Gold(III)/Sodium Diphenylphosphinobenzene-3-sulfonate (TPPMS) Catalyzed Dehydrative N-Benzylation of Electron-Deficient Anilines in Water

Article abstract of DOI:10.1055/s-0037-1611519

A strategy for the dehydrative N-benzylation of electron-deficient anilines in water has been developed. The gold(III)/sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) catalyst is highly effective as a Lewis acid for the activation of alcohols and tolerates aerobic conditions. A Hammett study in the reaction of para -substituted benzhydryl alcohols shows negative σ values, indicating a build-up of cationic charge during the rate-determining sp ³ C-O bond-cleavage step. The inverse kinetic solvent isotope effect (KSIE = 0.6) is consistent with a specific acid catalysis mechanism. This simple protocol can be performed under mild conditions in an atom-economic process without the need for base or other additives, furnishing the electron-deficient N -benzylic anilines in moderate to excellent yields along with water as a sole coproduct.

Full text of DOI:10.1055/s-0037-1611519

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–H
paper
A
en
H. Hikawa et al.
Paper
Synthesis
Gold(III)/Sodium Diphenylphosphinobenzene-3-sulfonate (TPPMS)
Catalyzed Dehydrative N-Benzylation of Electron-Deficient Anilines
in Water
R1
Hidemasa Hikawa*
Mika Matsumoto
Sayoko Tawara
0
0
0
0-0
0
0
2-
7
8
1
9-3
0
1
2
R1
R3
R3
cat. Au(III)/TPPMS
H
HO
N
H
N
H2O
R2
H
Shoko Kikkawa
Isao Azumaya*
0
0
0
0-
0
0
0
2-9
3
9
0-5
6
7
1
R2
R
1 = NO2, CN, CF3, Ac, CO2Et, SO2NH2
0
0
0
0-
0
0
0
2-6
6
5
1-2
7
6
8
55–98% yield
23 examples
R2 = H, MeO, Me, F, Cl
R3 = Ph, H, alkene, cyclopropyl
TPPMS: PPh2(m-C6H4SO3Na)
Faculty of Pharmaceutical Sciences, Toho University,
2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
hidemasa.hikawa@phar.toho-u.ac.jp
isao.azumaya@phar.toho-u.ac.jp
Received: 22.02.2019
Accepted after revision: 26.03.2019
Published online: 17.04.2019
tainable strategies for direct functionalization of organic
molecules due to their advantages in atom economy, the
use of hazardous organic solvents such as CH2Cl2 or
ClCH2CH2Cl under extrusion of moisture conditions is gen-
erally required. Recently, the Wang group developed a gold-
catalyzed borrowing-hydrogen reaction in good yields with
high chemoselectivity under wet conditions.5c Therefore,
developing more efficient and environmentally friendly
protocols is highly desirable due to the scope of applica-
tions and industrial utility.6,7
Water is widely recognized as a greener solvent alterna-
tive for organic synthesis because of its universal abun-
dance, nontoxicity and environmental compatibility.8,9 We
have been developing a strategy for dehydrative substitu-
tion of alcohols catalyzed by NaAuCl4·2H2O and sodium di-
phenylphosphinobenzene-3-sulfonate (TPPMS) in water.10
Recently, we described the first example of a selective N-
benzylation of water-soluble substrates such as unprotect-
ed anthranilic acids.10c As an extension of our investigation,
we herein report a strategy for the catalytic dehydrative N-
benzylation of electron-deficient anilines. To our knowl-
edge, this is the first report of a gold-catalyzed direct modi-
fication of nitroanilines under mild reaction conditions in
water without the need for base or other additives (Scheme
1). Notably, the gold(III)/TPPMS catalyst is highly effective
as a Lewis acid for the activation of alcohols, while common
Lewis or Brønsted acid such as Cu(II),11 Co(II),12 or Fe(III)
were ineffective for dehydrative N-benzylation of 4-nitro-
aniline (1a) (see Table 1).
DOI: 10.1055/s-0037-1611519; Art ID: ss-2019-f0117-op
Abstract A strategy for the dehydrative N-benzylation of electron-de-
ficient anilines in water has been developed. The gold(III)/sodium di-
phenylphosphinobenzene-3-sulfonate (TPPMS) catalyst is highly effec-
tive as a Lewis acid for the activation of alcohols and tolerates aerobic
conditions. A Hammett study in the reaction of para-substituted ben-
zhydryl alcohols shows negative  values, indicating a build-up of cat-
ionic charge during the rate-determining sp3 C–O bond-cleavage step.
The inverse kinetic solvent isotope effect (KSIE = 0.6) is consistent with
a specific acid catalysis mechanism. This simple protocol can be per-
formed under mild conditions in an atom-economic process without
the need for base or other additives, furnishing the electron-deficient
N-benzylic anilines in moderate to excellent yields along with water as a
sole coproduct.
Key words gold, water, benzylic alcohol, aniline, N-benzylation
The gold-catalyzed dehydrative substitution reaction of
alcohols with amines affords the desired products along
with water as the sole coproduct. This reaction has emerged
as a powerful methodology for the formation of C–N bonds
due to the advantages of being a salt-free and atom-eco-
nomical process that does not transform the hydroxyl
group into a good leaving group.1,2 In 2005, the pioneering
work of Campagne demonstrated the nucleophilic substitu-
tion of propargylic alcohols using the NaAuCl4·2H2O cata-
lyst, which activated the alcohols through coordination
with the -bond.3 Campagne and Prim et al. developed the
direct catalytic amination of benzylic alcohols with poor
amine nucleophiles.4 Such efficiency is mainly due to the
Lewis acidic character of the gold(III) catalyst for the activa-
tion of several sp3 C–O bonds, thus promoting unique
chemical transformations.5 While these are green and sus-
O2N
O2N
NaAuCl4•2H2O (5 mol%)
TPPMS (5 mol%)
Ph
Ph
+
NH2
HO
Ph
N
Ph
H2O, 70 °C, 1 h
H
1a
2a (1.2 equiv)
3a: 90%
Scheme 1 Catalytic dehydrative N-benzylation of 4-nitroaniline (1a)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

B
H. Hikawa et al.
Paper
Synthesis
Initially, 4-nitroaniline (1a) and benzhydrol (2a) were
chosen as model compounds to optimize the dehydrative
amination. The desired product 3a was obtained in 63%
yield when using NaAuCl4·2H2O (2 mol%) and TPPMS L1 (2
mol%) in water at 40 °C for 16 hours (Table 1, entry 1). A
control experiment using HCl indicated that the gold(III)
catalyst played a crucial role in the catalytic system (entry
2). Furthermore, no reaction occurred when using only
NaAuCl4·2H2O catalyst (entry 3). The yield of 3a was in-
creased to 90% in a shorter reaction time when using NaAu-
Cl4·2H2O (5 mol%) and TPPMS (5 mol%) at 70 °C (entry 4).
Increasing the amount of the TPPMS ligand resulted in a
slightly lower yield (entry 5). With regard to the gold cata-
lysts, NaAuCl4·2H2O gave the best result (entry 4 vs. entries
6–9). Other water-soluble phosphine ligands L2–7 resulted
in no reaction or lower yields (entries 10–15).13 Other chlo-
ride salts such as Cu(II), Co(II) or Fe(III) were less effective
than NaAuCl4·2H2O (entries 16–18). Organic solvents such
as EtOH, DMF, 1,4-dioxane or CH2Cl2 were not suitable com-
pared with water in our catalytic system (entries 19–22).
With the optimized conditions in hand, we examined
the substrate scope of the dehydrative amination (Scheme
2). First, the scope of benzylic alcohols 2 with 4-nitroani-
line (1a) as the coupling partner was examined. As expect-
ed, both electron-donating (OMe and Me) and electron-
withdrawing (Cl and F) groups on the benzene ring of sub-
stituted benzhydrols 2 were well tolerated, and the corre-
sponding N-benzylated products 3b–f were formed in mod-
erate to excellent yields (72–89%). In contrast, decafluoro-
benzhydrol failed to react under the same conditions,
suggesting that stability of the diarylcarbocation was criti-
cal to the success of the reaction. We explored the direct
amination of the hydroxyl group of -activated alcohols
such as trans-1,3-diphenyl-2-propen-1-ol, which afforded
the corresponding product 3g in 86% yield. Furthermore, a
simple benzylic alcohol such as 4-methoxybenzylalcohol
could be transformed into 3h in 70% yield.
Encouraged by these results, we next examined the
scope of electron-deficient anilines 1 with benzhydrol (2a)
as the coupling partner. Various nitroanilines 1 showed
good reactivities, regardless of whether they had electron-
donating or -withdrawing substituents (72–98%, 3i–q). The
carbon–bromine moiety in 3n was left intact, which could
be employed for further cross-coupling. Furthermore, re-
placement of the NO2 group with several electron-with-
drawing groups (CN, CF3, Ac and CO2Et) was also tolerated
to produce the corresponding N-benzylated products 3r–u
(55–83%). In contrast, electron-sufficient 4-anisidine did
not react due to poisoning of the Lewis acidic gold(III) cata-
lyst. A sterically demanding 4-nitro-1-naphthylamine (1b)
led to the corresponding N-benzylated 3v along with C-
benzylated 4 in 67% and 20% yields, respectively (Scheme
3). Ghorai et al. reported the dehydrative Friedel–Crafts
benzylation of 4-nitroaniline via Hofmann–Martius rear-
rangement catalyzed by Re2O7. Therefore, the benzyl cation
Table 1 Optimization of Reaction Conditionsa
O2N
Ph
catalyst (2–5 mol%)
ligand (2–10 mol%)
O2N
Ph
+
HO
Ph
solvent
NH2
2a
N
Ph
1a
3a
H
(1.2 equiv)
Entry Cat. (mol%)
Ligand
(mol%)
T (°C) t (h) Solv.
Yield
(%)b
1
2
NaAuCl4·2H2O (2)
HCl (2)
L1 (2)
none
40
40
40
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
50
16
16
16
1
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
EtOH
DMF
63
trace
3
NaAuCl4·2H2O (2)
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
AuCl (5)
none
trace
90
4
L1 (5)
L1 (10)
L1 (5)
L1 (5)
L1 (5)
L1 (5)
L2 (5)
L3 (5)
L4 (5)
L5 (5)
L6 (5)
L7 (5)
L1 (5)
L1 (5)
L1 (5)
L1 (5)
L1 (5)
L1 (5)
L1 (5)
5
1
84
6
1
62
7
HAuCl4·3H2O (5)
AuBr3 (5)
1
49
8
1
62
9
AuCl3 (5)
1
0
10
11
12
13
14
15
16
17
18
19
20
21
22
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
CuCl2 (5)
1
14
1
12
1
trace
trace
trace
trace
27
1
1
1
1
CoCl2·6H2O (5)
FeCl3 (5)
1
0
1
38
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
NaAuCl4·2H2O (5)
1
trace
trace
1
1
dioxane 48
16
CH2Cl2
48
SO3Na
SO3Na
SO3Na
Ph2P
L1: TPPMS
Ph2P
PhP
P
2
3
L2: TPPDS
CO2H
L3: TPPTS
Me
HO2C
Ph2P
Ph2P
N
Ph2P
N
L7
Me
L4
L5
L6
a Reaction conditions: 4-nitroaniline (1a) (1 mmol), catalyst (2 or 5 mol%),
ligand (2 or 5 mol%), benzhydrol (2a) (1.2 equiv), solvent (4 mL), in a sealed
tube under air.
b The yield was determined by 1H NMR analysis of the crude product using
1,3,5-trimethoxybenzene as an internal standard.
species would be generated from 3v followed by the forma-
tion of ortho-benzylated aniline 4 in our catalytic system.14
To demonstrate the electronic effect of the substituents
on the rates of the sp3 C–O bond cleavage of alcohols and
the C–N bond-formation reaction, Hammett studies were
conducted on the gold-catalyzed dehydrative amination.15
First, the relative rates of coupling of 4-substituted 2-ni-
troanilines 1 (X = OMe, Me, H, F, and Br groups) with benz-
hydrol (2a) were examined. Scheme 4A shows no correla-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

C
H. Hikawa et al.
Paper
Synthesis
H, F, and Br groups) were examined. Scheme 4B shows ex-
cellent correlation (R2 = 0.99) between the log (kX/kH) and
the  value of the respective substituents that resulted in a
negative  value of 2.8. This result indicates a build-up of
positive charge in the transition state.
R1
R3
R3
R1
NaAuCl4•2H2O (5 mol%)
TPPMS (5 mol%)
N
+
HO
H
H2O, 80 °C, 16 h
R2
NH2
R2
3
2
1
O2N
O2N
O2N
Ph
Ph
Ph
Benzhydrol (2a)
NaAuCl4•2H2O (5 mol%)
X
X
N
N
H
N
Ph
H
H
TPPMS (5 mol%)
(A)
3b, 82%
3c, 89%
3d, 76%
OMe
Me
Cl
N
H
Ph
H2O, 60 °C, 1 h
NH2
F
Cl
NO2
NO2
3X
3Y
1X
O2N
4-Nitroaniline (1a)
NaAuCl4•2H2O (5 mol%)
TPPMS (5 mol%)
Ph
O2N
O2N
O2N
Ph
Ph
HO
(B)
N
H
N
H
N
H
N
H
H2O, 60 °C, 1 h
Hammett ρ = –2.8
Y
2Y
Y
3e, 85%
3f, 72%
3g, 86%
F
Cl
Ph
O2N
MeO
Ph
Ph
N
H
N
Ph
N
H
Ph
H
NO2
NO2
OMe
F
3h, 70%
3i, 72%
3j, 79%
Me
Cl
Ph
Ph
Ph
Ph
N
H
Ph
N
H
Ph
N
H
Ph
NO2
NO2
NO2
3k,79%
3l, 79%
3m, 83%
Br
Ph
Ph
Ph
N
H
Ph
O2N
N
Ph
Ph
O2N
N
Ph
H
H
NO2
3n, 98%
Me
3o, 75%
3p, 72%
Scheme 4 Hammett plots for the reaction of (A) 4-substituted 2-nitro-
anilines 1 (X = OMe, Me, H, F, and Br groups) (circles) and (B) 4-substi-
tuted benzhydryl alcohols 2 (Y = OMe, Me, H, F, and Br groups)
(triangles).
O2N
CN
CN
Ph
Ph
N
H
Ph
N
H
Ph
F3C
N
H
OMe
3q, 98%
3r, 83%
3s, 76%
Ac
EtO2C
To gain insight into the catalytic sp3 C–O bond-activa-
tion step, we carried out kinetic isotope effect (KIE) experi-
ments. The reactions of 4-nitroaniline (1a) with benzhydrol
(2a) were monitored by 1H NMR spectroscopy to determine
the zero-order kinetics for construction of 3a (Scheme 5).
The rate of reaction was 1.8 times greater in D2O than in
H2O with an inverse kinetic solvent isotope effect (KSIE:
kH2O/kD2O) of 0.6,16 indicating a specific acid catalysis
mechanism as follows. Aqua complex A with alcohol 2a is in
a fast equilibrium with its Lewis acid adduct (conjugate ac-
id) B. The rate-determining step involving the sp3 C–O bond
cleavage occurs via B to form the benzyl cation species C.17
Since the overall rate of the reaction depends only on the
activation of alcohol 2a catalyzed by complex A, species B
should form more slowly in H2O than in D2O. This is ex-
plained by the fact that hydrogen bonds of H2O would be
better at solvating gold cation A, which makes it less able to
activate alcohol 2a in H2O than in D2O. Soper et al. investi-
gated the structures of light and heavy water with X-ray
diffraction and found that the OH bond length in H2O is 3%
longer than the OD bond length in D2O.18 Harada et al. re-
ported that the vibration profile of pre-edge excited HDO
Ph
Ph
N
H
Ph
N
Ph
H
3t, 55%
3u, 82% (120 °C)
Scheme 2 Scope of electron-deficient anilines 1 and benzylic alcohols
2. Reagents and conditions: 1 (1 mmol), NaAuCl4·2H2O (5 mol%), TPPMS
(5 mol%), alcohol 2 (1.2 mmol), H2O (4 mL), 80 °C, 16 h in a sealed tube
under air. Yield of isolated product.
Ph
O2N
Benzhydrol (2a)
NaAuCl4•2H2O (5 mol%)
TPPMS (5 mol%)
O2N
O2N
Ph
NH2
4: 20%
NH
+
NH2
H2O, 120 °C, 16 h
Ph
Ph
1b
3v: 67%
Scheme 3 The benzylation of 4-nitro-1-naphthylamine (1b)
tion of the substituent constant parameter, indicating that
the reaction is not sensitive to substituents and no charge is
developed on the anilines in the transition state. Next, the
relative rates of the reaction between 4-nitroaniline (1a)
and para-substituted benzhydryl alcohols 2 (Y = OMe, Me,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

D
H. Hikawa et al.
Paper
Synthesis
water has a greater OH-stretch contribution compared with
OD, which supports the preference for OH being the weak-
ened or broken hydrogen bond.19
NaAuCl4•2H2O/TPPMS
H2O
O2N
OH
H
NaCl, Cl
N
Ph
Ph
2a
3a
AuCl2L(H2O)n
H2O
step 1:
ligand exchange
A
Ph
Ph
OH
step 3:
N-benzylation
O2N
Ph
Ph H2O
2a
H
[Au]
Ph
H
[Au]
O
rate-determining
KSIE = 0.6
O
AuCl2L(OH2)n
Ph
Ph
NH
H
step 2:
C–O bond
cleavage
C
Ph
Ph
ligand exchange
C
A
1a
Ph
[Au]-OH
specific acid catalysis
B
Ph
Ph
B
HO [Au]
D
D
rate-determining
Hammett ρ = –2.8
KSIE = 0.6
Scheme 6 Proposed mechanism
butyl-4-hydroxyanisole, 1 equiv) or under an Ar atmo-
sphere, the yield of the desired product 3a remained un-
changed (Scheme 7B). These results suggest that a radical
pathway based on a SET is not involved in this catalytic sys-
tem.
4-Nitroaniline (1a)
NaAuCl4•2H2O (5 mol%)
O2N
Ph
TPPMS (5 mol%)
(A)
HO
N
H
Ph
Ph
H2O, 120 °C, 16 h
Scheme 5 Comparison of the reaction of 4-nitroaniline (1a) with benz-
hydrol (2a) ‘in H2O’ (circles) and ‘in D2O’ (squares) at 60 °C
2b
3w, 68%
(3 equiv)
Ar
N
H
not obtained
Benzhydrol (2a) (1 equiv)
NaAuCl4•2H2O (5 mol%)
TPPMS (5 mol%)
O2N
O2N
Based on these results and on previous reports, the fol-
lowing mechanism can be suggested (Scheme 6). Initially,
the treatment of NaAuCl4·2H2O with water-soluble phos-
phine ligand TPPMS generates an aqua complex A. Subse-
quently, the Lewis acidic gold(III) cation A coordinates with
the oxygen atom of alcohol 2a to form intermediate B (Step
1: ligand exchange), and sp3 C−O bond activation occurs to
generate the benzylic cation C (Step 2: C–O bond cleavage).
The observed negative Hammett  value of 2.8 in the reac-
tion of para-substituted benzhydryl alcohols 2 clearly
shows cationic charge build-up during the rate-determin-
ing sp3 C–O bond-cleavage step (see Scheme 4B). Further-
more, the inverse kinetic solvent isotope effect (KSIE) of 0.6
is consistent with the specific acid catalysis mechanism
(see Scheme 5). Next, the hydroxyl anion of gold species D
acts as a base to remove the acidic proton of substrate 1a,
which attacks the electrophilically active benzyl cation C to
afford the corresponding N-benzylated product 3a (Step 3:
N-benzylation).
Ph
(B)
H2O, 70 °C, 1 h
NH2
N
Ph
1a
H
3a
under air: 70% vs under Ar: 70%, with BHA: 66%
Scheme 7 Control experiments
Finally, to demonstrate the synthetic utility of our cata-
lytic system, a gram-scale reaction of substrate 1a with al-
cohol 2a in the presence of gold(III)/TPPMS catalyst in wa-
ter was carried out (Scheme 8). After 16 h, the reaction
mixture was extracted with EtOAc, then crude product 3a
was purified simply by recrystallization from n-hexane and
EtOAc to give desired 3a in 77% isolated yield. The devel-
oped process avoids the use of column chromatography.
Benzhydrol (2a)
NaAuCl4•2H2O (5 mol%)
TPPMS (5 mol%)
O2N
O2N
Ph
NH2
(1.38 g (10 mmol))
N
Ph
80 °C, 16 h
H
1a
3a
(2.33 g (7.7 mmol))
Several control experiments were performed to exam-
ine the possibility of a radical pathway based on a single-
electron transfer (SET). First, radical clock experiments us-
ing -cyclopropylbenzyl alcohol (2b) were conducted to
observe the rapid isomerization of the cyclopropylmethyl
radical to the allylmethyl radical, which is well known in
free-radical chemistry (Scheme 7A). As expected, corre-
sponding 3w was obtained in 68% isolated yield via the
cyclopropylmethyl cation and not the ring-opened product.
Next, in the presence of a radical scavenger (BHA: 3-tert-
Scheme 8 Scale-up experiment
In summary, we have reported an environmentally be-
nign protocol for the direct dehydrative amination of ben-
zylic alcohols using a water-soluble gold(III)/TPPMS catalyst
in water. This catalytic system is applicable for the direct
modification of electron-deficient anilines and proceeds in
moderate to excellent yields. This greener method has re-
duced waste generation, uses safer solvents and reaction
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

E
H. Hikawa et al.
Paper
Synthesis
conditions, and increases energy efficiency, all of which
contribute to the efficiency of a chemical transformation.
Moreover, this reaction can be easily amplified to a gram
level without the use of column chromatography for purifi-
cation. Therefore, this strategy has emerged as an attractive
alternative to traditional synthetic methods.
IR (KBr): 3408, 1600, 1513 cm–1
.
1H NMR (400 MHz, CDCl3):  = 2.34 (s, 3 H), 4.97 (br d, J = 4.8 Hz, 1 H),
5.59 (d, J = 4.8 Hz, 1 H), 6.50 (d, J = 9.2 Hz, 2 H), 7.15–7.20 (m, 4 H),
7.27–7.38 (m, 5 H), 8.03 (d, J = 9.4 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6):  = 20.6, 60.0, 111.9, 125.9, 127.2,
127.3, 127.4, 128.6, 129.2, 136.2, 136.5, 138.9, 142.1, 153.6.
MS (FAB): m/z = 319 [M + H]+.
Anal. Calcd for C20H18N2O2: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.41;
H, 5.79; N, 8.63.
All of the starting materials and solvents were purchased from Sig-
ma–Aldrich Japan (Tokyo, Japan), FUJIFILM Wako Pure Chemical Co.
(Osaka, Japan), and TCI Co., Ltd. (Tokyo, Japan). All commercially avail-
able reagents and solvents were used without further purification.
CHROMATOREX Q-PACK SI50 (Fuji Silysia Chemical Ltd, Japan) was
used for flash column chromatography. All melting points were deter-
mined using a Yanako micro melting point apparatus without correc-
tion. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were re-
corded on a JEOL ECS400 spectrometer. IR spectra were measured
with a JASCO FT/IR-4100 spectrometer. Mass spectra were obtained
using a JEOL the JMS-700 MStation Mass Spectrometer.
N-[(4-Chlorophenyl)(phenyl)methyl]-4-nitroaniline (3d)4
By following the general procedure, 3d was obtained.
Yield: 258 mg (76%); yellow solid; mp 138–140 °C.
IR (KBr): 3371, 1599, 1531 cm–1
.
1H NMR (400 MHz, CDCl3):  = 4.93 (brd, J = 4.6 Hz, 1 H), 5.60 (d, J =
4.8 Hz, 1 H), 6.50 (d, J = 9.2 Hz, 2 H), 7.24–7.40 (m, 9 H), 8.04 (d, J =
9.4 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6):  = 59.4, 112.0, 125.9, 127.4, 127.5,
128.6, 128.7, 129.3, 131.9, 136.5, 140.9, 141.5, 153.4.
MS (FAB): m/z = 339 [M + H]+.
General Procedure
A mixture of aniline 1 (1 mmol), NaAuCl4·2H2O (20 mg, 0.05 mmol),
sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) (18 mg,
0.05 mmol) and benzylic alcohol 2 (1.2 mmol) in H2O (4 mL) was
heated at 80 °C for 16 h in a sealed tube under air. After cooling, the
reaction mixture was poured into water and extracted with EtOAc.
The organic layer was washed with brine, dried over MgSO4 and con-
centrated in vacuo. The residue was purified by flash column chroma-
tography (silica gel, hexanes/EtOAc) to give desired product 3.
N-[Bis(4-fluorophenyl)methyl]-4-nitroaniline (3e)20
By following the general procedure, 3e was obtained.
Yield: 291 mg (85%); yellow powder; mp 123–125 °C.
IR (KBr): 3401, 1604, 1510 cm–1
.
1H NMR (400 MHz, CDCl3):  = 5.61 (s, 1 H), 6.50 (d, J = 9.2 Hz, 2 H),
7.06 (dd, J = 8.5, 8.5 Hz, 4 H), 7.26 (dd, J = 7.1, 7.1 Hz, 4 H), 8.05 (d, J =
9.1 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6):  = 58.6, 115.5 (d, JCF = 22.0 Hz), 125.9,
129.4 (d, JCF = 7.7 Hz), 136.5, 138.0 (d, JCF = 3.8 Hz), 153.3, 161.4 (d,
JCF = 244.4 Hz); MS (FAB): m/z = 341 [M + H]+.
N-Benzhydryl-4-nitroaniline (3a)11
By following the scale-up experiment procedure (Scheme S5), 3a was
obtained.
Yield: 2.34 g (77%); pale-yellow solid; mp 178–181 °C.
IR (KBr): 3407, 1602, 1513 cm–1
1H NMR (400 MHz, CDCl3):  = 5.01 (br s, 1 H), 5.63 (s, 1 H), 6.51 (d, J =
9.2 Hz, 2 H), 7.25–7.38 (m, 10 H), 8.03 (d, J = 9.2 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6):  = 60.2, 111.9, 125.9, 127.3, 127.4,
128.6, 136.3, 141.9, 153.6.
.
N-[Bis(4-chlorophenyl)methyl]-4-nitroaniline (3f)20
By following the general procedure, 3f was obtained.
Yield: 268 mg (72%); yellow solid; mp 191–192 °C.
IR (KBr): 3402, 1605, 1520 cm–1
.
1H NMR (400 MHz, CDCl3):  = 4.87 (br d, J = 4.8 Hz, 1 H), 5.58 (d, J =
4.8 Hz, 1 H), 6.49 (d, J = 9.1 Hz, 2 H), 7.21–7.36 (m, 8 H), 8.04 (d, J =
9.1 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6):  = 58.7, 112.1, 125.9, 128.7, 129.3,
132.1, 136.6, 140.5, 153.3.
MS (FAB): m/z = 305 [M + H]+.
N-[(4-Methoxyphenyl)(phenyl)methyl]-4-nitroaniline (3b)4
By following the general procedure, 3b was obtained.
Yield: 273 mg (82%); yellow solid; mp 120–123 °C.
MS (FAB): m/z = 373 [M + H]+.
IR (KBr): 3408, 1602, 1515 cm–1
.
(E)-N-(1,3-Diphenylallyl)-4-nitroaniline (3g)20
By following the general procedure, 3g was obtained.
Yield: 285 mg (86%); yellow solid; mp 144–146 °C.
1H NMR (400 MHz, CDCl3):  = 3.80 (s, 3 H), 4.97 (br d, J = 4.6 Hz, 1 H),
5.59 (d, J = 4.8 Hz, 1 H), 6.50 (d, J = 9.2 Hz, 2 H), 6.88 (d, J = 8.7 Hz,
2 H), 7.21 (d, J = 8.5 Hz, 2 H), 7.27–7.83 (m, 5 H), 8.02 (d, J = 9.2 Hz,
2 H).
13C NMR (100 MHz, DMSO-d6):  = 55.1, 59.6, 111.9, 114.0, 125.9,
127.2, 127.3, 128.6, 133.9, 136.2, 142.3, 153.6, 158.5.
IR (KBr): 3377, 1600, 1530 cm–1
.
1H NMR (400 MHz, CDCl3):  = 4.88 (br d, J = 5.5 Hz, 1 H), 5.21 (t, J =
5.7 Hz, 1 H), 6.38 (dd, J = 15.8, 6.0 Hz, 1 H), 6.55–6.62 (m, 3 H), 7.29–
7.41 (m, 10 H), 8.06 (d, J = 9.2 Hz, 2 H).
MS (FAB): m/z = 335 [M + H]+.
13C NMR (100 MHz, DMSO-d6):  = 58.5, 111.8, 126.0, 126.4, 127.1,
127.4, 127.8, 128.6, 128.7, 130.0, 130.4, 136.1, 136.2, 141.3, 153.4.
MS (FAB): m/z = 331 [M + H]+.
4-Nitro-N-[phenyl(p-tolyl)methyl]aniline (3c)
By following the general procedure, 3c was obtained.
Yield: 283 mg (89%); yellow solid; mp 131–134 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

F
H. Hikawa et al.
Paper
Synthesis
N-(4-Methoxybenzyl)-4-nitroaniline (3h)21
13C NMR (100 MHz, CDCl3):  = 62.5, 112.2 (d, JCF = 25.9 Hz), 116.6 (d,
JCF = 6.7 Hz), 124.9 (d, JCF = 23.0 Hz), 127.3, 128.2, 129.3, 131.5 (d, JCF
7.7 Hz), 141.2, 141.4, 142.3, 152.9 (d, JCF = 239.6 Hz).
HRMS (FAB): m/z [M + H]+ calcd for C19H15FN2O2: 323.1196; found:
=
By following the general procedure, 3h was obtained.
Yield: 181 mg (70%); yellow solid; mp 135–137 °C.
IR (KBr): 3357, 1598, 1511 cm–1
.
323.1196.
1H NMR (400 MHz, CDCl3):  = 3.81 (s, 3 H), 4.35 (s, 2 H), 6.57 (d, J =
9.2 Hz, 2 H), 6.90 (d, J = 8.7 Hz, 2 H), 7.26 (d, J = 8.7 Hz, 2 H), 8.09 (d,
J = 9.1 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6):  = 45.4, 55.1, 111.3, 113.9, 126.2,
128.6, 130.3, 135.8, 154.4, 158.4.
N-Benzhydryl-4-chloro-2-nitroaniline (3m)
By following the general procedure, 3m was obtained.
Yield: 281 mg (83%); pale-yellow solid; mp 136–138 °C.
IR (KBr): 3372, 1610, 1564 cm–1
.
MS (FAB): m/z = 259 [M + H]+.
1H NMR (400 MHz, CDCl3):  = 5.71 (d, J = 5.5 Hz, 1 H), 6.68 (d, J =
9.2 Hz, 1 H), 7.23–7.39 (m, 11 H), 8.20 (d, J = 2.5 Hz, 1 H), 8.57 (br d,
J = 4.8 Hz, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 60.3, 117.4, 119.5, 125.0, 126.8,
127.7, 129.0, 131.8, 136.2, 141.5, 142.6.
N-Benzhydryl-2-nitroaniline (3i)7a
By following the general procedure, 3i was obtained.
Yield: 219 mg (72%); brown solid; mp 98–100 °C.
IR (KBr): 3382 cm–1
.
MS (EI): m/z (%) = 338 (37) [M]+, 340 (21) [M+ + 2], 165 (100).
1H NMR (400 MHz, CDCl3):  = 4.60 (d, J = 3.7 Hz, 1 H), 5.57 (d, J =
4.5 Hz, 1 H), 6.80 (dd, J = 8.1, 2.4 Hz, 1 H), 7.50 (ddd, J = 8.1, 1.7,
0.8 Hz, 1 H).
Anal. Calcd for C19H15ClN2O2: C, 67.36; H, 4.46; N, 8.27. Found: C,
67.65; H, 4.57; N, 8.05.
13C NMR (100 MHz, CDCl3):  = 62.0, 115.2, 116.0, 126.8, 127.2, 127.9,
129.1, 132.5, 136.1, 141.3, 144.2.
MS (EI): m/z = 304 [M + H]+.
N-Benzhydryl-4-bromo-2-nitroaniline (3n)
By following the general procedure, 3n was obtained.
Yield: 377 mg (98%); pale-yellow solid; mp 130–132 °C.
IR (KBr): 3377, 1614, 1560 cm–1
.
N-Benzhydryl-4-methoxy-2-nitroaniline (3j)
By following the general procedure, 3j was obtained.
Yield: 264 mg (79%); brown solid; mp 144–146 °C.
1H NMR (400 MHz, CDCl3):  = 5.70 (d, J = 5.5 Hz, 1 H), 6.63 (d, J =
9.2 Hz, 1 H), 7.28–7.39 (m, 11 H), 8.34 (d, J = 2.5 Hz, 1 H), 8.57 (br d,
J = 5.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 62.3, 107.4, 117.1, 127.3, 128.2, 128.5,
129.0, 129.3, 138.9, 140.9, 143.2.
MS (FAB): m/z 383 [M + H]+.
HRMS-FAB: m/z [M + H]+ calcd for C19H16N2O2Br: 383.0395; found:
IR (KBr): 3372, 1541, 1518 cm–1
.
1H NMR (400 MHz, CDCl3):  = 3.77 (s, 3 H), 5.71 (d, J = 5.5 Hz, 1 H),
6.69 (d, J = 9.4 Hz, 1 H), 7.01 (dd, J = 9.3, 3.2 Hz, 1 H), 7.26–7.36 (m,
10 H), 7.65 (d, J = 3.0 Hz, 1 H), 8.51 (br d, J = 5.0 Hz, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 55.6, 60.4, 106.8, 117.1, 126.8,
126.9, 127.6, 129.0, 130.9, 139.5, 142.0, 149.6.
383.0395.
MS (FAB): m/z = 335 [M + H]+.
N-Benzhydryl-3-nitroaniline (3o)22
Anal. Calcd for C20H18N2O3: C, 71.84; H, 5.43; N, 8.38. Found: C, 71.87;
H, 5.46; N, 8.32.
By following the general procedure, 3o was obtained.
Yield 229 mg (75%); yellow solid; mp 111–113 °C.
IR (KBr): 3386 cm–1
.
N-Benzhydryl-4-methyl-2-nitroaniline (3k)
1H NMR (400 MHz, CDCl3):  = 5.74 (d, J = 5.5 Hz, 1 H), 6.66 (ddd, J =
9.1, 7.2, 1.3 Hz, 1 H), 6.72 (d, J = 8.6 Hz, 1 H), 8.20 (dd, J = 8.6, 1.6 Hz,
1 H), 8.61 (d, J = 5.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 62.8, 107.6, 112.3, 119.0, 127.2, 127.9,
129.1, 132.5, 136.5, 141.3, 144.2.
By following the general procedure, 3k was obtained.
Yield: 252 mg (79%); pale-yellow solid; mp 123–126 °C.
IR (KBr): 3382, 1631, 1567, 1525 cm–1
.
1H NMR (400 MHz, CDCl3):  = 2.24 (s, 3 H), 5.72 (d, J = 5.5 Hz, 1 H),
6.63 (d, J = 8.7 Hz, 1 H), 7.01 (dd, J = 9.3, 3.2 Hz, 1 H), 7.26–7.39 (m,
10 H), 7.65 (d, J = 3.0 Hz, 1 H), 8.51 (br d, J = 5.0 Hz, 1 H).
MS (EI): m/z = 304 [M + H]+.
13C NMR (100 MHz, DMSO-d6):  = 19.4, 60.3, 115.6, 125.2, 125.5,
126.6, 126.8, 127.6, 128.5, 129.0, 131.4, 137.9, 141.9, 142.0.
HRMS (FAB): m/z [M + H]+ calcd for C20H18N2O2: 319.1447; found:
319.1447.
N-Benzhydryl-2-methyl-3-nitroaniline (3p)
By following the general procedure, 3p was obtained.
Yield: 228 mg (72%); brown solid; mp 95–97 °C.
IR (KBr): 3383 cm–1
.
N-Benzhydryl-4-fluoro-2-nitroaniline (3l)
1H NMR (400 MHz, CDCl3):  = 5.54 (d, J = 4.5 Hz, 1 H), 5.64 (d, J =
5.2 Hz, 1 H), 6.32 (d, J = 8.8 Hz, 1 H), 7.65 (d, J = 2.2 Hz, 1 H), 7.75 (dd,
J = 8.8, 2.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 12.6, 63.0, 112.5, 114.7, 115.5, 126.9,
127.4, 127.8, 129.0, 141.9, 146.2, 151.5.
By following the general procedure, 3l was obtained.
Yield: 255 mg (79%); pale-yellow solid; mp 116–119 °C.
IR (KBr): 3379, 1578, 1523 cm–1
.
1H NMR (400 MHz, CDCl3):  = 5.70 (d, J = 5.5 Hz, 1 H), 6.70 (dd, J = 9.6,
4.6 Hz, 1 H), 7.11 (ddd, J = 9.6, 7.3, 3.0 Hz, 1 H), 7.27–7.38 (m, 10 H),
7.92 (dd, J = 9.2, 2.8 Hz, 1 H), 8.49 (br d, J = 4.6 Hz, 1 H).
MS (EI): m/z = 318 [M + H]+.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

G
H. Hikawa et al.
Paper
Synthesis
N-Benzhydryl-2-methoxy-4-nitroaniline (3q)
By following the general procedure, 3q was obtained.
Yield: 329 mg (98%); yellow solid; mp 159–161 °C.
1H NMR (400 MHz, CDCl3):  = 1.33 (t, J = 7.1 Hz, 3 H), 4.29 (q, J =
7.1 Hz, 2 H), 4.66 (br s, 1 H), 5.59 (s, 1 H), 6.51 (d, J = 8.9 Hz, 2 H),
7.26–7.34 (m, 10 H), 7.81 (d, J = 8.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 14.6, 60.3, 62.5, 112.5, 119.4, 127.6,
127.8, 129.0, 131.5, 142.1, 150.9, 166.9.
IR (KBr): 3418, 1594, 1498, 1329 cm–1
.
1H NMR (400 MHz, DMSO-d6):  = 3.94 (s, 3 H), 5.96 (d, J = 7.1 Hz,
1 H), 6.39 (d, J = 7.1 Hz, 1 H), 6.57 (d, J = 8.9 Hz, 1 H), 7.28 (tt, J = 7.1,
1.4 Hz, 2 H), 7.36 (dt, J = 7.1, 1.8 Hz, 4 H), 7.41 (dt, J = 6.9, 1.6 Hz, 4 H),
7.62 (d, J = 2.3 Hz, 1 H), 7.75 (dd, J = 8.9, 2.5 Hz, 1 H).
MS (FAB): m/z = 332 [M + H]+.
Synthesis of 3v and 4
A mixture of 4-nitronaphthalen-1-amine 1b (188 mg, 1 mmol),
NaAuCl4·2H2O (20 mg, 0.05 mmol), sodium diphenylphosphinoben-
zene-3-sulfonate (TPPMS) (18 mg, 0.05 mmol) and benzhydrol 2a (1.2
mmol) in H2O (4 mL) was heated at 120 °C for 16 h under air. After
cooling, the reaction mixture was poured into water and extracted
with EtOAc. The organic layer was washed with brine, dried over
MgSO4 and concentrated in vacuo. The residue was washed with hex-
anes, then purified by flash column chromatography (silica gel, hex-
anes/EtOAc) to give N-benzylated product 3v (237 mg, 0.67 mmol)
and C-benzylated product 4 (71 mg, 0.20 mmol).
13C NMR (100 MHz, DMSO-d6):  = 56.6, 60.6, 105.1, 108.8, 119.8,
127.8, 128.0, 129.2, 137.0, 142.3, 143.7, 145.9.
MS (EI): m/z (%) = 334 (73) [M]+, 167 (100).
Anal. Calcd for C20H18N2O3: C, 71.84; H, 5.43; N, 8.38. Found: C, 71.78;
H, 5.48; N, 8.38.
2-(Benzhydrylamino)benzonitrile (3r)23
By following the general procedure, 3r was obtained.
Yield: 237 mg (83%); white solid; mp 97–112 °C.
IR (KBr): 3421 cm–1
.
N-Benzhydryl-4-nitronaphthalen-1-amine (3v)
1H NMR (400 MHz, CDCl3):  = 5.10 (s, 1 H), 5.60 (d, J = 4.1 Hz, 1 H),
6.50 (d, J = 8.6 Hz, 1 H), 6.68 (t, J = 15.2, 7.6 Hz, 1 H), 7.42 (dd, J = 7.8,
1.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 62.3, 96.3, 112.2, 117.1, 117.8, 127.3,
127.9, 129.0, 132.7, 134.1, 141.3, 149.1.
Mp 198–200 °C; brown solid.
IR (KBr): 3437 cm–1
.
1H NMR (400 MHz, CDCl3):  = 5.69 (br d, J = 4.4 Hz, 1 H), 5.83 (d, J =
4.7 Hz, 1 H), 6.39 (d, J = 8.9 Hz, 1 H), 7.55 (ddd, J = 9.2, 6.2, 1.3 Hz,
1 H), 7.72 (ddd, J = 8.8, 5.7, 1.3 Hz, 1 H), 7.88 (d, J = 8.5 Hz, 1 H), 8.31
(d, J = 8.8 Hz, 1 H), 9.00 (dd, J = 8.8, 0.6 Hz, 1 H).
MS (EI): m/z = 284 [M + H]+.
13C NMR (100 MHz, CDCl3):  = 62.7, 103.6, 102.1, 122.0, 125.0, 126.0,
126.5, 127.4, 128.2, 128.5, 128.9, 129.2, 129.6, 135.8, 140.9, 148.0.
MS (EI): m/z = 354 [M + H]+.
2-(Benzhydrylamino)-4-(trifluoromethyl)benzonitrile (3s)12
By following the general procedure, 3s was obtained.
Yield: 268 mg (76%); white solid; mp 126–128 °C.
IR (KBr): 3407, 2220 cm–1
.
2-Benzhydryl-4-nitronaphthalen-1-amine (4)
1H NMR (400 MHz, CDCl3):  = 5.33 (br d, J = 4.6 Hz, 1 H), 5.64 (d, J =
5.0 Hz, 1 H), 6.73 (s, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 7.29–7.39 (m, 10 H),
7.53 (d, J = 8.0 Hz, 1 H), 8.76 (d, J = 1.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 62.4, 99.4, 108.9 (q, JCF = 3.8 Hz), 113.6
(q, JCF = 3.8 Hz), 116.7, 123.3 (q, JCF = 273.2 Hz), 127.4, 128.3, 129.3,
133.6, 135.9 (q, JCF = 32.6 Hz), 140.6, 149.3.
Brown solid; mp 198–201 °C.
IR (KBr): 3377, 1641, 1558 cm–1
1H NMR (400 MHz, CDCl3):  = 4.89 (br s, 2 H), 5.59 (s, 1 H), 7.16 (dd,
J = 6.9, 1.6 Hz, 4 H), 7.54 (t, J = 7.4 Hz, 1 H), 7.70 (t, J = 7.7 Hz, 1 H),
7.80 (d, J = 8.5 Hz, 1 H), 7.96 (s, 1 H), 8.91 (d, J = 8.8 Hz, 1 H).
.
13C NMR (400 MHz, DMSO-d6):  = 49.7, 119.2, 121.9, 124.0, 124.1,
125.9, 127.1, 127.2, 129.1, 129.7, 130.6, 130.9, 132.2, 142.6, 150.5.
MS (FAB): m/z = 353 [M + H]+.
MS (EI): m/z (%) = 354 (100) [M]+.
HRMS-EI: m/z [M+] calcd for C23H18N2O2: 354.1368; found: 354.1367.
1-[4-(Benzhydrylamino)phenyl]ethan-1-one (3t)24
By following the general procedure, 3t was obtained.
Yield: 166 mg (55%); white powder; mp 139–141 °C.
N-[Cyclopropyl(phenyl)methyl]-4-nitroaniline (3w)20
By following the general procedure, 3w was obtained.
Yield: 181 mg (68%); yellow solid; mp 60–62 °C.
IR (KBr): 3358, 1596 cm–1
.
1H NMR (400 MHz, CDCl3):  = 2.46 (s, 3 H), 4.75 (br d, J = 3.9 Hz, 1 H),
5.61 (d, J = 4.6 Hz, 1 H), 6.53 (d, J = 8.9 Hz, 2 H), 7.26–7.37 (m, 10 H),
7.79 (d, J = 8.9 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 26.2, 62.5, 112.5, 127.3, 127.5, 127.9,
129.1, 130.8, 141.9, 151.1, 196.5.
IR (KBr): 3411, 1598, 1513 cm–1
.
1H NMR (400 MHz, CDCl3):  = 0.39 (ddd, J = 9.6, 9.6, 5.3 Hz, 1 H), 0.48
(ddd, J = 9.4, 9.4, 4.8 Hz, 1 H), 0.57–0.71 (m, 2 H), 1.19–1.28 (m, 1 H),
3.84 (br d, J = 8.0 Hz, 1 H), 5.17 (br s, 1 H), 6.41 (d, J = 9.2 Hz, 2 H),
7.26–7.37 (m, 5 H), 7.97 (d, J = 9.4 Hz, 2 H).
MS (FAB): m/z = 302 [M + H]+.
13C NMR (100 MHz, DMSO-d6):  = 3.4, 4.8, 18.4, 60.7, 111.4, 126.0,
126.4, 127.0, 128.4, 135.7, 142.8, 153.7.
Ethyl 4-(Benzhydrylamino)benzoate (3u)25
By following the general procedure, 3u was obtained.
MS (FAB): m/z = 269 [M + H]+.
Yield: 272 mg (82%); white solid; mp 120–122 °C.
IR (KBr): 3349, 1686, 1602 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

H
H. Hikawa et al.
Paper
Synthesis
Funding Information
(10) (a) Hikawa, H.; Kotaki, F.; Kikkawa, S.; Azumaya, I. J. Org. Chem.
2019, 84, 1972. (b) Hikawa, H.; Tada, A.; Kikkawa, S.; Azumaya, I.
Adv. Synth. Catal. 2016, 358, 395. (c) Hikawa, H.; Suzuki, H.;
Yokoyama, Y.; Azumaya, I. J. Org. Chem. 2013, 78, 6714.
(11) For copper-catalyzed dehydrative coupling reactions, see:
(a) Xu, Z.; Wang, D.-S.; Yu, X.; Yang, Y.; Wang, D. Adv. Synth.
Catal. 2017, 359, 3332. (b) Hikawa, H.; Mori, Y.; Kikkawa, S.;
Azumaya, I. Adv. Synth. Catal. 2016, 358, 765. (c) Wei, X.-F.; Shi,
S.; Xie, X.-W.; Shimizu, Y.; Kanai, M. ACS Catal. 2016, 6, 6718.
(d) Shcherbinin, V. A.; Shpuntov, P. M.; Konshin, V. V.; Butin, A.
V. Tetrahedron Lett. 2016, 57, 1473. (e) Babu, S. A.; Yasuda, M.;
Tsukahara, Y.; Yamauchi, T.; Wada, Y.; Baba, A. Synthesis 2008,
1717.
This work was supported by JSPS KAKENHI Grant Number 16K08179.
J
a
p
a
n
S
o
c
i
etyforth
e
Pro
m
oti
o
n
of
S
c
i
e
n
c
e
■
■
o
k
?
■
■
(1
6
K
0
8
1
7
9)
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611519.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
References
(12) For cobalt-catalyzed dehydrative coupling reactions, see:
(a) Sen, M.; Dahiya, P.; Premkumar, J. R.; Sundararaju, B. Org.
Lett. 2017, 19, 3699. (b) Hikawa, H.; Ijichi, Y.; Kikkawa, S.;
Azumaya, I. Eur. J. Org. Chem. 2017, 465. (c) Bunno, Y.;
Murakami, N.; Suzuki, Y.; Kanai, M.; Yoshino, T.; Matsunaga, S.
Org. Lett. 2016, 18, 2216. (d) Lu, Q.; Vasquez-Cespedes, S.;
Gensch, T.; Glorius, F. ACS Catal. 2016, 6, 2352. (e) Sen, M.; Kalsi,
D.; Sundararaju, B. Chem. Eur. J. 2015, 21, 15529. (f) Suzuki, Y.;
Sun, B.; Sakata, K.; Yoshino, T.; Matsunaga, S.; Kanai, M. Angew.
Chem. Int. Ed. 2015, 54, 9944.
(13) (a) Kadina, A.; Kietrys, A. M.; Kool, E. T. Angew. Chem. Int. Ed.
2018, 57, 3059. (b) Komatsuda, M.; Muto, K.; Yamaguchi, J. Org.
Lett. 2018, 20, 4354. (c) Yu, H.; Gao, B.; Hu, B.; Huang, H. Org.
Lett. 2017, 19, 3520. (d) Elie, B. T.; Levine, C.; Ubarretxena-
Belandia, I.; Varela-Ramirez, A.; Aguilera, R. J.; Ovalle, R.; Contel,
M. Eur. J. Inorg. Chem. 2009, 3421.
(1) (a) Morita, N.; Miyamoto, M.; Yoda, A.; Yamamoto, M.; Ban, S.;
Hashimoto, Y.; Tamura, O. Tetrahedron Lett. 2016, 57, 4460.
(b) Borrero, N. V.; DeRatt, L. G.; Barbosa, L. F.; Abboud, K. A.;
Aponick, A. Org. Lett. 2015, 17, 1754. (c) Minkler, S. R. K.; Isley,
N. A.; Lippincott, D. J.; Krause, N.; Lipshutz, B. H. Org. Lett. 2014,
16, 724. (d) Mukherjee, P.; Ross, A. W. Org. Lett. 2011, 13, 1334.
(e) Ohshima, T.; Nakahara, Y.; Ipposhi, J.; Miyamoto, Y.;
Mashima, K. Chem. Commun. 2011, 8322.
(2) For reviews, see: (a) Biannic, B.; Aponick, A. Eur. J. Org. Chem.
2011, 6605. (b) Debleds, O.; Gayon, E.; Vrancken, E.; Campagne,
J.-M. Beilstein J. Org. Chem. 2011, 7, 866. (c) Corma, A.; Leyva-
Perez, A.; Maria, J. S. Chem. Rev. 2011, 111, 1657. (d) Arcadi, A.
Chem. Rev. 2008, 108, 3266.
(3) Georgy, M.; Boucard, M.; Campagne, J.-M. J. Am. Chem. Soc.
2005, 127, 14180.
(4) Terrasson, V.; Marque, S.; Georgy, M.; Campagne, J.-M.; Prim, D.
Adv. Synth. Catal. 2006, 348, 2063.
(14) Nallagonda, R.; Rehan, M.; Ghorai, P. J. Org. Chem. 2014, 79,
2934.
(15) (a) Ye, D.; Huang, R.; Zhu, H.; Zou, L.-H.; Wang, D. Org. Chem.
Front. 2019, 6, 62. (b) Yu, X.; Wang, D.-S.; Xu, Z.; Yang, B.; Wang,
D. Org. Chem. Front. 2017, 4, 1011.
(5) (a) Morita, N.; Tsunokake, T.; Narikiyo, Y.; Harada, M.;
Tachibana, T.; Saito, Y.; Ban, S.; Hashimoto, Y.; Okamoto, I.;
Tamura, O. Tetrahedron Lett. 2015, 56, 6269. (b) Morita, N.;
Yasuda, A.; Shibata, M.; Ban, S.; Hashimoto, Y.; Okamoto, I.;
Tamura, O. Org. Lett. 2015, 17, 2668. (c) Huang, R.; Yang, Y.;
Wang, D.-S.; Zhang, L.; Wang, D. Org. Chem. Front. 2018, 5, 203.
(6) For solvent-free conditions, see: (a) Xu, Q.; Xie, H.; Zhang, E.-L.;
Ma, X.; Chen, J.; Yu, X.-C.; Li, H. Green Chem. 2016, 18, 3940.
(b) Li, L.; Zhu, A.; Zhang, Y.; Fan, X.; Zhang, G. RSC Adv. 2014, 4,
4286. (c) Yu, J.-J.; Wang, L.-M.; Guo, F.-L.; Liu, J.-Q.; Liu, Y.; Jiao,
N. Synth. Commun. 2011, 41, 1609.
(7) For ionic liquid as a reaction medium, see: (a) Han, F.; Yang, L.;
Li, Z.; Xia, C. Adv. Synth. Catal. 2012, 354, 1052. (b) Zhu, A.; Li, L.;
Wang, J.; Zhuo, K. Green Chem. 2011, 13, 1244. (c) Qureshi, Z. S.;
Deshmukh, K. M.; Tambade, P. J.; Dhake, K. P.; Bhanage, B. M.
Eur. J. Org. Chem. 2010, 6233.
(8) (a) Xu, Z.; Yu, X.; Sang, X.; Wang, D. Green Chem. 2018, 20, 2571.
(b) Ge, C.; Sang, X.; Yao, W.; Zhang, L.; Wang, D. Green Chem.
2018, 20, 1805. (c) Hikawa, H.; Imamura, H.; Kikkawa, S.;
Azumaya, I. Green Chem. 2018, 20, 3044. (d) Hikawa, H.;
Ichinose, R.; Kikkawa, S.; Azumaya, I. Green Chem. 2018, 20,
1297. (e) Morioka, Y.; Matsuoka, A.; Binder, K.; Knappett, B. R.;
Wheatley, A. E. H.; Naka, H. Catal. Sci. Technol. 2016, 6, 5801.
(f) Sawama, Y.; Kawajiri, T.; Niikawa, M.; Goto, R.; Yabe, Y.;
Takahashi, T.; Marumoto, T.; Itoh, M.; Kimura, Y.; Monguchi, Y.;
Kondo, S.; Sajiki, H. ChemSusChem 2015, 8, 3773.
(16) (a) Calvo, P.; Crugeiras, J.; Rios, A.; Rios, M. A. J. Org. Chem. 2007,
72, 3171. (b) Junttila, M. H.; Hormi, O. E. O. J. Org. Chem. 2007,
72, 2956. (c) Horenstein, B. A.; Bruner, M. J. Am. Chem. Soc. 1998,
120, 1357. (d) Humeres, E.; Debacher, N. A.; de S. Sierra, M. M.;
Franco, J. D.; Schutz, A. J. Org. Chem. 1998, 63, 1598. (e) Fife, T.
H.; Bembi, R.; Natarajan, R. J. Am. Chem. Soc. 1996, 118, 12956.
(17) (a) Goto, K.; Yano, Y.; Okada, E.; Liu, C.-W.; Yamamoto, K.;
Ueoka, R. J. Org. Chem. 2003, 68, 865. (b) Humeres, E.; Lee, B. S.;
Debacher, N. A. J. Org. Chem. 2008, 73, 7189. (c) Junttila, M. H.;
Hormi, O. E. O. J. Org. Chem. 2007, 72, 2956. (d) Freccero, M.;
Gandolfi, R. J. Org. Chem. 2005, 70, 7098.
(18) Soper, A. K.; Benmore, C. J. Phys. Rev. Lett. 2008, 101, 065502.
(19) Harada, Y.; Tokushima, T.; Horikawa, Y.; Takahashi, O.; Niwa, H.;
Kobayashi, M.; Oshima, M.; Senba, Y.; Ohashi, H.; Wikfeldt, K. T.;
Nilsson, A.; Pettersson, L. G. M.; Shin, S. Phys. Rev. Lett. 2013,
111, 193001.
(20) Li, W.; Zheng, X.; Li, Z. Adv. Synth. Catal. 2013, 355, 181.
(21) Zhang, C.; Zhan, Z.; Lei, M.; Hu, L. Tetrahedron 2014, 70, 8817.
(22) Yu, A.; Wu, Y.; Cheng, B.; Wei, K.; Li, J. Adv. Synth. Catal. 2009,
351, 767.
(23) Strekowski, L.; Cegla, M. T.; Harden, D. B.; Kong, S. B. J. Org.
Chem. 1989, 54, 2464.
(24) Aziz, J.; Brion, J.-D.; Hamze, A.; Alami, M. Adv. Synth. Catal. 2013,
355, 2417.
(25) van As, D. J.; Connell, T. U.; Brzozowski, M.; Scully, A. D.;
Polyzos, A. Org. Lett. 2018, 20, 905.
(9) For reviews, see: (a) Kitanosono, T.; Masuda, K.; Xu, P.;
Kobayashi, S. Chem. Rev. 2018, 118, 679. (b) Ortiz, R.; Herrera, R.
P. Molecules 2017, 22, 574.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H