Palladium Complexes Bearing Chiral bis(NHC) Chelating Ligands on a Spiro Scaffold: Synthesis, Characterization, and Their Application in the Oxidative Kinetic Resolution of Secondary Alcohols

Article abstract of DOI:10.1021/acs.organomet.9b00833

A series of chiral bis-N-heterocyclic carbene ligands H₂[(S)-1a-d]X₂ (X = Br, I) on a spiro scaffold and their palladium complexes (S)-2a-d and (S)-3a,b were prepared and applied in the enantioselective oxidative kinetic resolution of secondary alcohols. The corresponding alcohols can be obtained in high yields with moderate to excellent ee values.

Full text of DOI:10.1021/acs.organomet.9b00833

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Article
Palladium Complexes Bearing Chiral bis(NHC) Chelating Ligands on
a Spiro Scaffold: Synthesis, Characterization, and Their Application
in the Oxidative Kinetic Resolution of Secondary Alcohols
Dao Zhang* and Jueqin Yu
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ABSTRACT: A series of chiral bis-N-heterocyclic carbene ligands H2[(S)-
1a−d]X2 (X = Br, I) on a spiro scaffold and their palladium complexes (S)-
2a−d and (S)-3a,b were prepared and applied in the enantioselective
oxidative kinetic resolution of secondary alcohols. The corresponding
alcohols can be obtained in high yields with moderate to excellent ee values.
As we know, complexes bearing bis(NHC) ligands are
stabilized due to the chelate effect and offer various
possibilities for tuning their geometric and electronic proper-
ties. However, until now, few effective bis(NHC) systems have
been developed.8,9 Two representative examples with chiral
BINAM and dioxolane as chiral linker units, respectively, are
shown in Scheme 1. Although theses chiral bis(NHC) ligands
have been applied in variety of asymmetric transition-metal
catalyses, the enantioselective transformations remain some-
what limited. Hence, the search for novel chiral bis(NHC)
auxiliary ligands still is the continuing focus of this research
area.
1,1′-Spirobiindane, as a privileged chiral scaffold, provides an
excellent platform for chiral ligand and catalyst diversification.
In pioneering studies by the Zhou group, an array of chiral
spiro-phosphino and/or -oxazoline ligands have been derived
from 1,1′-spirobiindane-7,7′-diol (SPINOL) and have shown
impressive activity in asymmetric organic transformation
reactions.12 Inspired by these elegant pioneering studies, we
recently synthesized the series of chiral bis(NHC) ligands (S)-
1a−d on a spiro scaffold and their palladium complexes (S)-
2a−d and (S)-3a,b (Scheme 2). These chiral complexes could
catalyze the asymmetric oxidative kinetic resolution of
secondary alcohols effectively with moderate to high
INTRODUCTION
■
To date, a large number of N-heterocyclic carbene (NHC)
ligands have been prepared and applied as strong σ donors in
transition-metal catalysis.1 Enders2a and Hermann2b employed
chiral NHCs as an ancillary in the Rh-catalyzed asymmetric
hydrosilylation of ketones with moderate ee values in 1996.
Years later, Burgess reported the first highly enantioselective
reaction using chiral NHC complexes in the Ir-catalyzed
hydrogenation of olefins.3 Since then, the rational design and
development of novel chiral NHC ligands has been an
important issue in versatile catalytic asymmetric organic
transformations.4 However, the design of appropriate NHC
auxiliary ligands for highly efficient metal catalysts is still a
challenging topic. The most popular design strategy is to
introduce all sorts of chiral elements at the N1,3 and/or C4,5
position of the NHC backbone. It should be noted that the
major problem encountered is the rotation around the metal−
carbon(NHC) bond, which may lead to an enantioselectivity
erosion in asymmetric transition-metal catalysis. Two well-
known strategies have been developed to avoid this situation.
One is to introduce bulky or cyclic N substituents on the NHC
scaffolds, and the other way is to incorporate a second
coordinating group to form a chelate ligand. According to this
guiding idea, a manifold of chiral monodentate NHCs bearing
different chiral N substituents,2,5 an NHC backbone,6 or
multicyclic fragments,7 together with chiral bidentate bis-
(NHC)s8,9 and N-,3 O-,10 S-,11a or P-chelating11b NHC ligands
have been achieved. These privileged NHCs play a central role
in asymmetric transition-metal catalysis.
Received: December 6, 2019
https://dx.doi.org/10.1021/acs.organomet.9b00833
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carbon of (S)-2a appears at 176.0 pm (Figure S10), similar to
what is seen for (S)-2b−d with the respective signals at 173.6−
176.5 ppm in CDCl3 as solvent. The result showed clearly that,
despite the different substituents on the N position of the
NHC, these NHC-palladium complexes have strikingly similar
structural parameters.
Scheme 1. Representative Examples of Chiral Bis(NHC)
Ligands
Moreover, the chiral links affect the 13C NMR spectra of the
formed bis(NHC)-Pd complexes in the characteristic peaks of
carbene carbons (Scheme 3). As mentioned above, only one
kind of carbon (NHC) resonance can be observed for the C2-
symmetric complexes (S)-2a−d, which is similar to the case for
other BINAM-bridged complexes such as (aR)-8 reported by
Shi et al.8a,b,14 However, in some cases, there existed two types
of carbene carbon atoms. For example, the signals for the two
CNHC atoms of the (1R,2R)-cyclohexane-linked complex
(1R,2R)-9 (Scheme 3) appear at 177.2−171.1 and 171.7−
166.6 ppm, respectively.9 The result indicates that the complex
is C1-symmetric and sometimes two distinct ligand resonances
1
could be found in their H NMR spectra, which is similar to
the case for the chiral trans-9,10-dihydro-9,10-ethanoanthra-
cene-11,12-diyl (DEA)-bridged bis(NHC)-Pd complex re-
ported by Veige et al.8h,i,15
In addition, all of these bis(NHC)-Pd compounds were
identified by high-resolution mass spectrometry (HRMS), and
the results were in line with the characterization results.
Although the molecular ion peaks of their HRMS spectra were,
in most instances, not observed, the peaks of dominant
fragment ions ([M − X]+ and [M − 2I]2+ for 2a; [M − Br]+
for 2b−d; [M − CF3COO]+ and [M − CF3COO + H]+ for
3a; [M − OTf]+ and [M − 2H2O − OTf]+ for 3b) have much
stronger intensities.
Crystals of (S)-2a and (S)-2b suitable for X-ray structure
determination were developed by diffusion of hexane into their
concentrated chloroform solutions. Their chiral spiro struc-
tures were confirmed unambiguously by X-ray crystallographic
analyses. As shown in Figure 1, they feature a square-planar
coordination of the palladium with the two halide ligands in a
cis disposition.
A comparison between the structures of (S)-2b and the
reported chiral chelating bis(NHC)-Pd complexes (aR)-814a
and (1R,2R)-99d (R = Bn, X = Br; Scheme 3) revealed some
interesting aspects (Table 1). First, the difference in the
lengths of the Pd−CNHC (1.983(8) and 2.008(8) Å for 2b) was
obviously larger than those of the other two complexes.
Second, the CNHC−Pd−CNHC bite angle (94.8(3)°) in 2b is
closer to the ideal 90° than in (aR)-8 (97.1(3)°) and (1R,2R)-
9 (83.69(19)°). In addition, complex 2b (12.3°) has a square-
planar distortion similar to that of 9 (11.7°), while the BINAM
linker complex 8 has a greater distortion (17.5°). Finally, the
P(CNHC)/P(CNHC) dihedral angle in 8 (80.6°) deviates from
90° more seriously than those in 2b (92.7°) and 9 (90.8°).
These distinctive features of (S)-2b were largely due to the
rigidness of the spiro fragments. Therefore, a better chiral
environment around the Pd center in these spiro complexes
might be expected.
Asymmetric Oxidative Kinetic Resolution of Secon-
dary Alcohols. Encouraged by the above structural
information on these spiro chiral complexes, we next tested
their asymmetric catalytic properties. Palladium-catalyzed
aerobic oxidation reactions have proven attractive due to the
mild conditions, high chemo- and stereoselectivities, and the
use of air or oxygen as the terminal oxidant.16 Considering that
NHC derivatives have been shown to be oxidatively stable
enantioselectivities. Herein, we report the preliminary results
of this study.
RESULTS AND DISCUSSION
■
Synthesis of Ligands and Complexes. The syntheses of
spiro chiral bis(NHC) ligands H2[(S)-1a−d]X2 and their
palladium complexes {[(S)-2a−d]PdX2} (X = Br, I) started
from the known 1,1′-spirobiindane-7,7′-diamine (S)-413
(Scheme 2). The palladium-catalyzed Buchwald−Hartwig
amination of 2-bromo-1-nitrobenzene afforded the nitro-
benzene derivative (S)-5, which was smoothly reduced by
hydrogen gas at atmospheric pressure using Pd/C as the
catalyst to give the tetraamine compound (S)-6 in almost
quantitative yield. The subsequent cyclization using excess
triethyl orthoformate provided the bis(benzimidazole) (S)-7.
The corresponding bis(benzimidazolium) salts H2[(S)-1a]I2
and H2[(S)-1b−d]Br2 were obtained in almost quantitative
yields by the direct alkylation reactions of (S)-7 with excess
iodomethane or benzyl bromide. As we previously reported,
deprotonation and metalation with Pd(OAc)2 proved to be a
reliable synthetic pathway for chelating bis(NHC) palladium
complexes.9 Spiro chiral (S)-2a−d were obtained as yellow
solids in 60−73% yield. Considering that the coligands, such as
Br−, I−, CF3COO−, and water, might have little influence on
the catalytic results, the complex {[(S)-1a]Pd(OCOCF3)2}
((S)-3a), bearing weakly coordinating acetate counterions, and
the cationic diaqua complex {[(S)-1b]Pd(OH2)2}(OTf)2 ((S)-
3b) were synthesized by precipitation reactions of (S)-2a or
−
(S)-2b with the different silver salts AgX (X = OC(O)CF3,
−OTf) in the mixed solvent MeCN/CH2Cl2 (Scheme 2).
Characterization and Structural Analysis. All com-
plexes were characterized by NMR, HRMS, and elemental
analysis. The singlets centered at ca. 9.31 ppm for H2[(S)-
1a]I2, representing the NCHN of bis(NHC) precursors
1
(Figure S7), were notably absent in the H NMR spectra of
the corresponding NHC-Pd complex (S)-2a (Figure S9). It is
worth noting that in the 13C NMR spectrum the carbene
B
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Scheme 2. Synthesis of Spiro Chiral Bis(NHC) Ligands H2[(S)-1a−d]X2 and Their Palladium Complexes (S)-2a−d and (S)-
3a,b
Scheme 3. Three Bis(NHC)-Pd Complexes with Different Chiral S Linkers
ligands and Shi’s work,14 we tried to apply the newly
synthesized (S)-2a in the oxidative kinetic resolution of
secondary alcohols. To our delight, with (S)-2a (10 mol %) as
the catalyst, the model reaction of rac-1-phenylethanol (10a)
proceeded smoothly under the optimized conditions, giving
the desired chiral (R)-10a in 74% ee (entry 2, Table 2). It was
found that the steric bulkiness of the substituents at the N
positions of NHC scaffold exerts a great influence on the
reaction outcomes. The catalysts (S)-2b−d with a larger benzyl
substituent resulted in diminished conversation and enantio-
selectivity (entries 9−11). Moreover, in comparison with
halides (Br− and I−) in (S)-2a,b, the coligands, including
CF3COO− in (S)-3a and water in (S)-3b, have little influence
on the catalytic results.
With the optimized conditions in hand, we next evaluated
the generality of (S)-2a as the catalyst in this transformation.
As shown in Scheme 4, a variety of aryl-/alkyl-substituted
secondary alcohol enantiomers were obtained with high
conversions and good to excellent enantionselectivities. An
aryl ring with either an electron-withdrawing group (F, Cl) or
C
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Figure 1. Molecular structures of (S)-2a (left) and (S)-2b (right). H atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg) for
2a: Pd1−C1 1.98(2), Pd1−C25 1.990(19), Pd1−I1 2.673(2), Pd1−I1 2.648(2), C1−Pd1−C25 95.0(8), I1−Pd1−I2 92.66(7), C25−Pd1−I1
87.7(6), C1−Pd1−I2 87.3(6). For the bond lengths and angles for 2b, see Table 1.
Table 1. Selected Bond Lengths (Å) and Bond Angles (deg)
for (S)-2b, (aR)-8, and (R)-9 (R = Bn, X = Br, Scheme 3)
Table 2. Optimization of the Enantioselective Oxidative
Kinetic Resolution Using (S)-2a−d
a
(S)-2b
(aR)-814a
(1R,2R)-99a
Bond Lengths
1.983(8)
2.008(8)
2.4711(13)
2.4792(14)
Bond Angles
94.8(3)
90.71(4)
86.4(2)
89.4(2)
171.6(2)
170.0(2)
12.3
Dihedral Angles
92.7
Pd(1)−C(1)
Pd(1)−C(2)
Pd(1)−Br(1)
Pd(1)−Br(2)
1.997(7)
1.983(7)
2.4876(11)
2.4862(10)
1.971(5)
1.974(5)
2.3460(12)
2.3786(12)
b
time
(h)
conversn
(%)
c
entry cat.
solv
base
ee (%)
d
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
toluene
toluene
toluene
DCE
1,4-dioxane
toluene
toluene
toluene
toluene
toluene
toluene
K2CO3
Cs2CO3
K3PO4
72
72
72
72
72
24
48
96
96
96
96
41
55
46
17
28
43
51
58
19
21
14
N.D.
74
N.D.
N.D.
N.D.
N.D.
63
76
39
35
41
C(1)−Pd(1)−C(2)
Br(1)−Pd(1)−Br(2)
C(2)−Pd(1)−Br(1)
C(1)−Pd(1)−Br(2)
C(1)−Pd(1)−Br(1)
C(2)−Pd(1)−Br(2)
square-planar distortion
97.1(3)
89.89(4)
87.5(2)
88.36(19))
167.0(2)
166.6(2)
17.5
83.69(19)
93.34(5)
91.60(14)
91.77(13)
174.67(13)
167.61(14)
11.7
d
d
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
d
d
a
9
10
11
b
c
P(C1) /P(C2)
80.6
103.0
55.4
90.8
101.5
58.3
b
d
P(C1) /P(Pd)
113.2
52.3
c
d
a
P(C2) /P(Pd)
All reactions were carried out under the following conditions: (S)-
a
2a−d, 0.05 mmol; base, 0.25 mmol; solvent, 5.0 mL; alcohol, 0.50
Angle between the planes defined by C(1)−Pd−C(14) and Br(1)−
b
b
mmol; O2; 1 atm; 4A MS; 80 °C; 72 h. Measured by GC: conversn
Pd−Br(2). Plane defined by C(1)−N(1)−C(8)−C(3)−N(2).
c
c
d
(%) = [11]/[(S)-10 + (R)-10 + 11] × 100%. Measured by chiral
Plane defined by C(2)−N(3)−C(26)−C(31)−N(4). Coordination
d
GC: ee (%) = [(S)-10 − (R)-10]/[(S)-10 + (R)-10] × 100%; Not
plane defined by Pd(1)−C(1)−C(24)−Br(1)−Br(2).
determined.
catalysts. Moreover, the reaction of substrates with large
carbon rings became retarded and delivered 10j in 8%
conversation with 5% ee, probably due to the more congested
chiral environment around the palladium center.
electron-donating group (OMe) was well tolerated, and the
desired products (10b−e) were obtained in satisfying
conversations (39−57%) and good enantioselectivity (up to
78% ee). However, replacement of the Me group with a long-
carbon-chain substituent (for example, Et, 10f) slightly
decreased both the alcohol conversion and ee value. To our
delight, the alcohol substrates 10g,h bearing either a five- or
six-membered ring gave promising resolution results. The
oxidative kinetic resolution reaction worked with uniformly
better enantioselectivity (>99% ee) and fractional conversion
(60−63%) in comparison to those obtained using other
CONCLUSIONS
■
In summary, we have developed a series of novel chiral
bis(NHC) ligands based on the 1,1′-spirobiindane scaffold,
and one of their corresponding Pd(II) complexes behaved as a
superior catalyst in the asymmetric oxidative kinetic resolution
of secondary alcohols. Notably, the reaction could be run using
D
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Å3, Z = 8, ρcalcd = 1.751 g cm−3, μ = 2.454 mm−1, F(000) = 3712, T =
203(2) K; all data, R1 = 0.1064 and wR2 = 0.2382; I > 2σ(I), R1 =
0.0995 and wR2 = 0.2344; GOF 1.113, 7943 independent reflections
(3.32 ≤ 2θ ≤ 50.00°) and 399 parameters, 0 restraints.
a
Scheme 4. Substrate Scope
Crystal data for (S)-2b: C45H36Br2N4Pd, Mr = 899.00, colorless
block, 0.50 × 0.10 × 0.10 mm, orthorhombic, space group P212121, a
= 12.506(6) Å, b = 15.559(7) Å, c = 119.577(9) Å, α = β = γ = 90°, V
= 3615(3) Å3, Z = 4, ρcalcd = 1.652 g cm−3, μ = 2.764 mm−1, F(000) =
1800, T = 173(2) K; all data, R1 = 0.0859 and wR2 = 0.1068; I >
2σ(I), R1 = 0.0437 and wR2 = 0.0917; GOF 1.003, 8377 independent
reflections (3.93 ≤ 2θ ≤ 55.37°) and 469 parameters, 0 restraints.
Synthesis of (S)-N7,N7′-Bis(2-nitrophenyl)-2,2′,3,3′-tetrahy-
dro-1,1′-spirobi[indene]-7,7′-diamine ((S)-5). Under an argon
atmosphere, a mixture of (S)- 2,2′,3,3′-tetrahydro-1,1′-spirobi-
[indene]-7,7′-diamine (4; 1.050 g, 42 mmol), 2-bromonitrobenzene
(2.556 g, 12.66 mmol), Pd2(dba)3 (102 mg, 0.108 mmol), DPE-phos
(168 mg, 0.318 mmol), and Cs2CO3 (4.392 g, 13.5 mmol) was stirred
in anhydrous toluene (35.0 mL) at 80 °C for 48 h. After the reaction
mixture was cooled to room temperature, water (50 mL) was added
to quench the reaction. The organic compound was extracted with
EtOAc (2 × 50 mL) and dried over anhydrous Na2SO4. The solvent
was removed under reduced pressure, and the residue was purified by
silica gel flash column chromatography to give (S)-5 as a red solid:
yield 2.0 g (100%). HRMS (positive ions): m/z 493.1871 (calcd for
[M + H]+ 493.1876). 1H NMR (400 MHz, CDCl3): δ 2.18−2.26 (m,
2H), 2.33−2.39 (m, 2H), 3.05−3.09 (m, 4H), 6.62−6.66 (m, 2H),
7.02 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 7.2 Hz, 2H), 7.17−7.22 (m,
6H), 7.97 (s, 1H), 7.99 (d, J = 0.8 Hz, 1H), 8.65 (br s, 2H, NH). 13C
NMR (100 MHz, CDCl3): δ 31.0 (CH2), 38.5 (CH2), 59.7 (C),
116.1, 117.3, 122.3, 126.3, 128.4, 134.4, 135.4, 140.6, 142.1, 145.9.
Synthesis of (S)-N1,N1′-(2,2′,3,3′-Tetrahydro-1,1′-spirobi-
[indene]-7,7′-diyl)bis(benzene-1,2-diamine) ((S)-6). A mixture
of (S)-5 (1.9 g, 3.858 mmol) and 10% Pd−C (345 mg) in a mixed
solution of EtOAc (250 mL) was stirred under an H2 atmosphere
(11.5 atm) at 60 °C overnight. After the mixture was cooled to room
temperature, Pd−C was removed by filtration. The solvent was
evaporated under reduced pressure. The residue was purified by silica
gel flash column chromatography to give (S)-6 as a white solid: yield
1.6 g (97%). HRMS (positive ions): m/z 433.2383 (calcd for [M +
H]+ 433.2392). 1H NMR (400 MHz, CDCl3): δ 2.32−2.43 (m, 2H),
2.98−3.15 (m, 4H), 3.34 (br s, 4H, NH2), 5.06 (s, 2H, NH), 6.60 (d,
J = 8.0 Hz, 2H), 6.66−3.69 (m, 4H), 6.77 (d, J = 7.2 Hz, 2H), 6.94 (t,
J = 7.6 Hz, 2H), 6.60 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H),
7.10 (t, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 31.3
(CH2), 35.8 (CH2), 59.1 (C), 110.8, 116.0, 116.1, 118.7, 124.6, 125.5,
127.5, 129.2, 129.8, 141.6, 142.0, 145.3.
a
Reaction conditions: rac-10b−j, 0.50 mmol; (S)-2a, 0.05 mmol;
Cs2CO3, 0.25 mmol; toluene, 5.0 mL; O2; 1 atm; 4A MS; 80 °C; 72 h.
molecular oxygen as a terminal oxidant, and moderate to
excellent enantioselectivity could be achieved in most cases.
Expanding the applications of these chiral spiro NHC ligands
to other synthetically useful enantioselective transformations is
currently under investigation in our laboratory.
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
methods and freshly distilled prior to use if needed. All chemicals
unless noted otherwise were purchased from major commercial
suppliers and used without purification. The compound (S)-4 was
prepared according to the literature methods.13
Synthesis of (S)-7,7′-Bis(1H-benzo[d]imidazol-1-yl)-
2,2′,3,3′-tetrahydro-1,1′-spirobi[indene] ((S)-7). Compound
(S)-6 (1.0 g, 2.312 mmol) and triethyl orthoformate (HC(OEt)3;
25.0 mL) containing TsOH (73 mg) were heated at 100 °C for 24 h.
After the excess amount of HC(OEt) was removed under reduced
pressure, the residue was purified by silica gel flash column
chromatography to give (S)-7 as a white solid: yield 0.55 g (53%).
HRMS (positive ions): m/z 453.2076 (calcd for [M + H]+ 453.2079).
1H 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 30.3
(CH2), 42.2 (CH2), 60.8 (C), 109.9, 120.0, 122.5, 123.6, 126.7, 127.9,
129.2, 132.2, 135.7, 142.6, 142.9, 146.9 (Ar).
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
was carried out on silica gel (300−400 mesh). GC chromatograms
were recorded on a HP 4890A GC instrument equipped with a
Chrompak CP-Chirasil-Dex CB column (25 m × 0.25 mm, 0.25 μm
i.d).
X-ray Structure Determination Details. Single crystals suitable
for X-ray crystallography were obtained by diffusion of hexane into
concentrated chloroform solutions of (S)-2b and (S)-2b at room
temperature over several days. The data were collected on a CCD
Bruker Smart APEX system with graphite-monochromated Mo Kα
radiation (λ = 0.71073 Å) at 293 K. The structure was solved using
direct methods, while further refinement of all non-hydrogen atoms
with full-matrix least squares on F2 was obtained with the SHELXTL
program package.17 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 1970213 and 1970214 contain the crystallographic data for this
paper.
Synthesis of the Complex {[(S)-(1a)PdI2]} ((S)-2a). Compound
(S)-7 (181 mg, 0.40 mmol) and CH3I (0.48 mL, 8 mmol) in CH3CN
(8.0 mL) were stirred under reflux for 5 h. After the mixture was
cooleto room temperature, volatiles were removed under reduced
pressure and the obtained solid compound H2[(S)-(1a)]I2 was used
for the next reaction without further purification. HRMS (positive
ions): m/z 481.2420, 241.1241 (calcd for [M − I − I − H]+
1
481.2381, [M − I − I]2+ 241.1230). H NMR (400 MHz, CDCl3):
δ 2.00−2.06 (4H), 2.30 (2H), 2.89 (2H), 4.10 (6H, CH3), 7.29−7.35
(3H), 7.52 (2H), 7.70−7.78 (7H), 8.13 (2H), 9.31 (2H, NCHN).
13C NMR (100 MHz, CDCl3): δ 30.8 (CH2), 35.2 (CH3), 41.6
Crystal data for (S)-2a·CHCl3: C34H29Cl3I2N4Pd, Mr = 960.16,
yellow sheet, 0.42 × 0.35 × 0.08 mm, tetragonal, space group P41212,
a = 12.7326(19) Å, b = 12.7326(19) Å, c = 44.921(7) Å, V = 7283(2)
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(CH2), 60.5 (C), 112.7, 114.5, 128.3, 128.7, 128.8, 129.0, 129.5,
130.7, 130.9, 132.9, 141.7, 146.7, 147.1.
The H2[(S)-(1d)]Br2 obtained above and Pd(OAc)2 (33.6 mg,
0.15 mmol) were refluxed in THF (7.5 mL) for 16 h. The volatiles
were then removed under reduced pressure and the residue was
purified by silica gel flash column chromatography to give (S)-2d as a
yellow solid: yield 129 mg (60%). Anal. Calcd for
C47H34Br2F6N4O6PdS2 (Mr = 1195.1445 g mol−1): C, 47.23.12; H,
2.87; N, 4.69. Found: C, 47.41; H, 3.01; N, 4.77. HRMS (positive
ions): m/z 1113.0046, 1115.0037 (calcd for [M − Br]+ 1113.0042,
1115.0046). 1H NMR (400 MHz, CDCl3): δ 1.57−1.78 (m, 6H,
CH2), 2.57−2.65 (m, 2H, CH2), 4.91 (d, J = 17.2 Hz, 2H, CH2),
6.57−6.65 (m, 4H, CH + CH2), 6.98 (d, J = 8.0 Hz, 2H, CH), 7.09 (t,
J = 7.6 Hz, 2H, CH), 7.20−7.13 (m, 6H, CH), 7.28−7.36 (m, 4H,
CH), 7.41 (d, J = 8.0 Hz, 2H, CH), 7.72 (t, J = 7.6 Hz, 2H, CH), 7.84
(d, J = 7.6 Hz, 2H, CH). 13C NMR (100 MHz, CDCl3): δ 29.9
(CH2), 40.3 (CH2), 49.1 (CH2), 60.9 (C), 112.4, 113.2, 120.6, 123.4,
123.9, 126.8, 127.0, 127.7, 127.8, 129.4, 129.9, 132.6, 132.9, 134.2,
135.7, 144.1, 146.5, 146.7 (Ar), 176.5 (NCN). 19F NMR (376 MHz,
CDCl3): δ −73.0.
The H2[(S)-(1a)]I2 obtaine above and Pd(OAc)2 (89.8 mg, 0.4
mmol) were refluxed in THF (20 mL) for 16 h. The volatiles were
then removed under reduced pressure, and the residue was purified by
silica gel flash column chromatography to give (S)-2a as a yellow
solid: yield 246 mg (73%). Anal. Calcd for C33H28I2N4Pd (Mr =
840.8312 g mol−1): C, 47.14; H, 3.36; N, 6.66. Found: C, 47.20; H,
3.53; N, 6.78. HRMS (positive ions): m/z 713.0399, 293.0679 (calcd
1
for [M − I]+ 713.0388, [M − I − I]2+ 293.0674). H NMR (400
MHz, CDCl3): δ 1.53−1.85 (m, 6H, CH2), 2.50−2.61 (m, 2H, CH2),
3.75 (s, 6H, NCH3), 6.97 (d, J = 8.0 Hz, 2H, CH), 7.05 (d, J = 7.6
Hz, 2H, CH), 7.18−7.21 (m, 4H, CH), 7.28−7.32 (m, 4H, CH), 7.46
(t, J = 7.6 Hz, 2H, CH), 7.69 (d, J = 7.6 Hz, 2H, CH). 13C NMR (100
MHz, CDCl3): δ 29.7 (CH2), 39.0 (CH3), 40.4 (CH2), 60.9 (C),
109.7, 112.7, 123.7, 126.1, 127.9, 129.0, 134.3, 134.4, 135.4, 144.6,
146.0 (C−Ar), 176.0 (NCN).
Synthesis of the Complex {[(S)-(1b)]PdBr2} ((S)-2b). Com-
pound (S)-7 (181 mg, 0.40 mmol) and PhCH2Br (0.48 mL, 4 mmol)
in 1,4-dioxane (6.0 mL) were stirred under reflux for 24 h. After the
mixture was cooled to room temperature, volatiles were removed
under reduced pressure and the obtained solid compound H2[(S)-
(1b)]Br2 was washed with hexane (15 mL × 2) and used for the next
reaction without further purification.
Synthesis of the Complex {[(S)-(1a)]Pd(OCOCF3)2} ((S)-3a).
Complex (S)-2a (168.1 mg, 0.20 mmol) was suspended in a mixture
of CH2Cl2 (15 mL) and CH3CN (5 mL). Next, AgOTf (92.6 mg,
0.42 mmol) was added and the mixture was stirred at room
temperature for 3 h. The resulting suspension was filtered from the
precipitated AgI through Celite, and the solvent was removed under
reduced pressure to give (S)-3a as a white powder: yield 151 mg
(93%). Anal. Calcd for C37H28F6N4O4Pd (Mr = 813.0530 g mol−1):
C, 54.66; H, 3.47; N, 6.89; .Found: C, 54.44; H, 3.62; N, 6.99. HRMS
(positive ions): m/z 587.1373, 699.1147 (calcd for [M − 2CF3COO
+ H]+, 817.1153, [M − CF3COO]+, 699.1199). 1H NMR (400 MHz,
CDCl3): δ 1.63−1.70 (m, 2H, CH2), 1.82−1.94 (m, 4H, CH2), 2.60−
2.69 (m, 2H, CH2), 3.79 (s, 6H, NCH3), 6.99 (d, J = 8.4 Hz, 2H,
CH), 7.05 (d, J = 7.6 Hz, 2H, CH), 7.22−7.25 (m, 4H, CH), 7.28−
7.34 (m, 2H, CH), 7.49 (t, J = 7.6 Hz, 2H, CH), 7.92 (d, J = 7.6 Hz,
2H, CH). 13C NMR (100 MHz, CDCl3): δ 29.8 (CH2), 34.8 (CH3),
40.2 (CH2), 60.5 (C), 109.8, 112.9, 123.7 (C−Ar), 124.2 (CF3),
126.4, 128.2, 129.1, 133.6, 133.8, 134.6, 144.3, 145.9 (C−Ar), 161.9
(CO), 166.8.
The H2[(S)-(1b)]Br2 obtained above and Pd(OAc)2 (89.8 mg, 0.4
mmol) were refluxed in THF (20 mL) for 16 h. The volatiles were
then removed under reduced pressure, and the residue was purified by
silica gel flash column chromatography to give (S)-2b as a yellow
solid: yield 248 mg (69%). Anal. Calcd for C45H36Br2N4Pd (Mr =
899.0221 g mol−1): C, 60.12; H, 4.04; N, 6.23. Found: C, 60.04; H,
4.11; N, 6.37. HRMS (positive ions): m/z 817.1175 (calcd for [M −
1
Br]+ 817.1153). H NMR (400 MHz, CDCl3): δ 1.70−1.87 (m, 6H,
CH2), 2.66−2.70 (m, 2H, CH2), 5.32 (d, J = 16.0 Hz, 2H, CH2),
6.44−6.49 (m, 4H, CH + CH2), 6.81 (d, J = 8.0 Hz, 2H, CH), 6.98
(td, J = 7.6 Hz, 1.2 Hz, 2H, CH), 7.07 (td, J = 7.6 Hz, 1.2 Hz, 2H,
CH), 7.15−7.19 (m, 6H, CH), 7.27−7.30 (m, 4H, CH), 7.47 (t, J =
8.4 Hz, 2H, CH), 7.68 (d, J = 7.6 Hz, 2H, CH). 13C NMR (100 MHz,
CDCl3): δ 29.8 (CH2), 39.5 (CH2), 56.0 (CH2), 61.0 (C), 112.9,
123.0, 123.4, 126.6, 127.8, 128.1, 128.2, 128.5, 129.2, 133.5, 134.0,
134.3, 136.1, 144.1, 146.3 (Ar), 173.6 (NCN).
Synthesis of the Complex {[(S)-(1b)]Pd(OH2)2}(OTf)2 ((S)-3b).
Complex (S)-2b (179.0 mg, 0.20 mmol) was suspended in a mixture
of CH2Cl2 (15 mL) and CH3CN (5 mL). Next, AgOTf (108 mg, 0.
42 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 (S)-3b as a white powder: yield 195 mg (91%). Anal.
Calcd for C47H4oF6N4O8PdS2 (Mr = 1073.3835 g mol−1): C, 52.59;
H, 3.76; N, 5.22. Found: C, 52.38; H, 3.90; N, 5.37. HRMS (positive
ions): m/z 887.1481, 781.2449, 737.1887 (calcd for [M − OTf]+
887.1459, [M − Pd − 2H2O − OTf]+, 781.2460, [M − 2H2O −
Synthesis of the Complex {[(S)-(1c)]PdBr2} ((S)-2c). Com-
pound (S)-7 (181 mg, 0.40 mmol) and (C6F5)CH2Br (0.50 mL, 4
mmol) in 1,4-dioxane (6.0 mL) were stirred under reflux for 24 h.
After the mixture was cooled to room temperature, volatiles were
removed under reduced pressure and the obtained solid compound
H2[(S)-(1c)]Br2 was washed with hexane (15 mL × 2) and used for
the next reaction without further purification.
The H2[(S)-(1c)]Br2 obtained above and Pd(OAc)2 (89.6 mg, 0.4
mmol) were refluxed in THF (20 mL) for 16 h. The volatiles were
then removed under reduced pressure, and the residue was purified by
silica gel flash column chromatography to give (S)-2c as a yellow
solid: yield 129 mg (60%). Anal. Calcd for C45H26Br2F10N4Pd (Mr =
1078.9268 g mol−1): C, 50.09; H, 2.43; N, 5.19. Found: C, 51.15; H,
2.55; N, 5.30. HRMS (positive ions): m/z 999.0213 (calcd for [M −
1
2OTf − H]+, 737.1897). H NMR (400 MHz, CDCl3): δ 1.70−1.88
(m, 6H, CH2), 2.66−2.70 (m, 2H, CH2), 4.91−5.03 (m, 6H,
CH2+H2O), 6.21 (brs, 2H, CH2), 6.76 (d, J = 6.0 Hz, 2H, CH), 7.00
(d, J = 6.4 Hz, 1.2 Hz, 7H, CH), 7.16−7.29 (m, 11H, CH), 7.65 (t, J
= 7.6 Hz, 2H, CH), 7.97 (d, J = 7.2 Hz, 2H, CH). 13C NMR (100
MHz, CDCl3): δ 29.9 (CH2), 39.8 (CH2), 53.4 (CH2), 60.6 (C),
112.79, 123.6, 118.6, 121.8, 124.6, 124.9, 126.7, 127.2, 127.7, 128.3,
128.6, 130.0, 132.9, 133.0, 135.3, 146.4 (Ar).
1
Br]+ 999.0228). H NMR (400 MHz, CDCl3): δ 1.62−1.80 (m, 6H,
CH2), 2.58−2.64 (m, 2H, CH2), 5.69 (d, J = 16.8 Hz, 2H, CH2), 6.20
(d, J = 16.8 Hz, 2H, CH2), 6.85 (d, J = 8.0 Hz, 2H, CH), 7.01−7.06
(m, 4H, CH), 7.18−7.28 (m, 4H, CH), 7.35 (t, J = 7.6 Hz, 2H, CH),
7.63 (d, J = 7.6 Hz, 2H, CH). 13C NMR (100 MHz, CDCl3): δ 29.7
(CH2), 39.7 (CH2), 44.5 (CH2), 60.9 (C), 110.3, 113.0, 123.7, 124.4,
126.5, 127.6, 128.8, 143.8, 146.5 (Ar), 174.7 (NCN). 19F NMR (376
MHz, CDCl3): δ −137.7 (q, J = 7.52 Hz, o-F-Ar), −153.8 (t, J = 18.8
Hz, p-F-Ar), −161.3 (m, m-F-Ar).
Typical Procedure for the Oxidative Kinetic Resolution of
Secondary Alcohols. In a flame-dried Schlenk tube with with
molecular sieves and a magnetic stir bar were placed the bis(NHC)-
Pd complex (0.05 mmol) and base (0.25 mmol), solvent (5.0 mL),
and secondary alcohol (0.50 mmol) in turn under an inert
atmosphere. The reaction system was vacuum-evacuated using liquid
dinitrogen and filled with O2 three times. After it was stirred at the set
temperature for a certain time, the reaction mixture was cooled to
room temperature and filtered through a small plug of silica gel. The
percent conversion of the racemic secondary alcohol and the
enantionselective of the product were measued directly by chiral
GC analysis. The percent conversion (conversn %) and the
enantioselectivity (ee %) were defined as [11]/[(S)-10 + (R)-10 +
Synthesis of the Complex {[(S)-(1d)]PdBr2} ((S)-2d). Com-
pound (S)-7 (67.9 mg, 0.15 mmol) and 2-(CF3SO2O-(C6H4)CH2Br
(220 mg, 0.68 mmol) in 1,4-dioxane (3.0 mL) were stirred under
reflux for 24 h. After the mixture was cooled to room temperature,
volatiles were removed under reduced pressure and the obtained solid
compound H2[(S)-(1d)]Br2 was washed with hexane (15 mL × 2)
and used for the next reaction without further purification.
F
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̈
̈
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.9b00833.
■
Ligands and Iron: An Effective Association for Catalysis. Adv. Synth.
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Full NMR spectra for bis-NHC-Pd complexes together
with all relevant intermediates and typical GC character-
ization and analysis data of products (PDF)
Accession Codes
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Synthesis and Stereochemistry of the First Chiral (Imidazolinyli-
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CCDC 1970213−1970214 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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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
■
́
Asymmetry 2003, 14, 951−961. (b) Cesar, V.; Bellemin-Laponnaz, S.;
Gade, L. H. Chiral N-Heterocyclic Carbenes as Stereodirecting
Ligands in Asymmetric Catalysis. Chem. Soc. Rev. 2004, 33, 619−636.
(c) Michon, C.; Angelici, R. J. Novel Chiral Functionalized N-
Heterocyclic Carbenes and their Rhodium(I) complexes: Applications
in Asymmetric Catalysis. ChemTracts 2004, 17, 534−541. (d) Wang,
F.; Liu, L.-j.; Wang, W.; Li, S.; Shi, M. Chiral NHC-Metal-Based
Asymmetric Catalysis. Coord. Chem. Rev. 2012, 256, 804−853.
(e) Zhao, D.; Candish, L.; Paul, D.; Glorius, F. N-Heterocyclic
Carbenes in Asymmetric Hydrogenation. ACS Catal. 2016, 6, 5978−
Author
Jueqin Yu − Department of Chemistry, Fudan University
200438 Shanghai, People’s Republic of China
Complete contact information is available at:
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Notes
5988. (f) Janssen-Muller, D.; Schlepphorst, C.; Glorius, F. Privileged
̈
Chiral N-Heterocyclic Carbene Ligands for Asymmetric Transition-
The authors declare no competing financial interest.
Metal Catalysis. Chem. Soc. Rev. 2017, 46, 4845−4854.
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