8, 128.0, 127.7, 127.4, 127.3, 127.1, 126.5,
122.8, 122.6, 85.9, 74.7. MS (positive ESI; m/z): 377.2 [M + H]+.
(S)-4-Phenyl-2-(6-(naphthalen-1-yl)pyridin-2-yl)-4,5-dihydrooxa-
zole (2f). White solid (217.3 mg, 62%). Mp: 56−58 °C. [α]20D = −105
(c 0.130, CH2Cl2). IR (KBr): ν 3381, 3057, 2920, 1637, 1566, 1509,
1
580, 450 cm−1. H NMR (400 MHz, CDCl3): δ 7.62−7.55 (m, 2H,
ArH), 7.34 (d, J = 8.4 Hz, 3H, ArH), 7.29−7.26 (m, 2H, ArH), 7.23−
7.19 (m, 1H, ArH), 7.16−7.13 (m, 1H, ArH), 7.08 (d, J = 7.6 Hz, 1H,
ArH), 7.04−6.97 (m, 2H, ArH), 4.97−4.89 (m, 2H, OxH), 4.50−4.43
(m, 1H, OxH), 3.48 (dd, J = 2.8, 14.0 Hz, 1H, CHHPh), 3.08 (dd, J =
7.7, 14.0 Hz, 1H, CHHPh). 13C NMR (100 MHz, CDCl3): δ 167.3,
165.1, 153.5, 145.6, 143.6, 138.7, 136.3, 136.1, 130.4, 129.8, 128.6,
126.8, 124.6, 123.8, 120.4, 120.1, 75.1, 64.7, 39.4. Anal. Calcd for
C21H17ClN2OPd (455.25): C, 55.40; H, 3.76; N, 6.15. Found: C,
55.42; H, 3.68; N, 5.93.
1
1450, 1363, 1249, 1108, 1080, 992, 950, 801, 778, 699, 622 cm−1. H
NMR (400 MHz, CDCl3): δ 8.27 (dd, J = 0.9, 7.8 Hz, 1H, ArH),
8.05−8.03 (m, 1H, ArH), 7.95−7.90 (m, 3H, ArH), 7.71 (dd, J = 0.9,
7.8 Hz, 1H, ArH), 7.66 (dd, J = 1.1, 7.0 Hz, 1H, ArH), 7.58−7.54 (m,
1H, ArH), 7.51−7.46 (m, 2H, ArH), 7.40−7.35 (m, 4H, ArH), 7.33−
7.28 (m, 1H, ArH), 5.48 (dd, J = 8.6, 10.2 Hz, 1H, OxH), 4.91 (dd, J =
8.6, 10.3 Hz, 1H, OxH), 4.40 (app t, J = 8.6 Hz, 1H, OxH). 13C NMR
(100 MHz, CDCl3): δ 164.3, 159.3, 146.7, 142.0, 137.9, 136.9, 133.9,
131.3, 129.1, 128.8, 128.4, 127.83, 127.76, 127.3, 126.9, 126.6, 125.9,
125.4, 125.3, 122.8, 75.5, 70.3. MS (positive ESI; m/z): 351.1 [M +
H]+.
[(4S,5R)-4,5-Diphenyl-2-(6-phenylpyridin-2-yl)-4,5-
dihydrooxazole]palladium(II) Chloride (3e). Orange solid (42.4 mg,
41%). Mp: 279−281 °C. [α]20 = +0.235 (c 0.100, CH2Cl2). IR
D
(KBr): ν 3032, 1580, 1495, 1454, 1419, 1379, 1341, 1316, 1286, 1208,
1187, 1156, 1117, 1068, 1023, 952, 812, 766, 739, 725, 696, 654, 636,
1
600, 584, 454 cm−1. H NMR (400 MHz, CDCl3): δ 7.67−7.63 (m,
General Procedure for the Synthesis of CNN Pincer
Chloropalladium(II) Complexes 3a−f. To a stirred solution of
2a−f (0.20 mmol) and sodium bicarbonate (33.6 mg, 0.40 mmol) in
toluene (15 mL) was added PdCl2 (42.2 mg, 0.24 mmol) under a N2
atmosphere, and the reaction mixture was refluxed for 16 h. After
cooling, filtration, and evaporation, the residue was purified by
preparative TLC on silica gel plates to afford the corresponding chiral
CNN pincer palladium complexes 3a−f.
2H, ArH), 7.41 (d, J = 7.8 Hz, 1H, ArH), 7.32 (d, J = 7.6 Hz, 1H,
ArH), 7.20−7.16 (m, 1H, ArH), 7.10−7.05 (m, 6H, ArH), 7.02−7.00
(m, 4H, ArH), 6.95−6.93 (m, 2H, ArH), 6.57 (d, J = 10.4 Hz, 1H,
OxH), 6.02 (d, J = 10.4 Hz, 1H, OxH). 13C NMR (100 MHz, CDCl3):
δ 168.2, 165.2, 153.1, 145.4, 143.8, 138.7, 136.6, 134.8, 134.1, 130.6,
128.3, 127.9, 127.8, 127.5, 126.9, 124.6, 123.8, 120.52, 120.46, 89.7,
70.9. Anal. Calcd for C26H19ClN2OPd (517.31): C, 60.37; H, 3.70; N,
5.42. Found: C, 60.34; H, 3.69; N, 5.26.
[(S)-4-Isopropyl-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole]-
palladium(II) Chloride (3a). Orange solid (38.2 mg, 47%). Mp: 291−
[(S)-4-Phenyl-2-(6-(naphthalen-1-yl)pyridin-2-yl)-4,5-
dihydrooxazole]palladium(II) chloride (3f). Orange solid (49.2 mg,
50%). Mp: 225−227 °C. [α]20D = +638 (c 0.104, CH2Cl2). IR (KBr):
ν 3044, 1656, 1594, 1493, 1467, 1440, 1418, 1379, 1353, 1325, 1266,
293 °C. [α]20 = +0.166 (c 0.120, CH2Cl2). IR (KBr): ν 2966, 2926,
D
2872, 1577, 1470, 1454, 1417, 1383, 1372, 1337, 1308, 1268, 1187,
1
1109, 1018, 938, 921, 815, 763, 742, 723, 706 cm−1. H NMR (400
1
1185, 1158, 922, 808, 765, 732, 695, 543 cm−1. H NMR (400 MHz,
MHz, CDCl3): δ 7.72−7.68 (m, 2H, ArH), 7.46−7.43 (m, 1H, ArH),
7.27−7.25 (m, 1H, ArH), 7.22−7.20 (m, 1H, ArH), 7.08−7.00 (m,
2H, ArH), 4.82 (dd, J = 8.2, 9.6 Hz, 1H, OxH), 4.57−4.47 (m, 2H,
OxH), 2.61−2.53 (m, 1H, CH(CH3)2), 0.97 (d, J = 6.8 Hz, 3H,
CH3CHCH3), 0.93 (d, J = 6.8 Hz, 3H, CH3CHCH3). 13C NMR (100
MHz, CDCl3): δ 166.5, 165.2, 152.8, 145.2, 143.4, 138.5, 136.3, 130.4,
124.5, 123.6, 120.3, 119.8, 71.7, 68.7, 29.4, 18.8, 15.2. Anal. Calcd for
C17H17ClN2OPd (407.20): C, 50.14; H, 4.21; N, 6.88. Found: C,
50.33; H, 4.19; N, 6.64.
[(S)-4-(tert-Butyl)-2-(6-phenylpyridin-2-yl)-4,5-dihydrooxazole]-
palladium(II) Chloride (3b). Orange solid (40.4 mg, 48%). Mp: >300
°C. [α]20D = +0.298 (c 0.110, CH2Cl2). IR (KBr): ν 2963, 2868, 1584,
1462, 1415, 1380, 1366, 1283, 1260, 1242, 1182, 1118, 1068, 1022,
951, 918, 819, 765, 748, 728, 711, 690, 636 cm−1. 1H NMR (400 MHz,
CDCl3): δ 7.83 (t, J = 7.8 Hz, 2H, ArH), 7.60 (d, J = 8.2 Hz, 1H,
ArH), 7.38 (d, J = 7.6 Hz, 1H, ArH), 7.30 (dd, J = 1.8, 7.3 Hz, 1H,
ArH), 7.13−7.05 (m, 2H, ArH), 4.73−4.64 (m, 2H, OxH), 4.17 (dd, J
= 5.2, 9.6 Hz, 1H, OxH), 1.07 (s, 9H, C(CH3)3). 13C NMR (100
MHz, CDCl3): δ 166.8, 165.3, 151.5, 145.2, 143.5, 138.9, 137.0, 130.8,
d6-DMSO): δ 8.80 (d, J = 8.0 Hz, 1H, ArH), 8.51 (d, J = 7.3 Hz, 1H,
ArH), 8.44−8.39 (m, 2H, ArH), 8.11 (d, J = 8.2 Hz, 2H, ArH), 7.71
(d, J = 7.2 Hz, 1H, ArH), 7.65 (t, J = 7.8 Hz, 1H, ArH), 7.44−7.42 (m,
2H, ArH), 7.35 (t, J = 7.3 Hz, 2H, ArH), 7.31−7.28 (m, 1H, ArH),
7.23 (t, J = 7.6 Hz, 1H, ArH), 5.61 (dd, J = 5.6, 10.0 Hz, 1H, OxH),
5.27 (dd, J = 8.9, 9.8 Hz, 1H, OxH), 4.79 (dd, J = 5.7, 8.8 Hz, 1H,
OxH). 13C NMR (100 MHz, d6-DMSO): δ 167.1, 153.2, 144.3, 140.5,
139.3, 138.7, 137.0, 134.3, 133.0, 132.5, 130.0, 129.1, 128.3, 127.6,
127.1, 126.9, 125.9, 124.4, 124.3, 123.9, 78.9, 65.8. Anal. Calcd for
C24H17ClN2OPd·0.5CH2Cl2 (533.74): C, 55.13; H, 3.40; N, 5.25.
Found: C, 55.35; H, 3.38; N, 5.36.
General Procedure for the Catalytic Asymmetric Allylation
of Isatins. Under an argon atmosphere, a Schlenk tube equipped with
a magnetic stirring bar was charged with the pincer Pd catalyst 3 (5
mol %), isatin (0.20 mmol), and CH2Cl2 (1 mL). The reaction mixture
was stirred at −60 °C; then allyltributyltin (0.30 mmol, 93.0 μL) was
added. After the resulting solution mixture was stirred at that
temperature for 12 h, the residue was purified by preparative TLC on
201
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silica gel plates eluting with CH2Cl2/ethyl acetate to afford the
corresponding catalysis products. The analytical data of the new
catalysis products are given here, and those of the known products are
shown in the Supporting Information.
propanol = 90/10, flow = 1.0 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 10.3 min, 39.3 min (major),
77% ee. [α]20 = +25.8 (c 0.852, CH2Cl2). 1H NMR (400 MHz,
D
CDCl3): δ 7.31−7.23 (m, 5H, ArH), 7.14 (d, J = 8.1 Hz, 1H, ArH),
7.02 (t, J = 8.0 Hz, 1H, ArH), 6.59 (d, J = 7.7 Hz, 1H, ArH), 5.41−
5.27 (m, 1H, CH2CHCH2), 5.13 (d, J = 16.9 Hz, 1H, CH2Ph),
5.03−4.94 (m, 2H, CH2CHCH2), 4.66 (d, J = 15.8 Hz, 1H,
CH2Ph), 3.69 (br s, 1H, OH), 3.35−3.30 (m, 1H, CH2CHCH2),
2.94−2.88 (m, 1H, CH2CHCH2). 13C NMR (100 MHz, CDCl3): δ
176.9, 144.6, 134.9, 130.9, 130.1, 128.8, 127.8, 127.5, 127.3, 127.2,
120.5, 119.4, 108.6, 77.9, 43.9, 40.1. HRMS (positive ESI; m/z): [M +
H]+ calcd for C18H17BrNO2 358.0443, found 358.0451.
(S)-3-Allyl-3-hydroxy-1-(4-methylbenzyl)indolin-2-one (6b).
White solid (55.7 mg, 95%). Mp: 128−130 °C. The enantiomeric
excess was determined on a Daicel Chiralcel OJ-H column with
hexane/2-propanol = 95/5, flow = 1.0 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 15.5 min, 31.9 min (major),
79% ee. [α]20 = −0.4 (c 0.664, CH2Cl2). 1H NMR (400 MHz,
D
CDCl3): δ 7.38 (d, J = 7.4 Hz, 1H, ArH), 7.20−7.15 (m, 3H, ArH),
7.10−7.02 (m, 3H, ArH), 6.69 (d, J = 7.8 Hz, 1H, ArH), 5.65−5.55
(m, 1H, CH2CHCH2), 5.14−5.06 (m, 2H, CH2CHCH2), 4.95
(d, J = 15.6 Hz, 1H, CH2Ph), 4.65 (d, J = 15.6 Hz, 1H, CH2Ph), 3.62
(br s, 1H, OH), 2.84−2.79 (m, 1H, CH2CHCH2), 2.73−2.67 (m,
1H, CH2CHCH2), 2.29 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3): δ 178.0, 142.5, 137.3, 132.4, 130.6, 129.8, 129.5, 129.4, 127.3,
124.1, 123.0, 120.4, 109.5, 76.0, 43.6, 43.0, 21.1. HRMS (positive ESI;
m/z): [M + Na]+ calcd for C19H19NNaO2 316.1313, found 316.1307.
(S)-3-Allyl-3-hydroxy-1-(2-methylbenzyl)indolin-2-one (6c). White
solid (53.4 mg, 91%). Mp: 141−143 °C. The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol = 80/20, flow = 1.0 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 5.6 min, 9.3 min (major),
(S)-3-Allyl-4-bromo-3-hydroxy-1-methylindolin-2-one (6i). Color-
less oil (50.8 mg, 90%). The enantiomeric excess was determined on a
Daicel Chiralcel OJ-H column with hexane/2-propanol = 90/10, flow
= 1.0 mL/min, and detected at a UV wavelength of 254 nm. Retention
times: 9.2 min, 10.5 min (major), 84% ee. [α]20 = +5.4 (c 0.910,
D
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.21−7.15 (m, 2H, ArH),
6.75 (dd, J = 1.4, 7.0 Hz, 1H, ArH), 5.38−5.28 (m, 1H, CH2CH
CH2), 5.11−5.06 (m, 1H, CH2CHCH2), 4.95−4.92 (m, 1H,
CH2CHCH2), 3.47 (br s, 1H, OH), 3.25−3.20 (m, 1H, CH2CH
CH2), 3.14 (s, 3H, CH3), 2.87−2.82 (m, 1H, CH2CHCH2). 13C
NMR (100 MHz, CDCl3): δ 176.6, 145.4, 131.0, 129.9, 127.5, 127.2,
120.2, 119.4, 107.4, 77.9, 40.0, 26.2. HRMS (positive ESI; m/z): [M +
H]+ calcd for C12H13BrNO2 282.0130, found 282.0139.
76% ee. [α]20 = +3.5 (c 0.572, CH2Cl2). 1H NMR (400 MHz,
D
CDCl3): δ 7.42 (d, J = 7.3 Hz, 1H, ArH), 7.19−7.14 (m, 3H, ArH),
7.09−7.01 (m, 3H, ArH), 6.58 (d, J = 7.8 Hz, 1H, ArH), 5.72−5.62
(m, 1H, CH2CHCH2), 5.16−5.10 (m, 2H, CH2CHCH2), 4.98
(d, J = 16.4 Hz, 1H, CH2Ph), 4.70 (d, J = 16.4 Hz, 1H, CH2Ph), 3.67
(br s, 1H, OH), 2.87−2.82 (m, 1H, CH2CHCH2), 2.75−2.70 (m,
1H, CH2CHCH2), 2.37 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3): δ 178.1, 142.7, 135.6, 132.8, 130.65, 130.57, 129.8, 129.6,
127.5, 126.3, 126.2, 124.2, 123.1, 120.6, 109.7, 76.0, 43.0, 42.0, 19.3.
HRMS (positive ESI; m/z): [M + Na]+ calcd for C19H19NNaO2
316.1313, found 316.1309.
(S)-3-Allyl-3-hydroxy-5-methyl-1-(4-methylbenzyl)indolin-2-one
(6k). White solid (57.2 mg, 93%). Mp: 123−124 °C. The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with
hexane/2-propanol = 80/20, flow = 1.0 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 4.9 min, 6.0 min (major),
83% ee. [α]20 = +10.8 (c 0.878, CH2Cl2). 1H NMR (400 MHz,
D
CDCl3): δ 7.21 (s, 1H, ArH), 7.14 (d, J = 8.0 Hz, 2H, ArH), 7.07 (d, J
= 8.0 Hz, 2H, ArH), 6.96 (d, J = 8.0 Hz, 1H, ArH), 6.56 (d, J = 7.9 Hz,
1H, ArH), 5.64−5.53 (m, 1H, CH2CHCH2), 5.15−5.04 (m, 2H,
CH2CHCH2), 4.92 (d, J = 15.6 Hz, 1H, CH2Ph), 4.61 (d, J = 15.6
Hz, 1H, CH2Ph), 3.83 (br s, 1H, OH), 2.83−2.78 (m, 1H, CH2CH
CH2), 2.74−2.69 (m, 1H, CH2CHCH2), 2.28 (s, 6H, CH3). 13C
NMR (100 MHz, CDCl3): δ 178.0, 140.1, 137.2, 132.6, 132.5, 130.8,
129.9, 129.7, 129.4, 127.3, 124.9, 120.3, 109.3, 76.2, 43.6, 43.0, 21.08,
21.06. HRMS (positive ESI; m/z): [M + Na]+ calcd for C20H21NNaO2
330.1470, found 330.1479.
(S)-3-Allyl-3-hydroxy-1-(naphthalen-1-ylmethyl)indolin-2-one
(6f). White solid (59.3 mg, 90%). Mp: 143−145 °C. The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with
hexane/2-propanol = 80/20, flow = 1.0 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 8.2 min, 16.9 min (major),
1
68% ee. [α]20 = +11.1 (c 0.966, CH2Cl2). H NMR (400 MHz,
D
CDCl3): δ 8.09 (d, J = 8.3 Hz, 1H, ArH), 7.88 (d, J = 7.6 Hz, 1H,
ArH), 7.78 (d, J = 8.1 Hz, 1H, ArH), 7.59−7.51 (m, 2H, ArH), 7.41
(d, J = 6.8 Hz, 1H, ArH), 7.36 (t, J = 7.6 Hz, 1H, ArH), 7.29 (d, J = 6.8
Hz, 1H, ArH), 7.17−7.12 (m, 1H, ArH), 7.05 (t, J = 7.3 Hz, 1H, ArH),
6.66 (d, J = 7.8 Hz, 1H, ArH), 5.76−5.65 (m, 1H, CH2CHCH2),
5.55 (d, J = 16.2 Hz, 1H, NCH2), 5.18−5.11 (m, 3H, NCH2,
CH2CHCH2), 3.28 (br s, 1H, OH), 2.87−2.82 (m, 1H, CH2CH
CH2), 2.75−2.70 (m, 1H, CH2CHCH2). 13C NMR (100 MHz,
CDCl3): δ 178.0, 142.8, 133.9, 131.0, 130.5, 130.2, 129.72, 129.66,
128.9, 128.4, 126.6, 126.0, 125.2, 124.7, 124.1, 123.1, 122.9, 120.7,
109.9, 76.0, 43.1, 42.1. HRMS (positive ESI; m/z): [M + Na]+ calcd
for C22H19NNaO2 352.1313, found 352.1310.
(S)-3-Allyl-5-chloro-3-hydroxy-1-(4-methylbenzyl)indolin-2-one
(6p). Colorless oil (60.3 mg, 92%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol = 80/20, flow =1.0 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 5.5 min, 7.2 min (major),
77% ee. [α]20 = +12.2 (c 0.933, CH2Cl2). 1H NMR (400 MHz,
D
CDCl3): δ 7.36 (d, J = 2.1 Hz, 1H, ArH), 7.15−7.07 (m, 5H, ArH),
6.58 (d, J = 8.3 Hz, 1H, ArH), 5.61−5.51 (m, 1H, CH2CHCH2),
5.14−5.07 (m, 2H, CH2CHCH2), 4.92 (d, J = 15.6 Hz, 1H,
CH2Ph), 4.61 (d, J = 15.6 Hz, 1H, CH2Ph), 4.12 (br s, 1H, OH),
2.83−2.78 (m, 1H, CH2CHCH2), 2.73−2.67 (m, 1H, CH2CH
CH2), 2.29 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3): δ 177.7,
140.9, 137.5, 131.9, 131.6, 130.1, 129.5, 129.4, 128.5, 127.3, 124.7,
120.8, 110.6, 76.1, 43.7, 42.9, 21.1. HRMS (positive ESI; m/z): [M +
Na]+ calcd for C19H18ClNNaO2 350.0924, found 350.0917.
(S)-3-Allyl-3-hydroxy-1-tritylindolin-2-one (6g). White solid (78.5
mg, 91%). Mp: 149−150 °C. The enantiomeric excess was determined
on a Daicel Chiralcel OJ-H column with hexane/2-propanol = 95/5,
flow = 1.0 mL/min, and detected at a UV wavelength of 254 nm.
Retention times: 8.8 min, 14.8 min (major), 32% ee. [α]20D = −3.0 (c
(S)-3-Allyl-6-bromo-3-hydroxy-1-methylindolin-2-one (6s). Color-
less oil (53.0 mg, 94%). The enantiomeric excess was determined on a
Daicel Chiralcel OJ-H column with hexane/2-propanol = 90/10, flow
= 1.0 mL/min, and detected at a UV wavelength of 254 nm. Retention
1
0.500, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.41 (d, J = 7.2 Hz,
6H, ArH), 7.33−7.31 (m, 1H, ArH), 7.25−7.17 (m, 9H, ArH), 6.96−
6.87 (m, 2H, ArH), 6.28 (d, J = 8.0 Hz, 1H, ArH), 5.72−5.61 (m, 1H,
CH2CHCH2), 5.18−5.14 (m, 2H, CH2CHCH2), 2.80−2.75 (m,
1H, CH2CHCH2), 2.72−2.67 (m, 1H, CH2CHCH2). 13C NMR
(100 MHz, CDCl3): δ 179.8, 143.0, 141.8, 131.0, 130.0, 129.4, 129.1,
128.3, 128.1, 127.7, 127.0, 125.3, 123.4, 122.6, 120.4, 116.1, 75.6, 74.6,
44.1. HRMS (positive ESI; m/z): [M + Na]+ calcd for C30H25NNaO2
454.1783, found 454.1779.
times: 10.3 min (major), 14.0 min, 76% ee. [α]20 = −6.3 (c 0.772,
D
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.25−7.21 (m, 2H, ArH),
6.97 (s, 1H, ArH), 5.64−5.53 (m, 1H, CH2CHCH2), 5.09−5.06 (m,
2H, CH2CHCH2), 3.76 (br s, 1H, OH), 3.13 (s, 3H, CH3), 2.75−
2.70 (m, 1H, CH2CHCH2), 2.61−2.55 (m, 1H, CH2CHCH2).
13C NMR (100 MHz, CDCl3): δ 177.8, 144.5, 130.1, 128.7, 125.8,
125.5, 123.3, 120.6, 112.0, 75.7, 42.7, 26.3. HRMS (positive ESI; m/z):
[M + H]+ calcd for C12H13BrNO2 282.0130, found 282.0137.
(S)-3-Allyl-1-benzyl-7-bromo-3-hydroxyindolin-2-one (6t). Color-
less oil (68.1 mg, 95%). The enantiomeric excess was determined on a
(S)-3-Allyl-1-benzyl-4-bromo-3-hydroxyindolin-2-one (6h). White
solid (63.7 mg, 89%). Mp: 154−155 °C. The enantiomeric excess was
determined on a Daicel Chiralcel OJ-H column with hexane/2-
202
dx.doi.org/10.1021/om400945d | Organometallics 2014, 33, 194−205

Organometallics
Article
Daicel Chiralcel OJ-H column with hexane/2-propanol = 90/10, flow
3H, OCH3). 13C NMR (100 MHz, CDCl3): δ 154.9, 134.5, 132.1,
131.4, 131.2, 130.9, 130.3, 129.7, 129.1, 129.0, 127.9, 127.6, 127.4,
126.6, 125.9, 125.8, 125.6, 125.1, 125.01, 124.97, 124.8, 123.7, 123.6,
113.9, 56.8. HRMS (positive ESI; m/z): [M + H]+ calcd for C27H19O
359.1436, found 359.1438.
= 1.0 mL/min, and detected at a UV wavelength of 254 nm. Retention
times: 10.2 min, 17.9 min (major), 76% ee. [α]20 = −9.3 (c 0.973,
D
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.35 (d, J = 7.7 Hz, 2H,
ArH), 7.29−7.24 (m, 2H, ArH), 7.23−7.17 (m, 3H, ArH), 6.92 (t, J =
7.7 Hz, 1H, ArH), 5.60−5.50 (m, 1H, CH2CHCH2), 5.35−5.26 (m,
2H, CH2Ph), 5.10−5.04 (m, 2H, CH2CHCH2), 4.06 (br s, 1H,
OH), 2.81−2.76 (m, 1H, CH2CHCH2), 2.73−2.68 (m, 1H,
CH2CHCH2). 13C NMR (100 MHz, CDCl3): δ 179.0, 140.0,
137.0, 135.5, 133.2, 130.1, 128.5, 127.1, 126.4, 124.5, 123.4, 120.9,
102.8, 75.3, 44.6, 43.3. HRMS (positive ESI; m/z): [M + Na]+ calcd
for C18H16BrNNaO2 380.0262, found 380.0263.
(S)-3-Allyl-7-bromo-3-hydroxy-1-methylindolin-2-one (6u). White
solid (53.6 mg, 95%). Mp: 106−108 °C. The enantiomeric excess was
determined on a Daicel Chiralcel OJ-H column with hexane/2-
propanol = 90/10, flow = 1.0 mL/min, and detected at a UV
(R)-1-(2-Ethoxynaphthalen-1-yl)pyrene (9i). White solid (69.3 mg,
93%). Mp: 157−159 °C. The enantiomeric excess was determined on
a Daicel Chiralpak AD-H column with hexane/2-propanol = 98/2,
flow = 0.8 mL/min, and detected at a UV wavelength of 254 nm.
Retention times: 7.7 min, 11.7 min (major), 43% ee. [α]20D = −25.3 (c
1
0.724, CH2Cl2). H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 7.8 Hz,
1H, ArH), 8.22−8.12 (m, 4H, ArH), 8.02−7.95 (m, 3H, ArH), 7.91−
7.86 (m, 2H, ArH), 7.59 (d, J = 9.2 Hz, 1H, ArH), 7.48 (d, J = 9.0 Hz,
1H, ArH), 7.34 (t, J = 6.9 Hz, 1H, ArH), 7.21−7.17 (m, 1H, ArH),
7.12 (d, J = 8.6 Hz, 1H, ArH), 4.08−3.99 (m, 2H, OCH2CH3), 1.00 (t,
J = 7.0 Hz, 3H, OCH2CH3). 13C NMR (100 MHz, CDCl3): δ 154.2,
134.5, 132.3, 131.4, 131.1, 130.7, 130.2, 129.5, 129.2, 129.1, 127.9,
127.6, 127.3, 127.1, 126.4, 125.91, 125.85, 125.7, 125.0, 124.92,
124.89, 124.7, 124.6, 123.7, 115.8, 65.4, 15.0. HRMS (positive ESI; m/
z): [M + H]+ calcd for C28H21O 373.1592, found 373.1591.
wavelength of 254 nm. Retention times: 6.8 min (major), 8.7 min,
1
81% ee. [α]20 = −17.4 (c 0.614, CH2Cl2). H NMR (400 MHz,
D
CDCl3): δ 7.42 (d, J = 8.2 Hz, 1H, ArH), 7.31 (d, J = 7.3 Hz, 1H,
ArH), 6.94 (t, J = 7.7 Hz, 1H, ArH), 5.63−5.52 (m, 1H, CH2CH
CH2), 5.10−5.06 (m, 2H, CH2CHCH2), 3.66 (br s, 1H, OH), 3.53
(s, 3H, CH3), 2.74−2.69 (m, 1H, CH2CHCH2), 2.64−2.58 (m, 1H,
CH2CHCH2). 13C NMR (100 MHz, CDCl3): δ 178.4, 140.5, 135.2,
133.0, 130.1, 124.3, 123.2, 120.7, 102.7, 75.4, 43.2, 29.8. HRMS
(positive ESI; m/z): [M + Na]+ calcd for C12H12BrNNaO2 303.9949,
found 303.9954.
(S)-9-(2-Methoxynaphthalen-1-yl)phenanthrene (9j). White solid
(49.5 mg, 74%). Mp: 213−214 °C. The enantiomeric excess was
determined on a Daicel Chiralpak AD-H column with hexane/2-
propanol = 98/2, flow = 0.8 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 13.2 min (major), 14.3 min,
67% ee. [α]20 = +44.6 (c 0.454, CH2Cl2). 1H NMR (400 MHz,
D
CDCl3): δ 8.78 (t, J = 7.3 Hz, 2H, ArH), 7.98 (d, J = 9.0 Hz, 1H,
ArH), 7.87 (d, J = 7.9 Hz, 2H, ArH), 7.71−7.66 (m, 2H, ArH), 7.64−
7.58 (m, 2H, ArH), 7.44 (d, J = 9.1 Hz, 1H, ArH), 7.39−7.37 (m, 2H,
ArH), 7.33−7.27 (m, 2H, ArH), 7.21−7.17 (m, 1H, ArH), 3.74 (s, 3H,
OCH3). 13C NMR (100 MHz, CDCl3): δ 154.8, 134.4, 133.3, 132.2,
131.9, 130.6, 130.3, 129.6, 129.14, 129.12, 128.8, 127.9, 126.9, 126.7,
126.6, 126.58, 126.52, 126.4, 125.6, 123.7, 123.2, 122.9, 122.7, 113.9,
56.8. HRMS (positive ESI; m/z): [M + H]+ calcd for C25H19O
335.1436, found 335.1438.
(S)-9-(2-Ethoxynaphthalen-1-yl)phenanthrene (9k). White solid
(55.7 mg, 80%). Mp: 115−117 °C. The enantiomeric excess was
determined on a Daicel Chiralpak AD-H column with hexane/2-
propanol = 98/2, flow = 0.6 mL/min, and detected at a UV
General Procedure for the Catalytic Asymmetric Suzuki−
Miyaura Coupling Reaction. A Schlenk flask was charged with 1-
iodo-2-methoxynaphthalene (0.20 mmol), 1-naphthaleneboronic acid
(0.30 mmol), pincer palladium complex 3 (5 mol %), K2CO3 (1.0
mmol), and DCE (2 mL). The mixture was stirred at 80 °C for 48 h
under N2. After cooling, the reaction mixture was evaporated and the
product was isolated by preparative TLC on silica gel plates. The
analytical data of the new catalysis products are given here, and those
of the known products are shown in the Supporting Information.
(S)-2-Ethoxy-1-(o-tolyl)naphthalene (9e). White solid (50.4 mg,
96%). Mp: 86−87 °C. The enantiomeric excess was determined on a
Daicel Chiralpak AD-H column with hexane/2-propanol = 98/2, flow
= 0.8 mL/min, and detected at a UV wavelength of 254 nm. Retention
times: 4.8 min, 6.1 min (major), 29% ee. [α]20 = +18.0 (c 0.508,
wavelength of 254 nm. Retention times: 15.5 min (major), 16.7 min,
D
1
1
68% ee. [α]20 = +129.2 (c 0.616, CH2Cl2). H NMR (400 MHz,
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 9.0 Hz, 1H,
D
ArH), 7.83−7.80 (m, 1H, ArH), 7.35−7.26 (m, 7H, ArH), 7.17 (d, J =
7.2 Hz, 1H, ArH), 4.08 (q, J = 7.0 Hz, 2H, OCH2CH3), 2.00 (s, 3H,
CH3), 1.21 (t, J = 7.0 Hz, 3H, OCH2CH3). 13C NMR (100 MHz,
CDCl3): δ 153.0, 137.6, 136.3, 133.6, 130.9, 129.7, 129.2, 128.9, 127.8,
127.3, 126.2, 125.54, 125.45, 125.2, 123.5, 115.6, 65.1, 19.8, 15.1.
HRMS (positive ESI; m/z): [M + H]+ calcd for C19H19O 263.1436,
found 263.1434.
CDCl3): δ 8.78 (dd, J = 3.3, 8.3 Hz, 2H, ArH), 7.96 (d, J = 9.0 Hz, 1H,
ArH), 7.87 (t, J = 6.7 Hz, 2H, ArH), 7.71−7.67 (m, 2H, ArH), 7.64−
7.60 (m, 2H, ArH), 7.44−7.29 (m, 5H, ArH), 7.23−7.18 (m, 1H,
ArH), 4.12−3.98 (m, 2H, OCH2CH3), 1.01 (t, J = 7.0 Hz, 3H,
OCH2CH3). 13C NMR (100 MHz, CDCl3): δ 154.1, 134.4, 133.4,
132.2, 132.0, 130.5, 130.3, 129.5, 129.2, 129.1, 128.7, 127.9, 127.0,
126.6, 126.49, 126.46, 126.4, 126.3, 125.7, 124.0, 123.7, 122.8, 122.7,
115.7, 65.3, 15.0. HRMS (positive ESI; m/z): [M + H]+ calcd for
C26H21O 349.1592, found 349.1590.
(S)-2-(Benzyloxy)-1-(o-tolyl)naphthalene (9f). White solid (60.3
mg, 93%). Mp: 53−54 °C. The enantiomeric excess was determined
on a Daicel Chiralpak AD-H column with hexane/2-propanol = 98/2,
flow = 0.8 mL/min, and detected at a UV wavelength of 254 nm.
(S)-9-(2-(Benzyloxy)naphthalen-1-yl)phenanthrene (9l). White
solid (64.0 mg, 78%). Mp: 134−136 °C. The enantiomeric excess
was determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol = 98/2, flow = 0.25 mL/min, and detected at a UV
wavelength of 254 nm. Retention times: 44.2 min, 47.0 min (major),
Retention times: 7.8 min, 9.4 min (major), 21% ee. [α]20 = +9.5 (c
D
1
0.888, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.83−7.79 (m, 2H,
ArH), 7.36−7.29 (m, 7H, ArH), 7.27−7.19 (m, 4H, ArH), 7.13 (d, J =
6.5 Hz, 2H, ArH), 5.08 (s, 2H, OCH2C6H5), 2.00 (s, 3H, CH3). 13C
NMR (100 MHz, CDCl3): δ 152.9, 137.7, 137.6, 136.2, 133.6, 131.0,
129.9, 129.4, 128.9, 128.4, 127.9, 127.6, 127.5, 126.9, 126.4, 126.2,
125.6, 125.3, 123.9, 116.2, 71.5, 19.9. HRMS (positive ESI; m/z): [M
+ H]+ calcd for C24H21O 325.1592, found 325.1591.
62% ee. [α]20 = +93.6 (c 1.120, CH2Cl2). 1H NMR (400 MHz,
D
CDCl3): δ 8.78 (t, J = 8.1 Hz, 2H, ArH), 7.90 (d, J = 9.0 Hz, 1H,
ArH), 7.86−7.83 (m, 2H, ArH), 7.70−7.58 (m, 4H, ArH), 7.43−7.29
(m, 5H, ArH), 7.21−7.17 (m, 1H, ArH), 7.12−7.04 (m, 3H, ArH),
6.93 (d, J = 6.6 Hz, 2H, ArH), 5.06 (d, J = 12.6 Hz, 1H, OCHHC6H5),
5.01 (d, J = 12.6 Hz, 1H, OCHHC6H5). 13C NMR (100 MHz,
CDCl3): δ 153.8, 137.2, 134.4, 133.3, 132.2, 132.0, 130.6, 130.4, 129.5,
129.4, 129.3, 128.8, 128.3, 127.9, 127.6, 127.1, 127.0, 126.7, 126.64,
126.60, 126.53, 126.47, 125.7, 124.5, 124.0, 122.9, 122.7, 116.0, 71.4.
HRMS (positive ESI; m/z): [M + Na]+ calcd for C31H22NaO
433.1568, found 433.1563.
(R)-1-(2-Methoxynaphthalen-1-yl)pyrene (9h). White solid (61.7
mg, 86%). Mp: 205−207 °C. The enantiomeric excess was determined
on a Daicel Chiralpak AD-H column with hexane/2-propanol = 98/2,
flow = 0.8 mL/min, and detected at a UV wavelength of 254 nm.
Retention times: 9.3 min, 10.9 min (major), 39% ee. [α]20D = −39.6 (c
1
0.580, CH2Cl2). H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 7.8 Hz,
1H, ArH), 8.19−8.09 (m, 4H, ArH), 8.03−7.94 (m, 3H, ArH), 7.90
(d, J = 8.2 Hz, 1H, ArH), 7.86 (d, J = 9.2 Hz, 1H, ArH), 7.57 (d, J =
9.2 Hz, 1H, ArH), 7.48 (d, J = 9.1 Hz, 1H, ArH), 7.35−7.31 (m, 1H,
ArH), 7.22−7.16 (m, 1H, ArH), 7.11 (d, J = 8.5 Hz, 1H, ArH), 3.74 (s,
X-ray Diffraction Studies. Crystals of 3c−f (CCDCs 857258,
857257, 857259, 857260) were obtained by recrystallization from
CH2Cl2/n-hexane at ambient temperature. Their data were collected
on an Oxford diffraction Gemini E diffractometer with graphite-
203
dx.doi.org/10.1021/om400945d | Organometallics 2014, 33, 194−205

Organometallics
Article
monochromated Mo Kα radiation (λ = 0.71070 Å). The structures
were solved by direct methods using the SHELXS-97 program, and all
non-hydrogen atoms were refined anisotropically on F2 by the full-
matrix least-squares technique, which used the SHELXL-97 crystallo-
graphic software package.25 The hydrogen atoms were included but
not refined. Details of the crystal structure determination of the Pd(II)
complexes are summarized in Table S1 in the Supporting Information.
(5) (a) Wu, L.-Y.; Hao, X.-Q.; Xu, Y.-X.; Jia, M.-Q.; Wang, Y.-N.;
Gong, J.-F.; Song, M.-P. Organometallics 2009, 28, 3369. (b) Yang, M.-
J.; Liu, Y.-J.; Gong, J.-F.; Song, M.-P. Organometallics 2011, 30, 3793.
(6) (a) Ohara, M.; Nakamura, S.; Shibata, N. Adv. Synth. Catal. 2011,
353, 3385. (b) Hyodo, K.; Nakamura, S.; Shibata, N. Angew. Chem., Int.
Ed. 2012, 51, 10337. (c) Hyodo, K.; Kondo, M.; Funahashi, Y.;
Nakamura, S. Chem.Eur. J. 2013, 19, 4128. (d) Nakamura, S.;
Hyodo, K.; Nakamura, M.; Nakane, D.; Masuda, H. Chem.Eur. J.
2013, 19, 7304.
ASSOCIATED CONTENT
■
(7) Arai, T.; Oka, I.; Morihata, T.; Awata, A.; Masu, H. Chem.Eur.
S
* Supporting Information
J. 2013, 19, 1554.
Crystallographic details for complexes 3c−f. Additional
catalytical results on the allylation of a ketimine derived from
N-benzylisatin. Proposed reaction mechanisms for the asym-
metric allylation of isatins and the Suzuki−Miyaura reaction.
Characterization data of the known catalysis products, 1H NMR
(8) (a) Gong, J.-F.; Zhang, Y.-H.; Song, M.-P.; Xu, C. Organometallics
2007, 26, 6487. (b) Zhang, B.-S.; Wang, C.; Gong, J.-F.; Song, M.-P. J.
Organomet. Chem. 2009, 694, 2555. (c) Zhang, B.-S.; Wang, W.; Shao,
D.-D.; Hao, X.-Q.; Gong, J.-F.; Song, M.-P. Organometallics 2010, 29,
2579. (d) Niu, J.-L.; Chen, Q.-T.; Hao, X.-Q.; Zhao, Q.-X.; Gong, J.-F.;
Song, M.-P. Organometallics 2010, 29, 2148. (e) Hou, A.-T.; Liu, Y.-J.;
Hao, X.-Q.; Gong, J.-F.; Song, M.-P. J. Organomet. Chem. 2011, 696,
2857.
1
and 13C NMR spectra of all new compounds 1−3, and H or/
and 13C NMR spectra of all catalysis products as well as their
chiral HPLC spectra and CIF files for the four pincer Pd
complexes including 3c, 3d, 3e·(n-hexane), and (2 × 3f)·
CH2Cl2. This material is available free of charge via the Internet
at http://pubs.acs.org.
(9) Wang, T.; Hao, X.-Q.; Zhang, X.-X.; Gong, J.-F.; Song, M.-P.
Dalton Trans. 2011, 40, 8964.
(10) Selected recent publications: (a) Niu, J.-L.; Hao, X.-Q.; Gong, J.-
F.; Song, M.-P. Dalton Trans. 2011, 40, 5135. (b) Hao, X. -Q.; Niu, J.-
L.; Zhao, X.-M.; Gong, J.-F.; Song, M.-P. Chin. J. Org. Chem. 2013, 33,
663. (c) Wang, T.; Niu, J.-L.; Liu, S.-L.; Huang, J.-J.; Gong, J.-F.; Song,
M.-P. Adv. Synth. Catal. 2013, 355, 927. (d) Wang, T.; Hao, X.-Q.;
Huang, J.-J.; Niu, J.-L.; Gong, J.-F.; Song, M.-P. J. Org. Chem. 2013, 78,
8712.
(11) Ishihara, M.; Togo, H. Tetrahedron 2007, 63, 1474.
(12) (a) Neve, F.; Crispini, A.; Pietro, C. D.; Campagna, S.
Organometallics 2002, 21, 3511. (b) Song, D.; Morris, R. H.
Organometallics 2004, 23, 4406. (c) Bianchini, C.; Lenoble, G.;
Oberhauser, W.; Parisel, S.; Zanobini, F. Eur. J. Inorg. Chem. 2005,
4794.
(13) (a) Galliford, C. V.; Scheidt, K. A. Angew. Chem., Int. Ed. 2007,
46, 8748. (b) Trost, B. M.; Brennan, M. K. Synthesis 2009, 3003.
(c) Zhou, F.; Liu, Y. L.; Zhou, J. Adv. Synth. Catal. 2010, 352, 1381.
(14) (a) Kawasaki, T.; Nagaoka, M.; Satoh, T.; Okamoto, A.; Ukon,
R.; Ogawa, A. Tetrahedron 2004, 60, 3493. (b) Kawasaki, T.;
Takamiya, W.; Okamoto, N.; Nagaoka, M.; Hirayama, T. Tetrahedron
Lett. 2006, 47, 5379. (c) Kitajima, M.; Mori, I.; Arai, K.; Kogure, N.;
Takayama, H. Tetrahedron Lett. 2006, 47, 3199.
AUTHOR INFORMATION
■
Corresponding Authors
*(J.-F. Gong) E-mail: gongjf@zzu.edu.cn.
*(M.-P. Song) E-mail: mpsong@zzu.edu.cn. Tel/Fax: (+86)-
371-6778-3012.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the National Natural Science
Foundation of China (21272217), Program for Science
&Technology Innovation Talents in Universities of Henan
Province (2012HASTIT003), and Key Technologies R & D
Program of Henan Province (102101210200) for financial
support of this work.
(15) (a) Sano, D.; Nagata, K.; Itoh, T. Org. Lett. 2008, 10, 1593.
(b) Yang, Y.; Moinodeen, F.; Chin, W.; Ma, T.; Jiang, Z.; Tan, C.-H.
Org. Lett. 2012, 12, 4762.
(16) For synthesis of 3-allyl-3-hydroxyoxindoles from isatins, see:
(a) Nair, V.; Ros, S.; Jayan, C. N.; Viji, S. Synthesis 2003, 2542.
(b) Alcaide, B.; Almendros, P.; Rodríguez-Acebes, R. J. Org. Chem.
2005, 70, 3198. (c) Grant, C. D.; Krische, M. J. Org. Lett. 2009, 11,
REFERENCES
■
(1) Selected and recent reviews on pincer Pd(II) complexes:
(a) Singleton, J. T. Tetrahedron 2003, 59, 1837. (b) Dupont, J.;
Consorti, C. S.; Spencer, J. Chem. Rev. 2005, 105, 2527. (c) Szabo, K.
́
J. Synlett 2006, 811. (d) The Chemistry of Pincer Compounds; Morales-
Morales, D.; Jensen, C. M., Eds.; Elsevier: Amsterdam, 2007.
(e) Morales-Morales, D. Mini-Rev. Org. Chem. 2008, 5, 141.
(f) Serrano-Becerra, J. M.; Morales-Morales, D. Curr. Org. Synth.
2009, 6, 169. (g) Selander, N.; Szabo,
(h) Selander, N.; Szabo, K. J. Chem. Rev. 2011, 111, 2048. (i) Szabo,
J. Top. Organomet. Chem. 2013, 40, 203.
(2) (a) Baber, R. A.; Bedford, R. B.; Betham, M.; Blake, M. E.; Coles,
S. J.; Haddow, M. F.; Hursthouse, M. B. A.; Orpen, A. G.; Pilarski, L.
T.; Pringle, P. G.; Wingad, R. L. Chem. Commun. 2006, 3880.
(b) Aydin, J.; Kumar, K. S.; Sayah, M. J.; Wallner, O. A.; Szabo,
Org. Chem. 2007, 72, 4689. (c) Aydin, J.; Ryden, A.; Szabo,
Tetrahedron: Asymmetry 2008, 19, 1867.
(3) (a) Feng, J.-J.; Chen, X.-F.; Shi, M.; Duan, W.-L. J. Am. Chem. Soc.
2010, 132, 5562. (b) Du, D.; Duan, W.-L. Chem. Commun. 2011, 47,
11101. (c) Chen, Y.-R.; Duan, W.-L. Org. Lett. 2011, 13, 5824.
(d) Feng, J.-J.; Huang, M.; Lin, Z.-Q.; Duan, W.-L. Adv. Synth. Catal.
2012, 354, 3122. (e) Huang, M.; Li, C.; Huang, J.; Duan, W.-L.; Xu, S.
Chem. Commun. 2012, 48, 11148.
4485. (d) Vyas, D. J.; Frohlich, R.; Oestreich, M. J. Org. Chem. 2010,
̈
75, 6720. For catalytic asymmetric allylation of isatins, see: (e) Qiao,
X. C.; Zhu, S. F.; Zhou, Q. L. Tetrahedron: Asymmetry 2009, 20, 1254.
(f) Itoh, J.; Han, S. B.; Krische, M. J. Angew. Chem., Int. Ed. 2009, 48,
6313. (g) Cao, Z.-Y.; Zhang, Y.; Ji, C.-B.; Zhou, J. Org. Lett. 2011, 13,
6398. (h) Zheng, K.; Yin, C.; Liu, X.; Lin, L.; Feng, X. Angew. Chem.,
Int. Ed. 2011, 50, 2573. (i) Hanhan, N. V.; Tang, Y. C.; Tran, N. T.;
Franz, A. K. Org. Lett. 2012, 14, 2218. (j) Silverio, D. L.; Torker, S.;
Pilyugina, T.; Vieira, E. M.; Snapper, M. L.; Haeffner, F.; Hoveyda, A.
H. Nature 2013, 494, 216.
́
K. J. Dalton Trans. 2009, 6267.
́
́
K.
́
K. J. J.
K. J.
́
́
(17) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147. (c) Kotha, S.;
Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633. (d) Suzuki, A. J.
Organomet. Chem. 2002, 653, 83. (e) Bellina, F.; Carpita, A.; Rossi, R.
Synthesis 2004, 15, 2419. (f) Alonso, F.; Beletskaya, I. P.; Yus, M.
Tetrahedron 2008, 64, 3047. (g) Molander, G. A.; Canturk, B. Angew.
Chem., Int. Ed. 2009, 48, 9240.
(18) (a) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 12051.
(b) Cammidge, A. N.; Crepy, K. V. L Chem. Commun. 2000, 1723.
́
(c) Castanet, A.-S.; Colobert, F.; Broutin, P.-E.; Obringer, M.
(4) (a) Takenaka, K.; Uozumi, Y. Org. Lett. 2004, 6, 1833.
(b) Takenaka, K.; Minakawa, M.; Uozumi, Y. J. Am. Chem. Soc.
2005, 127, 12273.
204
dx.doi.org/10.1021/om400945d | Organometallics 2014, 33, 194−205

Organometallics
Article
Tetrahedron: Asymmetry 2002, 13, 659. (d) Jensen, J. F.; Johannsen, M.
Org. Lett. 2003, 5, 3025. (e) Willis, M. C.; Powell, L. H. W.; Claverie,
C. K.; Watson, S. J. Angew. Chem., Int. Ed. 2004, 43, 1249. (f) Mikami,
K.; Miyamoto, T.; Hatano, M. Chem. Commun. 2004, 2082.
(g) Baudoin, O. Eur. J. Org. Chem. 2005, 4223. (h) Genov, M.;
Almor ín, A.; Espinet, P. Tetrahedron: Asymmetry 2007, 18, 625.
(i) Bronger, R. P. J.; Guiry, P. J. Tetrahedron: Asymmetry 2007, 18,
1094. (j) Shen, X.; Jones, G. O.; Watson, D. A.; Bhayana, B.;
Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 11278. (k) Kamei, T.;
Sato, A. H.; Iwasawa, T. Tetrahedron Lett. 2011, 52, 2638. (l) Castillo,
A. B.; Perandones, B. F.; Zangrando, E.; Gladiali, S.; Godard, C.;
Claver, C. J. Organomet. Chem. 2013, 743, 31.
(19) Bermejo, A.; Ros, A.; Fernan
Chem. Soc. 2008, 130, 15798.
́
dez, R.; Lassaletta, J. M. J. Am.
(20) Snead, D. R.; Inagaki, S.; Abboud, K. A.; Hong, S.
Organometallics 2010, 29, 1729.
(21) Zhang, S.-S.; Wang, Z.-Q.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2010,
12, 5546.
(22) Takemoto, T.; Iwasa, S.; Hamada, H.; Shibatomi, K.;
Kameyama, M.; Motoyama, Y.; Nishiyama, H. Tetrahedron Lett.
2007, 48, 3397.
(23) Reddy, K. S. K.; Narender, N.; Rohitha, C. N.; Kulkarni, S. J.
Synth. Commun. 2008, 38, 3894.
(24) Lim, C. W.; Tissot, O.; Mattison, A.; Hooper, M. W.; Brown, J.
M.; Cowley, A. R.; Hulmes, D. I.; Blacker, A. J. Org. Process Res. Dev.
2003, 7, 379.
(25) (a) Sheldrick, G. M. SHELXS-97, Program for Crystal Structure
Solution; University of Gottingen: Gottingen, Germany, 1997.
̈
̈
(b) Sheldrick, G. M. SHELXL-97, Program for Crystal Structure
Refinement; University of Gottingen: Gottingen, Germany, 1997.
̈
̈
205
dx.doi.org/10.1021/om400945d | Organometallics 2014, 33, 194−205