Chiral 1,2-cyclohexane-bridged bis-NHC palladium catalysts for asymmetric Suzuki-Miyaura coupling: Synthesis, characterization, and steric effects on enantiocontrol

Article abstract of DOI:10.1021/om400825e

The series of chiral 1,2-cyclohexane-bridged bis-N-heterocyclic carbene ligand precursors H₂[(1R,2R)-(1a-i)]Br with different substituent groups and their neutral and cationic diaqua palladium complexes, namely {Pd[(1R,2R)-(1a-i)]Br₂} (2a-i), {Pd[(1R,2R)-(1a)]X₂} (X = Cl (3), OAc (4-OAc), OC(O)CF₃ (4-OCH(O)CF₃)), and {Pd[(1R,2R)-(L^OMe)](OH₂)₂}X₂ (X = OTf (5-OTf), SbF₆ (5-SbF₆)) have been prepared in moderate to good yields. These chiral palladium complexes were fully characterized by elemental analysis, high-resolution mass spectra, ¹H and ¹³C NMR, and optical rotation determinations. The crystal structures of the chiral complexes 2a and 5-OTf were further confirmed to adopt a distorted-square-planar coordination geometry around the palladium center. The obtained chiral NHC-Pd compounds were able to catalyze the asymmetric Suzuki-Miyaura couplings of aryl halides with arylboronic acids in good yields (up to 96%) and moderate enantioselectivities (up to 64% ee). The coligand and steric effects were studied carefully. The coligands, including Br^-, Cl^-, AcO^-, CF₃COO^-, and water molecules, have little influence on the catalytic results. However, a strong steric effect of the two aromatic substituents R on the enantiocontrol has been proved in the catalytic asymmetric Suzuki-Miyaura coupling reaction. The highest enantioselectivity of 64% ee could be achieved under the standard reaction conditions.

Full text of DOI:10.1021/om400825e

Article
pubs.acs.org/Organometallics
Chiral 1,2-Cyclohexane-Bridged Bis-NHC Palladium Catalysts for
Asymmetric Suzuki−Miyaura Coupling: Synthesis, Characterization,
and Steric Effects on Enantiocontrol
Yinle Li,†,‡ Junkai Tang,† Jun Gu,† Quanrui Wang,† Peipei Sun,*,‡ and Dao Zhang*,†
†Department of Chemistry, Fudan University, Handan Road 220 Shanghai, People’s Republic of China
‡College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210097, People’s Republic of China
S
* Supporting Information
ABSTRACT: The series of chiral 1,2-cyclohexane-bridged
bis-N-heterocyclic carbene ligand precursors H2[(1R,2R)-(1a−
i)]Br with different substituent groups and their neutral and
cationic diaqua palladium complexes, namely {Pd[(1R,2R)-
(1a−i)]Br2} (2a−i), {Pd[(1R,2R)-(1a)]X2} (X = Cl (3), OAc
(4-OAc), OC(O)CF3 (4-OCH(O)CF3)), and {Pd[(1R,2R)-
(LOMe)](OH2)2}X2 (X = OTf (5-OTf), SbF6 (5-SbF6)) have
been prepared in moderate to good yields. These chiral
palladium complexes were fully characterized by elemental
1
analysis, high-resolution mass spectra, H and 13C NMR, and
optical rotation determinations. The crystal structures of the
chiral complexes 2a and 5-OTf were further confirmed to
adopt a distorted-square-planar coordination geometry around
the palladium center. The obtained chiral NHC-Pd compounds were able to catalyze the asymmetric Suzuki−Miyaura couplings
of aryl halides with arylboronic acids in good yields (up to 96%) and moderate enantioselectivities (up to 64% ee). The coligand
and steric effects were studied carefully. The coligands, including Br−, Cl−, AcO−, CF3COO−, and water molecules, have little
influence on the catalytic results. However, a strong steric effect of the two aromatic substituents R on the enantiocontrol has
been proved in the catalytic asymmetric Suzuki−Miyaura coupling reaction. The highest enantioselectivity of 64% ee could be
achieved under the standard reaction conditions.
excellent catalytic properties,11 using a chiral NHC as the ligand
in palladium-catalyzed asymmetric cross-coupling transforma-
tions still remains a difficult problem. Quite recently, Labande
and Poli reported the first example of asymmetric Suzuki−
INTRODUCTION
■
Palladium-catalyzed asymmetric Suzuki−Miyaura coupling has
recently emerged as an attractive alternative to standard
methods for the controlled synthesis of axially chiral biaryls
Miyaura coupling utilizing a palladium precatalyst with planar
that are present in numerous natural products and are the core
for many of the most effective chiral ligands.1 To obtain good
enantioselectivity, one of the challenges is to find suitable chiral
ligands to support the catalysts. To date, several kinds of chiral
chiral ferrocenyl phosphine-NHC ligands (the ee value is less
than 42%).9 Snead et al. explored chiral acylic diaminocar-
bene−Pd catalyzed Suzuki-cross-coupling; unfortunately, only
enantioselectivities of less than 4% ee were achieved.10a In
general, the direct construction of chiral biaryls with chiral
NHC-Pd precatalysts has provided some limited success; thus
further improvement of the enantioselectivity is a challenging
problem.
ligands, including monophosphine,2 kenphos,3 bis-phosphine,4
bis-hydrazones,5 phosphino-hydrazones,6 diene,7 phosphora-
mite-oxazoline,8 and phosphine-NHCs,9 have been designed
for palladium-catalyzed asymmetric Suzuki−Miyaura reactions,
and some of them showed evident asymmetric induction
activity. The studies also revealed the potential of chiral ligands
applied in asymmetric cross-coupling reactions. The design of
new and efficient chiral catalysts is still essential.
We have focused our attention on the synthesis of
functionalized NHC ligands, with the aim of producing robust
and highly active catalysts.12 Late-transition-metal complexes
bearing chiral bis-NHC ligands have proved to form higher
stable catalysts capable of tolerating reaction conditions harsher
than those for monodentate NHCs in asymmetric reactions.13
Recently, we designed a series of chiral bis-N-heterocyclic
N-heterocyclic carbenes (NHCs) have proved to be a
versatile class of spectator ligands in homogeneous catalysis.10
In some cases, NHC ligands outperformed phosphine ligands
in aspects such as the air and thermal stability of the resulting
complexes and now are frequently encountered as ancillary
ligands for different reactions. Although chiral NHCs have been
applied to transition-metal-catalyzed reactions and delivered
Received: August 16, 2013
Published: February 7, 2014
© 2014 American Chemical Society
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Scheme 1. Synthesis of Chiral Bis-N-Heterocyclic Carbene Precursors H2[(1R,2R)-(1a−i)]Br2
Scheme 2. Synthesis of Chiral Bis-NHC Palladium Complexes 2−5
carbene ligands (1a−i) derived from chiral 1,2-cyclohexanedi-
amine (Scheme 1) and prepared their neutral and cationic
diaqua palladium complexes (2−5) (Scheme 2). These chiral
palladium compounds were able to catalyze the asymmetric
Suzuki−Miyaura couplings of aryl bromides with arylboronic
acids in good yields and moderate enantioselectivities (up to
64% ee). We herein describe the preparation and character-
ization of these bis-NHC Pd complexes and their coligand and
steric effects in asymmetric Suzuki−Miyaura coupling reactions.
Chart 1
RESULTS AND DISCUSSION
■
Design and Synthesis of Chiral Bis-NHC Precursors
and Palladium Complexes. Chart 1 gives two reported
examples of metal complexes bearing chiral bis-NHC ligands
derived from 1,2-cyclohexanediamine.13 These chelating
bidentate bis-NHC ligands are expected to form more highly
stable catalysts capable of tolerating reaction conditions harsher
than than those for monodentate NHCs. We proposed that the
introduction of various coligands (Br−, Cl−, H2O) and the
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Figure 1. Molecular structure of the chiral palladium complex 2a·2H2O·CHCl3. All hydrogen atoms and solvent molecules are omitted for clarity.
steric effect of the two aromatic substituents R would modulate
the steric and electronic nature of the palladium reactive site,
promoting the catalytic performance of the chiral bis-NHC
palladium complexes 2−5 (as shown in Scheme 2) in
asymmetric Suzuki−Miyaura coupling reactions. Moreover,
the introduction of bulky t-Bu groups would improve the
solubility of palladium complexes in common organic solvents.
Chiral Bis-NHC Precursor Synthesis. The required chiral bis-
NHC precursor H2[(1R,2R)-(1a−h)]Br2 was prepared in a
multistep sequence, as shown in Scheme 1. Chiral bis-
imidazole, obtained from easily available (1R,2R)-(−)-diami-
nocyclohexene L-tartrate as the chiral starting material, reacted
with 2-(alkyloxyl)-1-(bromomethyl)-3,5-di-tert-butylbenzene to
afford the crude desired bis-imidazolium salts. After purification
by silica gel column chromatography, the proligands
H2[(1R,2R)-(1a−h)]Br2 were isolated as white solids in high
yields. The hydroxy-substituted precursor H2[(1R,2R)-(1i)]Br2
was obtained in 80% yield by deprotection of the hydroxy
group in H2[(1R,2R)-(1a)]Br2 using BBr3 to cleave the
methoxy groups.14
Bis-NHC-Pd Complex Synthesis. With the expected bis-
NHC precursors in hand, the corresponding metalation
reaction was attempted to prepare chiral palladium complexes.
The synthetic route for chelating chiral bis-NHC palladium
complexes 2−5 is depicted in Scheme 2. In general there are
two reliable synthetic pathways for the synthesis of chelating
NHC-Pd complexes.10 One is the in situ deprotonation of
imidazolium salts by Pd(OAc)2;15 the other is use of a silver-
NHC complex as a transmetalating agent.16 The proligands
H2[(1R,2R)-(1a−h)]Br2 were combined directly with Pd-
(OAc)2, and the chiral palladium complexes {Pd[(1R,2R)-
(1a−h)]Br2} (2a−h) were successfully obtained as white solids
in 70−94% yield. The reaction of the bis(imidazolium) salt
H2[(1R,2R)-(1a)]Br2 with Ag2O afforded the silver-NHC
complex, which was not isolated but continuously reacted as
the carbene transfer reagent with Pd(CH3CN)2Cl2 to give the
complex {Pd[(1R,2R)-(1a)]Cl2} (3) in 60% yield. Upon
treatment of NHC-PdII complexes 2a with the different silver
salts AgX (X = OAc, OC(O)CF3, OTf, SbF6) in the mixed
solvent MeCN/CH2Cl2 at room temperature for 3 h, the
corresponding neutral complexes {Pd[(1R,2R)-(1a)]X2} (X =
OAc (4-OAc), OC(O)CF3 (4-OCH(O)CF3)), bearing weakly
coordinating acetate counterions, and the cationic diaqua
complexes {Pd[(1R,2R)-(1a)](OH2)2}X2 (X = OTf (5-OTf),
SbF6 (5-SbF6)) were obtained in 85−95% yield.17 Attempts to
prepare 2-hydroxyphenyl-containing NHC-Pd complexes by
direct reaction of the imidazolium salts H2[(1R,2R)-(1i)]Br2
with Pd(OAc)2 proved unsuccessful; an insoluble palladium
compound always formed, which prohibited us from further
exploration. However, the complex {Pd[(1R,2R)-(1i)]Br2} (2i)
could be directly prepared in high yield (>90%) by
deprotection of the hydroxy group in {Pd[(1R,2R)-(1a)]Br2}
(2a), using BBr3 to cleave the methoxy groups.14
Characterization of Palladium Complexes. All chiral
palladium complexes 2−5 are air- and moisture-stable in the
solid state and even in solution. Their structures were
confirmed by elemental analysis, high-resolution mass spectra
1
(HRMS), H and 13C NMR, and optical rotation determi-
nations. All palladium complexes were in good agreement with
the results by HRMS. For the neutral complexes 2a−i, 3 and 4,
although no peak was observed at the position corresponding
to the parent molecule M, there was a dominant fragment ion
[M − X]+ (X = Br−, Cl−, AcO−, CF3COO−, Br−) (see the
Supporting Information) that showed the most dominant
intensity (100%) as the base peak in their mass spectra. For the
cationic diaqua complexes 5-OTf and 5-SbF6, in addition to the
presence of the fragment ion [M − 2H2O − X] at m/z
−
−
1035.3945 (X = CF3SO3 ), and 1123.3351 (X = SbF6 ), the
fragment ion at m/z 653.2498 (100%) showed the most
dominant intensity as the base peak. It was formed by bond
cleavage between the alkyl carbon and nitrogen in the fragment
ion [M − 2H2O − 2X]2+ to lose the {2-CH3O-3,5-t-
+
+
Bu2C6H2CH2 } (for short, RCH2 ) moiety.
The formation of the NHC-Pd(II) complexes was
conformed by the loss of the CH proton resonance of the
imidazolium salt and the presence of a carbene carbon (Pd-C)
at 176.4−168.0 ppm, which is a characteristic peak for metal
carbene complexes.10,17 Notably, from their 13C NMR spectra
there existed two types of NHC carbenes in these cyclo-
metalated palladium(II) complexes. For example, the signals for
the carbene carbon atom of compounds 2a and 3 appear at
176.4 and 171.0 ppm and at 175.3 and 169.2 ppm, respectively.
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Moreover, the resonance of weakly coordinating water
molecules in the cationic diaqua complexes 5-OTf and 5-
SbF6 was observed at around 2.2 ppm, which is downshifted in
comparison with that of free residual water at 1.56 ppm in
deuterated chloroform.
A single crystal of the neutral complex 2a·2H2O·CHCl3 was
obtained from hexane/chloroform. Its crystal structure (Figure
1) exhibited that the synthesis of such a chiral palladium(II)
complex did not lead to appreciable racemization; the absolute
configuration at each chiral center was assigned to be 1R,2R,
which was in accordance with the absolute configuration of the
primarily employed chiral 1,2-cyclohexanediamine. Moreover,
the cationic diaqua complex 5-OTf·CH2Cl2 was crystallized
from hexane/dichloromethane solution and its structure also
undoubtedly confirmed by X-ray crystallography (Figure 2).
The selected bond lengths and angles of these two complexes
are given in Table 1.
The bis-carbene ligand chelated the Pd(II) center in a cis
arrangement, and the two remaining coordination sites were
occupied by bromo anions or water molecules. The seven-
membered palladacycle adopted a pseudo-boatlike conforma-
tion, and the bis-NHC C−Pd−C bite angles were 84.3(3) and
83.0(3)°, respectively. The Pd−C distances (1.982(10) and
2.003(10) Å for 2a; 1.960(7) and 1.947(6) Å for 5-OTf) fall
comfortably within the range found for the neutral chiral
chelating bis(carbene)palladium(II) complexes (1.987(5) and
2.003(5) Å)13b and dibromo{1,1′-bis[(R)-1″-phenylethyl]-3,3-
methylenediimidazolin-2,2′-diylidene}palladium(II) (1.992(3)
and 1.974(3) Å)18 and the axially chiral bis-NHC-Pd(II)
complex (1.997(7) and 1.984(3) Å) as well as with those
reported for the related nonchiral neutral and dicationic bis-
NHC palladium complex cis-CH2{NC(H)C(H)N(CH3)-
C}2PdI2 (1.990(3) and 1.997(3) Å)19 and cis-CH2{NC(H)
C(H)N(CH3)C}2Pd(NCCH3)2]2−[BF4 ]2 (1.966(2) and
−
1.972(3) Å).20
Suzuki−Miyaura Cross-Coupling. We chose complex 2a
to catalyze the Suzuki−Miyaura coupling between 1-bromo-2-
methoxynaphthalene (6) and naphthylboronic acid (7) to
optimize the reaction conditions, including primarily palladium
catalyst, base, and solvent. As shown in Table S1 (Supporting
Information), THF and Cs2CO3 proved to be the best solvent
and base, respectively. The coligands, including Br−, Cl−, AcO−,
CF3COO−, and water, have little influence on the catalytic
results (Table S2, Supporting Information). The neutral
complexes 2a and 3 with halide coligands (Br, Cl) were
found to give the best results, with 92% yield and 14−16% ee
values (entries 1 and 2, Table S2). Complex 2i revealed no
activity for this model reaction (entry 7, Table S2). A possible
reason for this is that the two hydroxyl groups were
deprotonated with cesium carbonate, leading to the formation
of a stable palladium complex bearing a tetracoordinated bis-
phenol-bis-NHC ligand.21
Noncovalent interactions involving aromatic rings are myriad
areas of chemistry, materials science, and molecular biology.22
We envisioned that the aromatic interactions between the two
R groups in the chiral bis-NHC ligand might modulate the
steric and electronic nature of Pd(0)/Pd(II) reactive sites
during the oxidative addition/reductive elimination process,
promoting the enantioselectivity of Suzuki−Miyaura coupling
reactions. On the basis of this concept, we synthesized
complexes 2b−h (Scheme 2) for comparison. Table S3
(Supporting Information) and Figure 3 give the catalytic
results of model Suzuki−Miyaura coupling reactions between 6
and 7 using 2b−h as procatalysts.
Figure 2. Molecular structure of the complex 5-OTf·CH2Cl2. All
hydrogen atoms, triflate counterions, and solvent molecules are
omitted for clarity.
Table 1. Selected Bond Distances (Å) and Angles (deg) for
2a and 5-OTf
When a 4-methoxybenzyl group was introdced, the yield was
75−95% with an ee value of 11−17% (complex 2b; entries 1−
4, Table S3). This result is similar to that of complex 2a with
methyl group (entries 4−6, Table S1). Notably, complexes 2c−
e bearing ester or nitro groups promoted the reaction,
providing the biaryl product in 50−88% yield with 30−45%
ee values (entries 9−17, Table S3; see also Figure 3). This
result suggested a strong steric effect of the R groups of the
NHC ligand on the enantiocontrol in the catalytic asymmetric
Suzuki−Miyaura coupling reactions. Complex 2h with more
bulky naphthylmethyl groups also gave a poor result of 10%
yield and 20% ee (entry 20, Table S3). Further investigation
showed that the position of a weakly coordinating substituent
on the aryl group influenced the catalytic results. For example,
complexes 2e with 4-nitro, 2f with 3-nitro, and 2g with 2-nitro
gave almost similar yields of 83−85%, but quite different ee %
Complex 2a
Pd(1)−C(17)
Pd(1)−Br(1)
C(17)−Pd(1)−C(30)
C(30)−Pd(1)−Br(1)
C(30)−Pd(1)−Br(2)
1.982(10)
2.4800(12)
84.3(3)
Pd(1)−C(30)
Pd(1)−Br(2)
C(17)−Pd(1)−Br(1)
C(17)−Pd(1)−Br(2)
Br(1)−Pd(1)−Br(2)
2.003(10)
2.4637(13)
171.6(2)
93.6(2)
89.7(2)
177.2(2)
92.51(4)
Complex 5-OTf
Pd(1)−C(1)
Pd(1)−O(3)
C(1)−Pd(1)−C(30)
C(30)−Pd(1)−O(4)
C(30)−Pd(1)−O(3)
1.960(7)
2.090(4)
Pd(1)−C(30)
Pd(1)−O(4)
1.947(6)
2.085(5)
175.9(2)
96.2(2)
87.7(2)
83.0(3)
C(1)−Pd(1)−O(4)
C(1)−Pd(1)−O(3)
O(4)−Pd(1)−O(3)
93.1(2)
178.1(2)
Complexes 2a and 5-OTf showed similar crystal structures
with a distorted square planar coordinated palladium center.
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Figure 3. Steric effects on the ee values of Suzuki−Miyaura coupling.
a
Table 2. Typical Substrate Scope of Suzuki−Miyaura Coupling Using 2e
a
b
Reagents and conditions: aryl halide (1.0 equiv), arylboronic acid (1.5 equiv), Pd cat. 2e (3 mol %), CsF (2.5 equiv), THF, 65 °C, 24 h. Isolated
c
d
yields after column chromatography. The ee value was determined by HPLC, using a Chirlcel OJ-H column. No reaction.
values (45% for 2e, 28% for 2f, 16% for 2g) were achieved
under the same conditions (entries 16, 18, and 19, Table S3).
Previously we conducted DFT calculations to explore the
energy difference between the cis- and trans-dihalido-bis(NHC)
nickel(II) complexes.23 We used a similar DFT method to
study the substituent effect of the bis-NHC-Pd catalysts.
Complexes 2e (R = CH2Ph-NO2-4) and 2g (R = CH2Ph-NO2-
2) were chosen as model compounds. The minimized energy
values of the two complexes are 18.6244 kcal/mol (for 2e) and
22.3492 kcal/mol (for 2g), respectively. From the optimized
structures of 2e,g (see the Supporting Information, Figure S0),
we found that aromatic interactions22 exist between the two R
groups. Also in 2e, hydrogen bonding (N−O−H) could be
found. The observed high ee value of 2e is due to the combined
effect of the noncovalent interaction and hydrogen bonding
between the two substituted aromatic groups.
A typical substrate scope screening test of the Suzuki−
Miyaura reaction with 2e as the catalyst was performed. These
results are summarized in Table 2. Under the representative
conditions (CsF, THF, 65 °C, 24 h), several naphthyl halides
and arylboronic acids with different steric substituents were
investigated for coupling with each other (Table 2). We did
observe an obvious improvement in coupling enantioselectivity
(from 45% to 57% ee) with a decrease of product yield (from
83% to 45%) when a more bulky substituent was introduced to
the bromide substrate (entry 2 vs 1, Table 2). We failed to
obtain the polysubstituted biary compounds by Suzuki coupling
using the above palladium catalyst (entry 3, Table 2).
Interestingly, aryl chloride was also successfully coupled to
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The X-ray crystallographic files, in CIF format, are available from
the Cambridge Crystallographic Data Centre on quoting the
deposition numbers CCDC 909112 for 2a·2H2O·CHCl3 and CCDC
909113 for 5-OTf·CH2Cl2. Copies of this information may be
obtained free of charge from the Director, CCDC, 12 Union Road,
Cambridge CB2IEZ, U.K. (fax, +44-1223-336033; e-mail, deposit@
ccdc.cam.ac.uk; web, http://www.ccdc.cam.ac.uk). X-ray crystallo-
graphic data and refinement details for 2a and 5-OTf are given in
the Supporting Information, and selected bond lengths and angles are
given in Table 1.
arylboronic acid with a moderate yield of ca. 50%. The Suzuki−
Miyaura coupling between 1-chloro-2-methoxynaphthalene and
naphthylboronic acid provided the highest enantioselectivity of
64% ee (entry 4, Table 2).
CONCLUSIONS
■
In summary, a series of new neutral and cationic palladium(II)
complexes bearing chiral-bridged bis-NHC ligands have been
synthesized and fully characterized. These palladium complexes
showed good activities in Suzuki−Miyaura reactions of
naphthyl halides with naphthylboronic acids. The coligands,
including Br−, Cl−, AcO−, CF3COO−, and water, have little
influence on the catalytic results. However, a strong steric effect
of the aromatic interactions between the two R groups in the
chiral bis-NHC ligand on the enantiocontrol has been proved
in the catalytic asymmetric Suzuki−Miyaura coupling reaction.
A moderate enantioselectivity of 64% ee could be achieved
under the standard reaction conditions. This protocol provides
a promising method for the synthesis of bis-aryl products.
Synthesis of {Pd[(1R,2R)-(1a)]Br2} (2a). A mixture of
H2[(1R,2R)-(1a)]Br2 (188 mg, 0.2 mmol) and 98% Pd(OAc)2 (44.8
mg, 0.2 mmol) in DMSO (3.0 mL) was stirred at 50 °C for 2 h and
then at 110 °C for 3 h. After the solvent was removed by reduced
pressure while heating, the residue was purified by silica gel column
chromatography (eluent 1/9 EtOAc/CH2Cl2) to afford a brown crude
product. The crude product was then washed with toluene to afford
the pure palladium complex 2a as a white solid. Yield: 188 mg (90%).
Anal. Calcd for C52H68Br2N4O2Pd [1047.35 g/mol]: C, 59.63; H, 6.54;
N, 5.35. Found: C, 59.44; H, 6.66; N, 5.57. HRMS (positive ions): m/
z 967.3609 (calcd for [M − Br−]+ 967.36). [α]2D0 = 26.89° (c = 0.1,
1
CHCl3). H NMR (400 MHz, CDCl3): δ 7.65−7.67 (d, J = 8.86 Hz,
1H), 7.55 (t, J = 12.80 Hz, 1H), 7.34 (d, J = 10.00 Hz, 1H), 7.12−7.24
(m, 4H), 7.03 (t, J = 9.60 Hz, 1H), 6.93 (t, J = 9.60 Hz, 1H), 6.68−
6.80 (d, J = 7.80 Hz, 2H), 6.56 (d, J = 7.80 Hz, 1H), 5.94−6.17 (m,
4H), 5.45 (s, 1H), 4.68−4.74 (t, J = 10.42 Hz, 1H), 3.85 (s, 3H), 3.40
(s, 3H), 2.97−3.00 (d, J = 11.92 Hz, 1H), 2.77−2.79 (m, 1H), 2.62−
2.64 (d, J = 11.92 Hz, 1H), 2.15−2.34 (m, 3H),1.99−2.03 (m, 1H),
1.83 (m, 1H), 1.24−1.37 (d, J = 9.64 Hz, 18H, t-Bu), 0.94 (s, 9H, t-
Bu), 0.77 (s, 9H, t-Bu). 13C NMR (100 MHz, CDCl3): δ 176.4, 171.0
(Ccarbene), 155.5, 155.2 (CAr‑O), 146.4, 145.9, 142.0, 141.4 (CAr‑t‑Bu),
134.2, 134.0(CAr), 131.8, 129.1, 128.3, 127.2, 125.0, 126.8, 124.1,
123.8, 123.3, 113.1, 111.4, 109.8 (CHAr), 63.3, 62.8 (OCH3), 62.4,
61.1 (CHcyclohexyl), 50.2, 47.6 (CH2−N), 35.3, 34.4, 34.3 (Ct‑Bu), 31.1,
31.0 (CH3t‑Bu), 25.8, 25.1. 21.0 (CH2cyclohexyl).
Synthesis of {Pd[(1R,2R)-(1b)]Br2} (2b). A mixture of
H2[(1R,2R)-(1b)]Br2 (231 mg, 0.2 mmol) and 98% Pd(OAc)2 (44.8
mg, 0.2 mmol) in DMSO (3.0 mL) was stirred at 50 °C for 2 h and
then at 110 °C for 3 h. After the solvent was removed by reduced
pressure with heating, the residue was purified by silica gel column
chromatography (eluent 1/9 EtOAc/CH2Cl2) to afford the pure
palladium complex 2b as a white solid. Yield: 201 mg (80%). HRMS
(positive ions): m/z 1179.4392 (calcd for [M − Br−]+ 1179.4402). 1H
NMR (400 MHz, CDCl3): δ 7.50−7.65 (m, 4H), 7.29−9.31 (d, J =
8.00 Hz, 3H), 7.21 (s, 2H), 7.08−7.14 (q, J = 16.00 Hz, 2H), 6.87−
6.96 (dt, J = 20.80, 8.00 Hz, 2H), 6.76 (m, 4H), 6.49−6.54 (m, 2H),
4.49 (m, 2H), 4.71 (m, 2H), 3.71 (s, 3H), 3.57 (s, 3H), 2.91 (m, 1H),
2.79 (m, 1H), 2.58 (m, 1H), 2.12−2.25 (m, 3H), 1.84−1.99 (m, 1H),
1.60−1.72 (m, 4H), 1.44−1.46 (d, J = 9.60 Hz, 18H), 0.89 (s, 18H).
13C NMR (100 MHz, CDCl3): δ 175.6, 169.8, 159.1, 159.0, 154.1,
153.7, 146.5, 145.7, 141.6, 134.6, 134.0, 133.4, 132.3, 129.7, 129.2,
129.0, 127.7, 127.4, 123.7, 123.7, 123.5, 123.3, 123.1, 113.8, 113.7,
113.0, 112.6, 111.6, 109.9, 76.3, 63.0, 60.6, 55.1, 54.8, 50.1, 47.7, 35.3,
34.1, 33.8, 31.0, 30.9, 30.6, 29.6, 25.5, 24.7.
Synthesis of {Pd[(1R,2R)-(1c)]Br2} (2c). A mixture of
H2[(1R,2R)-(1c)]Br2 (248 mg, 0.2 mmol) and 98% Pd(OAc)2 (44.8
mg, 0.2 mmol) in DMSO (3.0 mL) was stirred at 50 °C for 2 h and
then at 110 °C for 3 h. After the solvent was removed by reduced
pressure with heating, the residue was purified by silica gel column
chromatography (eluent 1/9 EtOAc/CH2Cl2) to afford the pure
palladium complex 2c as a white solid. Yield: 252 mg (94%). HRMS
(positive ions): m/z 1263.4642 (calcd for [M − Br−]+ 1263.4613). 1H
NMR (400 MHz, CDCl3): δ 7.94 (s, 4H), 7.69−7.71 (d, J = 8.24 Hz,
1H), 7.55 (s, 3H), 7.37−7.39 (d, J = 8.24 Hz, 3H), 7.09−7.18 (m,
4H), 6.90−6.92 (m, 2H), 6.51−6.53 (d, J = 7.80 Hz, 2H), 6.45−6.47
(d, J = 7.80 Hz, 2H), 4.98 (s, 2H), 4.79−4.82 (m, 2H), 4.64 (s, 1H),
4.31−4.34 (q, J = 12.36 Hz, 4H), 2.81 (s, 2H), 2.55−2.58 (d, J = 12.84
Hz, 1H), 2.29 (s, 2H), 2.06 (s, 2H), 1.91 (s, 2H), 1.33−1.36 (d, J =
11.80 Hz, 18H), 0.80−0.81 (d, J = 3.68 Hz, 18H). 13C NMR (100
MHz, CDCl3): δ 175.7, 169.8, 166.4, 153.5, 153.4, 146.5, 146.4, 142.1,
EXPERIMENTAL SECTION
■
General Considerations. All manipulations were performed
under an inert atmosphere of dry argon by using vacuum line and
Schlenk tube techniques. All chemical reagents were purchased from
commercial sources (Acros, Aldrich, Alfa Aesar, or Fluka) and used as
received unless otherwise indicated. The solvents were dried and
distilled prior to use by literature methods. H and 13C{1H} NMR
1
spectra were recorded on JEOL ECA-400 and Bruker AV500
1
spectrometers. H and 13C chemical shifts (δ) are given in ppm (the
residual peak of deuterated solvents was used as reference). Elemental
and high-resolution mass spectral (HRMS) analyses were carried out
by the Analysis Center, Fudan University. Optical rotations were
measured in a 100 mm cell with a Perkin-Elmer 241 photopolarimeter.
Flash column chromatography was performed on silica gel (300−400
mesh). GC chromatograms were recorded on a HP 4890A GC
equipped with a DB-5 MS UI capillary column, and the products were
identified by comparison with authentic samples. HPLC chromato-
grams were recorded on a Shimadzu LC-2010A (HT) equipped with a
Chiralcel OJ-H column.
X-ray Crystallographic Studies. Single crystals of 2a and 5-OTf
suitable for X-ray analysis were sealed into a glass capillary, and the
intensity data of the single crystals were collected on the CCD Bruker
Smart APEX system. Data obtained with the ω−2θ scan mode were
collected on a Bruker SMART 1000 CCD diffractometer with
graphite-monochromated Mo Kα radiation (λ = 0.71073 Å) at 293 K.
The structures were solved using direct methods, while further
refinement with full-matrix least squares on F2 was obtained with the
SHELXTL program package.24 All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were introduced in calculated
positions with the displacement factors of the host carbon atoms.
Crystal Data for 1a·2H2O·CHCl3: C53H73Br2Cl3N4O4Pd, Mr
1202.72, colorless block, 0.18 × 0.15 × 0.13 mm, triclinic, space group
=
P1, a = 9.141(3) Å, b = 10.484(4) Å, c = 15.961(6) Å, α = 91.789(5)°,
β = 104.749(4)°, γ = 96.057(4)°, V = 1468.2(9) Å3, Z = 1, ρcalcd
=
1.360 g cm−3, μ = 1.857 mm−1, F(000) = 618, T = 293(2) K; all data,
R1 = 0.0591 and wR2 = 0.1569; I > 2σ(I), R1 = 0.0554 and wR2 =
0.1503; GOF 1.034, 6090 independent reflections (2θ ≤ 50.04°) and
595 parameters, 3 restraints.
Crystal Data for 5-OTf·CH2Cl2: C55H72Cl2F6N4O10PdS2, Mr
=
1304.59, colorless prism, 0.51 × 0.23 × 0.20 mm, monoclinic, space
group P21/c, a = 22.615(7) Å, b = 15.136(5) Å, c = 18.857(6) Å, β =
95.865(5)°, V = 6421(3) Å3, Z = 4, ρcalcd = 1.350 g cm−3, μ = 0.509
mm−1, F(000) = 2704, T = 293(2) K; all data, R1 = 0.1381 and wR2 =
0.2654; I > 2σ(I), R1 = 0.0831 and wR2 = 0.2409; GOF 1.015, 11291
independent reflections (2θ ≤ 50.02°) and 708 parameters, 6
restraints.
881
dx.doi.org/10.1021/om400825e | Organometallics 2014, 33, 876−884

Organometallics
Article
141.9, 134.6, 134.0, 133.8, 132.2, 129.8, 127.3, 126.9, 124.1, 123.9,
112.9, 112.7, 111.8, 110.2, 75.8, 63.2, 60.9, 35.4, 35.3, 31.1, 30.9, 30.8,
25.8, 25.2, 14.4.
26.05° (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.93−8.06 (m,
5H), 7.66−7.74 (m, 4H), 7.36- 7.46 (m, 3H), 7.10−7.18 (m, 4H),
6.93−7.00 (m, 2H), 6.76−6.78 (d, J = 8.00 Hz, 1H), 6.56−6.58 (d, J =
8.40 Hz, 1H), 5.98 (m, 2H), 5.16−5.42 (m, 4H), 4.77−4.82 (m, 1H),
2.83 (s, 2H), 2.54−2.56 (d, J = 11.60 Hz, 1H), 2.20 (s, 2H), 2.08−2.11
(m, 1H), 1.85−1.91 (m, 2H), 1.28 (s, 18H), 0.83 (s, 18H). 13C NMR
(100 MHz, CDCl3): δ 176.0, 170.0, 153.3, 153.1, 147.2, 147.1, 146.6,
146.4, 141.6, 134.9, 134.2, 134.1, 134.0, 133.6, 133.4, 133.0, 132.5,
129.7, 129.0, 128.4, 128.3, 128.0, 127.4, 124.9, 124.7, 124.2, 123.9,
123.8, 123.7, 123.3, 113.0, 112.7, 111. 8, 110.0, 73.5, 73.3, 63.0, 60.7,
35.2, 34.3, 33.8, 31.0, 25.6, 24.9.
Synthesis of {Pd[(1R,2R)-(1d)]Br2} (2d). A mixture of
H2[(1R,2R)-(1d)]Br2 (246 mg, 0.2 mmol) and 98% Pd(OAc)2
(44.8 mg, 0.2 mmol) in DMSO (3.0 mL) was stirred at 50 °C for 2
h and then at 110 °C for 3 h. After the solvent was removed by
reduced pressure with heating, the residue was purified by silica gel
column chromatography (eluent 1/10 EtOAc/CH2Cl2) to afford the
pure palladium complex 2d as a white solid. Yield: 187 mg (70%).
HRMS (positive ions): m/z 1255.39 (calcd for [M − Br−]+ 1255.39).
[α]2D0 = 27.15° (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.67−
7.69 (d, J = 8.40 Hz, 3H), 7.52 (s, 7H), 7.33−7.35 (d, J = 8.40 Hz,
1H), 7.13−7.22 (m, 4H), 6.92−6.98 (m, 2H), 6.51−6.56 (m, 2H),
4.99−5.01 (m, 2H), 4.88 (m, 1H), 4.71−4.77 (m, 1H), 2.81 (m, 2H),
2.57−2.60 (d, J = 12.40 Hz, 1H), 2.22−2.25 (d, J = 12.40 Hz, 2H),
2.13−2.16 (d, J = 13.20 Hz, 1H), 1.96 (m, 1H), 1.82−1.86 (d, J =
13.20 Hz, 1H), 1.39−1.43 (d, J = 17.20 Hz, 18H), 0.86 (m, 18H). 13C
NMR (100 MHz, CDCl3): δ 175.9, 170.0, 153.47, 153.3, 146.9, 141.8,
140.9, 134.8, 133.6, 132.4, 128.0, 127.8, 127.4, 127.0, 125.4, 124.1,
123.9, 123.8, 123.7, 123.4, 122.7, 113.0, 112.8, 111.6, 109.9, 77.4, 77.0,
76.7, 75.5, 63.0, 60.8, 35.4, 34.3, 33.9, 31.0, 30.8, 25.6, 25.0.
Synthesis of {Pd[(1R,2R)-(1e)]Br2} (2e). A mixture of
H2[(1R,2R)-(1e)]Br2 (236.8 mg, 0.2 mmol) and 98% Pd(OAc)2
(44.8 mg, 0.2 mmol) in DMSO (3.0 mL) was stirred at 50 °C for 2
h and then at 110 °C for 3 h. After the solvent was removed by
reduced pressure with heating, the residue was purified by silica gel
column chromatography (eluent 1/9 EtOAc/CH2Cl2) to afford the
pure palladium complex 2e as a white solid. Yield: 219 mg (85%).
HRMS (positive ions): m/z 1209.3929 (calcd for [M − Br−]+
1209.3892). 1H NMR (400 MHz, CDCl3): δ 8.06−8.09 (dd, J =
14.64 Hz, 8.68 Hz, 4H), 7.75 (s, 2H), 7.68−7.71 (d, J = 8.24 Hz, 1H),
7.53 (m, 3H), 7.35 (d, J = 8.24 Hz, 1H), 7.19−7.21 (d, J = 7.32 Hz,
2H), 7.12−7.16 (t, J = 7.32 Hz, 2H), 6.94−6.98 (m, 2H), 5.17 (s, 1H),
5.04−5.07 (d, J = 12.84 Hz, 1H), 4.91−4.94 (d, J = 10.08 Hz, 1H),
4.68−4.79 (m, 2H), 2.79 (s, 2H), 2.55−2.58 (d, J = 12.36 Hz, 1H),
2.16−2.22 (t, J = 10.48 Hz, 1H), 2.09−2.13 (d, J = 13.76 Hz, 1H),
1.79−1.95 (m, 3H), 1.41 (s, 9H), 1.34 (s, 9H), 0.82−0.83 (d, J = 4.12
Hz, 18H). 13C NMR (100 MHz, CDCl3): δ 175.6, 169.8, 153.1, 147.4,
146.7, 144.3, 142.0, 135.2, 134.2, 134.0, 132.8, 128.2, 127.6, 126.8,
124.1, 124.0, 123.8, 112.7, 111.8, 110.2, 74.5, 63.1, 60.8, 50.2, 47.8,
35.4, 34.4, 34.2, 31.1, 30.9, 24.9.
Synthesis of {Pd[(1R,2R)-(1h)]Br2} (2h). A mixture of
H2[(1R,2R)-(1h)]Br2 (238.8 mg, 0.2 mmol) and 98% Pd(OAc)2
(44.8 mg, 0.2 mmol) in DMSO (3.0 mL) was stirred at 50 °C for 2
h and then at 110 °C for 3 h. After the solvent was removed by
reduced pressure with heating, the residue was purified by silica gel
column chromatography (eluent 1/9 EtOAc/CH2Cl2) to afford the
pure palladium complex 2h as a white solid. Yield: 187 mg (72%).
HRMS (positive ions): m/z 1219.4545 (calcd for [M − Br−]+
1
1219.4479). H NMR (400 MHz, CDCl3): δ 8.25 (s, 1H), 7.85 (s,
3H), 7.40−7.65 (m, 8H), 7.10−7.28 (m, 8H), 7.00 (s, 3H), 6.79 (s,
2H), 6.47 (d, J = 8.24 Hz, 1H), 6.28 (s, 1H), 5.13 (s, 2H), 4.52 (s,
1H), 2.86 (s, 1H), 2.64 (m, 1H), 2.47 (m, 1H), 1.93−2.15 (m, 5H),
1.33−1.45 (m, 18H), 1.18 (s, 18H). 13C NMR (100 MHz, CDCl3): δ
176.2, 170.5, 154.0, 153.6, 146.8, 145.6, 141.5, 134.9, 134.6, 133.9,
133.7, 133.5, 133.2, 133.0, 132.8, 132.4, 128.5, 128.2, 128.0, 127.8,
127.5, 127.3, 126.8, 125.9, 125.7, 124.9, 123.7, 123.5, 123.3, 123.2,
113.3, 112.9, 111.1, 109.5, 62.9, 60.9, 51.0, 47.5, 35.5, 35.4, 33.8, 31.4,
31.0, 29.7, 29.4, 25.6, 25.0, 14.1.
Synthesis of {Pd[(1R,2R)-(1i)]Br2} (2i). Boron tribromide (0.30
mL, 3.13 mmol) was added dropwise to a stirred solution of the
palladium complex {Pd[(1R,2R)-(2a)]Br2} (105 mg, 0.1 mmol) in
DCM (15 mL) previously cooled in an acetone/liquid nitrogen slush
bath (−80 °C). The mixture was kept at this temperature for 1 h and
then warmed to room temperature and stirred overnight. The mixture
was cooled again in an acetone/liquid nitrogen slush bath, and
methanol (30 mL) was added slowly. The solvent was then removed
under vacuum to give a brown-orange solid, which was recrystallized
from methanol to yield a white solid. Yield: 96 mg (95%). Anal. Calcd
for C50H64Br2N4O2Pd [1019.3 g/mol]: C, 58.92; H, 6.33; N, 5.50.
Found: C, 58.81; H, 6.42; N, 5.71. HRMS (positive ions): m/z
939.3427 (calcd for [M − Br−]+ 939.33), 639.2320 (calcd for [M −
+
+
+
Synthesis of {Pd[(1R,2R)-(1f)]Br2} (2f). A mixture of H2[(1R,2R)-
(1f)]Br2 (240 mg, 0.2 mmol) and 98% Pd(OAc)2 (45 mg, 0.2 mmol)
in DMSO (3.0 mL) was stirred at 50 °C for 2 h and then at 110 °C for
3 h. After the solvent was removed by reduced pressure with heating,
the residue was purified by silica gel column chromatography (eluent
1/10 EtOAc/CH2Cl2) to afford the pure palladium complex 2f as a
white solid. Yield: 190 mg (73%). HRMS (positive ions): m/z 1209.39
2Br− − RCH2 ]+ (RCH2 = [2-HO-3,5-(t-Bu)2(C6H2)CH2 ])
1
639.23). H NMR (400 MHz, CD3SOCD3): δ 7.99−7.79 (m, 6H),
7.40−7.10 (m, 4H), 6.88 (m, 2H), 6.47 (m, 2H), 6.25 (m, 1H), 5.79
(m, 2H), 5.06 (s, 1H), 3.06 (s, 4H), 2.72 (s, 2H), 2.22 (s, 2H), 2.02−
1.80 (m, 4H), 1.36 (s, 18H), 0.97 (s, 9H), 0.91 (s, 9H). No
satisfactory 13C NMR could be obtained due to the low solubility of 2i
in organic solvent.
1
(calcd for [M − Br−]+ 1209.39). [α]D20 = 25.03° (c 0.1, CHCl3). H
Synthesis of {Pd[(1R,2R)-(1a)]Cl2} (3). Ag2O (23.2 mg, 0.1
mmol) was added to a dichloromethane solution (10 mL) of
H2[(1R,2R)-(1a)]Br2 (94 mg, 0.1 mmol). The suspension became
clear after it was stirred for 2 h at room temperature. Pd(CH3CN)2Cl2
was then added, and the resultant solution was stirred for an additional
2 h. After the precipitate was filtered, the solvent was removed by
reduced pressure with heating and the residue was further purified by
silica gel column chromatography (eluent 1/9 EtOAc/CH2Cl2) to
afford a brown crude product. The crude product was washed with
toluene to afford the pure palladium complex 3 as a white solid. Yield:
57.5 mg (60%). Anal. Calcd for C52H68Cl2N4O2Pd [958.45 g/mol]: C,
65.16; H, 7.15; N, 5.85. Found: C, 64.99; H, 7.26; N, 5.95. HRMS
NMR (400 MHz, CDCl3): δ 8.20 (s, 2H), 8.07−8.09 (d, J = 7.60 Hz,
1H), 8.03 (s, 1H), 7.914 (s, 1H), 7.66−7.73 (m, 2H), 7.45−7.53 (m,
3H), 7.35−7.37 (d, J = 8.00 Hz, 1H), 7.13−7.20 (m, 4H), 6.93−7.02
(m, 2H), 6.51−6.55 (t, J = 7.60 Hz, 3H), 6.15 (m, 1H), 5.14 (m, 1H),
4.99−5.02 (d, J = 12.80 Hz, 2H), 4.72−4.78 (m, 2H), 2.78 (s, 2H),
2.56 (d, 1H), 2.14−2.21 (m, 3H), 1.85−1.94 (m, 2H), 1.34−1.36 (d, J
= 9.60 Hz, 18H), 0.85−0.86 (t, J = 3.40 Hz, 18H). 13C NMR (100
MHz, CDCl3): δ 175.6, 169.7, 153.1, 153.0, 148.3, 148.2, 147.0, 146.7,
141.9, 139.2, 134.8, 133.9, 133.7, 133.5, 132.9, 132.3, 129.5, 127.8,
127.0, 124.1, 124.0, 123.9, 123.8, 123.5, 122.6, 121.6, 121.4,112.9,
112.7, 111.6, 110.0, 77.4, 77.1, 76.8, 74.4, 63.0, 60.7, 35.3, 34.3, 33.8,
31.0, 30.9, 25.6, 24.9.
(positive ions): m/z 921.4104 (calcd for [M − Cl−]+ 921.41). [α]D20
=
1
Synthesis of {Pd[(1R,2R)-(1g)]Br2} (2g). A mixture of
H2[(1R,2R)-(1g)]Br2 (240 mg, 0.2 mmol) and 98% Pd(OAc)2 (45
mg, 0.2 mmol) in DMSO (3.0 mL) was stirred at 50 °C for 2 h and
then at 110 °C for 3 h. After the solvent was removed by reduced
pressure with heating, the residue was purified by silica gel column
chromatography (eluent 1/9 EtOAc/CH2Cl2) to afford the pure
palladium complex 2g as a white solid. Yield: 189 mg (73%). HRMS
21.52° (c = 0.1, CHCl3). H NMR (400 MHz, CDCl3): δ 7.64−7.67
(d, J = 11.72 Hz, 1H), 7.55 (t, J = 14.00 Hz, 1H), 7.30 (d, J = 9.20 Hz,
1H), 7.15−7.24 (m, 3H), 7.05 (t, J = 9.60 Hz, 1H), 6.95 (t, J = 9.60
Hz, 1H), 6.80 (s, 1H), 6.77 (d, J = 9.60 Hz, 1H), 6.69 (d, J = 10.04 Hz,
1H), 6.60 (s, 1H), 5.94−6.07 (m, 4H), 5.46 (s, 1H), 4.68−4.74 (t, J =
9.60 Hz, 1H), 3.83 (s, 3H), 3.44 (s, 3H), 2.96−2.99 (d, J = 11.00 Hz,
1H), 2.80 (m, 1H), 2.1−2.64 (d, J = 11.92 Hz, 1H), 2.15−2.26 (m,
2H), 2.03 (m, 1H), 1.84 (m, 1H), 1.59 (m, 1H), 1.37−1.39 (d, J =
(positive ions): m/z 1209.39 (calcd for [M − Br−]+ 1209.39). [α]2D0
=
882
dx.doi.org/10.1021/om400825e | Organometallics 2014, 33, 876−884

Organometallics
Article
8.24 Hz, 18H, t-Bu), 0.84 (s, 9H, t-Bu), 0.76 (s, 9H, t-Bu). 13C NMR
(100 MHz, CDCl3): δ 175.3, 169.2 (Ccarbene), 155.5, 155.2 (CAr‑O),
146.5, 145.8, 142.0, 141.4 (ArC‑t‑Bu), 134.8, 134.0, 132.4(CAr), 128.0
(CHAr), 127.0, 124.1, 123.8, 123.4, 113.0, 111.4, 109.8 (CHAr), 63.3,
62.6 (OCH3), 61.1(CHcyclohexyl), 49.7, 47.3 (CH2-N), 35.3, 34.2
(Ct‑Bu), 31.1, 31.0 (CH3t‑Bu), 30.2, 25.7, 25.0 (CH2cyclohexyl).
2.65−2.69 (d, J = 15.60 Hz, 1H), 2.42 (m, 1H), 2.25 (br, <4H, H2O-
Pd), 1.80 (m, 1H), 1.39−1.41 (d, J = 7.80 Hz, 18H), 0.78−0.81 (d, J =
11.44 Hz, 18H). 13C NMR (100 MHz, CDCl3): δ 161.3 (Ccarbene),
155.5, 155.4 (CAr‑OMe), 146.5, 142.8 (CAr‑t‑Bu), 134.8, 134.2, 133.7,
132.6, 125.0, 125.8, 124.9, 124.5, 124.4, 124.3, 121.9, 119.8, 117.0,
CF3SO3
113.3, 112.9, 112.8 (CHAr + CF3
), 65.0, 63.2 (OCH3), 62.7, 62.6,
61.3(CHcyclohexyl), 49.4, 47.7 (CH2-N), 35.5, 34.8 (Ct‑Bu), 31.1, 31.0
(CH3t‑Bu), 30.9, 24.9, 24.6 (CH2cyclohexyl).
Synthesis of {Pd[(1R,2R)-(1a)](OAc2} (4-OAc). Complex 2a
(104.8 mg, 0.1 mmol) was suspended in a mixture of CH2Cl2 (7.5 mL)
and CH3CN (2.5 mL). AgOAc (35 mg, 0.21 mmol) was added, and
the mixture was stirred at room temperature for 3 h. The resulting
suspension was filtered from the precipitated AgBr through Celite, and
the solvent was removed under reduced pressure to give complex 4-
OAc as a white powder. Yield: 90.4 mg (90%). Anal. Calcd for
C56H74N4O6Pd [1005.63 g/mol]: C, 66.88; H, 7.42; N, 5.57. Found:
C, 66.65; H, 7.31; N, 5.71. HRMS (positive ions): m/z 945.4545
Synthesis of {Pd[(1R,2R)-(1a)] (OH2)2}[SbF6]2 (5-SbF6). Com-
plex 2a (104.8 mg, 0.1 mmol) was suspended in a mixture of CH2Cl2
(7.5 mL) and CH3CN (2.5 mL). AgSb6 (54 mg, 0.21 mmol) was
added, and the mixture was stirred at room temperature for 3 h. The
resulting suspension was filtered from the precipitated AgBr through
Celite, and the solvent was removed under reduced pressure to give
complex 5-SbF6 as a white powder. Yield: 132.4 mg (95%). Anal.
Calcd for C52H72F12N4O4PdSb2 [1395.07 g/mol]: C, 44.77; H, 5.20;
N, 4.02. Found: C, 44.89; H, 5.22; N, 4.11. HRMS (positive ions): m/
(calcd for [M − AcO−]+ 945.45). [α]D20 = 7.84° (c 0.1, CHCl3). H
1
NMR (400 MHz, CDCl3): δ 8.04 (m, 1H), 7.66−7.68 (d, J = 6.88 Hz,
1H), 7.15−7.31 (m, 6H), 6.92−6.97 (m, 2H), 6.53−6.55 (m, 2H),
5.92−6.18 (m, 4H), 5.56 (m, 1H), 4.72 (m, 1H), 3.88 (s, 3H), 3.59 (s,
3H), 3.01−3.03 (d, J = 10.52 Hz, 1H), 2.77 (m, 2H), 2.55 (m, 1H),
2.19 (s, 2H), 1.97 (s, 2H), 1.82 (s, 6H), 1.39−1.42 (d, J = 12.36 Hz,
18H), 0.77 (s, 18H). 13C NMR (100 MHz, CDCl3): δ 176.6, 175.3
(Ccarbene), 168.0 (CAcO), 154.4, 154.3 (CAr‑O), 145.2, 144.9, 141.2,
141.0 (ArC‑t‑Bu), 133.7, 133.2, 132.8, 131.8 (CAr), 126.0, 125.4, 122.7,
122.6, 122.0, 121.3, 120.9, 111.8, 111.7, 110.8, 109.2 (CHAr), 61.8,
61.6 (OCH3), 60.7 (CHcyclohexyl), 48.0, 46.4 (CH2-N), 34.5, 33.3
(Ct‑Bu), 31.2 (CH3t‑Bu), 30.3, 30.2, 24.7, 24.5 (CH2cyclohexyl), 22.8, 22.7
(CH3AcO).
−
z 1123.3351 (calcd for [M − 2H2O − SbF6 ]+ 1123.33), 653.2498
+
(calcd for [M − 2H2O − 2SbF6− − RCH2 ]+ (RCH2+ = [2-PhCH2O-
+
3,5-(t-Bu)2(C6H2)CH2 ]) 653.25). [α]2D0 = −16.65° (c 0.1, CHCl3).
1H NMR (400 MHz, CDCl3): δ 7.94−7.96 (d, J = 6.44 Hz, 1H), 7.60
(s, 1H), 7.25 (m, 7H), 7.05 (m, 1H), 6.80−6.82 (m, 2H), 6.20−6.24
(d, J = 16.04 Hz, 1H), 5.86−5.90 (m, 3H), 5.73−5.77 (d, J = 15.12 Hz,
1H), 5.02 (s, 1H), 3.89 (s, 3H), 3.79 (s, 3H), 3.45−3.47 (d, J = 6.88
Hz, 1H), 2.94 (s, 1H), 2.64 (s, 1H), 1.96−2.19 (m, 9H, CH2 of
cyclohexyl + H2O-Pd), 1.42 (s, 18H), 0.84 (s, 9H), 0.74 (s, 9H). 13C
NMR (100 MHz, CDCl3): δ 160.5 (Ccarbene), 155.5, 153.7 (CAr‑O),
146.4, 143.1, 142.9 (ArC‑t‑Bu), 134.0, 133.5, 133.0, 132.4 (CAr), 126.8.
126.0, 125.6, 124.9, 124.6, 124.5, 121.1, 113.0, 112.9, 112.0 (CHAr),
66.0, 63.4 (OCH3), 62.6, 60.9 (CHcyclohexyl), 49.3, 47.9 (CH2-N), 35.5,
34.2, 34.1(Ct‑Bu), 31.1(CH3t‑Bu), 30.9, 22.8, 22.0 (CH2cyclohexyl).
General Procedure for Asymmetric Suzuki−Miyaura Cou-
pling Reactions. The desired aryl bromides (0.2 mmol), the
corresponding palladium complex (0.006 mmol), the corresponding
boronic acid (0.3 mmol), and base (0.50 mmol) were introduced into
an oven-dried Schlenk tube (25 mL). Deoxygenated solvent (2 mL)
was added, the flask was sealed, and the mixture was stirred and heated
at the indicated temperature. After the reaction mixture was heated to
reflux (when THF was used as a reaction solvent) or maintained at 70
°C for 24 h, it was treated with distilled water (10 mL), extracted with
CH2Cl2 (3 × 10 mL), dried (MgSO4), and purified by flash
chromatography (1/50 EtOAc/hexane) to give the corresponding
product.
Synthesis of {Pd[(1R,2R)-(1a)](OC(O)CF3} (4-OCH(O)CF3).
Complex 2a (104.8 mg, 0.1 mmol) was suspended in a mixture of
CH2Cl2 (7.5 mL) and CH3CN (2.5 mL). AgOC(O)CF3 (46 mg, 0.21
mmol) was added, and the mixture was stirred at room temperature
for 3 h. The resulting suspension was filtered from the precipitated
AgBr through Celite, and the solvent was removed under reduced
pressure to give 4-OCH(O)CF3 as a white powder. Yield: 102.3 mg
(92%). Anal. Calcd for C56H68F6N4O6Pd [1113.57 g/mol]: C, 60.40;
H, 6.15; N, 5.03. Found: C, 60.33; H, 6.22; N, 5.14. HRMS (positive
ions): m/z 999.4289 (calcd for [M − CF3COO−]+ 999.42). [α]D20
=
11.68° (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.81−7.84 (t, J
= 11.00 Hz, 1H), 7.71−7.73 (d, J = 8.28 Hz, 1H), 7.36 (d, J = 8.28 Hz,
1H), 7.17−7.25 (m, 5H), 7.05 (t, J = 8.80 Hz, 1H), 6.98 (t, J = 9.60
Hz, 1H), 6.65 (d, J = 11.80 Hz, 1H), 6.51−6.53 (d, J = 11.80 Hz, 1H),
6.27−6.31 (d, J = 16.04 Hz, 1H), 6.03−6.10 (m, 2H), 5.79 (s, 1H),
5.47−5.51 (d, J = 16.00 Hz, 1H), 4.77−4.78 (m, 1H), 3.89 (s, 3H),
3.51 (s, 3H), 3.05−3.07 (d, J = 9.16 Hz, 1H), 2.82−2.85 (m, 1H), 2.62
(m, 2H), 2.16−2.24 (m, 3H), 1.77−1.84 (m, 1H), 1.38−1.42 (d, J =
17.88 Hz, 18H), 0.75−0.77 (d, J = 6.84 Hz, 18H). 13C NMR (100
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, figures, tables, and CIF files giving X-ray crystal data,
experimental syntheses of the chiral bis-NHC precursors
H2[(1R,2R)-(1a−i)]Br2, 1H and 13C NMR spectra and
complete HRMS spectra of NHC palladium compounds, and
typical chiral HPLC spectra of biaryl products. This material is
available free of charge via the Internet at http://pubs.acs.org.
MHz, CDCl3): δ 169.6 (Ccarbene), 162.1 (CCF COO), 154.3, 154.1
3
(CAr‑O), 145.2, 144.8, 141.4, 140.9(ArC‑t‑Bu), 133.5, 132.9, 132.5, 131.0
(CAr), 126.2, 125.4, 123.2, 123.0, 122.5, 120.8, 120.1, 111.9, 110.8,
109.2 (CHAr + CF3CF COO), 62.2, 61.5 (OCH3), 61.0, 60.4
3
(CHcyclohexyl), 48.1, 46.5 (CH2-N), 34.3, 33.0 (Ct‑Bu), 31.8 (CH3t‑Bu),
30.1, 29.9, 24.6, 24.1 (CH2cyclohexyl).
Synthesis of {Pd[(1R,2R)-(1a)] (OH2)2}[OTf]2 (5-OTf). Complex
2a (104.8 mg, 0.1 mmol) was suspended in a mixture of CH2Cl2 (7.5
mL) and CH3CN (2.5 mL). AgOTf (54 mg, 0.21 mmol) was added,
and the mixture was stirred at room temperature for 3 h. The resulting
suspension was filtered from the precipitated AgBr through Celite, and
the solvent was removed under reduced pressure to give complex 5-
OTf as a white powder. Yield: 111.6 mg (94%). Anal. Calcd for
C54H72F6N4O10PdS2 [1221.71 g/mol]: C, 53.09; H, 5.94; N, 4.59.
Found: C, 53.07; H, 6.00; N, 4.65. HRMS (positive ions): m/z
AUTHOR INFORMATION
Corresponding Author
*E-mail for D.Z.: daozhang@fudan.edu.cn.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
−
1035.3945 (calcd for [M − 2H2O − CF3SO3 ]+ 1035.39), 653.2498
We are grateful for the financial support of the National Natural
Science Foundation of China, Grant Nos. 20972031, 21272040,
and 21272117.
−
+
+
(calcd for [M − 2H2O − 2CF3SO3 − RCH2 ]+ (RCH2 = [2-
PhCH2O-3,5-(t-Bu)2(C6H2)CH2 ]) 653.25). [α]2D0 = −7.00° (c = 0.1,
+
1
CHCl3). H NMR (400 MHz, CDCl3): δ 7.77−7.79 (d, J = 8.28 Hz,
1H), 7.50 (m, 1H), 7.42−7.44 (d, J = 8.72 Hz, 1H), 7.25 (m, 5H),
7.05 (m, 2H), 6.70 (m, 2H), 6.82 (s, 1H), 6.11−6.20 (m, 2H), 5.90 (d,
J = 16.04 Hz, 1H), 5.65 (d, J = 18.80 Hz, 1H), 4.80−4.82 (d, J = 9.16
Hz, 1H), 3.79 (s, 3H), 3.55 (s, 3H), 3.09−3.41 (m, 4H), 2.83 (m, 1H),
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