Fine Tuning of Chiral Bis(N-heterocyclic carbene) Palladium Catalysts for Asymmetric Suzuki-Miyaura Cross-Coupling Reactions: Exploring the Ligand Modification

Article abstract of DOI:10.1021/acs.organomet.0c00036

Novel chiral N,N′-bisaryl bis(NHC) ligand precursors H2[(S)-2]Cl2 on a spiro scaffold and H2[(S)-3b-g]Cl2 with a binaphthyl linkage were rationally designed and their cyclometalated cis-chelated NHC palladium complexes (S)-5, (S)-6, and (S)-7b-g have been synthesized and fully characterized. Complexes 6 and 7b were further confirmed by X-ray single-crystal analysis. Both complexes adopted a slightly distorted square planar geometry around the Pd(II) center. The structure of 6 consists of a rare dimeric arrangement incorporating two palladium(II) centers bonded through a short metal-metal bond (2.853(2) ?), indicating a PdII-PdII intramolecular interaction (<3.00 ?). These N,N′-bisaryl-bis(NHC)-Pd complexes together with N,N′-bisalkyl analogues {[(S)-1a-d]PdX2} (X = I, (S)-4a; X = Br, (S)-4b-d) have been used in the asymmetric aryl-aryl cross-coupling reactions of arylboronic acids and aryl halides. The enantioselectivity of the biaryl products was greatly improved within 24 h (up to 74% ee) when complexes 7a-g were used as catalysts. The results show that for these types of bis(NHC) palladium catalysts the structural characters of the chiral scaffolds play a decisive role in the enantioselectivities of cross-coupling reactions.

Full text of DOI:10.1021/acs.organomet.0c00036

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Article
Fine Tuning of Chiral Bis(N-heterocyclic carbene) Palladium
Catalysts for Asymmetric Suzuki−Miyaura Cross-Coupling Reactions:
Exploring the Ligand Modification
Dao Zhang* and Jueqin Yu
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ABSTRACT: Novel chiral N,N′-bisaryl bis(NHC) ligand precursors H2[(S)-
2]Cl2 on a spiro scaffold and H2[(S)-3b−g]Cl2 with a binaphthyl linkage were
rationally designed and their cyclometalated cis-chelated NHC palladium
complexes (S)-5, (S)-6, and (S)-7b−g have been synthesized and fully
characterized. Complexes 6 and 7b were further confirmed by X-ray single-
crystal analysis. Both complexes adopted a slightly distorted square planar
geometry around the Pd(II) center. The structure of 6 consists of a rare
dimeric arrangement incorporating two palladium(II) centers bonded through
a short metal−metal bond (2.853(2) Å), indicating a PdII−PdII intramolecular
interaction (<3.00 Å). These N,N′-bisaryl-bis(NHC)-Pd complexes together
with N,N′-bisalkyl analogues {[(S)-1a−d]PdX2} (X = I, (S)-4a; X = Br, (S)-
4b−d) have been used in the asymmetric aryl−aryl cross-coupling reactions of
arylboronic acids and aryl halides. The enantioselectivity of the biaryl products
was greatly improved within 24 h (up to 74% ee) when complexes 7a−g were
used as catalysts. The results show that for these types of bis(NHC) palladium catalysts the structural characters of the chiral
scaffolds play a decisive role in the enantioselectivities of cross-coupling reactions.
types of chiral monodentate NHC6c−e and NHC-containing
INTRODUCTION
■
chelating ligands6b,7 have been developed in Pd-catalyzed
To date, the Pd-catalyzed asymmetric Suzuki−Miyaura cross-
asymmetric Suzuki−Miyaura cross coupling reactions (Scheme
coupling reaction has been recognized as one of the most
1). Among these, the ligand (R,R,R,R)-DTB-SIPE is
practical methods to construct the axially chiral biaryl skeletons
undoubtedly the first highly enantioselective (>90% ee)
that are common in a wide variety of natural products and
example that effectively suppresses the rotation around the
drugs.1 The most important problem in this realm is the design
metal−carbon(NHC) bond with its C2-symmetric bulky aryl
and synthesis of effective chiral ligands, because they control
substituents on the nitrogen positions of the NHC skeleton.6e
the spatial structure of the catalytic active center.2 Pioneered
During our investigation on chiral NHC ligands for metal-
by the groups of Buchwald and Cammidge in 2000,2 an array
catalyzed asymmetric C(sp2)−C(sp2) cross-coupling reactions,
of chiral auxiliary ligands such as (S)-KenPhos, (S,S,S,S)-bis-
several types of bis(NHC) chelating ligands with different
hydrazone, (R)-BI-DIME, (R,R,R,R)-DTB-SIPE, etc. has been
chiral linkers (Scheme 2) have been designed, although the
developed.3−7 Both experimental results and theoretical
best enantioselectity obtained was 64% ee.7 To further study
calculations have shown that a favorable chiral ligand is the
the influence of the chiral linker on the catalytic behavior, we
key to the excellent enantioselectivity of highly efficient metal
recently prepared the N,N′-bisalkyl-substituted bis(NHC)
catalysts. Accordingly, the search for new chiral ligands for the
ligands (S)-1a−d (Scheme 2) on a chiral spiro scaffold.10
broadest possible substrate scope is still a fundamental strategy
Although their palladium complexes achieved moderate to
for constructing atropisomers.
As a kind of highly strongly donating ligand, N-heterocyclic
carbenes (NHCs) usually form a palladium catalyst robust to
excellent ee values in enantioselective oxidative kinetic
resolution of secondary alcohols, biaryl atropisomers with up
air and moisture, which would be beneficial for the oxidative
Received: January 17, 2020
addition of aryl halides and tolerance to the coupling partners
with various coordination atoms.8 In comparison to the broad
study and application of chiral P-containing ligands in
enantioselective cross-coupling catalysis, much less attention
has been paid to chiral NHC ligands/catalysts.9 Since the
pioneering study disclosed by Labande et al. in 2010,6a several
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Scheme 1. Examples of Chiral NHC Ligands in Asymmetric
Suzuki−Miyaura Reactions
RESULTS AND DISCUSSION
■
Synthesis and Characterization. The complexes {[(S)-
1a−d]PdX2} (X = I, (S)-4a; X = Br, (S)-4b−d) were prepared
from N,N′-bisalkyl-substituted ligands H2[(S)-1a−d]X2 as we
previously reported.10 Complexes (S)-5, (S)-6 and (S)-7a−g
were synthesized from the tetraamine intermediates (S)-8 and
(S)-10, as shown in Schemes 3 and 4, respectively.
We first attempted to prepare the N,N′-bisaryl-substituted
palladium complex (S)-5 on a chiral spiro scaffold from
Pd2(dba)3 in THF using a way similar to that for (S)-7a with a
chiral BINAM linker.11 Unfortunately, the yield of the desired
complex was only ca. 10%. The worse outcome could be
1
explained by the rigid spiro framework of (S)-2. In the H
NMR spectra of (S)-5, the singlet centered at 9.99 ppm
representing its NCHN group of H2[(S)-2]Cl2 was notably
absent. The two resonances in low-field region (180.7 and
197.4 ppm, respectively) in its 13C NMR spectrum were very
close to those (180.4 and 197.5 ppm) of (S)-7a, which
indicated they should have structures similar to each other.
Given that the above strategy was inefficient in the
construction of the chiral bis(NHC) complex, we next
undertook a typical synthetic method using Pd(OAc)2 as the
starting material.7 A mixture of precursor H2[(S)-2]Cl2 and an
equivalent amount of Pd(OAc)2 in DMSO was heated and
kept at 50 °C for 2 h and 100 °C for 2 h, respectively, to give a
mixture of (S)-6 (major) and (S)-5 (minor) according to the
13C NMR spectrum in ca. 25% yield. Fortunately, the pure
complex (S)-6 could be obtained as orange bulk crystals by
slowly evaporating its chloroform solution over several weeks.
It is worth noting that there is a great difference between the
two NHC resonances (163.7, 178.6 ppm, respectively) in (S)-
6, which showed that the two carbene carbons coordinating
with palladium are more distinguishable.
Scheme 2. Bis(NHC) Ligands with a Chiral Linker
The crystal structure of (S)-6 was determined by X-ray
crystallography, and the ORTEP drawing is depicted in Figure
1. The structure of (S)-6 consists of a rare dimeric
arrangement incorporating two palladium(II) centers bonded
through two bridging chloride ligands. The distance (2.853(2)
Å) between the two palladium atoms is close to the generally
accepted value indicating a PdII···PdII interaction (<3.00 Å),
consistent with the previously reported μ-bridged dimeric
complexes {PdII}2.12 From its side view (Figure S1) it appears
that the coordination geometry around each metal atom could
be considered as a square-planar environment. The dihedral
angle between the coordination planes of P−Pd1 (defined by
C1, Cl3, Cl1, Cl2) and P−Pd2 (defined by C25, C33, Cl2,
Cl1) is 79.61°. The C1NHC ring is inclined to P−Pd1 at an
angle of 75.60°, while the C25NHC ring is approximately
parallel to P−Pd2 (9.94°). The Pd−Ccarbene (1.91(2)
−1.967(19) Å) and Pd−Cl bond distances (2.312(6)−
2.472(5) Å) are within the normal range.6,7
Considering that complexes (S)-7b−g contain two different
aryl groups on the nitrogen positions of the NHC ligands, we
planned to carry out the Pd-catalyzed C−N coupling reactions
of (S)-10 twice on the bais of the principle of “difficult first,
easy later”. From data summarized in Scheme 4, it would seem
that the isolated yields of the intermediates (S)-11b−g is
mainly related to the electronic effects and steric effects of
substitute groups (ArBr). Previously Shi et al. prepared the
disubstituted compound (S)-12a from the BINAM derivative
(S)-10 using 5.7 equiv of bromobenzene in 90% yield. In order
to get the more monosubstituted compound (S)-11, we
to 36% ee could be obtained for Pd-catalyzed Suzuki−Miyaura
cross-coupling reactions (see below). Later we synthesized the
N,N′-bisaryl-substituted bis(NHC) ligand (S)-2 with a spiro
linker (Scheme 3), together with its analogue (S)-3a with an
axially chiral binaphthyl linker11 (Scheme 4). The catalytic
experiments showed that the palladium complex of (S)-3a
revealed a better catalytic enantioselectivity in comparison to
that of (S)-2 under the same reaction conditions. Later the
structural fine-tuning of ligand (S)-3a was carried out to
further improve the chiral surroundings around palladium
centers ((S)-3b−g, Scheme 4). In the present contribution, we
describe the synthesis, characterization, and catalytic behaviors
of these chiral bis(NHC) palladium compounds.
B
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Scheme 3. Synthesis of Complexes (S)-5 and (S)-6
Scheme 4. Synthesis of Complexes (S)-7b−g
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Table 1. Selected 13C Data (ppm) of Palladium Complexes
(S)-7a−g
Ccarbene
−
Pd
C
2‑R(Ar)
complex (Ar)
(S)-7a (Ph)
major
minor
major
minor
197.5,
180.4
(S)-7b/7b′ (2-Me-C6H4)
198.4,
180.7
197.7,
180.3
198.1,
179.9
19.3
56.2
18.7
55.2
(S)-7c/7c′ (2-OMe-C6H4) 197.2,
180.9
(S)-7d/7d′ (2-Et-C6H4)
(S)-7e/7e′ (2-iPr-C6H4)
(S)-7f (2-Ph-C6H4)
197.7,
180.2
197.7,
180.2
197.5,
180.5
198.3,
180.6
180.4
13.9, 23.5 13.0, 23.7
22.9, 24.7, 24.3, 25.7,
27.1
28.1
(S)-7g/7g′ (1-Naph)
198.6,
180.0
198.9,
180.9
Figure 1. Molecular structure of (S)-6 (H atoms omitted for clarity).
Selected bond lengths (Å) and angles (deg): Pd1−C1 1.91(2), Pd1−
Cl1 2.328(6), Pd1−Cl2 2.405(5), Pd1−Cl3 2.312(6), Pd2−Cl1
2.472(5), Pd2−Cl2 2.403(6), Pd2−C25 1.967(19), Pd2−C33
2.03(2), Pd1···Pd2 2.853(2), C1−Pd1−Cl3 87.1(6), C1−Pd111−
Cl1 90.5(6), Cl3−Pd1−Cl1 173.8(2), C1−Pd1−Cl2 172.6(5), Cl3−
Pd1−Cl2 96.0(2), Cl1−Pd1−Cl2 85.6(2), C1−Pd1−Pd2 119.1(5),
Cl3−Pd1−Pd2 120.63(17), Cl1−Pd1−Pd2 55.88(13), Cl2−Pd1−
Pd2 53.57(14), C25−Pd2−C33 77.8(9), C25−Pd2−Cl2 173.6(6),
C33−Pd2−Cl2 96.3(7), C25−Pd2−Cl1 103.6(6), C33−Pd2−Cl1
171.5(6), Cl2−Pd2−Cl1 82.6(2), Pd1−Cl1−Pd2 72.88(17), Pd2−
Cl2−Pd1 72.80(15).
decided to reduce the amount of aryl halides. After many tries,
the reaction of (S)-10 with 1.2 equiv of ArBr gave better yields
for (S)-11b−e,g (36−55%) along with (S)-12b−e,g (20−
46%). It should be noted, however, that for (S)-11f with s
more bulky substituent a large excess (at least 6.0 equiv) of aryl
bromide was necessary together with a long reaction time,
although the yield still was very low (16%). Moreover,
compound (S)-11c with a 2-OMe-C6H4 group achieved the
highest yield of 55% and we tried but failed to obtain similar
analogues with an electron-withdrawing group such as 2-CF3-
C6H4. Compounds (S)-13b−g were obtained by a second N-
arylation reaction of (S)-11 with PhBr in good yields of 62−
93%.
Figure 2. Two isomeric complexes (S)-7 and (S)-7′.
Sometimes the signal of the minor product, such as (S)-7f′
with a phenyl group, was so weak that it was very difficult to
use NMR techniques to observe it. Of course, on the basis of
1
the values of chemical shifts and integral areas in H NMR
spectra, the molar ratio (S)-7/(S)-7′ could also be easily
estimated. For example, the value of (S)-7c/(S)-7c′ is 1.00/
0.55 on the basis of OCH3 centered at 2.82 and 3.57 ppm,
while that of (S)-7e and (S)-7e′ is 1.00/0.21 according to
CHiPr centered at 2.19 and 2.94 ppm.
A suitable single crystal of complex (S)-7b/(S)-7b′ was
successfully obtained by means of solvent diffusion (chloro-
form/hexane). The isomerism of these NHC palladium
complexes was further confirmed by X-ray single-crystal
diffraction analysis. There are two isomers ((S)-7b/(S)-7b′)
in the unit cell (Figure 3), and an ORTEP drawing of (S)-7b is
depicted in Figure 4. The methyl group and chloride ligand are
located on the same side of the benzimidazole ring defined by
N3−C34−N4−C35−C40 in (S)-7b, while they lie on opposite
sides in (S)-7b′.
According to an improved literature method for (S)-7a,11
(S)-13b−g underwent cyclization to produce the correspond-
ing bis(NHC) precursors H2[(S)-3b−g]Cl2 in very favorable
yields using excess triethyl orthoformate and concentrated
HCl. Treatment of the above bis(benzimidazolium) salts with
1.2 equiv of Pd2(dba)3 in anhydrous THF under reflux for 4 h
afforded the desired NHC metal complexes (S)-7b−g in
moderate yields (37−59%).
All palladium NHC complexes were characterized by 1H and
13C NMR, and selected 13C NMR data of CNHC and C2‑R(Ar)
are presented in Table 1. It is worth noting that two sets of
resonances in the low-field region (198.9−179.9 ppm) in their
13C NMR spectra showed that these NHC complexes had the
two isomers (S)-7b−g and (S)-7b′−g′ (Figure 2) and could
not easily be separated from each other by gel chromatog-
raphy. In general, the molar ratio of the major (S)-7b−g to the
minor (S)-7b′−g′ increased steadily with an increase in the
steric hindrance of the substituent R in the ortho position of
the phenyl ring (Figure S2).
As shown in Figure 4, two carbene carbon atoms, one phenyl
carbon atom, and one chloride coordinated with the palladium
center and the cyclometalated complex adopted a square-
planar geometry around the Pd(II) center. The two Pd−
Ccarbene bond distances (1.983(8) and 2.008(8) Å) are almost
equal to each other in N,N′-bisalkyl bis(NHC) complexes such
as the [Pd((S)-1a)I2] and [Pd((S)-1b)Br2] we previously
reported.10 However, there are clear and obvious differences
between them in the N,N′-bisaryl bis(NHC) palladium
complex(S)-7b (1.978(9) and 2.042(8) Å) due to the C−H
activation of the neighboring phenyl group. The difference in
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((S)-4a) and 47% ((S)-5) (entries 8 and 17). Both the
conversation and enantioselectivity of the Suzuki−Miyaura
reaction markedly decrease with an increase in steric hindrance
from alkyl groups on the nitrogen positions of bis(NHC) in
complexes (S)-4b−d (entries 9−11 vs entry 8). For (S)-4a,
when aryl halide 14a (R2 = OMe) was displaced by 14b (R2 =
OBn) or 14c (R2 = Me) their conversion ratios changed
significantly with a slightly reduced enantioselectivity (entries
12 and 13 vs entry 8). Moreover, the aryl boronic acids 15a−d
do suffer significant side reactions to afford homocoupling and
deboronation byproducts (17a,b and 19a,b), especially for
those bulky partners. For example, the cross-coupling reaction
of 2-methoxynaphthylboronic acid (15b) with 1-bromonaph-
thalene (14d) afforded not the desired biaryl product (16db)
but 2-methoxynaphthalene (19b) in about 60% isolated yield
based on 15b, together with a small amount of the
debromination byproduct (18d) of the aryl halide 14d
(entry 14).
Figure 3. Isomers (S)-7b (right) and (S)-7b′ (left) in a unit cell.
Next we investigated the catalytic behaviors of axially chiral
bis(NHC) palladium complexes (S)-7a−g that have a
structure similar to that of (S)-5 on a spiro scaffold. The
preliminary experiments were performed in isopropyl alcohol
at 40 °C, using K3PO4 as the base, an excess (1.5 equiv) of
15a, and 2.5 mol % of complexes (S)-7a−g as the catalyst
(Table 3). We were delighted to observe that the desired
product 16aa was obtained with significant ee values in most
cases, reaching a promising 74% ee when (S)-7b was used as a
catalyst (entries 1−5). Meanwhile, the molar ratio of the
desired product 16aa to the homocoupling counterpart 1,1′-
binaphthyl (17) also reaches a maximum of 2.2 (entry 2).
Moreover, complexes (S)-7f and (S)-7g could afforded only a
trace of biaryl product 16 (entries 6 and 7).
A typical substrate scope screening test of the Suzuki−
Miyaura reaction with (S)-7b as the catalyst was performed.
Under the representative conditions (entry 2, Table 4), several
naphthyl halides 14a-e and arylboronic acids 15a-f with
different steric substituents were investigated for coupling with
each other (Table 4). It is a great pity that we did not observe
an obvious improvement in coupling enantioselectivity (from
21% to 69%), albeit with relatively higher conversions (from
50% to 71%) in some cases (entries 1, 2, and 5). Moreover, we
failed to obtain the tetra-ortho-substituted biaryl products by
Suzuki coupling using these palladium catalysts (entry 7, Table
4).
Figure 4. Molecular structure of (S)-7b (H atoms omitted for clarity).
Selected bond lengths (Å) and angles (deg): Pd1−C1 2.028(8),
Pd1−C7 1.978(9), Pd1−C34 2.042(8), Pd1−Cl1 2.350(2), C7−
Pd1−C1 78.8(4), C7−Pd1−C34 101.4(3), C1−Pd1−C34 178.6(3),
C7−Pd1−Cl1 170.5(2), C1−Pd1−Cl1 94.5(3), C34−Pd1−Cl1
85.1(2).
CONCLUSIONS
bond length is more noticeable in (S)-7a (1.927(6) and
2.055(6) Å)11 because the ligand (S)-3a has a smaller
hindrance in comparison to (S)-3b−g. Moreover, the Pd−
CPh (2.028(8) Å) and Pd−Cl bond distances (2.350(2) Å)
were slightly longer than those (2.016(6), 2.3364(19) Å) in
(S)-7a. The complex (S)-7b (101.4(3)°) has a Ccarbene−Pd−
■
In conclusion, a variety of novel N,N′-bisaryl-substituted chiral
bis(NHC) ligand precursors on a spiro or axial bisaryl scaffold
and their palladium complexes have been prepared in good
yields and characterized by NMR, HRMS, elemental analysis
,and X-ray single-crystal diffraction. The obtained bis(NHC)−
Pd complexes (S)-7a−g with an axial chiral linkage proved to
be more efficient catalysts (up to 74% ee) in comparison to
those on a spiro scaffold (up to 47% ee) for asymmetric
Suzuki−Miyaura reactions of arylboronic acids and aryl
halides. Further fine tuning using different groups on the cis
positions of nitrogen seemed to have little effect on the
enantioselectivities (from 60% to 74% ee) of the axially chiral
biaryl products. At the same time, one side effect is that bulky
substituents usually decrease the chemical reaction rate,
causing low yield/conversion. The results show that for these
types of bis(NHC) palladium catalysts the structural characters
of the chiral scaffolds play a decisive role in the
C
carbene bite angle similar to that (S)-7a (102.3(2)°), which are
much bigger than that in an analogue (94.8(3)°) with a spiro
linker.10
Asymmetric Suzuki−Miyaura Coupling. The N-alkyl
substituted palladium complex (S)-4a and the N-aryl-
substituted analogue (S)-5 on a spiro scaffold were initially
tested in the asymmetric Suzuki−Miyaura cross-coupling
reaction between 1-bromo-2-methoxynaphthalene (14a) and
naphthylboronic acid (15a). As shown in Table 2 (entries 1−8
i
and entries 15−20), PrOH and K3PO4 proved to be the best
solvent and base, respectively. Under the optimum conditions
the ee % value of the axially chiral biaryl 16 can get up to 36%
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a
Table 2. Asymmetric Suzuki−Miyaura Coupling Reactions Using (S)-4a-d and (S)-5
b
b
c
entry
cat. (mol %)
coupling partners
base
solvent
time (h)
T (°C)
conversn (%)
sel (%)
ee (%)
1
2
3
4
5
6
4a (2)
4a (2)
4a (4)
4a (2)
4a (2)
4a (2)
4a (2)
4a (2)
4b (2)
4c (2)
4d (2)
4a (2)
4a (2)
4a (2)
5 (3)
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14b/15a
14c/15a
14d/15b
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
14a/15a
Cs2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
KtOBu
KtOBu
K3PO4
K2CO3
K3PO4
K3PO4
toluene
toluene
toluene
toluene
toluene
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
toluene
MeOH
24
24
24
48
96
80
80
80
80
80
80
60
40
40
40
40
40
40
40
40
40
40
40
40
40
5
92
95
97
97
97
85
95
93
59
94
94
95
84
d
3
7
1
d
2
30
32
55
31
88
50
82
77
37
58
82
81
e, f
18
11
36
5
48
7
48
24
36
21
5
8
120
120
120
120
120
120
120
24
9
10
11
12
13
14
15
16
17
18
19
20
31
33
31
21
24
7
5 (3)
72
2
5 (3)
24
83
47
d
5 (3)
24
>90
38
5 (3)
5 (3)
24
24
3
trace
d
a
b
Reaction conditions: 0.2 mmol of aryl bromides 14a−d, 0.3 mmol of aryl boronic acids 15a,b, 0.5 mmol of base, 2 mL of solvent. Determined by
c
GC-MS: conversn (%) = {[16 + 18]/14} × 100%; sel (%) = {16/[16 + 18]} × 100%. Determined by HPLC equipped with a Chiralcel IA
column. Not determined due to the low conversion. No desired biaryl peoduct. By GC analysis, there are 1-bromonaphthalene (53%), 2-
methoxynaphthalene (43%), and naphthalene (3%) in the reaction mixture.
d
e
f
a
Table 3. Asymmetric Suzuki−Miyaura Coupling Reactions Using Catalysts (S)-7a−g
b
b
c
d
b
entry
cat.
conversn (%)
sel (%)
ee (%)
confign
16aa/17
1
2
3
4
5
6
7
7a
7b
7c
7d
7e
7f
43
32
25
26
17
9
89
96
39
29
28
10
60
74
50
60
70
e
R
R
R
R
R
1.0
2.2
0.3
0.5
0.5
7g
trace
a
b
Reaction conditions: 0.2 mmol of 14a, 0.3 mmol of 15a, 0.5 mmol of K3PO4, 2 mL of iPrOH. Based on aryl bromide 14a and determined by GC-
MS. Determined by chiral HPLC equipped with a Chiralcel IA column. Configurations of biaryls were assigned according to the literature13 (the
S isomer should come before the R isomer). Not determined.
c
d
e
methods and freshly distilled prior to use if needed. All chemicals
unless noted otherwise were purchased from major commercial
enantioselectivities of aryl−aryl cross-coupling reactions.
Efforts to develop a perfect chiral fragment with strong
suppliers and used without purification. Ligands H2[(S)-1a−d]X2 (X
= I, Br) and H2[(S)-3a]Cl2, and their palladium complexes (S)-4a−d
and (S)-7a together with the intermediates (S)-8, (S)-10, and (S)-12a
were prepared according to the literature methods.10,11
Instrumentation. NMR spectra were measured on JEOL ECA-
400 spectrometers using TMS as an internal standard. Elemental and
high-resolution mass spectral (HRMS) analyses were performed by
the Analysis Center, Fudan University. Flash column chromatography
enantioselectivity from a large amount of chiral elements in the
chiral pool are ongoing.
EXPERIMENTAL SECTION
■
General Specifications. All manipulations, unless stated
otherwise, were performed using Schlenk or glovebox techniques
under a dry argon atmosphere. Solvents were dried with standard
F
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a
Table 4. Typical Substrate Scope of Suzuki−Miyaura Cross-Coupling Using (S)-7b
a
b
Reaction conditions: 5 μmol of (S)-7b, 0.2 mmol of 14a,c,e, 0.3 mmol of 15a−f, 0.5 mmol of K3PO4, 2 mL of iPrOH. Based on aryl bromides
c
d
14a,c,e and determined by GC-MS. Determined by chiral HPLC equipped with a Chiralcel IA column unless specified otherwise. Not
determined. No desired biaryl peoduct. With a Chiralcel OJ-H column. With a Chiralcel IC column.
e
f
g
was carried out on silica gel (300−400 mesh). GC chromatograms
were recorded on a HP 4890A GC instrument equipped with a DB-5
MS UI capillary column. Flash column chromatography was carried
out on silica gel (300−400 mesh). Analytical HPLC was performed
G
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1
using an Agilent 1100 series chromatograph equipped with a Chiralcel
IA, IC, or OJ-H column, and the products were identified by
comparison with authentic samples.
Found: C, 76.13; H, 5.21; N, 8.38. H NMR (400 MHz, CDCl3): δ
2.11−2.17 (m, 2H), 2.36−2.43 (m, 4H), 2.95−3.02 (m, 2H), 7.08−
7.11 (m, 4H), 7.39−7.41 (m, 4H), 7.63−7.67 (m, 3H), 7.71−7.81
(m, 7H), 9.99 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 30.7 (CH2),
41.8 (CH2), 60.6 (C), 113.3, 114.0, 124.1, 128.3, 128.8, 129.0, 129.1,
129.6, 130.2, 132.6, 133.3, 143.0, 146.4, 146.5. HRMS (positive ions):
m/z calcd for C43H33N4 [M − 2Cl − H]+, 605.2694; calcd for
C43H34N4 [M − 2Cl]2+, 303.1386; found, 605.2682, 303.1402.
Synthesis of Palladium Compound (S)-5. Under an argon
atmosphere, a mixture of H2[(S)-2]Cl2 (183 mg, 0.27 mmol) and
Pd2(dba)3 (293 mg, 0.32 mmol) was stirred in anhydrous THF (14
mL) under reflux for 4 h. The solvent was removed under reduced
pressure, and the residue was purified by flash chromatography on
X-ray Structure Determination Details. Single crystals suitable
for X-ray crystallography were obtained by diffusion of hexane into
concentrated chloroform solutions of (S)-6 and (S)-7b at room
temperature over several days. The data were collected on a Bruker
APEX-II CCD system with graphite-monochromated Mo Kα
radiation (λ = 0.71073 Å) at 293 K. The structure was solved using
direct methods, while all non-hydrogen atoms were further refined
with full-matrix least squares on F2 obtained with the SHELXTL
program package.14 All non-hydrogen atoms were refined anisotropi-
cally. The hydrogen atoms were introduced in calculated positions
with the displacement factors of the host carbon atoms. The CCDC
files 1978451 and 1978452 contain the crystallographic data for this
paper.
Crystal data for (S)-6·CHCl3: C44H32Cl6N4Pd2, Mr = 1042.23,
orange block, 0.220 × 0.110 × 0.060 mm, monoclinic, space group
P21, a = 11.7521(8) Å, b = 19.9880(13) Å, c = 17.5819(11) Å, α =
90°, β = 90.445(2)°, γ = 90°, V = 4122.5(5) Å3, Z = 4, ρcalcd = 1.679 g
cm−3, μ = 7.361 mm−1, F(000) = 2072, T = 296(2) K; all data, R1 =
0.0905 and wR2 = 0.2606; I > 2σ(I), R1 = 0.0883 and wR2 = 0.2578;
GOF 1.053, 16576 independent reflections (2.19 ≤ 2θ ≤ 56.998°),
1009 parameters, 38 restraints.
1
silica gel to give (S)-5 as a off-white solid. Yield: 0.020 g (10%). H
NMR (400 MHz, CDCl3): δ 1.47−1.51 (m, 2H), 2.13−2.26 (m, 4H),
2.62−2.70 (m, 2H), 6.82−7.20 (m, 10H), 7.28−7.33 (m, 4H), 7.82
(d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 29.7, 30.2
(CH2), 39.2, 41.7 (CH2), 60.9 (C), 111.3, 111.9, 112.6, 122.9, 123.1,
123.5, 124.1, 124.6, 124.7, 125.6, 126.6, 127.8, 128.3, 128.5, 128.8,
129.1, 129.7, 130.5, 133.2, 134.4, 134.7, 135.7, 137.0, 137.1, 137.5,
141.9, 143.4, 146.6, 147.6, 147.8, 150.2 (Ar), 180.7, 197.4 (C−Pd).
HRMS (positive ions): m/z calcd for C43H31N4Pd [M − Cl]+,
709.1584; found, 709.1580. Anal. Calcd for C43H31ClN4Pd (M =
745.6060 g mol−1): C, 69.27; H, 4.19; N, 7.51. Found: C, 69.38; H,
4.24; N, 7.47. Moreover, the unreacted ligand H2[(S)-2]Cl2 could be
easily recycled by increasing the polarity of the eluent (EA/MeOH, 1/
1). Yield: 0.065 g (40%).
Synthesis of Palladium Complex (S)-6. Under an argon
atmosphere, a mixture of H2[(S)-2]Cl2 (53 mg, 0.078 mmol) and
Pd(OAc)2 (17.5 mg, 44.8 mg, 0.078 mmol) in DMSO (2.0 mL) was
stirred at 50 °C for 2 h and then at 100 °C for 2 h. The solvent was
removed under reduced pressure, and the residue was purified by flash
chromatography on silica gel (eluent dichloromethane/ethyl acetate,
2/1) to give a mixture of (S)-6 (major) and (S)-5 (minor) according
to its 13C NMR spectra. Yield: ca. 0.034 g (25%). The pure complex
(S)-6 could be obtained as orange bulk crystals by slowly evaporating
its chloroform solution for several weeks. 1H NMR (400 MHz,
CDCl3): δ 1.23−1.32 (m, 1H), 1.44−1.52 (m, 1H), 1.99−2.07 (m,
1H), 2.23−2.31 (m, 2H), 2.37−2.48 (m, 2H), 2.56−2.61 (m, 1H),
6.85 (d, J = 6.8 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H), 6.99 (d, J = 7.6 Hz,
1H), 7.17−7.37 (m, 9H), 7.40−7.43 (m, 2H), 7.52−7.72 (m, 7H),
8.08 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H). 13C NMR (100
MHz, CDCl3): δ 30.1, 30.9 (CH2), 42.0, 43.7 (CH2), 62.0 (C), 111.2,
111.8, 112.0, 112.2, 112.4, 123.5, 124.4, 124.5, 124.9, 125.2, 126.6,
126.7, 127.3, 128.8, 128.9, 129.2, 129.5, 129.6, 129.9, 133.2, 133.8,
134.5, 135.9, 136.1, 136.9, 137.1, 137.2, 140.5, 142.4, 145.5, 146.1,
147.0, 147.4 (Ar), 163.7, 178.6 (C−Pd). Anal. Calcd for
C44H32Cl6N4Pd2 (M = 1042.3097 g mol−1): C, 50.70; H, 3.09; N,
5.38. Found: C, 50.58; H, 3.15; N, 5.49.
Crystal data for (S)-7b: C47H31ClN4Pd, Mr = 793.61, colorless
sheet, 0.420 × 0.120 × 0.040 mm, triclinic, space group P1, a =
10.5969(9) Å, b = 12.0850(10) Å, c = 18.3811(16) Å, α =
97.416(2)°, β = 105.557(3)°, γ = 108.022(3)°, V = 2097.9(3) Å3, Z =
2, ρcalcd = 1.256 g cm−3, μ = 2.981 mm−1, F(000) = 808, T = 173(2)
K; all data, R1 = 0.0615 and wR2 = 0.1772; I > 2σ(I), R1 = 0.0603
and wR2 = 0.1757; GOF 1.058, 17103 independent reflections (3.439
≤ 2θ ≤ 59.468°), 1066 parameters, 269 restraints.
Synthesis of (S)-N1,N1′-(2,2′,3,3′-Tetrahydro-1,1′-spirobi-
[indene]-7,7′-diyl)bis(N2-phenylbenzene-1,2-diamine) ((S)-9).
Under an argon atmosphere, a mixture of (S)-N1,N1′-(2,2′,3,3′-
tetrahydro-1,1′-spirobi[indene]-7,7′-diyl)bis(benzene-1,2-diamine)
((S)-8; 388 mg, 0.9 mmol), bromobenzene (0.30 mL, 2.8 mmol),
Pd2(dba)3 (24 mg, 0.002 mmol), BINAP (50 mg, 0.08 mmol), and
NaOBut (0.35 g, 3.6 mmol) were stirred in anhydrous toluene (14
mL) at 100 °C for 3 h. The reaction mixture was cooled to room
temperature, and water was added to quench the reaction. The
insoluble materials of the mixture were removed by filtration. The
organic compound was extracted with Et2O (30 mL), washed with
H2O (25 mL × 3) and brine (25 mL), and dried over anhydrous
MgSO4. The solvent was removed under reduced pressure, and the
residue was purified by silica gel flash column chromatography (PE/
DCM = 2/1, Rf = 0.55) to give (S)-9 as a red solid. Yield: 387.2 mg
(66%). Anal. Calcd for C41H36N4 (M = 584.75 g mol−1): C, 84.21; H,
1
6.21; N, 9.58. Found: C, 84.10; H, 6.27; N, 9.76. H NMR (400
MHz, CDCl3): δ 2.16−2.32 (m, 4H), 2.88−2.94 (m, 2H), 3.00−3.08
(m, 2H), 5.00 (br s, 2H, HN), 5.48 (s, 2H, NH), 6.69−6.71 (m, 6H),
6.82−6.93 (m, 8H), 6.99 (d, J = 8.0 Hz, 2H), 7.13−7.18 (m, 8H). 13C
NMR (100 MHz, CDCl3): δ 31.2 (CH2), 36.4 (CH2), 59.2 (C),
113.2, 117.2, 118.0, 119.6, 120.3, 120.6, 122.5, 123.1, 129.0, 132.2,
133.7 (CH), 135.7, 140.8, 143.7, 145.3 (C). HRMS (positive ions):
m/z calcd for C41H37N4 [M + H]+, 585.3018; found, 585.3024.
Synthesis of Chiral Bis(benzimidazolium) Salt H2[(S)-2]Cl2.
In a round-bottomed flamed flask (25 mL) equipped with a rubber
septum and magnetic stirbar were placed (S)-9 (0. 321 g, 0.55 mmol)
and HC(OEt)3 (14.0 mL). Then, 12.1 N HCl (0.1 mL) was added
dropwise using a syringe. The resulting suspension was stirred at
room temperature for 30 min under argon and then heated to 80 °C
until condensation was observed on the neck of the flask. At this
point, the rubber septum was removed, and the solution was allowed
to sit open to the air for 2 h. After the solution was cooled to room
temperature, the supernatant was removed by decantation. The white
solid obtained was washed several times with diethyl ether, followed
by removal of residual solvents under high vacuum to afford H2[(S)-
2]Cl2 as a yellow solid. Yield: 0.287 g (71%). Anal. Calcd for
C43H34Cl2N4 (M = 677.66 g mol−1): C, 76.21; H, 5.06; N, 8.27.
Synthesis of Intermediates (S)-11b−g and (S)-12b−g. Under
an argon atmosphere, a mixture of BINAM-tetraamine (S)-10 (200
mg, 0.43 mmol), 1-bromo-2-methylbenzene (62 μL, 0.52 mmol),
Pd2(dba)3 (24 mg, 0.02 mmol), BINAP (31 mg, 0.05 mmol), and
NaOBut (171 mg, 1.8 mmol) were stirred in anhydrous toluene (8
mL) at 100 °C for 2 h. The reaction mixture was cooled to room
temperature, and water was added to quench the reaction. The
insoluble materials of the mixture were removed by filtration. The
organic compound was extracted with Et2O (30 mL), washed with
H2O (25 mL × 3) and brine (25 mL), and dried over anhydrous
MgSO4. The solvent was removed under reduced pressure and the
residue was purified by silica gel flash column chromatography to give
(S)-12b (PE/EA = 50/1, 128.7 mg) and (S)-11b (PE/EA = 10/1, 87
mg), respectively. Compounds (S)-12c−g and (S)-11c−g were
prepared in a similar method from the different aryl bromides.
(S)-11b: white solid, 36% yield. Anal. Calcd for C39H32N4 (M =
556.26 g mol−1): C, 84.14; H, 5.79; N, 10.06. Found: C, 83.98; H,
5.83; N, 9.98. 1H NMR (400 MHz): δ 7.88−7.84 (m, 2H, Ar), 7.81−
7.78 (m, 2H, Ar), 7.39 (d, J = 9.2 Hz, 1H, Ar), 7.31−6.94 (m, 15H,
Ar), 6.89−6.86 (m, 2H, Ar), 6.70−6.63 (m, 2H, Ar), 5.48 (s, 2H,
NH), 5.10 (s, 1H, NH), 3.65 (br s, 2H, NH2), 1.91 (s, 3H, CH3). 13
C
H
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NMR (100 MHz): δ 143.0, 142.6, 141.9, 138.6, 133.8, 133.7, 131.6,
130.7, 129.8, 129.7, 129.2, 128.7, 128.4, 128.3, 127.5, 127.1, 125.8,
125.6, 125.5, 125.1, 124.0, 123.5, 123.3, 122.8, 121.9, 121.1 (Ar), 17.6
(CH3). HRMS (positive ions): m/z calcd for C39H33N4 [M + H]+,
557.2705; found, 557.2702.
142.4, 140.9, 140.6, 139.2, 133.8, 130.3, 129.8, 129.7, 129.1, 128.7,
128.4, 127.5, 127.1, 127.0, 126.6, 126.4, 125.9, 125.7, 125.0, 123.9,
123.6, 123.4, 123.2, 122.8, 121.8, 120.0, 118.8, 117.0, 116.1, 115.8,
115.7, 114.7, 113.2 (Ar), 27.7 (CH), 22.8, 22.7 (CH3). HRMS
(positive ions): m/z calcd for C41H37N4 [M + H]+, 585.3018; found,
585.3021.
(S)-12b: light yellow solid, 46% yield. Anal. Calcd for C46H38N4
(M = 646.82 g mol−1): C, 85.42; H, 5.92; N, 8.66. Found: C, 85.33;
(S)-12e: light yellow solid, 20% yield. Anal. Calcd for C50H46N4
1
H, 6.03; N, 8.77. H NMR (400 MHz): δ 7.83−7.81 (m, 4H, Ar),
(M = 702.93 g mol−1): C, 85.43; H, 6.60; N, 7.97. Found: C, 85.31;
1
7.34−7.26 (m, 3H, Ar), 7.21−7.11 (m, 7H, Ar), 7.07−6.95 (m, 8H,
Ar), 6.91−6.84 (m, 4H, Ar), 6.82−6.78 (m, 2H, Ar), 5.48 (br s, 2H,
NH), 5.39 (br s, 2H, NH), 1.88 (s, 3H, CH3). 13C NMR (100 MHz):
δ 141.9, 140.9, 138.8, 133.8, 131.5, 130.9, 129.9, 129.2, 128.7, 128.5,
127.3, 126.8, 125.3, 124.2, 123.8, 123.3, 122.1, 121.1, 118.8, 117.5,
117.0, 115.0 (Ar), 17.7 (CH3). HRMS (positive ions): m/z calcd for
C46H39N4 [M + H]+, 647.3175; found, 647.3181.
H, 6.57; N, 8.01. H NMR (400 MHz): δ 7.87−7.82 (m, 4H, Ar),
7.32−7.21 (m, 10H, Ar), 7.10−6.98 (m, 10H, Ar), 6.89 (t, J = 8.8 Hz,
2H, Ar), 6.74 (t, J = 7.6 Hz, 2H, Ar), 5.72 (br s, 2H, NH), 5.37 (br s,
2H, NH), 2.87−2.81 (m, 2H, CH), 1.02 (d, J = 7.6 Hz, 12H, CH3).
13C NMR (100 MHz): δ 142.3, 141.1, 140.8, 139.1, 133.7, 129.9,
129.8, 129.0, 128.4, 127.1, 126.4, 125.9, 125.8, 125.3, 123.8, 123.5,
123.1, 122.0, 119.8, 116.8, 115.3, 114.4 (Ar), 27.7 (CH), 22.8, 22.7
(CH3). HRMS (positive ions): m/z calcd for C50H47N4 [M + H]+,
703.3801; found, 703.3799.
(S)-11c: white solid, 55% yield. Anal. Calcd for C39H32N4O (M =
572.70 g mol−1): C, 81.79; H, 5.63; N, 9.78. Found: C, 81.58; H,
5.75; N, 9.81. 1H NMR (400 MHz): δ 7.86−7.83 (m, 2H, Ar), 7.77−
7.73 (m, 2H, Ar), 7.40 (d, J = 8.8 Hz, 1H, Ar), 7.31−7.13 (m, 8H,
Ar), 7.05−6.88 (m, 6H, Ar), 6.79−6.62 (m, 5H, Ar), 6.03 (br s, 1H,
NH), 5.54 (br s, 1H, NH), 5.54 (br s, 1H, NH), 3.60 (br s, 2H, NH2),
3.49 (s, 3H, OCH3). 13C NMR (100 MHz): δ 148.5, 143.5, 142.7,
141.8, 137.0, 133.9, 133.8, 133.3, 132.9, 129.7, 129.6, 129.3, 128.6,
128.4, 128.3, 127.4, 127.3, 127.1, 126.9, 126.6, 124.6, 124.1, 123.7,
123.4, 123.2, 122.6, 122.1, 120.8, 120.1, 119.2, 118.7, 117.3, 116.0,
115.7, 115.5, 115.0, 113.1, 110.5 (Ar), 55.4 (OCH3). HRMS (positive
ions): m/z calcd for C39H33N4O [M + H]+, 573.2654; found,
573.2657.
(S)-11f: white solid, 16% yield. Anal. Calcd for C44H34N4 (M =
618.77 g mol−1): C, 85.41; H, 5.54; N, 9.05. Found: C, 85.29; H,
1
5.71; N, 8.96. H NMR (400 MHz): δ 7.87 (d, J = 8.4 Hz, 2H, Ar),
7.75 (d, J = 8.8 Hz, 2H, Ar), 7.45 (d, J = 8.8 Hz, 1H, Ar), 7.39−7.32
(m, 2H, Ar), 7.22−7.08 (m, 10H, Ar), 7.05−6.86 (m, 10H, Ar),
6.68−6.61 (m, 2H, Ar), 5.56 (s, 1H, NH), 5.53 (s, 1H, NH), 4.89 (s,
1H, NH), 3.55 (br s, 2H, NH). 13C NMR (100 MHz): δ 143.3, 142.5,
141.3, 140.5, 138.6, 136.5, 134.3, 133.8, 133.6, 131.3, 130.5, 129.6,
129.3, 129.0, 128.5, 128.3, 128.2, 128.0, 127.3, 127.0, 126.6, 124.1,
124.0, 123.4, 123.3, 122.8, 122.7, 121.9, 120.9, 120.2, 118.6, 117.4,
117.3, 115.9, 115.6, 112.9 (Ar). HRMS (positive ions): m/z calcd for
C44H35N4 [M + H]+, 619.2862; found, 619.2864.
(S)-11g: white solid, 39% yield. Anal. Calcd for C42H32N4 (M =
592.73 g mol−1): C, 85.11; H, 5.44; N, 9.45. Found: C, 85.02; H,
5.67; N, 9.54. 1H NMR (400 MHz): δ 7.91−7.80 (m, 3H, Ar), 7.77−
7.74 (m, 2H, Ar), 7.65 (d, J = 8.4 Hz, 1H, Ar), 7.70−7.42 (m, 3H,
Ar), 7.32−7.24 (m, 6H, Ar), 7.19−7.15 (m, 2H, Ar), 7.191−6.87 (m,
8H, Ar), 6.65 (dd, J = 8.8 Hz, 1.2 Hz, 1H, Ar), 6.59 (t, J = 7.6 Hz, 1H,
Ar), 6.22 (br s, 1H, NH), 5.54 (br s, 1H, NH), 5.10 (s, 1H, NH), 3.58
(br s, 2H, NH). 13C NMR (100 MHz): δ 143.0, 142.6, 142.0, 139.5,
138.3, 134.5, 133.8, 133.6, 131.2, 129.8, 129.2, 128.6, 128.4, 128.3,
127.5, 127.2, 127.1, 126.9, 126.5, 125.9, 125.6, 125.4, 124.7, 123.9,
123.4, 123.3, 122.8, 122.6, 121.5, 121.2, 118.8, 117.7, 116.9, 116.1,
115.8, 115.1, 114.8, 113.2 (Ar). HRMS (positive ions): m/z calcd for
C42H33N4 [M + H]+, 593.2705; found, 593.2707.
(S)-12c: light yellow solid, 32% yield. Anal. Calcd for C46H38N4O2
(M = 678.82 g mol−1): C, 81.39; H, 5.64; N, 8.25. Found: C, 81.28;
1
H, 5.76; N, 8.34. H NMR (400 MHz): δ 7. 78−7.74 (m, 4H, Ar),
7.30−7.22 (m, 4H, Ar), 7.19−7.10 (m, 6H, Ar), 7.01−6.95 (m, 4H,
Ar), 6.83−6.67 (m, 8H, Ar), 6.08 (br s, 2H, NH), 5.47 (br s, 2H,
NH), 3.48 (s, 6H, OCH3). 13C NMR (100 MHz): δ 148.5, 141.7,
137.3, 133.8, 132.9, 132.7, 129.6, 129.1, 128.2, 126.7, 124.6, 124.0,
123.9, 122.9, 121.8, 120.7, 120.0, 118.5, 117.0, 115.1, 115.0, 110.4
(Ar), 55.3 (OCH3). HRMS (positive ions): m/z calcd for
C46H39N4O2 [M + H]+, 679.3073; found, 679.3081.
(S)-11d: white solid, 43% yield. Anal. Calcd for C40H34N4 (M =
570.72 g mol−1): C, 84.18; H, 6.00; N, 9.82. Found: C, 84.09; H,
1
6.04; N, 9.90. H NMR (400 MHz): δ 7.89−7.84 (m, 2H, Ar), 7.79
(d, J = 8.4 Hz, 2H, Ar), 7.38 (d, J = 8.8 Hz, 1H, Ar), 7.33−7.23 (m,
3H, Ar), 7.21−6.92 (m, 11H, Ar), 6.83 (t, J = 7.2 Hz, 1H, Ar), 6.71−
6.63 (m, 2H, Ar), 5.61 (s, 1H, NH), 5.54 (s, 1H, NH), 5.10 (s, 1H,
NH), 3.62 (br s, 2H, NH2), 3.28 (q, J = 7.6 Hz, 2H, CH2), 0.97 (t, J =
7.6 Hz, 3H, CH3). 13C NMR (100 MHz): δ 143.1, 142.6, 142.1,
140.2, 139.5, 134.7, 133.8, 131.2, 129.8, 129.7, 129.2, 128.7, 128.4,
127.5, 127.1, 126.9, 126.6, 125.3, 124.3, 124.0, 123.6, 123.2, 122.8,
122.5, 120.7, 119.8, 118.8, 117.0, 116.9, 116.1, 115.8, 115.0, 113.2
(Ar), 24.1 (CH2), 13.6 (CH3). HRMS (positive ions): m/z calcd for
C40H35N4 [M + H]+, 571.2862; found, 571.2863.
(S)-12g: white solid, 41% yield. Anal. Calcd for C52H38N4 (M =
718.88 g mol−1): C, 86.88; H, 5.33; N, 7.79. Found: C, 86.69; H,
1
5.55; N, 7.83. H NMR (400 MHz): δ 7.81−7.75 (m, 6H, Ar), 7.61
(d, J = 7.6 Hz, 2H, Ar), 7.46−7.36 (m, 6H, Ar), 7.28−6.98 (m, 18H,
Ar), 6.78 (t, J = 7.6 Hz, 2H, Ar), 6.13 (br s, 2H, NH), 5.49 (br s, 2H,
NH). 13C NMR (100 MHz): δ 141.8, 139.3, 138.4, 134.6, 133.6,
131.2, 129.8, 129.1, 128.4, 128.3, 127.2, 125.9, 125.5, 125.3, 124.6,
123.6, 123.2, 122.5, 121.5, 121.2, 117.8, 116.7, 115.0, 114.8 (Ar).
HRMS (positive ions): m/z calcd for C52H39N4 [M + H]+, 719.3175;
found, 719.3181.
(S)-12d: light yellow solid, 37% yield. Anal. Calcd for C48H42N4
(M = 674.87 g mol−1): C, 85.43; H, 6.27; N, 8.30. Found: C, 85.31;
Synthesis of Intermediates (S)-13b−g. Under an argon
atmosphere, a mixture of (S)-11b (200 mg, 0.36 mmol),
bromobenzene (45 μL, 0.43 mmol), Pd2(dba)3 (20 mg, 0.02
mmol), BINAP (26 mg, 0.042 mmol), and NaOBut (171 mg, 1.5
mmol) were stirred in anhydrous toluene (7 mL) at 100 °C for 2 h.
The reaction mixture was cooled to room temperature, and water was
added to quench the reaction. The insoluble materials of the mixture
were removed by filtration. The organic compound was extracted with
Et2O (30 mL), washed with H2O (25 mL × 3) and brine (25 mL),
and dried over anhydrous MgSO4. The solvent was removed under
reduced pressure, and the residue was purified by silica gel flash
column chromatography to give (S)-13b (196 mg). Compounds (S)-
13c−g were prepared in a similar method from (S)-11c−g.
1
H, 6.14; N, 8.44. H NMR (400 MHz): δ 7.85−7.81 (m, 4H, Ar),
7.35−7.29 (m, 3H, Ar), 7.23−7.05 (m, 11H, Ar), 7.00−6.93 (m, 8H,
Ar), 6.78 (t, J = 7.2 Hz, 2H, Ar), 5.61 (br s, 2H, NH), 5.39 (br s, 2H,
NH), 2.28 (q, J = 7.6 Hz, 4H, CH2), 0.98 (t, J = 7.6 Hz, 6H, CH3).
13C NMR (100 MHz): δ 142.0, 140.1, 139.6, 134.8, 133.7, 130.9,
129.7, 129.1, 128.7, 128.3, 127.1, 126.5, 125.4, 124.5, 123.8, 123.2,
122.5, 120.6, 119.9, 116.9, 114.7 (Ar), 24.1 (CH2), 13.6 (CH3).
HRMS (positive ions): m/z calcd for C48H43N4 [M + H]+, 675.3488;
found, 675.3487.
(S)-11e: white solid, 46% yield. Anal. Calcd for C41H36N4 (M =
584.75 g mol−1): C, 84.21; H, 6.21; N, 9.58. Found: C, 84.06; H,
6.31; N, 9.60. 1H NMR (400 MHz): δ 7.90−7.81 (m, 4H, Ar), 7.37−
7.25 (m, 6H, Ar), 7.27 (d, J = 6.4 Hz, 2H, Ar), 7.17 (t, J = 7.2 Hz, 2H,
Ar), 7.11−6.98 (m, 6H, Ar), 6.91 (d, J = 8.0 Hz, 1H, Ar), 6.81 (t, J =
7.2 Hz, 1H, Ar), 6.72−6.65 (m, 2H, Ar), 5.74 (s, 1H, NH), 5.43 (s,
1H, NH), 5.15 (s, 1H, NH), 3.61 (br s, 2H, NH2), 2.85 (m, 1H, CH),
1.03 (d, J = 6.8 Hz, 6H, CH3). 13C NMR (100 MHz): δ 143.1, 142.7,
(S)-13b: light yellow solid, 68% yield. Anal. Calcd for C45H36N4
(M = 632.79 g mol−1): C, 85.41; H, 5.73; N, 8.85. Found: C, 85.37;
H, 5.81; N, 8.92. 1H NMR (400 MHz): δ 7.84 (t, J = 7.2 Hz, 4H, Ar),
7.39−7.13 (m, 13H, Ar), 7.10−7.02 (m, 5H, Ar), 6.94−6.85 (m, 5H,
Ar), 6.75 (d, J = 7.6 Hz, 2H, Ar), 5.47 (br s, 4H, NH), 1.91 (s, 3H,
I
https://dx.doi.org/10.1021/acs.organomet.0c00036
Organometallics XXXX, XXX, XXX−XXX

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CH3). 13C NMR (100 MHz): δ 142.6, 141.7, 140.7, 138.5, 138.0,
133.6, 131.4, 130.6, 129.7, 129.0, 128.3, 128.2, 127.1, 126.5, 125.0,
124.3, 123.8, 123.7, 123.6, 123.1, 122.8, 121.3, 121.1, 120.9, 118.5,
117.9, 117.4, 117.3, 116.8, 116.6, 114.8, 114.7 (Ar), 17.5 (CH3).
HRMS (positive ions): m/z calcd for C45H37N4 [M + H]+, 633.3018;
found, 633.3028.
Synthesis of Palladium Complexes (S)-7b−g. In a round-
bottomed flamed flask (25 mL) equipped with a rubber septum and
magnetic stirbar were placed (S)-9 (190 mg, 0.55 mmol) and
HC(OEt)3 (6.0 mL). Then, 12.1 N HCl (60 μL) was added dropwise
using a syringe. The resulting suspension was stirred at room
temperature for 30 min under argon and then heated to 80 °C and
continuously stirred for 3 h. After the mixture was cooled to room
temperature, the volatile material was removed under vacuum and the
residue was washed several times with diethyl ether/hexane, followed
by removal of residual solvents under high vacuum to afford H2[(S)-
3b]Cl2 as a yellow solid. Under an argon atmosphere, a mixture of
H2[(S)-3b]Cl2 (216 mg, 0.30 mmol) and Pd2(dba)3 (333 mg, 0.36
mmol) was stirred in anhydrous THF (18 mL) under reflux for 4 h.
The solvent was removed under reduced pressure, and the residue
was purified by flash chromatography on silica gel to give (S)-7b.
Complexes (S)-7c−g were prepared in a similar method from (S)-
13c−g.
(S)-13c: light yellow solid, 62% yield. Anal. Calcd for C45H36N4O
(M = 648.79 g mol−1): C, 83.31; H, 5.59; N, 8.64. Found: C, 83.22;
1
H, 5.64; N, 8.71. H NMR (400 MHz): δ 7. 81−7.13 (m, 4H, Ar),
7.37 (d, J = 8.8 Hz, 1H, Ar), 7.29−7.09 (m, 11H, Ar), 7.03−6.98 (m,
3H, Ar), 6.92−6.66 (m, 10H, Ar), 6.03 (s, 1H, NH), 5.72 (s, 1H,
NH), 5.48 (s, 1H, NH), 5.33 (s, 1H, NH), 3.48 (s, 3H, OCH3). 13C
NMR (100 MHz): δ 148.4, 142.6, 141.8, 141.6, 138.6, 136.8, 133.86,
133.7, 133.2, 132.7, 131.2, 129.7, 129.6, 129.2, 129.1, 128.9, 128.4,
128.2, 127.1, 126.9, 125.2, 125.1, 124.5, 123.8, 123.3, 123.2, 122.9,
122.1, 121.1, 120.9, 120.7, 120.0, 119.1, 118.0, 117.2, 116.9, 116.4,
115.3, 114.9, 114.5, 110.4 (Ar), 55.3 (OCH3). HRMS (positive ions):
m/z calcd for C45H37N4O [M + H]+, 649.2967; found, 649.2970.
(S)-13d: light yellow solid, 79% yield. Anal. Calcd for C46H38N4
(M = 646.82 g mol−1): C, 85.42; H, 5.92; N, 8.66. Found: C, 85.37;
1
(S)-7b (+7b′): white solid, 54% yield. H NMR (400 MHz): δ
8.21 (d, J = 6.8 Hz, 1H, Ar), 8.16−8.06 (m, 6H, Ar), 8.01 (d, J = 8.4
Hz, 1H, Ar), 7.96 (d, J = 8.4 Hz, 1H, Ar), 7.09−7.87 (m, 4H, Ar),
7.76 (d, J = 8.0 Hz, 1H, Ar), 7.67 (d, J = 8.4 Hz, 2H, Ar), 7.50 (d, J =
8.8 Hz, 1H, Ar), 7.41−7.22 (m, 20H, Ar), 7.16−6.90 (m, 18H, Ar),
6.68 (d, J = 7.6 Hz, 1H, Ar), 6.64−6.62 (m, 1H, Ar), 2.33 (s, 3H,
CH3), 1.55 (s, 3H, CH3). 13C NMR (100 MHz): δ 198.4 (minor),
197.7 (major) (C−Pd), 180.7 (major), 180.3 (minor) (C−Pd),
150.2, 150.0, 147.7, 147.5, 137.4, 137.1, 137.0, 136.7, 136.1, 136.0,
135.9, 135.7, 134.8, 134.3, 133.7, 133.4, 132.9, 132.7, 132.5, 132.3,
132.0, 131.7, 131.2, 130.8, 130.3, 130.1, 130.0, 129.9, 129.7, 129.0,
128.9, 128.7, 128.6, 128.0, 127.7, 127.6, 127.4, 127.3, 127.1, 127.0,
126.9, 126.7, 126.4, 126.3, 126.1, 125.9, 125.7, 125.0, 124.3, 124.2,
123.3, 123.2, 122.9, 122.8, 122.5, 122.3, 112.3, 112.1, 111.6, 111.5,
111.4, 111.0, 110.9 (Ar), 19.3, 18.7 (CH3). Anal. Calcd for
C47H31ClN4Pd (M = 793.6488 g mol−1): C, 71.13; H, 3.94; N,
7.06. Found: C, 71.05; H, 3.40; N, 7.11.
1
H, 6.00; N, 8.74. H NMR (400 MHz): δ 7. 82−7.78 (m, 4H, Ar),
7.32−7.20 (m, 3H, Ar), 7.18−7.08 (m, 9H, Ar), 7.03−6.90 (m, 7H,
Ar), 6.85−6.77 (m, 4H, Ar), 6.71 (d, J = 7.6 Hz, 2H, Ar), 5.64 (br s,
1H, NH), 5.57 (br s, 1H, NH), 5.36 (s, 1H, NH), 5.34 (s, 4H, NH),
2.24 (q, J = 7.6 Hz, 2H, CH2), 0.93 (t, J = 7.6 Hz, 3H, CH3). 13C
NMR (100 MHz): δ 142.6, 142.0, 141.7, 140.1, 139.5, 138.1, 134.7,
133.7, 131.6, 131.1, 129.8, 129.7, 129.1, 128.7, 128.4, 128.3, 127.2,
127.1, 126.5, 125.3, 125.1, 124.4, 124.3, 123.8, 123.2, 123.1, 122.5,
121.4, 121.0, 120.7, 119.8, 118.0, 117.4, 116.9, 116.8, 116.7, 114.9,
114.8 (Ar), 24.1 (CH2), 13.6 (CH3). HRMS (positive ions): m/z
calcd for C46H39N4 [M + H]+, 647.3175; found, 6647.3178.
(S)-13e: light yellow solid, 93% yield. Anal. Calcd for C47H40N4 (M
= 660.85 g mol−1): C, 85.42; H, 6.10; N, 8.48. Found: C, 85.39; H,
6.14; N, 8.51. 1H NMR (400 MHz): δ 7.85−7.81 (m, 4H, Ar), 7.40−
7.02 (m, 20H, Ar), 6.92−6.83 (m, 3H, Ar), 6.78−6.74 (m, 3H, Ar),
5.70 (s, 2H, NH), 5.39 (s, 1H, NH), 5.35 (s, 1H, NH), 2.86−2.79 (m,
1H, CH), 1.01 (d, J = 6.8 Hz, 6H, CH3). 13C NMR (100 MHz): δ
142.6, 142.3, 141.8, 140.9, 140.6, 139.1, 138.2, 133.8, 133.7, 131.5,
130.1, 129.8, 129.1, 128.4, 127.2, 127.1, 126.4, 125.9, 125.7, 125.2,
125.0, 124.6, 123.8, 123.7, 123.4, 123.2, 121.8, 121.4, 121.0, 118.0,
117.3, 116.9, 116.7, 115.5, 114.8, 114.6 (Ar), 27.7 (CH), 22.8, 22.7
(CH3). HRMS (positive ions): m/z calcd for C47H41N4 [M + H]+,
661.3331; found, 6661.3333.
1
(S)-7c (+7c′): white solid, 59% yield. H NMR (400 MHz): δ
(major) 8.26−8.24 (m, 1H, Ar), 8.16−7.61 (m, 8H, Ar), 7.39−6.87
(m, 17H, Ar), 6.76−6.74 (m, 1H, Ar), 6.61 (d, J = 7.6 Hz, 1H, Ar),
3.82 (s, 3H, OCH3); (minor), 8.55 (d, J = 7.6 Hz, 1H, Ar), 8.16−7.61
(m, 8H, Ar), 7.39−6.87 (m, 18H, Ar), 6.76−6.74 (m, 1H, Ar), 3.57
(s, 3H, OCH3). 13C NMR (100 MHz): δ 198.1 (minor), 197.2
(major) (C−Pd), 180.9 (major), 179.9 (minor) (C−Pd), 154.8
(major), 154.2 (minor), 150.4, 150.2, 147.8, 147.6, 137.3, 137.0,
135.9, 134.8, 133.6, 133.3, 132.7, 132.6, 132.3, 132.1, 131.9, 131.7,
131.0, 130.1, 130.0, 129.9, 128.7, 128.6, 128.3, 127.6, 127.4, 127.3,
127.1, 126.9, 126.7, 126.2, 126.0, 125.9, 125.7, 125.3, 124.7, 124.6,
124.1, 123.2, 122.4, 122.0, 121.0, 120.5, 112.9, 112.2, 112.1, 112.0,
111.9, 111.5, 111.4, 111.3, 111.1 (Ar), 56.2 (major), 55.2 (minor)
(OCH3). Anal. Calcd for C47H31ClN4OPd (M = 809.6482 g mol−1):
C, 69.72; H, 3.86; N, 6.92. Found: C, 69.66; H, 3.94; N, 7.07.
(S)-13f: white solid, 73% yield. Anal. Calcd for C50H38N4 (M =
694.86 g mol−1): C, 86.42; H, 5.51; N, 8.06. Found: C, 86.29; H,
5.62; N, 8.23. 1H NMR (400 MHz): δ 7.87−7.83 (m, 2H, Ar), 7.78−
7.76 (m, 2H, Ar), 7.41 (d, J = 8.8 Hz, 2H, Ar), 7.36−7.32 (m, 2H,
Ar), 7.29−7.20 (m, 6H, Ar), 7.18−6.83 (m, 21H, Ar), 6.81 (t, J = 8.0
Hz, 1H, Ar), 6.74 (d, J = 8.0 Hz, 2H, Ar), 5.67 (s, 1H, NH), 5.55 (s,
1H, NH), 5.50 (s, 1H, NH), 5.14 (s, 1H, NH). 13C NMR (100
MHz): δ 142.6, 141.8, 141.3, 140.4, 138.7, 138.6, 136.5, 134.1, 133.8,
133.6, 131.2, 131.1, 130.6, 129.7, 129.3, 129.1, 129.0, 128.9, 128.5,
128.4, 128.3, 124.0, 123.9, 123.7, 123.3, 123.1, 122.9, 122.1, 121.1,
121.0, 120.9, 120.1, 118.3, 117.3, 117.2, 116.8, 116.5, 115.8, 114.5
(Ar). HRMS (positive ions): m/z calcd for C50H39N4 [M + H]+,
695.3175; found, 695.3179.
(S)-13g: white solid, 78% yield. Anal. Calcd for C48H36N4 (M =
668.83 g mol−1): C, 86.20; H, 5.43; N, 8.38. Found: C, 86.11; H,
5.50; N, 8.51. 1H NMR (400 MHz): δ 7.87−7.72 (m, 2H, Ar), 7.0 (d,
J = 8.8 Hz, 1H, Ar), 7.48−7.38 (m, 3H, Ar), 7.30−7.21 (m, 3H, Ar),
7.19−7.12 (m, 5H, Ar), 7.10−7.04 (m, 4H, Ar), 7.02−7.00 (m, 3H,
Ar), 6.95 (t, J = 7.6 Hz, 1H, Ar), 6.87−6.80 (m, 2H, Ar), 6.75 (t, J =
7.6 Hz, 1H, Ar), 6.67 (d, J = 8.0 Hz, 2H, Ar), 6.15 (s, 1H, NH), 5.59
(s, 1H, NH), 5.47 (s, 1H, NH), 5.33 (s, 1H, NH). 13C NMR (100
MHz): δ 142.8, 141.9, 141.7, 139.4, 138.3, 137.9, 134.6, 133.7, 133.6,
131.7, 131.2, 129.9, 129.8, 129.1, 129.0, 128.5, 128.4, 128.3, 127.3,
127.2, 125.9, 125.6, 125.4, 125.0, 124.7, 124.3, 123.7, 123.6, 123.2,
122.6, 121.5, 121.2, 120.9, 117.8, 117.7, 116.8, 116.6, 115.0, 114.9
(Ar). HRMS (positive ions): m/z calcd for C48H37N4 [M + H]+,
669.3018; found, 669.3015.
1
(S)-7d (+7d′): white solid, 52% yield. H NMR (400 MHz): δ
8.18−8.14 (m, 4H, Ar), 8.08−8.06 (m, 1H, Ar), 8.01−7.95 (m, 3H,
Ar), 7.89−7.87 (m, 3H, Ar), 7.76 (d, J = 8.0 Hz, 1H, Ar), 7.65 (d, J =
8.0 Hz, 1H, Ar), 7.52 (d, J = 7.6 Hz, 1H, Ar), 7.45−6.85 (m, 20H,
Ar), 6.66−6.60 (m, 2H, Ar), 2.89, 2.36 (m, 2H, CH2), 1.26 (t, J = 7.6
Hz, 3H, CH3). 13C NMR (100 MHz): δ 198.3 (minor), 197.7 (mjor)
(C−Pd), 180.6 (minor), 180.2 (major) (C−Pd), 150.2 (minor),
149.9 (major), 147.7 (minor), 147.4 (minor), 137.3, 137.1, 137.0,
136.4, 136.1, 136.0, 135.9, 135.3, 134.6, 134.2, 134.1, 133.6, 133.5,
133.4, 132.8, 132.7, 132.3, 131.9, 131.6, 131.1, 130.0, 129.8, 129.5,
129.2, 129.1, 128.7, 128.6, 127.9, 127.6, 127.4, 127.3, 127.0, 126.9,
126.4, 126.2, 126.0, 125.8, 125.7, 124.9, 124.7, 124.2, 124.1, 123.3,
122.9, 122.6, 122.4, 122.3, 112.3, 112.2, 112.1, 111.5, 111.4, 110.9
(Ar), 23.7 (minor), 23.5 (major) (CH2), 13.9 (major), 13.0 (minor)
(CH3). Anal. Calcd for C48H33ClN4Pd (M = 807.6754 g mol−1): C,
71.38; H, 4.12; N, 6.94. Found: C, 71.27; H, 4.27; N, 7.06.
1
(S)-7e (+7e′): white solid, 46% yield. H NMR (400 MHz): δ
(major) 8.17−8.10 (m, 2H, Ar), 8.07−8.00 (m, 2H, Ar), 7.86 (d, J =
8.4 Hz, 2H, Ar), 7.57 (d, J = 8.8 Hz, 1H, Ar), 7.40−7.19 (m, 11H,
Ar), 7.11−7.05 (m, 3H, Ar), 7.03−6.90 (m, 4H, Ar), 6.63 (d, J = 7.6
Hz, 1H, Ar), 2.19 (m, 1H, CH), 1.21 (d, J = 6.8 Hz, 3H, CH3), 0.61
J
https://dx.doi.org/10.1021/acs.organomet.0c00036
Organometallics XXXX, XXX, XXX−XXX

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Article
(d, J = 6.8 Hz, 3H, CH3); (minor) 8.19−6.63 (m, 28H, Ar), 2.94 (m,
1H, CH), 1.40 (d, J = 6.8 Hz, 3H, CH3), 1.18 (d, J = 6.8 Hz, 3H,
CH3). 13C NMR (100 MHz): δ 197.7 (major) (C−Pd), 180.4
(minor), 180.2 (major) (C−Pd), 150.1, 147.5, 145.2, 137.3, 137.0,
136.9, 135.9, 134.3, 134.2, 133.4, 132.8, 132.7, 132.3, 131.8, 131.6,
131.2, 129.8, 129.4, 129.3, 128.7, 128.4, 127.7, 127.6, 127.3, 127.1,
126.9, 126.3, 126.2, 126.0, 125.6, 125.5, 124.8, 124.7, 124.2, 123.3,
122.9, 122.4, 112.3, 112.2, 112.1, 111.5, 110.9 (Ar), 28.1 (CH,
minor), 27.1 (CH, major), 25.7 (CH3, minor), 24.7 (CH3, major),
24.4 (CH3, minor), 23.9 (CH3, major). Anal. Calcd for
C49H35ClN4Pd (M = 821.7020 g mol−1): C, 71.62; H, 4.29; N,
6.82. Found: C, 71.51; H, 4.38; N, 6.99.
AUTHOR INFORMATION
Corresponding Author
■
Dao Zhang − Department of Chemistry, Fudan University,
200438 Shanghai, People’s Republic of China; orcid.org/
0000-0002-5853-748X; Email: daozhang@fudan.edu.cn
Author
Jueqin Yu − Department of Chemistry, Fudan University,
200438 Shanghai, People’s Republic of China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.0c00036
1
(S)-7f: white solid, 37% yield. H NMR (400 MHz): δ 8.24−8.19
(m, 1H, Ar), 8.14−8.12 (m, 1H, Ar), 7.90−7.83 (m, 4H, Ar), 7.64−
7.59 (m, 3H, Ar), 7.56−7.53 (m, 2H, Ar), 7.43−7.29 (m, 5H, Ar),
7.22−6.95 (m, 12H, Ar), 6.77 (d, J = 8.0 Hz, 1H, Ar), 6.56 (t, J = 7.6
Hz, 1H, Ar), 6.38 (d, J = 7.6 Hz, 1H, Ar), 6.19 (d, J = 8.4 Hz, 1H, Ar).
13C NMR (100 MHz): δ 197.5 (C−Pd), 180.5 (C−Pd), 150.2, 147.8,
143.3, 138.9, 137.3, 137.2, 137.1, 136.2, 135.7, 134.6, 133.4, 132.5,
132.2, 131.8, 131.1, 130.1, 130.0, 129.3, 129.0, 128.7, 128.4, 128.3,
128.1, 128.0, 127.5, 127.2, 127.1, 127.0, 126.9, 126.8, 126.3, 125.9,
124.7, 124.6, 124.2, 123.2, 121.8, 121.7, 112.1, 111.9, 111.8, 111.4
(Ar). Anal. Calcd for C52H33ClN4Pd (M = 855.7182 g mol−1): C,
72.99; H, 3.89; N, 6.55; Found: C, 72.79; H, 3.97; N, 6.71.
Notes
The authors declare no competing financial interest.
REFERENCES
■
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1
(S)-7g (+7g′): white solid, 47% yield. H NMR (400 MHz): δ
(major) 8.67 (d, J = 7.2 Hz, 1H, Ar), 8.20−8.10 (m, 4H, Ar), 7.90−
7.62 (m, 7H, Ar), 7.46−6.82 (m, 17H, Ar), 6.44 (d, J = 8.0 Hz, 1H,
Ar), 5.95 (d, J = 8.0 Hz, 1H, Ar). 13C NMR (100 MHz): δ 198.9
(minor, C−Pd), 198.6 (major, C−Pd), 180.9 (minor, C−Pd), 180.0
(major, C−Pd), 149.9, 147.4, 137.4, 137.0, 136.4, 135.8, 134.4, 134.0,
133.9, 133.4, 133.0, 132.9, 132.7, 132.3, 132.0, 131.2, 129.8, 129.6,
129.4, 129.1, 128.4, 127.8, 127.7, 127.4, 127.1, 127.0, 126.2, 126.1,
125.8, 125.7, 125.2, 124.7, 124.3, 123.3, 123.0, 122.6, 112.2, 111.7,
111.3 (Ar). Anal. Calcd for C50H31ClN4Pd (M = 829.6809 g mol−1):
C, 72.38; H, 3.77; N, 6.75. Found: C, 72.27; H, 3.84; N, 6.90.
General Procedure for Asymmetric Aryl−Aryl Cross-Cou-
pling Reactions. Aryl halides 14a−e (0.2 mmol), arylboronic acids
15a−f (0.3 mmol, 1.5 equiv), base (0.50 mmol, 2.5 equiv), and
palladium catalysts (S)-4a−d, (S)-5, and (S)-7a−g (0.004 mmol, 0.02
equiv) together with solvent (5 mL) were introduced into an oven-
dried Schlenk tube (25 mL). The mixture was deoxygenated three
times using liquid dinitrogen, the flask was then sealed, and the
mixture was stirred and heated to the desired temperature. After the
reaction mixture was kept at a given temperature for 24 h, GC-MS
was carried out, and then the mixture was treated with distilled water
(10 mL), extracted with EA (3 × 10 mL), dried (Na2SO4), and
purified by flash chromatography to give the biaryl products 16.
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9346−9352. (g) Wang, S.; Li, J.; Miao, T.; Wu, W.; Li, Q.; Zhuang,
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.0c00036.
Full 1H and 13C NMR spectra for bis-NHC-Pd
complexes together with all relevant intermediates and
typical GC and chiral HPLC characterization and
analysis data (PDF)
Accession Codes
CCDC 1978451−1978452 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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Organometallics
pubs.acs.org/Organometallics
Article
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