Palladium-Catalyzed Hiyama Coupling of Benzylic Ammonium Salts via C-N Bond Cleavage

Article abstract of DOI:10.1021/acs.joc.9b02554

The first palladium-catalyzed Hiyama cross-coupling of arylsilanes with benzyltrimethylammonium salts is reported. The reaction proceeds smoothly to facilitate C(sp²)-C(sp³) bond formation via cleavage of the C-N bond and provides a useful approach to various diarylmethanes with a broad substrate scope and excellent functional group tolerance in good to excellent yields.

Full text of DOI:10.1021/acs.joc.9b02554

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Note
Palladium-Catalyzed Hiyama Coupling of
Benzylic Ammonium Salts via C-N Bond Cleavage
Chunyu Han, Zhenming Zhang, Silin Xu, Kai Wang, Kaiting Chen, and Junfeng Zhao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02554 • Publication Date (Web): 20 Nov 2019
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Page 1 of 6
The Journal of Organic Chemistry
Palladium-Catalyzed Hiyama Coupling of Benzylic Ammonium
Salts via C−N Bond Cleavage
Chunyu Han†, Zhenming Zhang†, Silin Xu†, Kai Wang†, Kaiting Chen†, Junfeng Zhao†‡*
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†College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022, P. R. China
‡School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, Guangdong, P. R. China
zhaojf@jxnu.edu.cn
Supporting Information
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ABSTRACT: The first palladium-catalyzed Hiyama cross-
coupling of arylsilanes with benzyltrimethyl-ammonium salts is
reported. The reaction proceeds smoothly to facilitate
C(sp2)−C(sp3) bond formation via cleavage of the C−N bond,
and provides a useful approach to various diarylmethanes with a
5 mol% PdCl2(CH3CN)2
20 mol% PPh2Cy
Si(OMe)3
NMe3OTf
Ar1
Ar2
Ar1
Ar2
+
TBAF (2 eq)
EtOH, 120 °C, 24 h
up to 97% yield
broad substrate scope and excellent functional group tolerance in good to excellent yields.
Diarylmethane is an important scaffold in a large number of
Figure 1. Bioactive Compounds Containing the
bioactive natural products and pharmaceuticals (Figure 1).1 For
example, the marine natural product Avrainvilleol (I) which
contains the diarylmethane unit, has been reported to exhibit
both antibacterial2 and antioxidant activities.3 Moreover, a
number of commercially available drugs such as Segontin (II)
(for the treatment of coronary heart disease),4 the antidepressant
Bifemelane (III),5 the antiallergic medicines Benadryl (IV)6
and Tolpropamine (V)7, and the anticancer agent Piritrexim
(VI),8 contain the diarylmethane sub-structure. The
development of efficient methods for the synthesis of this
skeleton has therefore attracted considerable attention over the
past few decades.9 More specifically, classic strategies
including the Friedel−Crafts reaction10 and the reduction of
diarylmethane derivatives11 have been established to construct
the diarylmethane skeleton. Although efficient, these methods
often suffer from disadvantages, such as harsh reaction
conditions, poor regioselectivities and difficult available
substrates. Recently, transition metal-catalyzed cross-coupling
reactions have emerged as powerful methods for the direct
construction of diarylmethane derivatives,12 with palladium
being undoubtedly one of the most effective catalysts due to its
widespread application and versatility.13 In these palladium-
catalyzed reactions, a variety of nucleophiles have been
employed for the syntheses of diarylmethane derivatives, with
examples including organoboranes,14 organoindium reagents15
and organostannanes.16 Compared with these organometallic
reagents, organosilicon nucleophiles are an attractive
alternative coupling partner in the palladium-catalyzed Hiyama
coupling reaction due to their facile synthesis and low toxicity.17
However, to date, nearly all studies of the palladium-catalyzed
Hiyama coupling reaction have focused on C(sp2)−C(sp2) bond
formation.18 In contrast, very few examples of the construction
of C(sp2)−C(sp3) bonds have been reported based on this
strategy.19 As such, a novel and efficient palladium-catalyzed
Hiyama cross-coupling reaction for the preparation of
diarylmethanes via C(sp2)−C(sp3) bond formation is highly
desirable.
Diarylmethane Motif
HO
Br
Me
N
H
Bn
H
Br
OH
OH
N
OH
O
Me
Avrainvilleol (I)
Segontin (II)
Bifemelane (III)
Me
Me
Me
NH2 Me
O
N
Me
N
Me
H2N
N
N
O
Me
N
O
Me
Tolpropamine (V)
Benadryl (IV)
Piritrexim (VI)
field by the groups of Wang,22 MacMillan,23 Watson,24 and
Tortosa,25 among others.26 In this context, our group is
interested in the palladium-catalyzed cross-coupling reaction
via the cleavage of C−N bond,27 and we have reported the
palladium-catalyzed Suzuki cross-coupling of benzyltrimeth-
ylammonium salts for the synthesis of diarylmethane28 and
triarylmethane derivatives.29 Based on our previous successes,
we envisioned that arylsilanes could also be used as coupling
partners to react with benzylic ammonium salts for the C(sp2)-
C(sp3) bond formation in the presence of palladium catalyst. In
such context, we herein report the first palladium-catalyzed
Hiyama cross-coupling of benzyltrimethyl-ammonium salts for
the construction of diarylmethane derivatives.
Initial exploratory experiments to optimize the reaction
conditions for the coupling reaction were performed with
benzyltrimethylammonium salt 1a and trimethoxy(phenyl)-
silane 2a as the model substrates (Table 1). To our delight, the
desired coupling product 3aa was indeed obtained, albeit in 20%
yield when the reaction was performed at 120 oC for 24 h in the
presence of 5 mol% Pd(OAc)2, 20 mol% PPh3, and 2.0 equiv of
tetrabutylammonium fluoride (TBAF) in EtOH under a
nitrogen atmosphere (Table 1, entry 1). A brief screening of
palladium catalysts revealed that PdCl2(CH3CN)2 gave a
relatively good performance (Table 1, entries 2−4). Rapid
screening with other solvents led to a complex reaction or lower
yields (Table 1, entries 5−9). When PPh2Cy was used as the
ligand instead of PPh3, the coupling product was obtained with
Recently, ammonium salts emerged as electrophiles which
have been widely used in transition metal-catalyzed cross-
coupling reactions via C−N cleavage.20 Since the pioneering
work by Sarandeses,21 many efforts have been made in this
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Page 2 of 6
a dramatically increased yield (85%) (Table 1, entries 10−11).
Scheme 1. Scope of the Benzylammonium Saltsa
1
2
3
4
5
6
7
8
For the bidentate ligand BINAP, trace amounts of the product
was obtained (Table 1, entry 12). Considering the beneficial
effect of the fluoride ion for activation of the C−Si bond,17b
other fluoride salts such as AgF, CsF, and KF were examined
in this coupling reaction, but a dramatic decrease in reactivity
was observed (Table 1, entries 13−15). In addition, only trace
amount of product was observed when the reaction was
performed in the absence of an additive (Table 1, entry 16).
Furthermore, reducing of the amount of 2a from 2.0 equiv to
1.5 equiv did not result in any remarkable decrease in the
reaction efficiency (Table 1, entry 18).
5 mol% PdCl2(CH3CN)2
20 mol% PPh2Cy
Si(OMe)3
NMe3OTf
+
Ar
Ar
TBAF (2 eq)
EtOH, 120 °C, 24 h
1
2a
3aa-3ma
Me
Me
3aa
3da
3ba
, 89%
, 78%
3ca
, 51%
MeO
9
Me
MeO
F3C
3ea
, 83%
, 59%
, 85%
, 92%
3fa
3ia
3la
, 83%
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59
60
F
F
F
3ga
3ha
, 90%
, 39%
, 88%
Table 1. Optimization of the Reaction Conditionsa
Pd cat., ligand
Si(OMe)3
tBuO
MeO
NMe3OTf
NC
+
additive, solvent
120 °C, 24 h
3ja
O
O
3ka
, 83%
1a
2a
3aa
addit
ive
solvent yield (%)b
HN
entry
catalyst
Pd(OAc)2
PdCl2
Pd2(dba)3
ligand
3ma
3na
, ND
, 94%
aReaction conditions: 1 (0.20 mmol), 2a (0.40 mmol), PdCl2(CH3CN)2
(5 mol%), PPh2Cy (20 mol%) and TBAF (0.40 mmol) in ethanol (2.0
mL) at 120 oC for 24 h under nitrogen atmosphere.
1
2
3
4
5
6
7
8
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
TBAF EtOH
TBAF EtOH
TBAF EtOH
TBAF EtOH
TBAF PhMe
TBAF DMSO 10
TBAF DMF
TBAF CH3CN 50
TBAF THF
TBAF EtOH
TBAF EtOH
TBAF EtOH
AgF
CsF
KF
--
20
26
11
55
7
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
the naphthyl substrate exhibited an excellent reactivity (3ma),
the indolyl substrate failed to afford the desired product (3na).
8
Having demonstrated the broad scope of benzylammonium
salts that can be used in the palladium-catalyzed Hiyama cross-
coupling reaction, we next sought to explore a variety of
arylsilane substrates (Scheme 2). Interestingly, substrate
PhSi(OEt)3 also reacted with benzylammonium salts (1j) under
the standard conditions to afford the coupling product 3ja in 88%
yield, thereby demonstrating a comparable reactivity to
PhSi(OMe)3. With respect to the trimethoxy arylsilanes, the
substrates bearing electron-donating groups (i.e., 2-Me-, 3-Me-,
4-Me-, and 4-OMe-) on the phenyl ring effectively provided the
desired coupling products (3jb−je) in
9
trace
85 (89)
63
10
11
12
13
14
15
16
17c
18d
PPh2Cy
X-Phos
BINAP
PPh2Cy
PPh2Cy
PPh2Cy
PPh2Cy
PPh2Cy
PPh2Cy
trace
trace
9
trace
trace
58
EtOH
EtOH
EtOH
EtOH
TBAF EtOH
TBAF EtOH
79
aReaction conditions: 1a (0.10 mmol), 2a (0.20 mmol), palladium
catalyst (5 mol%), ligand (20 mol%) and additive (2.0 eq) in solvent
(2.0 mL) at 120 oC under a nitrogen atmosphere. bGC yields with
naphthalene as an internal standard. Isolated yield is in parentheses. c3
mol% PdCl2(CH3CN)2 was uesd. d0.15 mmol 2a was used.
Scheme 2. Scope of the Arylsilanesa
5 mol% PdCl2(CH3CN)2
Si(OMe)3 20 mol% PPh2Cy
NMe3OTf
Ar
+
Ar
TBAF (2 equiv)
NC
NC
EtOH, 120 °C, 24 h
1j
2
3ja-3jj
With the optimized reaction conditions in hand, we then
evaluated the substrate scope of this palladium-catalyzed cross-
coupling of trimethoxy(phenyl)silane (2a) with various
benzylammonium salts (1). As shown in Scheme 1, electron-
donating groups such as 2-Me-, 3-Me-, 4-Me-, 3-OMe-, and 4-
OMe- on the phenyl ring were compatible and the
corresponding coupling products (3ba−fa) were obtained in
moderate to excellent yields. In addition, benzylammonium
salts bearing electron-withdrawing groups (i.e., 4-F and 3,4-
difluoro groups) afford the desired coupling products 3ga and
3ha in yields of 59% and 90%, respectively. In the case of the
4-trifluoromethyl benzylammonium salt, the coupling reaction
also proceeded smoothly to afford the expected product (3ia) in
an acceptable yield. Moreover, sensitive or strong electron-
withdrawing groups, such as CN (3ja) and ester functionalities
(3ka and 3la), were well-tolerated giving 83−88% yields under
the standard reaction conditions. However, although
Me
NC
NC
Me
NC
3jab
3jb
3je
3jc
3jf
, 88%
, 57%
, 93%
O
O
NC
NC
Me
NC
OMe NC
3jd
, 97%
, 82%
, 82%
, 97%
, 94%
O
NC
NC
3jg
, 95%
3jh
3ji
S
NC
NC
Cl
3jj
, 94%
3jk
, trace
aReaction conditions: 1j (0.20 mmol), 2 (0.40 mmol), PdCl2(CH3CN)2
(5 mol %), PPh2Cy (20 mol%) and TBAF (0.40 mmol) in ethanol (2.0
o
b
mL) at 120 C for 24 h under nitrogen atmosphere. PhSi(OEt)3 was
used as the substrate.
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The Journal of Organic Chemistry
chromatography (TLC); products purification was carried out using
moderate to excellent yields. The reaction also showed a good
tolerance toward a special substrate, namely benzo[d]-
[1,3]dioxol-5-yltrimethoxysilane, to give (3jf) in a 97% yield.
In addition, trimethoxy(naphthalen-2-yl)silane and trimethoxy
(naphthaalen-1-yl)silane reacted to afford the corresponding
products (3jg and 3jh) in yields of 95% and 82%, respectively.
Furthermore, substrates bearing heterocycles, such as the furan
(3ji) and thiophene (3jj) moieties, were well-tolerated in this
reaction. However, the p-chloro-substituted phenylsilane
derivative only provided a trace amount of the expected
coupling product (3jk).
1
2
3
4
5
6
7
8
silica gel column chromatography.
1H NMR and 13C NMR spectra were recorded on Bruker Avance
400 MHz and Bruker AMX 400 MHz spectrometer at 400 and 100
1
MHz, respectively. H NMR spectra were recorded in CDCl3 and
referenced to residual CHCl3 at 7.26 ppm, while the 13C NMR
spectra were referenced to the central peak of CDCl3 at 77.0 ppm.
GC yields were obtained using naphthalene as an internal standard.
Flash column chromatography purification was carried out by a
gradient elution method using ethyl acetate (EA) in light petroleum
ether (PE). Multiplicities are reported using the following
abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet.
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General Procedure and Characterization Data of 3. The
benzylic ammonium salts (0.20 mmol), PdCl2(CH3CN)2 (0.01
mmol), PPh2Cy (0.04 mmol), and TBAF (0.40 mmol) were added
sequentially to an oven-dried Schlenk tube equipped with a stirrer
bar. After the addition of all solid reagents, a balloon filled with N2
was connected to the Schlenk tube via the side tube and the reaction
vessel was purged three times. EtOH (2.0 mL) containing the
arylsilanes (0.40 mmol) was then added to the tube via a syringe.
After stirring the reaction mixture at 120 oC for 24 h, it was cooled
to room temperature. The reaction was then quenched using water
and extracted three times with ethyl acetate. The combined organic
layers were dried over anhydrous Na2SO4, filtered, and evaporated
under reduced pressure. The crude product was purified by silica
gel preparative thin layer chromatography to give the desired
product.
Scheme 3. Proposed Reaction Mechanism
PdCl2(CH3CN)2
NMe3OTf
R1
R2
R1
Pd0L
1
3
Oxidative
addition
A
Reductive
elimination
NMe3
L
L
L
Pdll
L
Pdll
Pd(II)
L
L
R1
R1
R1
OTf
R2
B
C
E
SiF(OMe)3
Si(OMe)3
Diphenylmethane (3aa).13d Purified by column chromatography
on silica gel (pure PE) to give the desired product: 29.9 mg, 89%
yield; colorless liquid. 1H NMR (400 MHz, CDCl3) δ 7.33−7.23 (m,
4H), 7.23−7.16 (m, 6H), 3.98 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 141.1, 129.0, 128.5, 126.1, 42.0.
Transmetalation
SiF(OMe)3

TBAF
R2
R2
2
D
1-Benzyl-2-methylbenzene (3ba).30 Purified by column
chromatography on silica gel (pure PE) to give the desired product:
28.4 mg, 78% yield; colorless liquid. 1H NMR (400 MHz, CDCl3)
δ 7.30−7.23 (m, 2H), 7.22−7.06 (m, 7H), 3.98 (s, 2H), 2.24 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 140.4, 139.0, 136.7, 130.3,
130.0, 128.8, 128.4, 126.5, 126.0, 125.9, 39.5, 19.7.
A plausible mechanistic pathway for the palladium-catalyzed
Hiyama cross-coupling reaction is described in Scheme 3.
Firstly, Pd(0) species A is formed in situ from PdCl2(CH3CN)2
under the optimized reaction conditions. Subsequently, A
underoges an oxidative addition with benzyltrimethyl-
ammonium salt 1 to produce C(sp3)−Pd complex B through
C−N bond cleavage, releasing trimethylamine as a by product.
Palladium complex E is then produced via transmetalation of
C(sp3)−Pd complex B with arylsilane D, the latter of which is
formed via the activation of substrate 2 by TBAF.17b, 18a Finally,
the coupling product 3 is released upon the reductive
elimination of palladium complex E, and Pd(0) is regenerated
to complete the catalytic cycle.
1-Benzyl-3-methylbenzene (3ca).30 Purified by column
chromatography on silica gel (pure PE) to give the desired product:
18.6 mg, 51% yield; colorless liquid. 1H NMR (400 MHz, CDCl3)
δ 7.33−7.24 (m, 2H), 7.22−7.14 (m, 4H), 7.00 (t, J = 7.2 Hz, 3H),
3.94 (s, 2H), 2.30 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
141.3, 141.1, 138.1, 129.8, 129.0, 128.5, 128.4, 126.9, 126.03,
126.00, 41.9, 21.4.
1-Benzyl-4-methylbenzene (3da).13d Purified by column
chromatography on silica gel (pure PE) to give the desired product:
30.2 mg, 83% yield; colorless liquid. 1H NMR (400 MHz, CDCl3)
δ 7.30−7.23 (m, 2H), 7.21−7.15 (m, 3H), 7.12−7.04 (m, 4H), 3.94
(s, 2H), 2.31 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.5,
138.1, 135.6, 129.2, 128.9, 128.8, 128.5, 126.0, 41.6, 21.0.
1-Benzyl-3-methoxybenzene (3ea).30 Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
desired product: 36.5 mg, 92% yield; yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.32−7.24 (m, 2H), 7.20 (t, J = 8.2 Hz, 4H), 6.76
(dd, J = 17.3, 7.0 Hz, 3H), 3.95 (s, 2H), 3.76 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 159.8, 142.7, 140.9, 129.4, 128.9, 128.5,
126.1, 121.4, 114.8, 111.4, 55.2, 42.0.
■ CONCLUSIONS
In summary, we have successfully developed an un-
precedented palladium-catalyzed Hiyama cross-coupling
reaction of benzyltrimethylammonium salts for the synthesis of
diarylmethane derivatives. The relatively mild and simple
reaction conditions employed, the use of readily available
substrates, and the moderate to excellent yields obtained render
this method synthetically attractive for organic synthesis.
1-Benzyl-4-methoxybenzene (3fa).13d Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
■ EXPERIMENTAL SECTION
1
desired product: 30.9 mg, 83% yield; colorless liquid. H NMR
(400 MHz, CDCl3) δ 7.30−7.24 (m, 2H), 7.22−7.14 (m, 3H),
7.12−7.06 (m, 2H), 6.86−6.77 (m, 2H), 3.91 (s, 2H), 3.76 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 158.0, 141.6, 133.2, 129.8,
128.8, 128.4, 125.9, 113.9, 55.2, 41.0.
All reactions were performed in oven-dried glassware under a
N2-atmosphere unless otherwise noted. Materials were obtained
from commercial suppliers and were used without further
purification. All of the reactions were monitored by thin-layer
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1-Benzyl-4-fluorobenzene (3ga).30 Purified by column
δ 146.9, 139.3, 138.5, 132.3, 129.8, 129.7, 128.7, 127.5, 126.0,
119.1, 110.0, 42.0, 21.4.
1
2
3
4
5
6
7
8
chromatography on silica gel (pure PE) to give the desired product:
22.0 mg, 59% yield; yellow liquid. 1H NMR (400 MHz, CDCl3) δ
7.32−7.25 (m, 2H), 7.23−7.09 (m, 5H), 7.00−6.91 (m, 2H), 3.95 (s,
4-(4-Methylbenzyl)benzonitrile (3jd).28 Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
desired product: 40.2 mg, 97% yield; yellow solid; mp 60−61 °C.
1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 8.1 Hz, 2H), 7.17 (d, J
= 7.2 Hz, 2H), 7.03 (d, J = 7.8 Hz, 2H), 6.96 (d, J = 7.9 Hz, 2H),
3.89 (s, 2H), 2.23 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
147.1, 136.3, 136.3, 132.3, 129.6, 129.5, 128.9, 119.1, 110.0, 41.6,
21.1.
1
2H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.4 (d, JC-F = 243.9
Hz), 141.0, 136.8 (d, 4JC-F = 3.2 Hz), 130.3 (d, 3JC-F = 7.8 Hz), 128.8,
128.6, 126.2, 115.2 (d, 2JC-F = 21.2 Hz), 41.1.
4-Benzyl-1,2-difluorobenzene (3ha).31 Purified by column
chromatography on silica gel (pure PE) to give the desired product:
36.8 mg, 90% yield; colorless liquid. 1H NMR (400 MHz, CDCl3)
δ 7.34−7.27 (m, 2H), 7.26−7.19 (m, 1H), 7.15 (dd, J = 7.8, 0.9 Hz,
2H), 7.05 (dt, J = 10.3, 8.3 Hz, 1H), 6.95 (ddd, J = 11.2, 7.6, 2.1
Hz, 1H), 6.92−6.86 (m, 1H), 3.92 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 150.8 (dd, JC-F = 132.4, 12.7 Hz), 148.4 (dd, JC-F = 130.8,
12.7 Hz), 140.1, 138.1 (dd, JC-F = 5.4, 3.9 Hz), 128.9, 128.7, 126.5,
124.6 (dd, JC-F = 6.1, 3.5 Hz), 117.6 (d, JC-F = 17.0 Hz), 117.1 (d,
JC-F = 16.9 Hz), 41.1 (d, JC-F = 1.1 Hz).
4-(4-Methoxybenzyl)benzonitrile (3je).28 Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
desired product: 36.6 mg, 82% yield; yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.60−7.50 (m, 2H), 7.30−7.23 (m, 2H), 7.11−7.03
(m, 2H), 6.88−6.80 (m, 2H), 3.96 (s, 2H), 3.78 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 158.4, 147.3, 132.3, 131.4, 130.0, 129.5,
119.0, 114.2, 110.0, 55.3, 41.1.
9
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25
26
27
28
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49
50
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53
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58
59
60
4-(Benzo[d][1,3]dioxol-5-ylmethyl)benzonitrile (3jf).28 Purified
by column chromatography on silica gel (PE/EtOAc = 100/1) to
give the desired product: 46.0 mg, 97% yield; white solid; mp
1-Benzyl-4-(trifluoromethyl)benzene (3ia).13d Purified by
column chromatography on silica gel (pure PE) to give the desired
product: 18.4 mg, 39% yield; colorless liquid. 1H NMR (400 MHz,
CDCl3) δ 7.53 (d, J = 8.1 Hz, 2H), 7.35−7.26 (m, 4H), 7.26−7.21
(m, 1H), 7.17 (d, J = 7.2 Hz, 2H), 4.03 (s, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ = 145.2, 140.0, 129.2, 129.0, 128.7, 128.6 (q, 2J C-
1
108−109 °C. H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.6 Hz,
2H), 7.26 (d, J = 7.6 Hz, 2H), 6.74 (d, J = 7.7 Hz, 1H), 6.62 (d, J =
10.6 Hz, 2H), 5.92 (s, 2H), 3.93 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 148.0, 146.9, 146.4, 133.1, 132.3, 129.5, 122.0, 119.0,
110.1, 109.4, 108.4, 101.1, 41.7.
3
1
= 33.0 Hz), 126.5, 125.4 (q, J C-F = 3.8 Hz), 124.3 (q, J
=
F
C-F
271.4 Hz), 41.7.
4-Benzylbenzonitrile
4-(Naphthalen-1-ylmethyl)benzonitrile (3jg).28 Purified by
column chromatography on silica gel (PE/EtOAc = 100/1) to give
the desired product: 39.9 mg, 82% yield; white solid; mp 88−90 °C.
1H NMR (400 MHz, CDCl3) δ 7.91−7.76 (m, 3H), 7.57−7.38 (m,
5H), 7.33−7.21 (m, 3H), 4.47 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 146.4, 134.9, 134.1, 132.3, 131.9, 129.4, 128.9, 127.9,
127.7, 126.3, 125.9, 125.6, 123.9, 119.0, 110.1, 39.2.
(3ja).28
Purified
by
column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
1
desired product: 32.9 mg, 85% yield; colorless liquid. H NMR
(400 MHz, CDCl3) δ 7.59−7.51 (m, 2H), 7.35−7.19 (m, 5H), 7.15
(dd, J = 7.7, 0.9 Hz, 2H), 4.02 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 146.8, 139.4, 132.3, 129.7, 129.0, 128.8, 126.7, 119.0,
110.1, 42.0.
4-(Naphthalen-2-ylmethyl)benzonitrile (3jh).28 Purified by
column chromatography on silica gel (PE/EtOAc = 100/1) to give
the desired product: 46.2 mg, 95% yield; white solid; mp
Methyl 4-benzylbenzoate (3ka).13e Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
1
desired product: 37.6 mg, 83% yield; colorless liquid. H NMR
1
114−116 °C. H NMR (400 MHz, CDCl3) δ 7.85−7.72 (m, 3H),
(400 MHz, CDCl3) δ 7.95 (d, J = 8.1 Hz, 2H), 7.34−7.21 (m, 5H),
7.17 (d, J = 7.5 Hz, 2H), 4.03 (s, 2H), 3.89 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 167.1, 146.5, 140.1, 129.8, 129.0, 128.6,
128.1, 126.4, 52.0, 41.9.
7.64−7.53 (m, 3H), 7.50−7.41 (m, 2H), 7.32 (d, J = 10.4 Hz, 2H),
7.28–7.21 (m, 1H), 4.18 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3)
δ 146.6, 136.8, 133.6, 132.4, 132.3, 129.8, 128.5, 127.7, 127.6,
127.4, 127.3, 126.3, 125.8, 119.0, 110.2, 42.1.
Tert-Butyl 4-benzylbenzoate (3la).13d Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
4-(Furan-2-ylmethyl)benzonitrile (3ji).33 Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
1
desired product: 47.2 mg, 88% yield; colorless liquid. H NMR
1
desired product: 34.4 mg, 94% yield; colorless oil. H NMR (400
(400 MHz, CDCl3) δ 7.94−7.86 (m, 2H), 7.33−7.19 (m, 5H), 7.16
(dd, J = 7.8, 0.9 Hz, 2H), 4.02 (s, 2H), 1.58 (s, 9H); 13C{1H} NMR
(100 MHz, CDCl3) δ 165.8, 145.9, 140.3, 130.0, 129.7, 128.9,
128.8, 128.6, 126.3, 80.8, 41.9, 28.2.
MHz, CDCl3) δ 7.58 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.5 Hz, 3H),
6.31 (dd, J = 3.0, 1.9 Hz, 1H), 6.06 (dd, J = 3.1, 0.6 Hz, 1H), 4.02
(s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 152.6, 143.7, 142.0,
132.3, 129.4, 118.8, 110.6, 110.4, 107.0, 34.5.
2-Benzylnaphthalene
(3ma).32
Purified
by
column
4-(Thiophen-2-ylmethyl)benzonitrile (3jj). Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
desired product: 37.5 mg, 94% yield; yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.59 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H),
7.22−7.13 (m, 1H), 6.95 (dd, J = 5.0, 3.5 Hz, 1H), 6.82 (d, J = 2.5
Hz, 1H), 4.21 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.9,
141.7, 132.4, 129.4, 127.1, 125.9, 124.7, 119.0, 110.4, 36.0. HRMS
(ESI, m/z) calcd for C12H10NS [M + H]+: 200.0528, found:
200.0527.
chromatography on silica gel (pure PE) to give the desired product:
41.0 mg, 94% yield; white solid; mp 56−58 °C. 1H NMR (400 MHz,
CDCl3) δ 7.84−7.72 (m, 3H), 7.63 (s, 1H), 7.43 (m, 2H), 7.29 (dd,
J = 11.6, 8.1 Hz, 3H), 7.21 (dd, J = 12.6, 7.1 Hz, 3H), 4.14 (s, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 141.0, 138.6, 133.7, 132.1,
129.1, 128.5, 128.1, 127.67, 127.66, 127.6, 127.1, 126.2, 126.0,
125.4, 42.1.
4-(2-Methylbenzyl)benzonitrile (3jb).28 Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
desired product: 23.6 mg, 57% yield; yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.59−7.51 (m, 2H), 7.24−7.14 (m, 5H), 7.12−7.05
(m, 1H), 4.03 (s, 2H), 2.19 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 146.2, 137.2, 136.6, 132.3, 130.6, 130.1, 129.4, 127.1,
126.3, 119.0, 109.9, 39.6, 19.6.
■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website at http://pubs.acs.org.
4-(3-Methylbenzyl)benzonitrile (3jc).28 Purified by column
chromatography on silica gel (PE/EtOAc = 100/1) to give the
desired product: 37.7 mg, 93% yield; yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.55 (d, J = 8.1 Hz, 2H), 7.32−7.23 (m, 2H),
7.22−7.15 (m, 1H), 7.04 (d, J = 7.5 Hz, 1H), 6.95 (d, J = 8.6 Hz,
2H), 3.97 (s, 2H), 2.31 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
Copies of 1H and 13C NMR spectra for all compounds
■ AUTHOR INFORMATION
Corresponding Author
ACS Paragon Plus Environment

Page 5 of 6
The Journal of Organic Chemistry
of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation
*E-mail: zhaojf@jxnu.edu.cn
with Subsequent Hydrodefluorination. Angew. Chem., Int. Ed. 2016, 55,
1417−1421. (f) Qin, Q.; Xie, Y.; Floreancig, P. E. Diarylmethane
synthesis through Re2O7-catalyzed bimolecular dehydrative Friedel–
Crafts reactions. Chem. Sci. 2018, 9, 8528−8534.
1
2
3
4
5
6
7
8
ORCID
Zhenming Zhang: 0000-0001-8550-5398
Junfeng Zhao: 0000-0003-4843-4871
(11) (a) Mahdi, T.; Stephan, D. W. Facile Protocol for Catalytic
Frustrated Lewis Pair Hydrogenation and Reductive Deoxygenation of
Ketones and Aldehydes. Angew. Chem., Int. Ed. 2015, 54, 8511−8514.
(b) Mehta, M.; Holthausen, M. H.; Mallov, I.; Pérez, M.; Qu, Z.-W.;
Grimme, S.; Stephan, D. W. Catalytic Ketone Hydrodeoxygenation
Mediated by Highly Electrophilic Phosphonium Cations. Angew.
Chem., Int. Ed. 2015, 54, 8250−8254. (c) Sai, M. An Efficient
Ga(OTf)3/Isopropanol Catalytic System for Direct Reduction of
Benzylic Alcohols. Adv. Synth. Catal. 2018, 360, 4330−4335. (d) Zhao,
G.; Yuan, L.-Z.; Alami, M.; Provot, O. Chlorotrimethylsilane and
Sodium Iodide: A Remarkable Metal-Free Association for the
Desulfurization of Benzylic Dithioketals under Mild Conditions. Adv.
Synth. Catal. 2018, 360, 2522−2536.
Notes
The authors declare no competing financial interests.
■ ACKNOWLEDGMENT
9
This work was supported by the National Natural Science
Foundation of China (21762021), and the Science and Technology
Project of Jiangxi Provincial Education Department (GJJ150297,
GJJ150324).
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