"bulky-Yet-Flexible" α-Diimine Palladium-Catalyzed Reductive Heck Cross-Coupling: Highly Anti-Markovnikov-Selective Hydroarylation of Alkene in Air

Article abstract of DOI:10.1021/acs.joc.0c01509

To pursue a highly regioselective and efficient reductive Heck reaction, a series of moisture-and air-stable α-diimine palladium precatalysts were rationally designed, readily synthesized, and fully characterized. The relationship between the structures of the palladium complexes and the catalytic properties was investigated. It was revealed that the"bulky-yet-flexible"palladium complexes allowed highly anti-Markovnikov-selective hydroarylation of alkenes with (hetero)aryl bromides under aerobic conditions. Further synthetic application of the present protocol could provide rapid and straightforward access to functional and biologically active molecules.

Full text of DOI:10.1021/acs.joc.0c01509

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Article
“
Bulky-yet-flexible” #-diimine palladium-catalyzed reductive Heck cross
coupling: highly anti-Markovnikov-selective hydroarylation of alkene in air
Xu-Wen Yang, Dong-Hui Li, A-Xiang Song, and Feng-Shou Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01509 • Publication Date (Web): 18 Aug 2020
Downloaded from pubs.acs.org on August 20, 2020
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“Bulky-yet-flexible” α-diimine palladium-catalyzed reductive Heck cross-coupling: highly
anti-Markovnikov-selective hydroarylation of alkene in air
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†
†
†
†
Xu-Wen Yang, Dong-Hui Li, A-Xiang Song, Feng-Shou Liu*
†
School of Chemistry and Chemical Engineering, Guangdong Cosmetics Engineering & Technology
Research Center, Guangdong Pharmaceutical University, Zhongshan, Guangdong, 528458, China
Correspondence authors: Feng-Shou Liu, E-mail: fengshou2004@126.com.
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ABSTRACT:
To pursue highly regioselective and efficient reductive Heck reaction, a series of moisture- and
air-stable α-diimine palladium precatalysts were rationally designed, readily synthesized and fully
characterized. The relationship between the structures of the palladium complexes and the catalytic
properties was investigated. It was revealed that the “ bulky-yet-flexible ” palladium complexes
allowed highly anti-Markovnikov-selective hydroarylation of alkenes with (hetero)aryl bromides
under aerobic conditions. Further synthetic application of the present protocol could provide rapid
and straightforward access to functional and biologically active molecules.
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Introduction
2
3
Over the past several decades, the metal-catalyzed Csp -Csp cross-coupling reactions have
attracted considerable attention as the resulting products are present in an array of natural compounds,
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pharmaceuticals and agrochemicals. Traditionally, these reactions suffered from the use of
stoichiometric organometallic reagents, poor atom economy and limited functional group tolerance.1,
2
Since the seminal work of Cacchi, the Pd-catalyzed hydroarylation of alkenes with aryl halides,
which is called as reductive Heck reaction, has undergone rapid development for their readily
accessible starting materials.3-5
Scheme 1.
In recent years, the increasing emphasis has been laid on highly efficient and readily available
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catalysts. As to the reductive Heck reaction, phosphine and NHC-based catalytic systems have
proven to be remarkably active for the hydroarylation of alkenes.4, 7 The group of Nakao discovered a
Markovnikov hydroarylation of aryl alkenes using a dual phosphine-Pd/NHC-Cu catalytic system
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with hydrosilanes as hydride source (scheme 1). Later on, Buchwald et al. reported a type of
phosphine-based Pd/Cu catalytic system, which could readily generate active chiral CuH species and
9
subsequently afford the enantioselective cross coupling products. On the other hand, practical and
efficient approach for anti-Markovnikov hydroarylation has been less explored. In 2018, the group of
Engle demonstrated the catalytic system of Pd
2
(dba)
3
/(NMe
4
)+(CO )- could enable anti-Markovnikov
2
hydroarylation reaction of alkene and ArI with a broad substrate scope, affording major
1
0
anti-Markovnikov hydroarylation product. Nearly at the same time, Hu et al. reported a similar
11
approach by the introduction of bulky iminopyridyl palladium complexes. More recently, Wu and
Loh et al. revealed that the Pd (dba) /Johnphos was catalytically active for anti-Markovnikov
hydroarylation of alkene and ArOTf when proton sponge/trifluoroacetic acid was selected as the
2
3
12
reductant. It is significant to note that the reaction proceeded with complete regioselectivity for the
terminal and internal alkenes.
Although a plethora of palladium catalytic systems have been developed for the reductive Heck
reaction over the past decades, these reactions often suffered from several challenges, such as the
regioselectivity control issues, undesired Heck-type byproduct, and catalyst instability. As depicted
in Scheme 2, the insertion and migration of the alkene toward LPdArBr (II) are controlled by the
surrounding environment of the catalytic species, which could afford highly regioselective products
by ligand choice.13a To suppress the side Heck-type byproduct, the transfer hydrogenation of
alkyl-palladium species (IV or IV’) must be faster than β-hydride elimination (Path 1 vs Path 2).
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Herrmann and Kühn have reported that the transfer hydrogenation could be significantly enhanced in
the presence of the ligands with π-accepting substituents.13b Moreover, Eisenstein and Crabtree
revealed that the introduction of the conjugated backbone on ligand also promote the transfer
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hydrogenation. Therefore, it is reasonable to assume that the conjugated ligands would become
excellent candidates due to their facile ability to accept electron density from the metal.15
Remarkably, the metal-hydride intermediates (V or V’, scheme 2) are generally highly sensitive
toward oxygen and moisture, rapidly forming the unreactive metal-hydroperoxide and
16
metal-hydroxide species. Until now, the employment of bulky hindered ligands have been proved
17
as an effective way to stabilize the metal-hydride species. It is worth noting that Buchwald et al.
have firstly reported the hydroarylation of alkene compounds in bench without glovebox, using both
bulky air-stable phsophine-based palladium and copper complexes as precatalysts.18
To achieve highly regioselective and efficient palladium precatalysts in the reductive Heck
reaction, it is rational that the ligands should be featured with bulky steric hindrance and facile
ability to delocalize electrons of the metal centers. It has been well established that α-diimine
1
9
ligands, can be easily fine-tuned in both steric and electronic properties. They have already been
2
0
21
22
reported as promising ligands in nickel, iron and cobalt-catalyzed hydrogenations of alkenes and
23
olefin polymerization . Therefore, we speculate that this type of ligands may facilitate the
Pd-catalyzed reductive Heck reactions in the presence of hydride donor. Herein we describe a robust
α-diimine palladium-catalyzed method for the mild hydroarylation of alkenes. A systematic
relationship between the precatalyst structure and catalytic properties was investigated. It was
revealed that the “bulky-yet-flexible” palladium complexes exhibit high efficiency toward broad
substrates scopes, exclusively affording anti-Markovnikov hydroarylation products under aerobic
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reaction conditions.
Scheme 2. Catalytic cycle of the reductive Heck and Heck reaction
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RESULTS AND DISCUSSION
Synthesis and characterization of the α-diimine palladium complexes
The new air-stable α-diimine palladium compounds of C1, and C3-C6 were prepared according
to our previous reported procedures (Scheme 3).24 All these palladium compounds were fully
characterized, and the molecular structures of C1 and C3 were determined by single crystal
diffraction analysis. The palladium complexes adopt square planar geometries, with the coordination
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angles average ca 80.0˚ (seen in Figures S1 and S2). Although different kinds of substituents are
introduced, the bond lengths of Pd-N and Pd-Cl are similar to those reported α-diimine palladium
complexes.24, 25
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Scheme 3. The structure of α-diimine palladium complexes
Figure 1. Mapping of the sterics for C1, C3 and C8 with %VBur values per quadrant.
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To further analyze the steric effect of the N-aryl moieties and backbone of the ligands on the
palladium complexes, the quantification of the percent buried volume (%Vbur) based on X-ray single
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crystal data using Cavallo’s SambVca 2.0 program was carried out. As shown in Figure 1, with the
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encumbered hindrance of 2-benzhydryl on N-aryl moieties, the values of C1, and C3 disclosed to be
4
7.6, and 48.5, respectively, which suggest preferential protection around the metal center. Moreover,
it is noteworthy that the distribution of the steric is not identical in these complexes, indicating the
existence of flexibility of the ligands. Thus, it is reasonable to assume that these “bulky-yet-flexible”
palladium complexes keep the balance of the protection of the palladium and provide space for the
incoming substrates for the following transformation. In contrast, when mono-ortho substituents of
tBu on N-aryl moieties was introduced, the %Vbur of C8 turned out to be a smaller value of 46.6.
Even more, some part of the axial sites of the palladium complex is naked, which suggest much less
protection of the metal center. Considering square-planar coordination geometry adopted by
palladium, the steric hindrance would exert significant influence on the catalytic performance.
Reductive Heck reaction catalyzed by α-diimine palladium complexes
To optimize the reaction conditions of the reductive Heck reaction, a model reaction of styrene
(1a) with phenyl bromide (2a) was carried out under aerobic conditions. The reaction was performed
in the presence of C3 (2 mol%) as the precatalyst, and KOH as the base. With the respect that the
alcohols have been widely employed as hydride source in transformations, the role of the alcohols
27
was initially investigated. As observed in Table 1, primary alcohols, such as methanol, ethanol, and
1
-propanol, prior afforded the Heck-type reaction product (Table 1, Runs 1-4). In contrast, the
secondary alcohols, such as 2-propanol, 2-methyl-1-propanol, 3-Pentanol, cyclopentanol and
cyclohexanol, led to moderate to high formations of anti-Markovnikov hydroarylation product 3a
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(Table 1, Runs 6-13). To our delight, 2-butanol gave the highest yield of 84% (Table1, Run 5), along
with an excellent regioselectivity of anti-Markovnikov hydroarylation (3a/3a’/3a’’ up to 98:1:1).
When 2 equiv. of phenyl bromide was added, the yield was further increased to 95% (Table 1, Run 6).
It is worth noting that only slightly higher yields of 3a were found when the reaction carried out
under inert atmosphere of nitrogen (Table 1, Runs 7 and 9), demonstrating that the palladium
precatalyst C3 maintained excellent catalytic performance toward the air. Other potential hydride
sources, such as triethylamine, DIPEA, DMF, NMP and HCOONa, were also screened. However,
they afforded the desired products in extremely low to moderate yields (Table 1, Runs 14-19).
Moreover, a series of bases were then evaluated, and it was shown that KOH were superior to others
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(Table 1, Runs 5 and 20-29).
Table 1: Optimum reaction conditions for the Pd-catalyzed reductive Heck reactiona
Run
Hydride source
and Solvent
Methanol
Base
Yield (%)b
3a
3
3a’
4
3a’’
50
1
KOH
KOH
KOH
KOH
KOH
KOH
KOH
2
Ethanol
<1
<1
28
84
95
97
11
18
2
28
3
1-Propanol
1-Butanol
2-Butanol
2-Butanol
2-Butanol
56
4
46
5
<1
<1
<1
<1
<1
<1
6c
7d
1
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2-Propanol
2-Propanol
KOH
KOH
81
89
62
66
53
2
<1
<1
2
3
9e
<1
16
<1
31
3
1
0
2-Methyl-1-propanol KOH
1
1
1
1
1
1
1
1
1
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3
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4
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3-Pentanol
Cyclopentanol
Cyclohexanol
Triethylamine
DIPEA
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
NaOH
<1
<1
0
1
2
13
1
1
4
0
0
8
5f,g
NR
1
NR
0
NR
14
NR
14
77
3
16
NMP
1
7g
DMF
NR
2
NR
<1
0
18h
HCOONa (THF)
HCOONa (dioxane)
2-Butanol
2-Butanol
2-Butanol
2-Butanol
2-Butanol
2-Butanol
2-Butanol
2-Butanol
2-Butanol
2-Butanol
1
2
9i
0
6
78
80
73
2
<1
2
t
21
KO Bu
1
t
2
2
NaO Bu
<1
<1
<1
<1
<1
<1
0
3
t
23
LiO Bu
6
2
2
4
5
CH
3
ONa
PO
CO
CO
CO
20
16
2
4
K
3
2
4
6
26
K
3
13
62
2
2
7
Cs
Na
KHCO
2
3
11
<1
2
28
2
3
3
2
9
0
12
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3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
Reaction conditions: styrene (1 mmol), phenyl bromide (1.5 mmol), palladium complex of C3 (0.02
b
mmol), base (2 mmol), solvent (6 mL), 80 °C for 4 h, under aerobic environment. The yield was
c
determined by GC using n-dodecane as internal standard. Reaction conditions: 2 equiv of phenyl
d
bromide was added, other reaction conditions was unchanged. Reaction conditions: styrene (1
mmol), phenyl bromide (2 mmol), palladium complex of C3 (0.02 mmol), base (2 mmol), solvent (6
e
0
1
2
3
4
5
6
7
8
9
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0
mL), 80 °C for 4 h, nitrogen atmosphere. Reaction conditions: styrene (1 mmol), phenyl bromide
(
1.5 mmol), palladium complex of C3 (0.02 mmol), base (2 mmol), solvent (6 mL), 75 °C for 12 h,
f
g
h
under nitrogen atmosphere. NR: no reaction occurred. DIPEA: N, N-Diisopropylethylamine. THF
i
as solvent (6 mL). Dioxane as solvent (6 mL).
With the encouraging results in hand, a systematic relationship of the catalytic structure and
catalytic performance was investigated. As shown in Table 2, it was revealed that the precatalysts of
α-diimine palladium complexes with 2,6-disubstituents on N-aryl moieties showed promising
activities. For instance, the palladium complexes of C1-C4 exhibited high activities. Especially, with
the “bulky-yet-flexible” 2,4-dibenzhydryl-6-methylaniline on N-aryl moieties, the palladium
complexes C3 provided satisfactory GC yield of 95%. In order to further explore the stability of the
palladium catalyst, the reaction was performed in the presence of 1 atm of oxygen. To our delight,
the complex of C3 could still give a yield of 15%. Nevertheless, further increase the steric bulk
resulted in diminished catalytic efficiency. The palladium complex C5, with rigid hindrance of
2
,6-dibenzhydryl-4-methoxyl on N-moieties, was found to be less efficient and afford the desired
product in a moderate yield of 74%, which suggest that the rigid steric might retard the oxidative
addition in the initial catalytic process. Moreover, the palladium complexes C6 and C7 bearing
flexible alkyl groups furnished excellent yields of 88 and 87%, respectively. However, in our further
attempt to screen the less bulky precatalyst with mono-ortho substituents on N-aryl moieties, C8 was
tested. The results revealed that it resulted in a lower conversion, wherein the yield of the product 3a
turned out to be 57%. Reasonably, these results are consistent with the analysis of the steric maps in
Figure 1, which demonstrate the crucial role of the “bulky-yet-flexible” steric profile in the
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transformation. The introduction of the bulky steric environment of the ligand would protect the
Pd-H species and suppress the β-hydride elimination. On the other hand, the flexibility of the
palladium complexes would provide preferential space for the oxidative addition and facilitate the
1,2-insertion of the incoming olefin. Therefore, limited side reaction and highly selective
anti-Markovnikov hydroarylation products were achieved.
0
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Table 2. Screening of α-diimine and NHCs palladium complexes for the reductive Heck reactiona
aReaction conditions: styrene (1 mmol), bromobenzene (2.0 mmol), palladium complex (0.02 mmol),
base (2 mmol), 2-butanol (6 mL), 80 °C for 4 h, under aerobic environment. The yield was
b
c
determined by GC using n-dodecane as internal standard. Isolated yield. The reaction was
performed under 1 atm of oxygen.
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Moreover, the role of the electronic effect of the ligand on the catalytic ability was also
investigated. As can be seen in Table 2, the N-heterocyclic carbene (NHC) palladium complexes
28
(
C9-C12) gave low yields of reductive product of 3a, with the significant amount of the Heck
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product found. On account of bearing similar bulky steric on N-aryl moieties, the observed
significant differences in catalytic performances between the α-diimine and N-heterocyclic carbene
(NHC) palladium complexes could be ascribed to the electron nature of the ligands. Fedushkin has
found that acenaphthyl based α-diimine can stabilize four electrons, wherein two electrons are placed
at the nitrogen atoms and the other two electrons at the conjugated planar naphthalene part.19b Thus,
it is reasonable to assume that, these α-diimine palladium complexes could enhance the π-accepting
ability and consequently accelerate the hydrogenation process. Comparatively, N-heteronitrogen
carbene (NHC) ligands, which featured with the strong σ-donating ability,29 might retard the
hydrogen transfer toward the palladium center, thereby diminishing the yield of reductive Heck
product.
Table 3: The Pd-catalyzed reductive Heck reaction of styrene with aryl bromidesa
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aReaction conditions: styrene (1.0 mmol), aryl bromide (2.0 mmol), palladium complex of C3 (0.02
mmol), KOH (2.5 mmol), 2-butanol (7 mL), 80 °C for 4 h, under aerobic environment, isolated yield.
With the optimized conditions in hand, palladium complex C3 was selected as the primary
choice precatalyst. We then sought to investigate the generality of the cross-coupling reaction with
respect to styrene (1a) and various aryl bromides (Table 3). It was found that aryl bromides with
different electronic groups, such as Me, OMe, NH
2
, Cl, F, CF , CHO and CN were all well tolerated,
3
furnishing the corresponding products in moderate to high yields (Table 3). As to the sterically
hindered aryl bromides, which could retard the oxidative addition and tend to be less active. To our
delight, it was revealed that no substantial effect on the overall efficiency of the reaction. For
example,
sterically
hindered
substrates
such
as
2-bromo-1,3-dimethylbenzene,
1-bromonaphthalene,
2
-bromo-1,3,5-trimethylbenzene,
1-bromo-2-isopropylbenzene,
9-bromophenanthrene and 1-bromo-2-methylnaphthalene, furnished the desired products in moderate
to high yields of 59, 83, 70, 89, 89 and 87% (3m-3s), respectively. Moreover, it is noteworthy that
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less reactive heteroaryl bromides, such as 5-bromobenzo[d][1,3]dioxole, 4-bromoisoquinoline,
-bromo-2-methylpyridine and 5-bromo-2-methoxypyridine were compatible with the catalytic
5
system, resulting in moderate to high yields of the products 3t-3w.
0
1
2
3
4
5
6
7
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9
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Table 4: The Pd-catalyzed reductive Heck reaction of olefins with aryl bromidesa
aReaction conditions: Aryl olefin (1.0 mmol), aryl bromide (2.0 mmol), palladium complex (0.02
mmol), KOH (2.5 mmol), 2-butanol (7 mL), 80 °C for 4 h, under aerobic environment, isolated yield.
Subsequently, we explored the generality of the reaction with other alkene substrates under the
optimized conditions (Table 4). Various aryl alkenes, such as 4-methylstyrene, 4-tert-butylstyrene,
4
-methoxystyrene, 4-chlorostyrene, 3-chlorostyrene, 2-chlorostyrene, 4-(trifluoromethyl)styrene and
4-fluorostyrene, were employed for coupling with aryl bromides. To our delight, it was found that
diverse functional aryl bromides could be well compatible with the procedure, affording the
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corresponding products 4a-4p in good to excellent yields. Notably, the challenging sterically
hindered aryl alkenes, such as 9-vinylanthracene, 2-phenyl-1-propene and 1,1-diphenylethylene were
also suitable substrates, providing the desired products in moderate to good yields. This powerful
capability of palladium complex C3 was further demonstrated that the “bulky-yet-flexible” structure
is essential for the catalyst design. Moreover, when heteroaryl alkenes such as 4-vinylpyridine and
2-vinylpyridine were tested in this reaction system, the corresponding products 4x-4ab could also be
isolated in moderate yields.
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To demonstrate the practicality of our protocol, further functionalization of 1,2-diphenylethane
was carried out (Scheme 4). It is desirable to perform the challenging Suzuki and C-N amination
cross-coupling starting from the dichlorides 5a to access disubstituted 1,2-diphenylethane at
4,4’-position of the phenyl ring in high yields. Gratifyingly, in the presence of Pd-PEPPSI-IPentAn
(C12), the reaction could stay at the monosubstituted step by subjecting 1.2 equiv. of
3
-thiopheneboronic acid or 3-methylaminopyridine, resulting in the desired product 5b and 5d in
good yield of 80% and 83%, respectively. Moreover, further difunctionalization of 5a was achieved
by adding an excess of 3-methylaminopyridine (4 equiv.), furnishing the desired product 5e in a
moderate yield of 70%. Moreover, we have extended the application of this method to the synthesis
1g
of biologically active compounds 5g, which is used as helicobacter pylori urease inhibitors. As can
be seen from Scheme 4, the intermediate of 5f could be easily accessed in high yield of 88% through
the reaction of 4-methoxystyrene and 4-bromo-1,2-dimethoxybenzene under our protocol. Having
this advanced intermediate, the inhibitor 5g could be synthesized in a convenient procedure in 81%
yield.
Scheme 4. The application of synthesis of functional and biologically active compounds
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Condition A: Reaction conditions: 4-chlorostyrene (4.0 mmol), 1-bromo-4-chlorobenzene (6.0
mmol), palladium complex (0.08 mmol), KOH (10.0 mmol), 2-butanol (24 mL), 80 °C for 4 h.
Condition B: Reaction conditions: 5a (0.5 mmol), 3-thiopheneboronic acid (0.6 mmol),
Pd-PEPPSI-IPentAn (0.01 mmol), KO Bu (1.0 mmol), 2-MeTHF/H
O (19:1, 2 mL), 100 °C for 2 h.
t
2
An
Condition C: Reaction conditions: 5a (0.5 mmol), amine (2.0 mmol), Pd-PEPPSI-IPent (0.01
t
mmol), KO Bu (1.0 mmol), dioxane (2 mL), 100 °C for 4 h. Condition D: Reaction conditions: 5a
An
t
(
0.5 mmol), amine (2.0 mmol), Pd-PEPPSI-IPent (0.02 mmol), KO Bu (1.0 mmol), dioxane (2 mL),
1
00 °C for 2 h. Condition E: Reaction conditions: 1-methoxy-4-vinylbenzene (1.0 mmol),
4
-bromo-1,2-dimethoxybenzene (2.0 mmol), palladium complex (0.02 mmol), KOH (2.5 mmol),
2-butanol (7 mL), 80 °C for 4 h. Condition F: Reaction conditions: 5f (0.5 mmol), BBr (2.0 mmol),
3
solvent, -48 °C for 2 h; -48 °C → rt, overnight.
The understanding of the mechanism of the palladium-catalyzed reductive Heck reaction could
shed some light on the development of more efficient catalytic systems. We noticed that in the
optimization experiments in Run 26, Table 1, a major product of (E)-1,2-diphenylethene (3a’’) was
afforded in the presence of weak base of Cs
2
CO . Other than the catalytic cycle illustrated in Scheme
3
2
, an alternative pathway involved the Heck reaction product of 3a’’ firstly generated followed by
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hydrogenation can’t be excluded. To investigate the possibility of the reaction process, the control
reaction and deuterium-labeling experiments was conducted. First of all, the treatment of
(E)-1,2-diphenylethene 3a under the standard reaction conditions failed to produce the desired
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compound 3a, suggesting that 3a’’ isn’t the intermediate of 3a. Secondly, the deuterium-labeling
experiments afforded the product 3a-d in 88% yield with 99% deuterium incorporation (SI, Figure
S132). On the contrary, 3a-2d wasn’t found after the reaction finished, further indicating that the
catalytic cycle via β-hydride elimination of Heck reaction and subsequent hydrogenation was
completely suppressed. Meanwhile, the fact of the high level of D incorporation (99%) suggested
that the hydrogen atom was derived from the secondary alcohol. On the basis of the above results,
the plausible mechanism is consistent with the path 1 as shown in Scheme 2.
Scheme 4. The control and deuterium-labeling experiments on reductive Heck reaction.
CONCLUSION
In summary, a type of α-diimine palladium complexes were synthesized, characterized and used
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in the Pd-catalyzed reductive Heck reaction. The steric as well as electronic effects of palladium
complexes on the catalytic efficiency were evaluated. It was revealed that the ligands with both
bulky-yet-flexible steric and π-accepting ability of backbones played crucial roles for their
extraordinary catalytic performances, which afforded the highly anti-Markovnikov-selective
hydroarylation of alkene. Under the optimized reaction condition, C3 has proven to be a versatile
precatalyst for the reaction of alkene with (hetero)aryl bromides. The developed protocol also
featured with easy-of-use manipulation in terms of the low catalyst loading and aerobic conditions.
Moreover, the potential utility of our protocol was demonstrated through a simple and practical
synthesis of functional and biologically active compounds.
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EXPERIMENTAL SECTION
1
. Physical Measurements and Materials
The NMR spectra were recorded on a Bruker DMX 400 MHz instrument at room temperature
with the decoupled nucleus, employing TMS as an internal standard and CDCl as solvent. Elemental
3
analysis was carried out using a Flash EA1112 microanalyzer. The X-ray diffraction data of single
crystals were obtained with the ω-2θ scan mode on a Bruker SMART 1000 CCD diffractionmeter
with graphite-monochromated Mo Kα radiation (λ=0.71073Å) at 173K for C1 and C3. Cell
parameters were obtained by global refinement of the positions of all collected reflections. Intensities
were corrected for Lorentz and polarization effects and empirical absorption. The structures were
2
solved by direct methods and refined by full-matrix least squares on F . All hydrogen atoms were
placed in calculated positions. Structure solution and refinement were performed by using the
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SHELXL-97 package. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were
introduced in calculated positions with the displacement factors of the host carbon atoms. The
a-diimine ligands were syntheisized according to the previous works , C2 24a, C7 28b, C8 24b, C9 ,
28
28c
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C10 28d, C1128e and C12 28f were prepared according to previous report.
2
. The Procedures for the Synthesis of α-diimine palladium complexes.
28
α-diimine palladium compounds were synthesized according to our previous report. A mixture
of α-diimine ligand (1 mmol), palladium dichloride (0.177 g, 1.1 mmol), and 20 ml MeOH was
added to a vial under a nitrogen atmosphere. The reaction was refluxed in oil bath at 80°C for 24 h.
When the solution was cooled to room temperature, 20 mL of dichloromethane was added, and then
the reaction mixture was passed through a short silica gel column using substantial dichloromethane
as elute. Evaporation of the filtrate furnished a brown solid. Then the solid was dissolved completely
with 1 mL dichloromethane, and dropped into a large amount of stirring hexane, causing the
formation of precipitate. The suspension was filtered through a sintered funnel. Drying the solid in
vacuo produced the desired palladium complex.
1
C1 was received as yellow powders in 86% yield (0.78 g). H NMR (400 MHz, CDCl
3
) δ 7.90 (d, J
=
8.3 Hz, 2H), 7.34 – 7.23 (m, 12H), 7.06 (dd, J = 15.8, 4.9 Hz, 6H), 6.69 (dd, J = 9.4, 2.4 Hz, 2H),
6
.62 (s, 2H), 6.39 (t, J = 7.6 Hz, 4H), 6.29 (d, J = 7.2 Hz, 2H), 6.09 (t, J = 7.4 Hz, 2H), 2.58 (s, 6H).
1
3
1
C{ H} NMR (101 MHz, CDCl
3
) δ 177.3, 163.1, 160.6, 146.4, 141.2, 140.6, 140.6, 140.1, 138.2,
1
32.2, 132.1, 131.9, 129.9, 129.7, 128.3, 128.1, 127.8, 126.9, 125.2, 123.4, 116.0, 115.8, 115.6, 115.4,
+
52.9, 18.7. HRMS (ESI) m/z: [M- Cl ] calcd for C52
H38ClF
2
N
2
Pd 869.1727, found 869.1721.
1
C3 was received as yellow powders in 87% yield (1.04 g). H NMR (400 MHz, CDCl
3
) δ 7.85 (d, J
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= 8.3 Hz, 2H), 7.35 – 7.28 (m, 8H), 7.27 – 7.18 (m, 6H), 7.17 – 7.09 (m, 18H), 7.04 – 6.98 (m, 6H),
6
.72 (s, 2H), 6.57 (s, 2H), 6.33 (t, J = 7.6 Hz, 4H), 6.13 (d, J = 7.2 Hz, 2H), 6.05 (t, J = 7.4 Hz, 2H),
13
1
5
.53 (s, 2H), 2.51 (s, 6H). C{ H} NMR (101 MHz, CDCl ) δ 176.9, 144.1, 143.4, 143.3, 141.9,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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6
7
8
9
0
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8
9
0
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8
9
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141.0, 140.7, 137.6, 131.4, 130.0, 129.8, 129.6, 129.5, 129.4, 129.3, 128.4, 128.3, 127.9, 127.6,
+
1
26.4, 126.4, 126.3, 125.3, 125.1, 123.8, 56.3, 52.7, 18.6. HRMS (ESI) m/z: [M- Cl ] calcd for
78
C H
60ClN
2
Pd 1165.3490, found 1165.3474.
C4 was received as yellow powders in 81% yield (1.02 g). H NMR (400 MHz, CDCl
8.3 Hz, 2H), 7.36 – 7.27 (m, 10H), 7.24 – 7.08 (m, 24H), 6.95 (d, J = 7.3 Hz, 4H), 6.72 (d, J = 1.3
Hz, 2H), 6.55 (s, 2H), 6.35 (t, J = 7.6 Hz, 4H), 6.14 – 6.05 (m, 4H), 5.56 (s, 2H), 3.53 – 3.42 (m, 2H),
1
3
) δ 7.82 (d, J
=
1
3
1
1
.57 (d, J = 6.7 Hz, 6H), 1.11 (d, J = 6.9 Hz, 6H). C{ H} NMR (101 MHz, CDCl
3
) δ 177.1, 146.3,
144.3, 143.5, 143.5, 142.3, 140.6, 140.2, 139.7, 137.3, 131.4, 129.9, 129.7, 129.6, 129.4, 129.3,
1
2
28.3, 128.3, 127.9, 127.8, 127.5, 126.4, 126.4, 126.3, 125.7, 125.5, 125.4, 123.9, 56.5, 52.9, 29.0,
+
4.5, 23.7. HRMS (ESI) m/z: [M- Cl ] calcd for C82
H
2
68ClN Pd 1221.4117, found 1221.4100.
1
C5 was received as yellow powders in 74% yield (0.91 g). H NMR (400 MHz, CDCl
3
) δ 7.62 (d, J
=
8.3 Hz, 2H), 7.39 (d, J = 7.0 Hz, 8H), 7.21 – 7.13 (m, 12H), 6.91 (d, J = 6.8 Hz, 8H), 6.84 (t, J =
7.8 Hz, 2H), 6.71 (s, 4H), 6.64 – 6.55 (m, 12H), 6.23 (s, 4H), 6.07 (d, J = 7.2 Hz, 2H), 3.64 (s, 6H).
1
3
1
C{ H} NMR (101 MHz, CDCl
3
) δ 177.8, 158.6, 142.4, 141.2, 138.5, 136.0, 130.8, 129.9, 129.7,
+
1
28.2, 128.1, 127.5, 126.6, 126.3, 123.5, 115.0, 55.2, 52.3. HRMS (ESI) m/z: [M- Cl ] calcd for
78
C H
2
60ClN O
2
Pd 1197.3391, found 1197.3373.
C6 was received as yellow powders in 88% yield (0.69 g). H NMR (400 MHz, CDCl
= 8.3 Hz, 2H), 7.49 (t, J = 7.9 Hz, 4H), 7.30 (s, 2H), 7.28 (s, 2H), 6.59 (d, J = 7.3 Hz, 2H), 3.22 –
.12 (m, 4H), 2.09 (dd, J = 7.5, 5.4 Hz, 4H), 2.00 (dd, J = 14.2, 7.0 Hz, 4H), 1.47 (dt, J = 32.1, 7.2
1
3
) δ 8.14 (d, J
3
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Hz, 8H), 1.10 (t, J = 7.4 Hz, 12H), 0.54 (t, J = 7.4 Hz, 12H). 13C{ H} NMR (101 MHz, CDCl
1
) δ
75.2, 142.4, 137.9, 132.5, 131.2, 128.7, 128.2, 126.4, 126.3, 125.6, 125.5, 125.1, 42.9, 26.8, 26.2,
2.3, 11.5. HRMS (ESI) m/z: [M- Cl Pd 717.3411, found 717.3395.
]+ calcd for C44
4
5
6
7
8
9
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H
56
N
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3. General Procedure for Reductive Heck Reaction
Unless otherwise noted, the cross coupling reactions were carried out in air. All solvents were
used as received without further purification. A parallel reactor containing a stirred bar was charged
with palladium complexes (0.02 mmol, 2 mol%), aryl olefin (1.0 mmol), aryl bromides (2.0 mmol),
base (2.0 mmol), and 6 mL of solvent. The reaction mixture was conducted at 80 °C for 4 h in heating
mantle. After completion of the reaction, the reaction mixture was cooled to room temperature, and
2
0 mL of water was added. The mixture was diluted with dichloromethane (5 mL) and extracted
three times (3 × 5 mL) with dichloromethane. The organic layer was dried with anhydrous
magnesium sulfate, filtered, and evaporated under reduce pressure. The crude cross-coupling
products were purified by silica-gel column chromatography using petroleum ether-ethyl acetate as
the eluent.
4
1
. NMR data of the cross-coupling products.
,2-diphenylethane (3a).30 The cross-coupling product was isolated by silica-gel column
chromatography using petroleum ether as the eluent to afford a white solid in 91% yield (166 mg).
1H NMR (400 MHz, CDCl
) δ 7.34 – 7.24 (m, 4H), 7.20 (dd, J = 15.5, 9.8 Hz, 6H), 2.92 (s, 4H).
C{ H} NMR (101 MHz, CDCl ) δ 141.8, 128.4, 128.3, 125.9, 37.9.
3
13
1
3
3
1
1
-methyl-4-phenethylbenzene (3b). The cross-coupling product was isolated by silica-gel column
1
chromatography using petroleum ether as the eluent to afford white solid in 90% yield (176 mg). H
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NMR (400 MHz, CDCl ) δ 7.30 (dd, J = 7.8, 6.9 Hz, 2H), 7.25 – 7.18 (m, 3H), 7.11 (s, 4H), 2.91 (s,
3
13
1
4
H), 2.35 (s, 3H). C{ H} NMR (101 MHz, CDCl
3
) δ 141.9, 138.7, 135.3, 129.0, 128.4, 128.3,
1
28.3, 125.8, 38.1, 37.5, 29.7, 21.0.
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3
2
1-methyl-2-phenethylbenzene (3c). The cross-coupling product was isolated by silica-gel column
1
chromatography using petroleum ether as the eluent to afford clear oil in 75% yield (147 mg). H
NMR (400 MHz, CDCl ) δ 7.31 (dd, J = 8.0, 7.3 Hz, 2H), 7.25 – 7.19 (m, 3H), 7.19 – 7.07 (m, 4H),
3
1
3
1
2
.90 (d, J = 2.2 Hz, 4H), 2.32 (s, 3H). C{ H} NMR (101 MHz, CDCl
3
) δ 142.0, 140.0, 135.9, 130.2,
1
28.8, 128.4, 128.4, 126.1, 126.0, 126, 36.7, 35.4, 19.2.
3
3
1-methyl-3-phenethylbenzene (3d). The cross-coupling product was isolated by silica-gel column
1
chromatography using petroleum ether as the eluent to afford clear oil in 85% yield (167 mg). H
NMR (400 MHz, CDCl ) δ 7.23 – 7.17 (m, 2H), 7.10 (ddd, J = 12.2, 6.8, 4.4 Hz, 4H), 6.97 – 6.87 (m,
3
1
3
1
3
H), 2.86 – 2.75 (m, 4H), 2.24 (s, 3H). C{ H} NMR (101 MHz, CDCl
3
) δ 141.9, 141.7, 137.9,
1
29.2, 128.6, 128.4, 128.3, 128.2, 126.6, 125.9, 125.4, 38.0, 38.0, 21.4.
1,3-dimethyl-5-phenethylbenzene (3e).34 The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether as the eluent to afford white solid in 69% yield (145
1
mg). H NMR (400 MHz, CDCl
3
) δ 7.25 – 7.17 (m, 2H), 7.15 – 7.08 (m, 3H), 6.76 (d, J = 2.9 Hz,
1
3
1
3
H), 2.84 – 2.72 (m, 4H), 2.21 (s, 6H). C{ H} NMR (101 MHz, CDCl
3
) δ 142.0, 141.8, 137.8,
1
28.4, 128.3, 127.5, 126.2, 125.8, 38.1, 37.9, 21.3.
1-methoxy-4-phenethylbenzene (3f).35 The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether-ethyl acetate (100:1) as the eluent to afford white
1
solid in 86% yield (182 mg). H NMR (400 MHz, CDCl
3
) δ 7.34 – 7.28 (m, 2H), 7.22 (ddd, J = 6.8,
3
.5, 2.4 Hz, 3H), 7.15 – 7.07 (m, 2H), 6.89 – 6.82 (m, 2H), 3.81 (s, 3H), 2.91 (d, J = 1.1 Hz, 4H).
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C{ H} NMR (101 MHz, CDCl
) δ 157.8, 141.8, 133.9, 129.3, 128.4, 128.3, 125.8, 113.7, 55.2,
3
3
8.2, 37.0.
2
-phenethylaniline (3g).36 The cross-coupling product was isolated by silica-gel column
0
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chromatography using petroleum ether-ethyl acetate (50:1) as the eluent to afford light yellow oil in
1
4
7% yield (93 mg). H NMR (400 MHz, CDCl
3
) δ 7.34 – 7.25 (m, 2H), 7.24 – 7.18 (m, 3H), 7.08 –
6.99 (m, 2H), 6.74 (td, J = 7.4, 1.2 Hz, 1H), 6.67 (dd, J = 8.3, 1.2 Hz, 1H), 4.00 – 3.05 (m, 2H), 2.93
1
3
1
(
dd, J = 9.7, 6.3 Hz, 2H), 2.78 (dd, J = 9.7, 6.3 Hz, 2H). C{ H} NMR (101 MHz, CDCl
3
) δ 144.1,
1
41.8, 129.4, 128.4, 128.4, 127.1, 126.0, 126.0, 118.9, 115.7, 35.3, 33.3.
1-(4-phenethylphenyl)ethan-1-one (3h).37 The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether-ethyl acetate (50:1) as the eluent to afford clear oil in
1
31% yield (69 mg). H NMR (400 MHz, CDCl
3
) δ 7.96 – 7.91 (m, 2H), 7.37 – 7.27 (m, 5H), 7.25 –
1
3
1
7
1
.19 (m, 2H), 3.02 (td, J = 7.4, 2.8 Hz, 4H), 2.64 (s, 3H). C{ H} NMR (101 MHz, CDCl
3
) δ 197.9,
47.5, 141.1, 135.2, 128.7, 128.5, 128.4, 128.4, 126.1, 37.8, 37.4, 26.6.
3
8
1-chloro-4-phenethylbenzene (3i). The cross-coupling product was isolated by silica-gel column
1
chromatography using petroleum ether as the eluent to afford white solid in 87% yield (188 mg). H
NMR (400 MHz, CDCl ) δ 7.30 – 7.17 (m, 5H), 7.16 – 7.11 (m, 2H), 7.10 – 7.03 (m, 2H), 2.88 (s,
3
1
3
1
4
3
H). C{ H} NMR (101 MHz, CDCl
3
) δ 141.2, 140.1, 131.6, 129.8, 128.4, 128.4, 128.3, 126.0, 37.7,
7.2.
3
5
1-fluoro-4-phenethylbenzene (3j). The cross-coupling product was isolated by silica-gel column
1
chromatography using petroleum ether as the eluent to afford white solid in 79% yield (158 mg). H
NMR (400 MHz, CDCl
3
) δ 7.30 (t, J = 7.3 Hz, 2H), 7.24 – 7.10 (m, 5H), 7.01 – 6.94 (m, 2H), 2.92 (s,
1
3
1
4
H). C{ H} NMR (101 MHz, CDCl ) δ 162.5, 160.1, 141.4, 137.3, 137.3, 129.8, 129.7, 128.4,
3
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128.3, 126.0, 115.1, 114.9, 38.0, 37.0.
-phenethyl-4-(trifluoromethyl)benzene (3k).38 The cross-coupling product was isolated by
1
silica-gel column chromatography using petroleum ether-ethyl acetate (100:1) as the eluent to afford
0
1
2
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4
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white solid in 81% yield (203 mg). H NMR (400 MHz, CDCl
3
) δ 7.45 (d, J = 8.0 Hz, 2H), 7.23 –
7
.16 (m, 4H), 7.15 – 7.10 (m, 1H), 7.10 – 7.05 (m, 2H), 2.94 – 2.88 (m, 2H), 2.88 – 2.82 (m, 2H).
1
3
1
C{ H} NMR (101 MHz, CDCl
3
) δ 145.7, 145.7, 141.0, 128.8, 128.4, 126.1, 125.3, 125.2, 125.2,
1
25.2, 37.6, 37.5.
1
-(tert-butyl)-4-phenethylbenzene (3l).39 The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether-ethyl acetate (100:1) as the eluent to afford white
1
solid in 70% yield (167 mg). H NMR (400 MHz, CDCl
3
) δ 7.35 – 7.28 (m, 4H), 7.23 (dd, J = 7.7,
1
3
1
3.3 Hz, 3H), 7.19 – 7.15 (m, 2H), 2.95 – 2.89 (m, 4H), 1.33 (s, 9H). C{ H} NMR (101 MHz,
CDCl ) δ 148.7, 142.0, 138.8, 128.4, 128.3, 128.0, 125.9, 125.2, 37.9, 37.4, 34.4, 31.4.
,3-dimethyl-2-phenethylbenzene (3m).40 The cross-coupling product was isolated by silica-gel
3
1
column chromatography using petroleum ether as the eluent to afford white solid in 59% yield (124
1
mg). H NMR (400 MHz, CDCl
3
) δ 7.24 (dd, J = 10.0, 4.7 Hz, 2H), 7.19 – 7.13 (m, 3H), 6.95 (s, 3H),
13
1
2.87 – 2.81 (m, 2H), 2.71 – 2.65 (m, 2H), 2.27 (s, 6H). C{ H} NMR (101 MHz, CDCl ) δ 142.2,
3
1
38.5, 136.1, 128.4, 128.3, 128.2, 126.0, 125.8, 35.3, 32.1, 19.7.
41
1
,3,5-trimethyl-2-phenethylbenzene (3n). The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether-ethyl acetate (100:1) as the eluent to afford white
1
solid in 83% yield (186 mg). H NMR (400 MHz, CDCl
3
) δ 7.24 (dd, J = 10.0, 4.6 Hz, 2H), 7.16
(ddd, J = 11.1, 6.3, 1.7 Hz, 3H), 6.79 (s, 2H), 2.84 – 2.78 (m, 2H), 2.70 – 2.63 (m, 2H), 2.25 (s, 6H),
1
3
1
2
.20 (s, 3H). C{ H} NMR (101 MHz, CDCl ) δ 142.3, 136.0, 135.4, 135.2, 128.9, 128.4, 128.2,
3
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125.9, 35.5, 31.8, 20.8, 19.6.
1
-isopropyl-2-phenethylbenzene (3o).42 The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether-ethyl acetate (100:1) as the eluent to afford white
0
1
2
3
4
5
6
7
8
9
0
1
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solid in 70% yield (157 mg). H NMR (400 MHz, CDCl
3
) δ 7.35 – 7.29 (m, 3H), 7.22 (dd, J = 10.2,
3
.9 Hz, 4H), 7.20 – 7.12 (m, 2H), 3.21 (dt, J = 13.7, 6.9 Hz, 1H), 3.02 – 2.94 (m, 2H), 2.92 – 2.87 (m,
1
3
1
2H), 1.26 (d, J = 6.9 Hz, 6H). C{ H} NMR (101 MHz, CDCl ) δ 146.6, 142.0, 138.5, 129.4, 128.4,
3
1
26.5, 126.0, 125.7, 125.3, 38.2, 34.9, 28.7, 24.1.
1
-phenethylnaphthalene (3p).42 The cross-coupling product was isolated by silica-gel column
1
chromatography using petroleum ether as the eluent to afford white solid in 89% yield (207 mg). H
NMR (400 MHz, CDCl
3
) δ 8.18 (d, J = 8.3 Hz, 1H), 7.97 – 7.92 (m, 1H), 7.80 (d, J = 8.2 Hz, 1H),
7.58 (dddd, J = 17.8, 8.0, 6.8, 1.4 Hz, 2H), 7.46 (dd, J = 8.1, 7.1 Hz, 1H), 7.42 – 7.35 (m, 3H), 7.34 –
1
3
1
7
.28 (m, 3H), 3.53 – 3.38 (m, 2H), 3.17 – 3.09 (m, 2H). C{ H} NMR (101 MHz, CDCl
3
) δ 142.0,
1
37.8, 133.9, 131.7, 128.8, 128.4, 128.4, 126.7, 126.0, 125.8, 125.5, 125.4, 123.6, 37.1, 35.1.
2-phenethylnaphthalene (3q).43 The cross-coupling product was isolated by silica-gel column
1
chromatography using petroleum ether as the eluent to afford white solid in 86% yield (200 mg). H
NMR (400 MHz, CDCl ) δ 7.87 (dd, J = 16.2, 7.8 Hz, 3H), 7.69 (s, 1H), 7.52 (dd, J = 9.5, 3.6 Hz,
3
1
3
1
2
H), 7.43 – 7.35 (m, 3H), 7.32 – 7.25 (m, 3H), 3.23 – 3.05 (m, 4H). C{ H} NMR (101 MHz,
CDCl ) δ 141.7, 139.2, 133.6, 132.0, 128.4, 128.3, 127.8, 127.6, 127.4, 127.3, 126.4, 125.9, 125.8,
3
125.1, 38.0, 37.8.
-phenethylphenanthrene (3r).44 The cross-coupling product was isolated by silica-gel column
9
chromatography using petroleum ether-ethyl acetate (50:1) as the eluent to afford white solid in 89%
1
yield (251 mg). H NMR (400 MHz, CDCl
3
) δ 8.85 – 8.77 (m, 1H), 8.72 (d, J = 8.0 Hz, 1H), 8.28 –
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8.20 (m, 1H), 7.87 (dd, J = 7.7, 1.5 Hz, 1H), 7.76 – 7.70 (m, 2H), 7.70 – 7.61 (m, 3H), 7.44 – 7.29 (m,
1
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H), 3.48 (dd, J = 9.8, 6.7 Hz, 2H), 3.23 – 3.16 (m, 2H). C{ H} NMR (101 MHz, CDCl
3
) δ 142.0,
35.8, 131.8, 131.1, 130.7, 129.7, 128.4, 128.4, 128.1, 126.6, 126.1, 126.1, 126.0, 126.0, 124.2,
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123.3, 122.4, 36.5, 35.4.
-methyl-1-phenethylnaphthalene (3s).45 The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether as the eluent to afford clear oil in 87% yield (214 mg).
1H NMR (400 MHz, CDCl
) δ 8.02 (d, J = 8.5 Hz, 1H), 7.76 – 7.71 (m, 1H), 7.56 (d, J = 8.4 Hz, 1H),
.43 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 7.34 (ddd, J = 7.9, 6.9, 1.0 Hz, 1H), 7.27 – 7.14 (m, 6H), 3.30 –
2
3
7
3
1
1
3
1
.24 (m, 2H), 2.87 – 2.78 (m, 2H), 2.35 (s, 3H). C{ H} NMR (101 MHz, CDCl
3
) δ 142.1, 134.7,
33.1, 132.6, 132.0, 129.2, 128.7, 128.5, 128.3, 126.3, 126.0, 126.0, 124.5, 123.4, 36.1, 30.9, 20.0.
5-phenethylbenzo[d][1,3]dioxole (3t).46 The cross-coupling product was isolated by silica-gel
column chromatography using petroleum ether-ethyl acetate (50:1) as the eluent to afford yellow
1
solid in 79% yield (179 mg). H NMR (400 MHz, CDCl
3
) δ 7.20 (dd, J = 10.1, 4.5 Hz, 2H), 7.15 –
7.06 (m, 3H), 6.61 (dd, J = 15.8, 4.7 Hz, 2H), 6.53 (dd, J = 7.9, 1.6 Hz, 1H), 5.82 (s, 2H), 2.82 – 2.72
13
1
(
m, 4H). C{ H} NMR (101 MHz, CDCl
108.9, 108.1, 100.7, 38.2, 37.6.
-phenethylisoquinoline (3u).47 The cross-coupling product was isolated by silica-gel column
3
) δ 147.5, 145.6, 141.6, 135.6, 128.4, 128.3, 125.9, 121.1,
4
chromatography using petroleum ether-ethyl acetate (30:1) as the eluent to afford white solid in 32%
1
yield (75 mg). H NMR (400 MHz, CDCl
3
) δ 8.75 (d, J = 2.2 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.87
(d, J = 1.6 Hz, 1H), 7.77 – 7.72 (m, 1H), 7.66 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.52 (ddd, J = 8.1, 6.9,
1.1 Hz, 1H), 7.31 – 7.26 (m, 2H), 7.24 – 7.16 (m, 3H), 3.16 – 3.09 (m, 2H), 3.07 – 3.01 (m, 2H).
1
3
1
C{ H} NMR (101 MHz, CDCl ) δ 152.0, 146.9, 140.8, 134.4, 134.2, 129.2, 128.8, 128.7, 128.5,
3
2
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The Journal of Organic Chemistry
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128.1, 127.3, 126.6, 126.2, 37.4, 35.1.
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-methyl-5-phenethylpyridine (3v). The cross-coupling product was isolated by silica-gel column
chromatography using petroleum ether-ethyl acetate (50:1) as the eluent to afford clear oil in 61%
0
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yield (120 mg). H NMR (400 MHz, CDCl
3
) δ 8.33 (s, 1H), 7.35 (dd, J = 7.9, 2.2 Hz, 1H), 7.29 (d, J
=
7.3 Hz, 2H), 7.26 – 7.20 (m, 1H), 7.20 – 7.16 (m, 2H), 7.07 (d, J = 7.9 Hz, 1H), 2.92 (s, 4H), 2.54
1
3
1
(s, 3H). C{ H} NMR (101 MHz, CDCl ) δ 155.9, 149.1, 141.0, 136.4, 133.7, 128.5, 128.4, 126.1,
3
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22.8, 37.6, 34.5, 24.0.
-methoxy-5-phenethylpyridine (3w).46 The cross-coupling product was isolated by silica-gel
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column chromatography using petroleum ether-ethyl acetate (50:1) as the eluent to afford clear oil in
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5
1% yield (109 mg). H NMR (400 MHz, CDCl
3
) δ 7.94 (d, J = 2.1 Hz, 1H), 7.33 (dd, J = 8.4, 2.5 Hz,
1H), 7.30 – 7.25 (m, 2H), 7.22 – 7.12 (m, 3H), 6.65 (d, J = 8.4 Hz, 1H), 3.91 (s, 3H), 2.91 – 2.80 (m,
1
3
1
4
H). C{ H} NMR (101 MHz, CDCl
3
) δ 162.7, 146.1, 141.1, 139.0, 129.4, 128.5, 128.4, 126.0,
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10.3, 53.3, 37.7, 33.9.
1,2-di-p-tolylethane (4a).31 The cross-coupling product was isolated by silica-gel column
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chromatography using petroleum ether as the eluent to afford white solid in 88% yield (185 mg). H
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3
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NMR (400 MHz, CDCl
δ 138.9, 135.3, 129.0, 128.3, 37.7, 21.0.
-fluoro-4-(4-methylphenethyl)benzene (4b).31 The cross-coupling product was isolated by
3
) δ 7.10 (s, 8H), 2.88 (s, 4H), 2.34 (s, 6H). C{ H} NMR (101 MHz, CDCl )
3
1
silica-gel column chromatography using petroleum ether as the eluent to afford white solid in 79%
1
yield (169 mg). H NMR (400 MHz, CDCl
3
) δ 7.20 – 7.08 (m, 6H), 7.04 – 6.97 (m, 2H), 2.92 (s, 4H),
) δ 162.5, 160.1, 138.3, 137.4, 137.4, 135.4, 129.8,
29.7, 129.0, 129.0, 129.0, 128.3, 128.3, 128.3, 128.2, 115.1, 114.9, 37.5, 37.1, 21.0.
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3
1
2.38 (s, 3H). C{ H} NMR (101 MHz, CDCl
3
1
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