Chemoselective benzylation of unprotected anthranilic acids with benzhydryl alcohols by water-soluble Au(III)/TPPMS in water

Article abstract of DOI:10.1021/jo401064f

A novel and efficient method for the benzylation of unprotected anthranilic acids with benzhydryl alcohols using water-soluble Au(III)/TPPMS in water is developed. Water plays an important role in our catalytic system. This new protocol could be used for not only N-benzylation, but also chemoselective C-benzylation by the Friedel-Crafts reaction.

Full text of DOI:10.1021/jo401064f

Article
pubs.acs.org/joc
Chemoselective Benzylation of Unprotected Anthranilic Acids with
Benzhydryl Alcohols by Water-Soluble Au(III)/TPPMS in Water
Hidemasa Hikawa,* Hideharu Suzuki, Yuusaku Yokoyama,* and Isao Azumaya
Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
S
* Supporting Information
ABSTRACT: A novel and efficient method for the
benzylation of unprotected anthranilic acids with benzhydryl
alcohols using water-soluble Au(III)/TPPMS in water is
developed. Water plays an important role in our catalytic
system. This new protocol could be used for not only N-
benzylation, but also chemoselective C-benzylation by the
Friedel−Crafts reaction.
a number of difficulties, not the least of which is chemo-
selectivity.4 One of the most effective ways for achieving
synthesis without protecting groups is the development of
selective reactions toward various functional groups in water.
We recently reported a unique strategy for benzylation and C−
H activation by the (η3-benzyl)palladium system from a
palladium catalyst and benzyl alcohol in water.5 Water first
activates the sp3 C−O bond, followed by stabilization of OH−
by hydration, for the smooth generation of the activated Pd(II)
cation species, which can then undergo innovative direct
transformation reactions.
In light of our ongoing efforts to develop new methods for
direct substitution reaction of benzyl alcohols, we herein report
the water-soluble gold(III)-catalyzed benzylation of unpro-
tected anthranilic acids with benzhydryl alcohols in water.
Notably, the reaction proceeds chemoselectively to give N-
benzylated 3 and C-benzylated 4 with the amino group left
intact. To the best of our knowledge, there are no examples of
the direct substitution of benzhydryl alcohols with unprotected
water-soluble anthranilic acids as nucleophiles by Au(III)/
TPPMS in water. Additionally, when using protocols based on
previous methods such as NaAuCl4·2H2O in CH2Cl2 or Pd(0)/
TPPMS in water, the substrate scope generally does not extend
to unprotected water-soluble anthranilic acids.
INTRODUCTION
■
The gold-catalyzed direct substitution reaction of alcohols with
various nucleophiles has become one of the most efficient and
environmentally friendly synthetic strategies for alkylation.1
Such efficiency is primarily due to the Lewis acid character of
the gold catalyst that allows the activation of several sp3 C−O
bonds, thus promoting unique chemical transformations.
Benzyl halides are chemically unstable, and their synthesis
from benzyl alcohols is achieved by halogenation, which is
undesirable from an environmental point of view. Therefore,
the application of alcohols as benzylating agents has the benefit
of high atom efficiency and the formation of water as the only
byproduct. However, the application of alcohols in nucleophilic
substitution reactions is limited due to the poor leaving group
ability of the hydroxyl groups. Thus, the direct catalytic
substitution of underivatized benzyl alcohols is a promising
strategy in organic chemistry.
Recently, Campagne and Prim reported the gold(III)-
catalyzed direct amination of benzhydryl alcohols.1l Ohshima
and Mashima also reported the direct amination of the hydroxyl
group with highly functionalized nitrogen nucleophiles such as
acid-sensitive Boc protected amines by Au(III).1b In these
cases, however, nucleophiles were limited to nitrogen
compounds such as 4-nitroaniline, amides, and carbamates.
Furthermore, most of these reactions are usually conducted in
organic solvents, and extrusion of moisture is essential.2 Water
has unique reactivity and selectivity that cannot be attained
with organic solvents. Therefore, in recent years, water has
emerged as an attractive tool for new transition metal-catalyzed
reactions.
Anthranilic acid 1a is a versatile and low-cost starting
material for synthesis of benzofused heterocycles. It also plays a
vital part in the biosynthesis of tryptophan and several types of
alkaloids. Derivatives of 1a have been used for medicinal
purposes, e.g., mefenamic acid, which has nonsteroidal
antiflammatory and analgesic properties. Therefore, the
chemistry of anthranilic acids 1 is of importance in medicinal
and biological chemistry.
We have been studying the development of syntheses
without protecting groups and selective reactions toward
various functional groups in water.3 Thus, we became interested
in further expanding the nucleophile scope in the gold-
catalyzed direct substitution reaction to water-soluble un-
protected substrates. In general, synthesis without protecting
groups represents a distinct challenge and has been fraught with
Received: May 15, 2013
Published: June 8, 2013
© 2013 American Chemical Society
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a
Table 1. Effect of Catalysts and Solvents
b
entry
catalyst
ligand
solvent
conversion (%)
1
AuCl4Na·2H2O
none
TPPMS
none
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
CH2Cl2
78 (77% yield)
d
2
NR
3
AuCl4Na·2H2O
none
none
14
29
75
39
57
4
TPPMS
TPPMS
TPPMS
TPPMS
none
5
HAuCl4·3H2O
AuCl3
6
7
AuCl
c
8
TsOH·H2O, MsOH or HCl
Sc(OTf)3, Yb(OTf)3, Y(OTf)3 or La(OTf)3
AuCl4Na·2H2O
Trace
c
9
none
Trace
d
c
10
11
12
13
14
15
none
Trace
e
f
c
Pd(OAc)2
TPPMS
TPPMS
TPPMS
none
H2O
Trace
AuCl4Na·2H2O
AuCl4Na·2H2O
AuCl4Na·2H2O
AuCl4Na·2H2O
1,4-dioxane
30
c
DMF, EtOH or Toluene
DMF, EtOH or Toluene
Trace
c
Trace
g
c
TPPMS
K2CO3 aq.
Trace
a
b
Reaction conditions: 1a (1 mmol), catalyst (5 mol %), ligand (5 mol %), benzhydrol 2a (1.2 equiv), solvent (4 mL), 80 °C, 16 h under air. The
c
d
conversion was determined by 1H NMR analysis of the crude product using p-nitroanisole as an internal standard. By TLC analysis. At 40 °C (bp).
e
f
g
10 mol %. At 120 °C in a sealed tube. 2 equiv.
resulted in low yields or no reaction when using 1,4-dioxane,
DMF, EtOH or toluene as solvents (entries 12, 13 and 14),
water is clearly essential for the N-benzylation in our catalytic
system. Under basic conditions in the presence of K2CO3 (2
equiv), the reaction did not proceed (entry 15). Therefore,
Au(III)/TPPMS functions as a Lewis acid for activation of
benzhydryl alcohol 2a, followed by formation of a benzylic
cation species.
RESULTS AND DISCUSSION
■
First, we heated a mixture of anthranilic acid 1a and benzhydryl
alcohol 2a (1.2 equiv) in the presence of AuCl4Na·2H2O (5
mol %) and sodium diphenylphosphinobenzene-3-sulfonate6
(TPPMS, 5 mol %) in water at 80 °C for 16 h under air.7 N-
Benzylated 3a was obtained in 78% yield and 77% isolated yield
(Table 1, entry 1). The reaction did not proceed in the absence
of the gold catalyst and phosphine ligand, and recovery of SM
1a was detected by TLC analysis (entry 2). Using only
AuCl4Na·2H2O or only TPPMS resulted in low yield (entry 3,
14%; entry 4, 29%). Komiya and co-workers reported that a
gold(III) complex having a water-soluble phosphine ligand,
AuMe2I(TPPTS), was prepared, and reductive elimination
involving C−C bond formation at Au(III) in water was faster
than in organic solvents.7f Kunz and co-workers reported that
gold(I) complexes with imidazolyl and thiazolyl-based water-
soluble diphos-type ligands were prepared, and their potential
as chemotherapeutics was investigated.7d Thus, in our catalytic
system, AuCl3(TPPMS) or a cationic aqueous complex
[AuCl2(TPPMS)(H2O)]+Cl− might be formed, which plays
an important role in activation of the sp3 C−O bond. With
regard to the gold catalyst, the use of HAuCl4·3H2O also gave
the product 3a in good yield (entry 5, 75%). In contrast, When
the AuCl3 or AuCl were used, the reaction proceeded slowly
(entry 6, 39%; entry 7, 57%). Thus, we decided to use more
stable and easier to handle AuCl4Na·2H2O as the catalyst for
further studies. To compare AuCl4Na·2H2O with other efficient
catalysts, we tested the reaction using Brønsted acids such as
TsOH·H2O, MsOH or HCl, and Lewis acids such as Sc(OTf)3
Yb(OTf)3, Y(OTf)3 or La(OTf)3. However, the reaction did
not proceed (entries 8 and 9). Furthermore, using
Results for the N-benzylation of a number of anthranilic acids
1 with benzhydryl alcohol 2a, or conversely, anthranilic acid 1a
with several benzhydryl alcohols 2, using AuCl4Na·2H2O and
TPPMS in water, are summarized in Figure 1. The anthranilic
acids with 5-bromo and 5-iodo groups resulted in moderate to
good yields with the carbon−halogen moieties left intact (3b,
84%; 3c, 51%), which could be employed for further
manipulation. The reaction of anthranilic acids with electron-
withdrawing fluoro and trifluoromethyl groups also proceeded
to give N-benzylated products in good yields (3d, 89%; 3e,
90%; 3f, 90%). In contrast, anthranilic acids with electron-
donating methyl groups proceeded slowly (3g, 79%; 3h, 22%).
The scope of the reaction with respect to alcohols 2 was further
examined, and the reactions of anthranilic acid 1a with
benzhydryl alcohols 2 with methyl, chloro and fluoro groups
resulted in good yields (3i, 91%; 3j, 90%; 3k, 88%).
Furthermore, N-benzylation of 2-amino-4-(trifluoromethyl)-
benzoic acid 1b with 1-phenylethylalcohol 2b or 1-phenyl-1-
propanol 2c also afforded desired N-benzylated product in
good yield (3l, 75%; 3m, 73% in Scheme 1). In contrast, 1-
hydroxyindan 2d resulted in no reaction.
Surprisingly, benzhydryl alcohol with electron-donating
methoxy groups 2e afforded only C-benzylated 4a by
Friedel−Crafts reaction in 86% yield with the amino group
left intact (Scheme 2).8 Furthermore, when using N-
methylanthranilic acid 1b as a substrate, C-benzylation occurred
to give C-benzylated 4 in good yield (4b, 74%; 4c, 84%; 4d,
1
AuCl4Na·2H2O in CH2Cl2 (entry 10) or Pd(0)/TPPMS in
water5 (entry 11) also resulted in no reaction, clearly showing
the superiority of Au(III)/TPPMS for the N-benzylation of
unprotected anthranilic acid 1a in water. Since the reaction
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Figure 1. Scope of anthranilic acids 1 and benzhydryl alcohols 2. Reaction conditions: anthranilic acids 1 (1 mmol), AuCl4Na·2H2O (5 mol %),
TPPMS (5 mol %), alcohols 2 (1.2 equiv), H2O (4 mL), 80 °C, 16 h in a sealed tube, except when (a) at 120 °C, 24 h in a sealed tube, or (b) at 100
°C, 24 h.
Scheme 1. Scope of Alcohols 2
results show that our Au(III)/TPPMS system might possibly
be used for C-benzylation with other substrates by Friedel−
Crafts reaction in water.9
Scheme 2. Chemoselective C-Benzylation of Anthranilic
On the basis of our results and literature reports, the
following mechanism can be suggested (Scheme 4). First,
water-soluble gold(III) intermediate 5 might form from
anthranilic acid 1a and benzhydryl alcohols 2 in the presence
of AuCl4Na·2H2O and TPPMS, since Au(III)-picolinate
complex I is reported as the active catalyst for direct amination
of alcohols.1b Water must play an important role for the
smooth generation of the intermediate 5, which is stabilized by
hydration, since the reaction did not occur without water and
water-soluble phosphine ligand, TPPMS. Additionally, anthra-
nilic acid 1a has been used to form coordination complexes
with many metals such as gallium, aluminum, and lithium, and
their structures were determined using X-ray crystallography.10
Next, benzyl cation species 7 forms, followed by nucleophilic
attack of the nitrogen of anthranilic acid 6, to give N-benzylated
3 (path A). In contrast, a benzyl cation with electron-donating
methoxy groups 8 directs the Friedel−Crafts reaction to afford
C-benzylated 4a (path B). According to the HSAB principle,
soft acids prefer to bind to soft bases. Therefore, the carbon
atom at the C5 position of anthranilic acid 6, being a soft
nucleophile center, will prefer to bind to soft acid 8 because of
the +R effect of the p-methoxy groups on the benzene ring.11
While benzyl cation 7 could form an ion pair with the water-
soluble Au(III) complex 6 in the aqueous hydrophilic arena, the
intermediate 8, which is a long-lived cation, might interact with
Acid 1a
Scheme 3. Chemoselective C-Benzylation with Benzyl
Alcohols 2
86%; 4e, 85%; 4f, 75% in Figure 2). Interestingly, C-benzylation
with simple benzyl alcohols such as 4-methoxybenzylalcohol 2f
or veratry alcohol 2g resulted in good yield (4g, 52%; 4h, 51%
in Scheme 3). The sterically demanding N-methyl substituent
would influence the selectivity of the direct substitution. These
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Figure 2. Chemoselective C-benzylation of N-methylanthranilic acid 1b with benzhydryl alcohols 2. Reaction conditions: N-methylanthranilic acid
1b (1 mmol), AuCl4Na·2H2O (5 mol %), TPPMS (5 mol %), alcohol 2 (1.2 equiv), H2O (4 mL), 80 °C, 24 h in a sealed tube, except when (a) at
100 °C in a sealed tube.
Scheme 4. Possible Mechanism
the benzene ring of anthranilic acid 6 by the hydrophobic effect.
Indeed the C-benzylation using benzhydryl alcohol with
electron-withdrawing chloro group 2 did not proceed (see
Figures 1 and 2). Additionally, the carboxyl group of anthranilic
acid would enhance the reaction, since the reaction of 4-
aminobenzoic acid 1c proceeded slowly (Scheme 5A vs entry 1
in Table 1). Anthranilic acid methyl ester 1d afforded N-
benzylated 3n in 92% yield (Scheme 5B). Ester 1d also might
form a coordination active complex with Au(III)/TPPMS in
water.
Scheme 5. N-Benzylation of 4-Aminobenzoic Acid 1c or
Ester 1d
CONCLUSIONS
■
In summary, we developed the first benzylation of unprotected
anthranilic acids with benzhydryl alcohols using a water-soluble
gold(III)/TPPMS catalyst system in water, one of the most
efficient and environmentally friendly synthetic strategies for
benzylation. Notably, water plays an important role in our
catalytic system. This new protocol could be used for N-
benzylation and chemoselective C-benzylation by Friedel−
Crafts reaction. We are currently investigating the scope of
various water-soluble nucleophiles, such as highly function-
alized bioactive compounds,12 and are developing new
reactions using the water-soluble Au(III)/TPPMS system in
aqueous media.
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60.0, 109.0 (d, J = 3.8 Hz), 110.7 (d, J = 3.8 Hz), 113.8, 123.6 (d, J =
273 Hz), 126.7, 127.4, 128.9, 132.9, 133.7 (q, J = 29.6 Hz), 142.3,
149.4, 169.3; MS (EI) m/z (%) 335 (M+, 1.5), 226 (100); HRMS (EI)
m/z calcd for C21H16F3NO2 [M+], 371.1133, found 371.1131.
2-(Benzhydrylamino)-4-methylbenzoic acid 3g (Figure 1).
Following the general procedure, 3g was obtained as a white solid: 250
EXPERIMENTAL SECTION
■
The mass analyzer type is double-focusing magnetic sector mass
spectrometer for the HRMS measurements.
General Procedure. A mixture of anthranilic acids 1 (1 mmol),
AuCl4Na·2H2O (20 mg, 0.05 mmol), sodium diphenylphosphinoben-
zene-3-sulfonate (TPPMS, 18 mg, 0.05 mmol) and benzhydryl
alcohols 2 (1.2 mmol) in H2O (4 mL) was heated at 80−120 °C
for 16−24 h in a sealed tube. 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 purified by flash column chromatography (silica gel,
hexanes/EtOAc) to give the desired product 3 or 4.
1
mg (79%); mp 206−207 °C; IR (KBr) (cm−1) 3368, 3030, 1658; H
NMR (400 MHz, DMSO-d6) δ 2.11 (s, 3H), 5.85 (d, J = 6.8 Hz, 1H),
6.40 (d, J = 8.0 Hz, 1H), 6.45 (s, 1H), 7.25 (tt, J = 7.2, 1.6 Hz, 2H),
7.35 (t, J = 8.0 Hz, 4H), 7.39 (dd, J = 8.0, 2.0 Hz, 4H), 7.71 (d, J = 8.4
Hz, 1H), 8.68 (d, J = 6.8 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ
21.7, 60.0, 108.2, 112.7, 116.3, 126.8, 127.2, 128.8, 131.6, 143.0, 144.4,
149.8, 170.1; MS (ESI) m/z 316 [M − H]−. Anal. Calcd for
C21H19NO2: C, 79.47; H, 6.03; N, 4.41. Found: C, 79.51; H, 5.91; N,
4.19.
2-(Benzhydrylamino)benzoic acid 3a (Table 1, Entry 1).13
Following the general procedure, 3a was obtained as a white solid: 234
mg (77%); mp 209−211 °C; IR (KBr) (cm−1) 3362, 2876, 1661; H
1
2-(Benzhydrylamino)-5-methylbenzoic acid 3h (Figure 1).
Following the general procedure, 3h was obtained as an off-white
solid: 292 mg (92%); mp 257−260 °C; IR (KBr) (cm−1) 3381, 3028,
1667; 1H NMR (400 MHz, DMSO-d6) δ 2.14 (s, 3H), 5.81 (d, J = 6.4
Hz, 1H), 6.52 (d, J = 8.8 Hz, 1H), 7.07 (dd, J = 8.8, 2.4 Hz, 1H), 7.24
(tt, J = 7.2, 1.6 Hz, 2H), 7.34 (t, J = 8.0 Hz, 4H), 7.38 (d, J = 8.0 Hz,
4H), 7.63 (d, J = 1.6 Hz, 1H), 8.49 (d, J = 6.4 Hz, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 19.7, 60.3, 110.5, 112.8, 123.4, 126.8, 127.1,
128.8, 131.4, 135.1, 143.1, 147.7, 170.1; MS (ESI) m/z 316 [M − H]−.
Anal. Calcd for C21H19NO2·0.7H2O: C, 76.43; H, 6.23; N, 4.24.
Found: C, 76.19; H, 5.82; N, 4.13.
NMR (400 MHz, DMSO-d6) δ 5.84 (d, J = 6.4 Hz, 1H), 6.57 (dd, J =
6.8, 6.8 Hz, 1H), 6.59 (d, J = 8.4 Hz, 1H), 7.25 (t, J = 7.2 Hz, 2H),
7.30−7.45 (m, 9H), 7.83 (dd, J = 8.0, 1.6 Hz, 1H), 8.68 (d, J = 6.4 Hz,
1H); 13C NMR (100 MHz, DMSO-d6) δ 60.2, 110.7, 112.6, 115.0,
126.8, 127.2, 128.8, 131.6, 134.3, 142.9, 149.6, 170.1; MS (ESI) m/z
302 [M − H]−.
2-(Benzhydrylamino)-5-bromobenzoic acid 3b (Figure 1).13
Following the general procedure, 3b was obtained as an off-white
solid: 321 mg (84%); mp 230−232 °C; IR (KBr) (cm−1) 3379, 3025,
1
1669; H NMR (400 MHz, DMSO-d6) δ 5.86 (dd, J = 6.4 Hz, 1H),
2-[Phenyl(p-tolyl)methylamino]benzoic acid 3i (Figure 1).14
Following the general procedure, 3i was obtained as a white solid: 289
6.56 (d, J = 9.2 Hz, 1H), 7.23−7.29 (m, 2H), 7.32−7.43 (m, 9H), 7.89
(d, J = 2.4 Hz, 1H), 8.68 (d, J = 6.4 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 60.1, 105.5, 112.4, 115.0, 126.8, 127.3, 128.9, 133.4,
136.6, 142.5, 148.6, 168.9; MS (EI) m/z (%) 383 (M++2, 17.3), 381
(M+, 17.4), 167 (100).
1
mg (91%); mp 191−192 °C; IR (KBr) (cm−1) 3357, 3024, 1665; H
NMR (400 MHz, DMSO-d6) δ 2.25 (s, 3H), 5.78 (d, J = 6.4 Hz, 1H),
6.50−6.60 (m, 2H), 7.15 (d, J = 7.6 Hz, 2H), 7.20−7.30 (m, 4H), 7.34
(t, J = 8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 7.6, 1.2 Hz,
1H), 8.63 (d, J = 6.4 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ
20.6, 60.0, 110.6, 112.6, 114.9, 126.7, 126.7, 127.1, 128.7, 129.3, 131.6,
134.2, 136.3, 139.9, 143.0, 149.7, 170.1; MS (EI) m/z (%) 317 (M+,
27.7), 181 (100).
2-(Benzhydrylamino)-5-iodobenzoic acid 3c (Figure 1).
Following the general procedure, 3c was obtained as a pale yellow
solid: 403 mg (94%); mp 233−234 °C; IR (KBr) (cm−1) 3355, 3036,
1
1672; H NMR (400 MHz, DMSO-d6) δ 5.85 (d, J = 6.4 Hz, 1H),
6.45 (d, J = 9.2 Hz, 1H), 7.22−7.29 (m, 2H), 7.32−7.40 (m, 8H), 7.52
(dd, J = 8.8, 2.4 Hz, 1H), 8.05 (d, J = 2.0 Hz, 1H), 8.68 (d, J = 6.4 Hz,
1H); 13C NMR (100 MHz, DMSO-d6) δ 60.0, 75.4, 113.1, 115.5,
126.8, 127.3, 128.9, 139.3, 142.0, 142.5, 148.9, 168.9; MS (ESI) m/z
428 [M − H]−. Anal. Calcd for C20H16INO2: C, 55.96; H, 3.76; N,
3.26. Found: C, 55.65; H, 3.84; N, 3.04.
2-[(4-Chlorophenyl)(phenyl)methylamino]benzoic acid 3j
(Figure 1).14 Following the general procedure, 3j was obtained as a
white solid: 304 mg (90%); mp 201−203 °C; IR (KBr) (cm−1) 3357,
1
3023, 1667; H NMR (400 MHz, DMSO-d6) δ 5.89 (d, J = 6.4 Hz,
1H), 6.55−6.65 (m, 2H), 7.20−7.30 (m, 2H), 7.30−7.45 (m, 8H),
7.83 (dd, J = 8.4, 1.4 Hz, 1H), 8.65 (d, J = 6.4 Hz, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 59.4, 110.8, 112.6, 115.2, 126.8, 127.4, 128.6,
128.8, 128.9, 131.6, 131.7, 134.3, 141.9, 142.4, 149.5, 170.1; MS (ESI)
m/z 338 [M − H+2] −, 336 [M − H]−.
2-[Bis(4-fluorophenyl)methylamino]benzoic acid 3k (Figure
1). Following the general procedure, 3k was obtained as a white solid:
299 mg (88%); mp 199−200 °C; IR (KBr) (cm−1) 3362, 2887, 1664;
1H NMR (400 MHz, DMSO-d6) δ 5.91 (d, J = 6.0 Hz, 1H), 6.55−6.65
(m, 2H), 7.19 (dd, J = 8.8, 2.0 Hz, 4H), 7.27 (t, J = 8.0 Hz, 1H), 7.41
(dd, J = 6.4, 6.4 Hz, 4H), 7.83 (d, J = 8.0 Hz, 1H), 8.60 (d, J = 5.6 Hz,
1H); 13C NMR (100 MHz, DMSO-d6) δ 58.6, 110.8, 112.6, 115.2,
115.6 (J = 21 Hz), 128.8 (J = 7.6 Hz), 131.7, 134.3, 138.8 (J = 2.8 Hz),
149.4, 161.26 (J = 242 Hz), 170.1; MS (EI) m/z (%) 339 (M+, 21.8),
203 (100); HRMS (EI) m/z calcd for C20H15F2NO2 [M+], 339.1071,
found 339.1073.
2-(Benzhydrylamino)-5-fluorobenzoic acid 3d (Figure 1).
Following the general procedure, 3d was obtained as a white solid: 285
mg (89%); mp 215−216 °C; IR (KBr) (cm−1) 3369, 3030, 1669; H
1
NMR (400 MHz, DMSO-d6) δ 5.84 (d, J = 6.0 Hz, 1H), 6.60 (dd, J =
9.2, 4.4 Hz, 1H), 7.16−7.30 (m, 3H), 7.32−7.42 (m, 8H), 7.54 (dd, J
= 10.0, 3.2 Hz, 1H), 8.49 (d, J = 6.4 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 60.5, 110.8 (d, J = 5.8 Hz), 114.1 (d, J = 7.6 Hz), 116.5
(d, J = 22.9 Hz), 121.8 (d, J = 22.9 Hz), 126.8, 127.3, 128.8, 142.8,
146.6, 152.4 (d, J = 231 Hz), 169.2; MS (ESI) m/z (%) 320 [M −
H]−. Anal. Calcd for C20H16FNO2: C, 74.75; H, 5.02; N, 4.36. Found:
C, 75.18; H, 4.99; N, 4.25.
2-(Benzhydrylamino)-4-fluorobenzoic acid 3e (Figure 1).
Following the general procedure, 3e was obtained as a white solid:
289 mg (90%); mp 200−201 °C; IR (KBr) (cm−1) 3357, 3024, 1672;
1H NMR (400 MHz, DMSO-d6) δ 5.89 (d, J = 6.4 Hz, 1H), 6.35−6.45
(m, 2H), 7.27 (tt, J = 6.8, 1.6 Hz, 2H), 7.36 (t, J = 7.6 Hz, 4H), 7.40
(dd, J = 8.4, 1.6 Hz, 4H), 7.89 (dd, J = 8.4, 6.8 Hz, 1H), 8.91 (d, J =
5.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 60.0, 98.7 (d, J =
25.7 Hz), 102.4 (d, J = 21.9 Hz), 107.7, 126.8, 127.4, 128.9, 134.5 (d, J
= 11.4 Hz), 142.4, 151.8 (d, J = 12.4 Hz), 166.0 (d, J = 247 Hz), 169.4;
MS (EI) m/z (%) 321 (M+, 23.3), 167 (100); HRMS (EI) m/z calcd
for C20H16FNO2 [M+], 321.1165, found 321.1165.
2-(1-Phenylethylamino)-4-(trifluoromethyl)benzoic acid 3l
(Scheme 1). Following the general procedure, 3l was obtained as a
white solid: 232 mg (75%); mp 156−158 °C; IR (KBr) (cm−1) 3370,
1
2986, 1668; H NMR (400 MHz, DMSO-d6) δ 1.50 (d, J = 6.4 Hz,
3H), 4.74−4.84 (m, 1H), 6.76 (s, 1H), 6.80 (d, J = 8.4 Hz, 1H), 7.23
(t, J = 6.8 Hz, 1H), 7.30−7.40 (m, 4H), 7.98 (d, J = 8.4 Hz, 1H), 8.50
(d, J = 6.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 24.4, 51.5,
108.7, 110.2 (d, J = 3.9 Hz), 113.4, 123.6 (d, J = 272 Hz), 125.7, 127.0,
128.7, 132.8, 133.6 (q, J = 31.4 Hz), 144.2, 149.6, 169.3; MS (EI) m/z
(%) 309 (M+, 31.1), 105 (100); HRMS (EI) m/z calcd for
C16H14F3NO2 [M+], 309.0977, found 309.0976.
2-(Benzhydrylamino)-4-(trifluoromethyl)benzoic acid 3f
(Figure 1). Following the general procedure, 3f was obtained as a
white solid: 334 mg (90%); mp 193−195 °C; IR (KBr) (cm−1) 3364,
1
3029, 1671; H NMR (400 MHz, DMSO-d6) δ 5.99 (d, J = 6.4 Hz,
1H), 6.86 (s, 1H), 6.87 (d, J = 8.0 Hz, 1H), 7.27 (tt, J = 7.6, 1.4 Hz,
2H), 7.37 (t, J = 8.0 Hz, 4H), 7.37 (d, J = 8.0 Hz, 4H), 8.01 (d, J = 8.0
Hz, 1H), 8.89 (d, J = 6.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ
2-(1-Phenylpropylamino)-4-(trifluoromethyl)benzoic acid
3m (Scheme 1). Following the general procedure, 3m was obtained
as a white solid: 236 mg (73%); mp 167−169 °C; IR (KBr) (cm−1)
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1
3363, 2973, 1671; H NMR (400 MHz, DMSO-d6) δ 0.92 (t, J = 7.3
347.1521, found 347.1520. Anal. Calcd for C22H21NO3: C, 76.06; H,
6.09; N, 4.03. Found: C, 76.23; H, 5.97; N, 3.88.
Hz, 3H), 1.75−1.90 (m, 2H), 4.57 (dd, J = 13.3, 6.6 Hz, 1H), 6.75 (s,
1H), 6.79 (dd, J = 8.3, 1.4 Hz, 1H), 7.20−7.28 (m, 1H), 7.30−7.40
(m, 4H), 7.97 (dd, J = 8.2, 0.5 Hz, 1H), 8.61 (d, J = 6.6 Hz, 1H); 13C
NMR (100 MHz, DMSO-d6) δ 10.4, 30.7, 57.3, 108.6, 110.0, 113.2,
123.5 (d, J = 272 Hz), 126.1, 127.0, 128.5, 132.8, 133.5 (q, J = 31.5
Hz), 142.8, 149.9, 169.3; MS (EI) m/z (%) 323 (M+, 12.5), 117
(100); HRMS (EI) m/z calcd for C17H16F3NO2 [M+], 323.1133,
found 323.1133.
5-[Bis(4-methoxyphenyl)methyl]-2-(methylamino)benzoic
acid 4e (Figure 2). Following the general procedure, 4e was obtained
as a white solid: 321 mg (85%); mp 177−179 °C; IR (KBr) (cm−1)
1
3396, 2940, 1665; H NMR (400 MHz, DMSO-d6) δ 2.81 (s, 3H),
3.71 (s, 6H), 5.35 (s, 1H), 6.64 (d, J = 8.8 Hz, 1H), 6.85 (d, J = 8.8
Hz, 4H), 6.99 (d, J = 8.8 Hz, 4H), 7.11 (dd, J = 8.4, 2.0 Hz, 1H), 7.51
(d, J = 2.4 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 29.3, 53.1,
55.0, 109.4, 110.9, 113.6, 129.8, 129.9, 131.5, 135.2, 136.6, 150.1,
157.4, 169.8; MS (EI) m/z (%) 377 (M+, 100); HRMS (EI) m/z calcd
for C23H23NO4 [M+], 377.1627, found 377.1628. Anal. Calcd for
C23H23NO4: C, 73.19; H, 6.14; N, 3.71. Found: C, 73.20; H, 6.24; N,
3.67.
4-(Benzhydrylamino)benzoic acid 3n (Scheme 5A).14 Follow-
ing the general procedure, 3n was obtained as a white solid: 181 mg
(57%); mp 203−205 °C; IR (KBr) (cm−1) 3420, 2867, 1668; H
1
NMR (400 MHz, DMSO-d6) δ 5.77 (d, J = 7.2 Hz, 1H), 6.69 (d, J =
8.8 Hz, 2H), 7.20 (d, J = 7.2 Hz, 1H), 7.24 (tt, J = 7.2, 1.2 Hz, 2H),
7.33 (dd, J = 7.2, 7.2 Hz, 4H), 7.39 (d, J = 7.2 Hz, 4H), 7.62 (d, J = 8.8
Hz, 2H), 12.0 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 60.2, 112.0,
117.6, 127.0, 127.3, 128.5, 130.8, 142.7, 151.6, 167.4; MS (EI) m/z
(%) 303 (M+, 26.4), 167 (100).
5-[Bis(4-fluorophenyl)methyl]-2-(methylamino)benzoic acid
4f (Figure 2). Following the general procedure, 4f was obtained as a
white solid: 265 mg (75%); mp 184−186 °C; IR (KBr) (cm−1) 3380,
1
2908, 1670; H NMR (400 MHz, DMSO-d6) δ 2.82 (s, 3H), 5.54 (s,
1H), 6.66 (d, J = 8.8 Hz, 1H), 7.05−7.20 (m, 9H), 7.50 (d, J = 2.4 Hz,
1H); 13C NMR (100 MHz, DMSO-d6) δ 29.2, 52.9, 109.5, 111.1,
115.1 (d, J = 21 Hz), 128.9, 130.6, 130.7, 135.1, 140.3 (d, J = 2.8 Hz),
150.3, 160.7 (d, J = 241 Hz), 169.7; MS (EI) m/z (%) 353 (M+, 100);
HRMS (EI) m/z calcd for C21H17F2NO2 [M+], 353.1227, found
353.1225.
Methyl 2-(benzhydrylamino)benzoate 3o (Scheme 5B).13
Following the general procedure, 3o was obtained as a white solid: 293
mg (92%); mp 108−110 °C; IR (KBr) (cm−1) 3356, 1683; H NMR
1
(400 MHz, CDCl3) δ 3.85 (s, 3H), 5.63 (d, J = 4.8 Hz, 1H), 6.54 (d, J
= 8.4 Hz, 1H), 6.59 (t, J = 8.0 Hz, 1H), 7.20−7.40 (m, 11H), 7.93 (d, J
= 8.0 Hz, 1H), 8.46 (brs, 1H); 13C NMR (100 MHz, CDCl3) δ 51.6,
61.9, 110.4, 112.7, 115.1, 127.2, 127.3, 128.8, 131.5, 134.5, 142.5,
150.0, 169.1; MS (EI) m/z (%) 317 (M+, 42.6), 167 (100).
5-(4-Methoxybenzyl)-2-(methylamino)benzoic acid 4g
(Scheme 3). Following the general procedure, 4g was obtained as a
pale yellow solid: 141 mg (52%); mp 155−157 °C; IR (KBr) (cm−1)
1
2-Amino-5-[bis(4-methoxyphenyl)methyl]benzoic acid 4a
(Scheme 2). Following the general procedure, 4a was obtained as a
white solid: 313 mg (86%); mp 185−187 °C; IR (KBr) (cm−1) 3475,
3390, 2905, 1665; H NMR (400 MHz, DMSO-d6) δ 2.80 (s, 3H),
3.70 (s, 3H), 3.74 (s, 2H), 6.57 (d, J = 8.7 Hz, 1H), 6.79 (dt, J = 8.7,
3.0 Hz, 2H), 7.05 (dt, J = 8.7, 3.0 Hz, 2H), 7.19 (dd, J = 8.7, 2.3 Hz,
1H), 7.55 (d, J = 2.3 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ
29.8, 55.5, 110.2, 111.5, 114.3, 127.6, 130.0, 131.7, 134.3, 135.6, 150.7,
158.0, 170.4; MS (EI) m/z (%) 271 (M+, 100); HRMS (EI) m/z calcd
for C16H17NO3 [M+], 271.1208, found 271.1209.
1
3365, 2961, 1661; H NMR (400 MHz, DMSO-d6) δ 3.71 (s, 6H),
5.31 (s, 1H), 6.68 (d, J = 8.4 Hz, 1H), 6.85 (d, J = 8.8 Hz, 4H), 6.94−
6.98 (m, 1H), 6.98 (d, J = 8.8 Hz, 4H), 7.40 (d, J = 2.0 Hz, 1H); 13C
NMR (100 MHz, DMSO-d6) δ 53.2, 55.0, 109.2, 113.6, 116.5, 129.8,
130.5, 130.9, 134.6, 136.6, 149.9, 157.4, 169.5; MS (EI) m/z (%) 363
(M+, 100). Anal. Calcd for C22H21NO4: C, 72.71; H, 5.82; N, 3.85.
Found: C, 72.61; H, 5.91; N, 3.54.
5-(3,4-Dimethoxybenzyl)-2-(methylamino)benzoic acid 4h
(Scheme 3). Following the general procedure, 4h was obtained as a
pale yellow solid: 153 mg (51%); mp 165−167 °C; IR (KBr) (cm−1)
1
3380, 2908, 1651; H NMR (400 MHz, DMSO-d6) δ 2.80 (s, 3H),
5-Benzhydryl-2-(methylamino)benzoic acid 4b (Figure 2).
Following the general procedure, 4b was obtained as a white solid: 235
3.71 (s, 6H), 3.73 (s, 2H), 6.63 (d, J = 8.7 Hz, 1H), 6.67 (dd, J = 8.3,
1.8 Hz, 1H), 6.79 (d, J = 1.8 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 7.25
(dd, J = 8.5, 2.1 Hz, 1H), 6.61 (d, J = 2.1 Hz, 1H); 13C NMR (100
MHz, DMSO-d6) δ 29.8, 55.9, 56.0, 110.2, 111.5, 112.4, 113.0, 120.9,
127.4, 131.7, 134.8, 135.6, 147.5, 149.2, 150.7, 170.4; MS (EI) m/z
(%) 301 (M+, 100); HRMS (EI) m/z calcd for C17H19NO4 [M+],
301.1314, found 301.1312.
mg (74%); mp 202−203 °C; IR (KBr) (cm−1) 3373, 3024, 1664; H
1
NMR (400 MHz, DMSO-d6) δ 2.81 (s, 3H), 5.49 (s, 1H), 6.66 (d, J =
8.8 Hz, 1H), 7.10 (d, J = 7.2 Hz, 4H), 7.14 (dd, J = 8.8, 2.4 Hz, 1H),
7.20 (tt, J = 7.2, 1.2 Hz, 2H), 7.30 (dd, J = 7.2, 7.2 Hz, 4H), 7.54 (d, J
= 2.4 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 29.3, 54.7, 109.6,
111.0, 126.1, 128.3, 128.9, 129.1, 131.7, 135.3, 144.2, 150.2, 169.8; MS
(EI) m/z (%) 317 (M+, 100). Anal. Calcd for C21H19NO2: C, 79.47;
H, 6.03; N, 4.41. Found: C, 79.41; H, 5.77; N, 4.27.
Table 1, Entry 1. (The yield was determined by 1H NMR analysis
of the crude product using p-nitroanisole as an internal standard.)
A mixture of anthranilic acid 1a (138 mg, 1 mmol), AuCl4Na·2H2O
(20 mg, 0.05 mmol), sodium diphenylphosphinobenzene-3-sulfonate
(TPPMS, 18 mg, 0.05 mmol) and benzhydryl alcohol 2a (221 mg, 1.2
mmol) in H2O (4 mL) was heated at 80 °C for 16 h in a sealed tube.
After the reaction mixture was cooled, p-nitroanisole (153 mg, 1
mmol, internal standard) was added to the reaction mixture, which was
extracted with AcOEt. The organic layer was washed with brine, and
concentrated in vacuo. The residue was analyzed by 1H NMR
spectroscopy.
2-(Methylamino)-5-[phenyl(p-tolyl)methyl]benzoic acid 4c
(Figure 2). Following the general procedure, 4c was obtained as a
white solid: 278 mg (84%); mp 217−219 °C; IR (KBr) (cm−1) 3389,
1
2887, 1674; H NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 2.81 (s,
3H), 5.43 (s, 1H), 6.64 (d, J = 8.8 Hz, 1H), 6.98 (d, J = 8.0 Hz, 2H),
7.05−7.15 (m, 5H), 7.19 (dd, J = 7.2, 7.2 Hz, 1H), 7.29 (dd, J = 7.2,
7.2 Hz, 2H), 7.52 (d, J = 2.0 Hz, 4H); 13C NMR (100 MHz, DMSO-
d6) δ 20.6, 29.2, 54.3, 109.4, 110.9, 126.0, 128.3, 128.8, 128.9, 129.3,
131.6, 135.1, 135.3, 141.2, 144.4, 150.2, 169.8; MS (EI) m/z (%) 331
(M+, 100); HRMS (EI) m/z calcd for C22H21NO2 [M+], 331.1572,
found 331.1573. Anal. Calcd for C22H21NO2: C, 79.73; H, 6.39; N,
4.23. Found: C, 79.63; H, 6.67; N, 4.23.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of H and 13C NMR spectra. This material is available
5-[(4-Methoxyphenyl)(phenyl)methyl]-2-(methylamino)-
benzoic acid 4d (Figure 2). Following the general procedure, 4d
was obtained as a white solid: 299 mg (86%); mp 165−167 °C; IR
1
free of charge via the Internet at http://pubs.acs.org.
(KBr) (cm−1) 33384, 2911, 1668; H NMR (400 MHz, DMSO-d6) δ
1
AUTHOR INFORMATION
2.81 (s, 3H), 3.71 (s, 3H), 5.42 (s, 1H), 6.65 (d, J = 8.8 Hz, 1H), 6.86
(d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 7.2 Hz, 2H),
7.13 (dd, J = 8.8, 2.0 Hz, 1H), 7.19 (dd, J = 7.2, 7.2 Hz, 1H), 7.29 (dd,
J = 7.6, 7.6 Hz, 2H), 7.53 (d, J = 2.0 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 29.3, 53.9, 55.0, 109.5, 110.9, 113.7, 126.0, 128.3, 128.8,
129.5, 129.9, 131.6, 135.3, 136.2, 144.6, 150.2, 157.5, 169.8; MS (EI)
m/z (%) 347 (M+, 100); HRMS (EI) m/z calcd for C22H21NO3 [M+],
■
Corresponding Author
*E-mail: hidemasa.hikawa@phar.toho-u.ac.jp; yokoyama@phar.
toho-u.ac.jp.
Notes
The authors declare no competing financial interest.
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68, 7077−7081. (f) Thirupathi, P.; Kim, S. S. Tetrahedron 2010, 66,
2995−3003. (g) Sun, G.; Wang, Z. Tetrahedron Lett. 2008, 49, 4929−
4932. (h) Bras, J. L.; Muzart, J. Tetrahedron 2007, 63, 7942−7948.
(10) (a) Branch, C. S.; Lewinski, J.; Justyniak, I.; Bott, S. G.;
Lipkowski, J.; Barron, A. R. J. Chem. Soc., Dalton Trans. 2001, 1253−
1258. (b) Wiesbrock, F.; Schmidbaur, H. J. Chem. Soc., Dalton Trans.
2002, 4703−4708.
(11) Panda, G.; Mishra, J. K.; Shagufta; Dinadayalane, T. C.; Sastry,
G. N.; Negi, D. S. Indian J. Chem. 2006, 45B, 276−287.
(12) Western, E. C.; Shaughnessy, K. H. J. Org. Chem. 2005, 70,
6378−6388.
(13) Kirincich, S. J.; Xiang, J.; x Green, J.; Tam, S.; Yang, H. Y.; Shim,
J.; McKew, J. C.; Shen, M. W. H.; Clark, J. D. Bioorg. Med. Chem. 2009,
17, 4383−4405.
(14) Takemura, S.; Terauchi, H.; Miki, Y.; Nakano, K.; Inamori, Y.;
Miyazeki, K.; Nishimura, H. Yakugaku Zasshi 1979, 99, 779−781.
REFERENCES
■
(1) (a) Corma, A.; Leyva-Perez, A.; Maria, J. S. Chem. Rev. 2011, 111,
1657−1712. (b) Ohshima, T.; Nakahara, Y.; Ipposhi, J.; Miyamoto, Y.;
Mashima, K. Chem. Commun. 2011, 8322−8324. (c) Mukherjee, P.;
Ross, A. W. Org. Lett. 2011, 13, 1334−1337. (d) Patil, N. T.
ChemCatChem 2011, 7, 1121−1125. (e) Mukherjee, P.; Ross, A. W.
Org. Lett. 2010, 12, 1184−1187. (f) Efe, C.; Lykakis, I. N.; Stratakis, M.
Chem.Commun. 2010, 803−805. (g) Lu, Y.; Fu, X.; Chen, H.; Du, X.;
Jia, X.; Liu, Y. Adv. Synth. Catal. 2009, 351, 129−134. (h) Georgy, M.;
Boucard, V.; Debleds, O.; Zotto, C. D.; Campagne, J.-M. Tetrahedron
2009, 65, 1758−1766. (i) Neatu
Genet, J.; Dumbuya, K.; Gottfried, J. M.; Steinruck, H.; Par
I.; Michelet, V. Chem.Eur. J. 2008, 30, 9412−9418. (j) Guo, S.;
Song, F.; Liu, Y. Synlett 2007, 964−968. (k) Corma, A.; Concepcion
P.; Domínguez, I.; Forne, V.; Sabater, M. J. J. Catal. 2007, 1, 39−47.
̧
, F.; Li, Z.; Richards, R.; Toullec, P. Y.;
̂
̂
vulescu, V.
̈
́
,
́
(l) Terrasson, V.; Marque, S.; Georgy, M.; Campagne, J.-M.; Prim, D.
Adv. Synth. Catal. 2006, 348, 2063−2067. (m) Carrettin, S.; Blanco,
M. C.; Corma, A.; Hashmi, A. S. K. Adv. Synth. Catal. 2006, 348,
1283−1288. (n) Georgy, M.; Boucard, V.; Campagne, J.-M. J. Am.
Chem. Soc. 2005, 127, 14180−14181.
(2) (a) Kitahara, H.; Sakurai, H. Chem. Lett. 2010, 39, 46−48.
(b) Feng, E.; Zhou, Y.; Zhao, F.; Chen, X.; Zhang, L.; Jiang, H.; Liu, H.
Green Chem. 2012, 14, 1888−1895. (c) Monopoli, A.; Cotugno, P.;
Palazzo, G.; Ditaranto, N.; Mariano, B.; Cioffi, N.; Ciminale, F.; Nacci,
A. Adv. Synth. Catal. 2012, 354, 2777−2788. (d) Xing, D.; Yang, D.
Beilstein J. Org. Chem. 2011, 7, 781−785.
(3) (a) Hikawa, H.; Yokoyama, Y. J. Org. Chem. 2011, 76, 8433−
8439. (b) Hikawa, H.; Yokoyama, Y. Org. Biomol. Chem. 2011, 9,
4044−4050. (c) Yokoyama, Y.; Hikawa, H.; Mitsuhashi, M.; Uyama,
A.; Hiroki, Y.; Murakami, Y. Eur. J. Org. Chem. 2004, 1244−1253.
(d) Yokoyama, Y.; Hikawa, H.; Mitsuhashi, M.; Uyama, A.; Murakami,
Y. Tetrahedron Lett. 1999, 40, 7803−7806.
(4) Afagh, N. A.; Yudin, A. K. Angew. Chem., Int. Ed. 2010, 49, 262−
310.
(5) (a) Hikawa, H.; Suzuki, H.; Yokoyama, Y.; Azumaya, I. Catalysts
2013, 3, 486−500. (b) Hikawa, H.; Yokoyama, Y. RSC Adv. 2013, 3,
1061−1064. (c) Hikawa, H.; Ino, Y.; Suzuki, H.; Yokoyama, Y. J. Org.
Chem. 2012, 77, 7046−7051. (d) Hikawa, H.; Yokoyama, Y. Org.
Biomol. Chem. 2012, 10, 2942−2945. (e) Hikawa, H.; Yokoyama, Y.
Org. Lett. 2011, 13, 6512−6515.
(6) (a) Karschin, A.; Klaeui, W.; Peters, W.; Spingler, B. Eur. J. Inorg.
Chem. 2010, 942−946. (b) Revew, see: Shaughnessy, K. H. Chem. Rev.
2009, 109, 643−710.
(7) Water-soluble gold complex, see: (a) Yao, Y.; Xue, M.; Chi, X.;
Ma, Y.; He, J.; Abliz, Z.; Huang, F. Chem. Commun. 2012, 6505−6507.
(b) Zhang, J.-J.; Raymond, W.-Y. S.; Che, C.-M. Chem. Commun. 2012,
3388−3390. (c) Yon, J.-N.; Chen, Y.-S.; Ojeda, J. J.; Allen, D. W.;
Cross, N. A.; Gardiner, P. H. E.; Bricklebank, N. RSC Adv. 2012, 2,
10345−10351. (d) Wetzel, C.; Kunz, P. C.; Kassack, M. U.; Hamacher,
A.; Boehler, P.; Watjen, W.; Ott, I.; Rubbiani, R.; Spingler, B. Dalton
Trans. 2011, 40, 9212−9220. (e) Wang, Y.; Zhu, D.-p.; Tang, L.;
Wang, S.-J.; Wang, Z.-Y. Angew. Chem., Int. Ed. 2011, 50, 8917−8921.
(f) Elie, B. T.; Levine, C.; Ubarretxena-Belandia, I.; Varela-Ramirez, A.;
Aguilera, R. J.; Ovalle, R.; Contel, M. Eur. J. Inorg. Chem. 2009, 3421−
3430. (g) Mohr, F.; Sanz, S.; Tiekink, E. R. T.; Laguna, M.
Organometallics 2006, 25, 3084−3087. (h) Komine, N.; Ichikawa, K.;
Mori, A.; Hirano, M.; Komiya, S. Chem. Lett. 2005, 34, 1704−1705.
(i) Assefa, Z.; Forward, J. M.; Grant, T. A.; Staples, R. J.; Hanson, B.
E.; Mohamed, A. A.; Fackler, J. P. Inorg. Chim. Acta 2003, 352, 31−45.
(8) Motokura, K.; Nakagiri, N.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
J. Org. Chem. 2007, 72, 6006−6015.
(9) Gold-catalyzed Friedel−Crafts reaction in organic solvents, see:
(a) Weidong, R.; Philip, W. H. C. Org. Biomol. Chem. 2008, 6, 2426−
2433. (b) Rubenbauer, P.; Bach, T. Adv. Synth. Catal. 2008, 350,
1125−1130. (c) Liu, J.; Muth, E.; Floerke, U.; Henkel, G.; Merz, K.;
Sauvageau, J.; Schwake, E.; Dyker, G. Adv. Synth. Catal. 2006, 348,
456−462. (d) Mertins, K.; Iovel, I.; Kischel, J.; Zapf, A.; Beller, M. Adv.
Synth. Catal. 2006, 348, 691−695. Direct alkylation with alcohols, see:
(e) Sato, Y.; Aoyama, T.; Takido, T.; Kodomari, M. Tetrahedron 2012,
6720
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