Tandem addition/cyclization for synthesis of 2-aroyl benzofurans and 2-aroyl indoles by carbopalladation of nitriles

Article abstract of DOI:10.1039/c9ob02408e

The first example of the palladium-catalyzed tandem addition/cyclization of 2-(2-acylphenoxy)acetonitriles with arylboronic acids has been developed, providing a new strategy for the synthesis of 2-aroyl benzofurans with excellent chemoselectivity and wid

Full text of DOI:10.1039/c9ob02408e

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Tandem addition/cyclization for synthesis of
2-aroyl benzofurans and 2-aroyl indoles by
Cite this: DOI: 10.1039/c9ob02408e
carbopalladation of nitriles†
Julin Gong,‡a Kun Hu,‡a Yinlin Shao,a Renhao Li,b Yetong Zhang,a Maolin Hu*a and
a
Jiuxi Chen
*
The first example of the palladium-catalyzed tandem addition/cyclization of 2-(2-acylphenoxy)aceto-
nitriles with arylboronic acids has been developed, providing a new strategy for the synthesis of 2-aroyl
benzofurans with excellent chemoselectivity and wide functional group compatibility. Preliminary
mechanistic experiments indicate that this tandem process involves sequential nucleophilic addition gen-
erating 2-(2-acylphenoxy)-1-phenylethan-1-one followed by an intramolecular cyclization. This method-
ology has also been applied to the synthesis of 2-aroyl indoles and the potent CYP19 inhibitor 1-(benzo-
furan-2-yl(phenyl)methyl)-1H-1,2,4-triazole.
Received 7th November 2019,
Accepted 13th December 2019
DOI: 10.1039/c9ob02408e
rsc.li/obc
because they are an important class of heterocycles found in
bioactive natural products and biologically active molecules,
Introduction
Owing to the inherently inert nature of the CuN bond, such as Rugchalcone A, Rugchalcone B and 1-(benzofuran-2-yl
nitriles, such as acetonitrile and benzonitrile, have been (phenyl)methyl)-1H-1,2,4-triazole (Fig. 1).12 Hence, effective
usually used as solvents or ligands in organometallic reac- methods for the construction of benzofurans have been
tions.1 The development of inert cyano group activation/ actively pursued during the past several decades.13 Although
carbon–carbon or carbon–heteroatom bond forming reactions transformation of nitriles into various functional groups has
catalyzed by transition metals has attracted a great deal of been well-established, only sporadic examples of the tandem
attention recently.2 A wide range of efficient transition metal- reaction of the readily available nitriles for access to benzofur-
catalyzed transformations of nitriles have been achieved with ans have been reported to date. For examples, Lu’s group14
organoboron reagents3 since the pioneering work on the (Scheme 1a) and our group5a (Scheme 1b) have developed syn-
addition of arylpalladium species to the cyano group reported thesis of benzofurans by Pd-catalyzed addition of arylboronic
by Larock and co-workers.4 In recent years, our group has also acids or sodium sulfinates to functionalized nitriles.
achieved a number of palladium-catalyzed tandem reactions of
In addition, because the highly reactive formyl group was
nitriles with organoboron reagents for access to alkyl aryl easier to take place nucleophilic addition than that of the inert
ketones, diketones, 2-aminobenzophenones, indoles, isoqui- cyano group (Scheme 1c), controlling the chemoselectivity to
nolines, isoquinolones, quinazolines.5 The scope of this chem- avoid the addition reaction of arylboronic acid to formyl group
istry has been expanded to other coupling partners, including is often difficult when multiple functional groups such as
sodium aryl sulfinates or arylsulfinic acids,6 aryl halides,7 formyl group and cyano group are simultaneously present in
benzoic acids,8 arylhydrazines,9 and arylsulfonyl hydrazides.10
the substrates.15 For examples, in this Pd-catalyzed addition of
Benzofurans are important structural motifs because of phenylboronic acid to 4-formylbenzonitrile, the cyano group
their ubiquity in natural products, pharmaceuticals, and remains intact while the 4-(hydroxy(phenyl)methyl)benzo-
materials.11 In particular, 2-aroyl benzofurans and their deriva- nitrile is obtained via addition to the formyl group in high
tives have become increasingly noticed in the past few years
aCollege of Chemistry & Materials Engineering, Wenzhou University,
Wenzhou 325035, P. R. China. E-mail: maolin@wzu.edu.cn, jiuxichen@wzu.edu.cn
bSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035,
P. R. China
†Electronic supplementary information (ESI) available: 1H and 13C NMR spectra
for products. See DOI: 10.1039/c9ob02408e
‡These authors contributed equally.
Fig. 1 Representative bioactive 2-aroyl benzofuran and its derivative.
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Table 1 Optimization of reaction conditionsa
Entry [Pd]
Ligand Additive
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
PdCl2
Pd(PPh3)4 L1
L1
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Trace
13
45
51
58
62
84
48
55
53
49
71
74
56
22
35
11
31
24
0
Pd(OAc)2
Pd(dba)2
Pd(acac)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
L1
L1
L1
L1
L2
L3
L4
L5
L6
L7
L8
L9
L10
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
Scheme 1 Design of new approach to 2-aroyl benzofurans.
yield.15a,e,f Therefore, the development of a practical and
general approach to benzofurans using formyl-substituted
nitriles as substrates remains a challenging area for explora-
tion. This work is part of the continuing efforts in our labora-
tory toward the development of novel transition metal-cata-
lyzed transformations of nitriles.5 Herein, we report the first
example of palladium-catalyzed tandem addition/cyclization of
2-(2-acylphenoxy)acetonitriles with arylboronic acids for the
synthesis of structurally diverse 2-aroyl benzofurans with excel-
lent chemoselectivity and wide functional group compatibility
(Scheme 1d). This methodology has also been applied to the
synthesis of 2-aroyl indoles and the potent CYP19 inhibitor 1-
(benzofuran-2-yl(phenyl)methyl)-1H-1,2,4-triazole.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
TsOH H2O THF
CF3SO3H
CH3CO2H
PhCO2H
HCl
ZnCl2
TFA
TFA
TFA
TFA
TFA
THF
THF
THF
THF
THF
Toluene
1,4-Dioxane 74
DMF
EtOH
H2O
2-MeTHF
2-MeTHF
2-MeTHF
0
43
73
37
46
92
0
TFA
TFA
TFA
Pd(TFA)2
0
Results and discussion
a Conditions: 1a (0.4 mmol), 2a (0.8 mmol), Pd catalyst (5 mol%),
ligand (10 mol%), additive (10 equiv.), solvent (2 mL), 80 °C, 24 h, air.
b Isolated yield.
Our study commenced by examining the reaction of readily
available 2-(2-formylphenoxy)acetonitrile (1a) with p-tolylboro-
nic acid (2a) for the screening of reaction conditions (Table 1).
Trace amount of the desired product benzofuran-2-yl(p-tolyl)
methanone (3a) was detected by GC/MS analysis when the 8–11, 14 and 15). Replacement of TFA with other acids, includ-
combination of PdCl2, trifluoroacetic acid (TFA) and 2,2′-bipyr- ing p-toluenesulfonic acid monohydrate (TsOH·H2O),
idine (L1) was used in THF (entry 1). We were pleased to find CH3CO2H PhCO2H, CF3SO3H, resulted in relatively lower yields
that the yield of 3a could be improved to 62% using Pd(TFA)2 (entries 16–19). This reaction did not work using HCl or ZnCl2
as a catalyst (entries 2–6). Among bidentate nitrogen ligands as an additive (entries 20 and 21). An investigation of the effect
(L1–L10), sterically bulky ligands 6,6′-dimethyl-2,2′-bipyridine of solvents (entries 7, 22–27) revealed that use of 2-methyl-
(L2), 2,9-dimethyl-1,10-phenanthroline (L7) and 2,2′-biquino- tetrahydrofuran (2-MeTHF) as a green solvent increased the
line (L8) were found to efficiently promoted the reaction and yield of 3a to 92% (entry 27). The role of the 2-MeTHF in the
afforded the desired product 3a in 84%, 71% and 74% yields, reaction is not clear. 2-MeTHF is known to be a unique solvent
respectively (entries 7, 12 and 13). L2 was the most effective as a valuable alternative to the normally used ethereal solvents
and gave 3a in 84% yield (entry 7). Other ligands, including in organic synthesis.16 The desired product 3a was not
4,4′-dimethyl-2,2′-bipyridine (L3), 5,5′-dimethyl-2,2′-bipyridine detected if either palladium catalyst or ligand was absent
(L4), 4,4′-dimethoxy-2,2′-bipyridine (L5), 1,10-phenanthroline (entries 28 and 29).
(L6), 4,7-diphenyl-1,10-phenanthroline (L9) and 2-(pyridin-2-
With the optimized conditions in hand, we next sought to
yl)-1H-benzo[d]imidazole (L10), were less efficient (entries investigate the substrate scope (Table 2). First, a wide range of
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Table 2 Synthesis of 2-aroyl benzofuransa
we attempted to perform this tandem reaction of 2-(2-formyl-
phenoxy)acetonitrile (1a) with alkylboronic acids (e.g. benzyl-
boronic acid, methylboronic acid, cyclopropylboronic acid)
under the standard conditions failed to give the desired
products.
In addition, transformation of (6-methoxybenzofuran-2-yl)
(p-tolyl)methanone (3c) as a representative example is shown
in Scheme 2, providing the corresponding (6-hydroxybenzo-
furan-2-yl)(p-tolyl)methanone (3z).
We next turned our attention to the scope of this reaction
with respect to the 2-(2-acylphenoxy)acetonitriles (Table 3).
First, reaction of 2-(2-acetylphenoxy)acetonitrile (1b) with aryl-
boronic acids was examined. Treatment of 1b with phenyl-
boronic acid gave the desired product (3-methylbenzofuran-2-
yl)(phenyl)methanone (4a) in 72% yield (entry 1). The reactiv-
ities of para-, meta-, and ortho-tolylboronic acids were evalu-
ated, and the results demonstrated that the steric effect of sub-
stituent had an obvious impact on the reaction. For example,
treatment of 1b with para-, and meta-tolylboronic acids pro-
vided 85% and 81% yields of 4b and 4c, respectively (entries 2
Scheme 2 Transformation of 3c.
a Conditions: 1 (0.4 mmol), 2 (0.8 mmol), Pd(TFA)2 (5 mol%), L2
(10 mol%), TFA (10 equiv.), 2-MeTHF (2 mL), 80 °C, 24 h, air, isolated
yield.
Table 3 Synthesis of 3-substituted 2-aroyl benzofuransa
2-(2-formylphenoxy)acetonitrile derivatives undergo tandem
addition/cyclization with p-tolylboronic acid (2a) efficiently,
thus including electron-rich methoxy, methyl and tert-butyl
substituents (3b–3f). Moreover, halogen-substituted (e.g., –F,
–Cl, –Br) substrates were well tolerated (3g–3l). However, sub-
strate bearing a strongly electron-withdrawing group (e.g.,
–NO2) decreased the yield of 3m to 54% (entry 12). Notably,
treatment of 2-((1-formylnaphthalen-2-yl)oxy)acetonitrile with
2a also proceeded smoothly and gave the desired product 3n
in 88% yield (entry 13). We were delighted to find that this
newly developed protocol to be compatible with a wide variety
of arylboronic acids. Functional groups, including electron-
donating groups such as methyl (3o–3p), tert-butyl (3q),
methoxy (3r), phenoxy (3s) and hydroxyl (3t) and electron-with-
drawing groups such as fluoro (3u) and chloro (3v), were well
tolerated. Polyaromatic substrates, such as biphenyl-4-ylboro-
nic acid and naphthalen-2-ylboronic acid, were also good part-
ners and coupled with 1a efficiently, affording the corres-
ponding products 3x and 3y in good yields (entries 23 and 24).
It is worth noting that the products derived from 2-(2-formyl-
phenoxy)acetonitriles bearing bromo and hydroxyl groups (3k,
3l, 3t) leave intact synthetic handles for further synthetic elab-
orations thereby broadening the molecular diversity. However,
a Conditions: 1 (0.4 mmol), 2 (0.8 mmol), Pd(TFA)2 (5 mol%), L2
(10 mol%), TFA (10 equiv.), 2-MeTHF (2 mL), 80 °C, 24 h, air, isolated
yield.
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Table 4 Synthesis of 2-aroyl indolesa
and 3), while the ortho-tolylboronic acid afforded the desired
product 4d in 50% yield (entry 4). Other electron-donating
groups, tert-butyl, methoxy and phenoxy, were well tolerated
and afforded the corresponding products 4e–4f in excellent
yields (entries 5–7). The reaction of fluoro-, phenyl- and
naphthyl-substituted arylboronic acids with 1b afforded the
corresponding products 4g–4j in acceptable yields (entries
8–10). However, the reaction failed to afford the desired
product 4k when substrate bearing the strong electron-with-
drawing CF3 group was used (entry 11). The reaction of methyl-
, methoxy-, and halogen-substituted substrates with p-tolyl-
boronic acid (2a) also proceeded smoothly and gave the
desired products 4l–4p in good to excellent yields (entries
12–16). Of significant interest is the bromo-substituted
product 4p, which could be amenable to further functionali-
zation. Reaction of 2-(2-benzoylphenoxy)acetonitrile (1c) with
phenylboronic acid gave the desired product 4q in 98% yield
(entry 17). An investigation of the reaction of other arylboronic
acids with 1c revealed that both electron-rich (e.g., –Me, –OMe)
and electron-deficient (e.g., –F) substituents were tolerated and
the desired products 4r–4t were obtained in 88–97% yield
(entries 18–20).
a Conditions: 8a (0.4 mmol), 2 (1.2 mmol), Pd(TFA)2 (5 mol%), L2
(10 mol%), TFA (10 equiv.), 2-MeTHF (2 mL), 80 °C, 24 h, air, isolated
yield.
yields of the reaction to some extent. Not only electron-donat-
ing groups, such as methyl (9b–9c), tert-butyl (9d), methoxy
(9e) and phenoxy (9e) but also electron-withdrawing groups,
such as fluoro (9g) and phenyl (9h) on the phenyl ring of aryl-
boronic acids, were tolerated in this transformation.
To gain insight into the reaction mechanism, further
experimental studies were performed (Scheme 4). Treatment of
benzofuran-2-carbonitrile (10a) with p-tolylboronic acid (2a)
deliver benzofuran-2-yl(p-tolyl)methanone (3a) in 14% yield
(Scheme 4a). However, we attempted to perform the reaction
in the absence of arylboronic acid under the standard con-
ditions failed to give 10a (Scheme 4b). We found that the
desired product 3a was obtained in 72% yield when 2-(2-oxo-2-
(p-tolyl)ethoxy)benzaldehyde (11a) was used (Scheme 4c).
These results indicated that 11a was proposed as a possible
intermediate for this transformation.
Then, the utility of this methodology was further applied to
the synthesis of 1-(benzofuran-2-yl(phenyl)methyl)-1H-1,2,4-
triazole, which was the representative compound identified as
the potent CYP19 inhibitor.12b As shown in Scheme 3, the key
intermediate
(4-fluorophenyl)(6-methoxybenzofuran-2-yl)
methanone (5a) was obtained in moderate yield by the treat-
ment of the readily available 2-(2-formyl-5-methoxyphenoxy)
acetonitrile (1d) with (4-fluorophenyl)boronic acid (2b). Next,
sodium borohydride reduction of 5a gave (4-fluorophenyl)(6-
methoxybenzofuran-2-yl)methanol (6a) in 91% yield, which
was converted into the target triazole 7a in 79% yield in the
presence of triazole and thionyl chloride. Compared with
other synthetic procedures, this process was easy to handle
with commercially available starting materials.
This methodology has also been applied to the synthesis of
2-aroyl indoles from the tandem addition/cyclization of 2-((2-
benzoylphenyl)amino)acetonitrile (8a) with arylboronic acids
(Table 4). Treatment of 8a with phenylboronic acid gave the
desired product phenyl(3-phenyl-1H-indol-2-yl)methanone (9a)
in 53% yield (entry 1). The electronic properties of the substi-
tuents on the phenyl ring of the arylboronic acids affected the
On the basis of the above-mentioned results, a possible
mechanism for the formation of 2-aroyl benzofurans is shown
in Scheme 5. Transmetallation of the palladium species with
ArB(OH)2 to give Ar[Pd], which was followed by the coordi-
nation of 2-(2-acylphenoxy)acetonitriles to produce intermedi-
Scheme 3 Synthesis of the potent CYP19 inhibitor.
Scheme 4 Control experiments (Ar = p-MeC6H4).
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Typical procedure for the synthesis of 8a
A mixture of (2-hydroxyphenyl)(phenyl)methanone (198 mg,
1 mmol), bromoacetonitrile (144 mg, 1.2 mmol), potassium
carbonate (165 mg, 1.2 mmol) and DMF (15 mL) was stirred at
60 °C for 24 h. The progress of the reaction was monitored
using TLC. After the completion of the reaction, the reaction
mixture was diluted with ethyl acetate (50 mL), washed with
water (3 × 100 mL), brine (2 × 10 mL), and dried over anhy-
drous Na2SO4. The residue was purified by flash column
chromatography (hexane/ethyl acetate) to afford 2-((2-benzoyl-
phenyl)amino)acetonitrile (8a).
2-((2-Benzoylphenyl)amino)acetonitrile (8a). Pale-yellow oil
(127 mg, 54%). 1H NMR (500 MHz, CDCl3) δ 8.66 (s, 1H),
7.63–7.46 (m, 7H), 6.88 (d, J = 8.0 Hz, 1H), 6.78 (t, J = 8.0 Hz,
1H), 4.26 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 199.7, 148.9,
139.7, 135.6, 135.2, 131.1, 129.2, 128.2, 119.4, 116.8, 116.3,
111.5, 31.4. HRMS calcd for C15H13N2O [M + H]+: 237.1023,
found 237.1024.
Scheme 5 Plausible reaction mechanism.
ate A. Next, carbopalladation of the cyano group gave imine
intermediate B. In the presence of TFA, protonation of the
intermediate B would afford intermediate C and regenerates
palladium catalyst. Hydrolysis of the intermediate C would
deliver ketone D. Finally, keto–enol tautomerism and a sub-
sequent cyclization/dehydration under acidic conditions would
afford the corresponding 2-aroyl benzofurans as the desired
products.
General procedure for the synthesis of 2-aroyl benzofurans or
2-aroyl indoles
Arylboronic acid, 2-(2-acylphenoxy)acetonitrile or 2-((2-benzoyl-
phenyl)amino)acetonitrile, Pd(TFA)2, 6,6′-dimethyl-2,2′-bipyri-
dine L2, TFA and 2-MeTHF were successively added into a
Schlenk reaction tube under air. The reaction mixture was
stirred for 10 minutes at room temperature for proper mixing
of the reactants, and then heated at 80 °C with vigorous stir-
ring for 24 hours. After the reaction equilibrium, the mixture
was poured into ethyl acetate, which was washed with satu-
rated NaHCO3 (2 × 10 mL) and then brine (10 mL). After the
aqueous layer was extracted with ethyl acetate, the combined
organic layers were dried over anhydrous Na2SO4 and evapor-
ated under a vacuum. The residue was purified by flash
column chromatography (hexane/ethyl acetate) to afford
2-aroyl benzofurans or 2-aroyl indoles.
(5-(tert-Butyl)benzofuran-2-yl)(p-tolyl)methanone (3f). Yellow
oil (86.6 mg, 74%). 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J =
8.4 Hz, 2H), 7.70 (s, 1H), 7.56 (d, J = 1.6 Hz, 2H), 7.49 (s, 1H),
7.32 (d, J = 8.0 Hz, 2H), 2.45 (s, 3H), 1.39 (s, 9H). 13C NMR
(125 MHz, CDCl3) δ 184.0, 154.3, 152.7, 147.1, 143.7, 134.7,
129.7, 129.2, 126.8, 126.6, 119.0, 116.3, 111.9, 34.8, 31.7, 21.7.
HRMS (ESI) calcd for C20H20O2Na [M + Na]+: 315.1361, found
Conclusions
In summary, we have developed a new strategy for the syn-
thesis of structurally diverse 2-aroyl benzofurans in moderate
to excellent yields by the Pd-catalyzed tandem addition/cycliza-
tion of 2-(2-acylphenoxy)acetonitriles with arylboronic acids.
This system shows remarkable chemoselectivity and broad
substrate scope. In addition, this protocol also applies to the
synthesis of 2-aroyl indoles and the potent CYP19 inhibitor 1-
(benzofuran-2-yl(phenyl)methyl)-1H-1,2,4-triazole.
Experimental section
General methods
Melting points are uncorrected. H NMR and 13C NMR spectra 315.1355.
1
were measured on a 500 MHz or 400 MHz spectrometer using
(4-(tert-Butyl)phenyl)(3-methylbenzofuran-2-yl)methanone (4e).
CDCl3 as the solvent with tetramethylsilane (TMS) as an Yellow oil (115.7 mg, 99%). 1H NMR (500 MHz, CDCl3)
internal standard at room temperature. Chemical shifts are δ 8.14–8.11 (m, 2H), 7.71–7.69 (m, 1H), 7.59–7.55 (m, 3H),
given n δ relative to TMS, and the coupling constants J are 7.51–7.46 (m, 1H), 7.36–7.32 (m, 1H), 2.68 (s, 3H), 1.41 (s, 9H).
given in hertz. High-resolution mass spectra were recorded 13C NMR (125 MHz, CDCl3) δ 185.4, 156.3, 154.3, 148.6, 135.2,
on an ESI-Q-TOF mass spectrometer. The starting materials 129.8, 129.3, 128.0, 126.4, 125.3, 123.3, 121.4, 112.2, 35.1, 31.2,
2-(2-formylphenoxy)acetonitriles (1),17 2-(2-acetylphenoxy) 10.0. HRMS (ESI) calcd for C20H20O2Na [M + Na]+: 315.1361,
acetonitrile (1b),18 2-(2-benzoylphenoxy)acetonitrile (1c)19 and found 315.1356.
2-(2-oxo-2-(p-tolyl)ethoxy) benzaldehyde (11a)20 were syn-
(4-Fluorophenyl)(3-phenylbenzofuran-2-yl)methanone (4t).
thesized according to the method described in the literature. Pale-yellow solid (111.3 mg, 88%), mp 143–144 °C. 1H NMR
Column chromatography was performed using EM silica gel 60 (500 MHz, CDCl3) δ 7.95–7.92 (m, 2H), 7.72 (d, J = 8.0 Hz, 1H),
(300–400 mesh).
7.65 (d, J = 8.5 Hz, 1H), 7.56–7.49 (m, 3H), 7.41–7.35 (m, 4H)
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7.03 (t, J = 7.5 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 184.1,
165.6 (d, J = 252.5 Hz), 154.6, 147.0, 133.6, 133.5, 132.5 (d, J =
Acknowledgements
8.8 Hz), 130.9, 130.0, 129.6, 128.5, 128.4, 128.1, 124.1, 122.4, We thank the National Natural Science Foundation of China
115.3 (d, 22.5 Hz), 112.4. HRMS (ESI) calcd for (No. 21572162), the Natural Science Foundation of Zhejiang
C21H13FO2Na [M + Na]+: 339.0798, found 339.0804.
Province (No. LY20B020015 and LQ18B020006), and the
J
=
3-Phenyl-1H-indol-2-yl(m-tolyl)methanone (9c). Pale-yellow Xinmiao Talent Planning Foundation of Zhejiang Province
solid (70.9 mg, 57%), mp 122–123 °C. 1H NMR (500 MHz, (No. 2017R426050) for financial support.
CDCl3) δ 9.68 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.47 (d, J =
8.0 Hz, 1H), 7.38–7.34 (m, 2H), 7.19–7.08 (m, 7H), 7.03–6.96
(m, 2H), 2.03 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 189.9,
137.4, 137.3, 136.5, 134.0, 132.5, 131.1, 130.8, 130.7, 127.9,
References
127.8, 127.7, 126.8, 126.6, 125.4, 122.1, 121.1, 112.1, 20.9.
HRMS calcd for C22H17NONa [M + Na]+: 334.1208, found
334.1220.
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(4-(tert-Butyl)phenyl)(3-phenyl-1H-indol-2-yl)methanone (9d).
Pale-yellow solid (101.7 mg, 72%), mp 199–200 °C. 1H NMR
(500 MHz, CDCl3) δ 9.39 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.51
(d, J = 8.0 Hz, 1H), 7.44–7.40 (m, 3H), 7.20 (m, 3H), 7.11–7.05
(m, 5H), 1.22 (s, 9H). 13C NMR (125 MHz, CDCl3) δ 189.5,
155.2, 136.4, 134.7, 133.9, 131.2, 130.9, 129.4, 127.9, 127.8,
126.6, 126.5, 125.4, 124.5, 122.2, 121.1, 112.0, 34.8, 31.0.
HRMS (ESI) calcd for C25H24NO [M + H]+: 354.1853, found
354.1860.
(4-Phenoxyphenyl)(3-phenyl-1H-indol-2-yl)methanone (9f).
White solid (116.7 mg, 75%), mp 179–180 °C. 1H NMR
(500 MHz, CDCl3) δ 9.35 (s, 1H), 7.74 (d, J = 8.0 Hz, 2H),
7.54–7.51 (m, 3H), 7.42 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz,
2H), 7.22–7.14 (m, 7H), 6.91 (d, J = 8.5 Hz, 2H), 7.66 (d, J =
8.5 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 188.3, 160.5, 156.2,
136.3, 134.3, 134.0, 132.4, 131.8, 131.0, 129.8, 128.1, 127.7,
126.8, 126.5, 124.9, 124.0, 122.0, 121.2, 119.4, 117.3, 112.0.
HRMS (ESI) calcd for C27H20NO2 [M + H]+: 390.1489, found
390.1484.
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(4-Fluorophenyl)(3-phenyl-1H-indol-2-yl)methanone
(9g).
Pale-yellow solid (65.5 mg, 52%), mp 144–145 °C. 1H NMR
(500 MHz, CDCl3) δ 9.55 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H),
7.57–7.51 (m, 3H), 7.42 (t, J = 7.5 Hz, 1H), 7.21–7.17 (m, 6H),
6.74 (t, J = 8.5 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 188.2,
165.8, 163.8, 136.6, 133.8, 133.7, 132.1, 132.0, 130.9, 130.8,
128.1, 126.9, 127.6, 127.1, 126.7, 125.4, 122.1, 121.3, 114.8,
114.6, 112.1. HRMS (ESI) calcd for C21H14FNONa [M + Na]+:
338.0957, found 338.0956.
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(g) X. Yao, Y. Shao, M. Hu, Y. Xia, T. Cheng and J. Chen,
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[1,1′-Biphenyl]-4-yl(3-phenyl-1H-indol-2-yl)methanone (9h).
Pale-yellow solid (94.0 mg, 63%), mp 144–145 °C. 1H NMR
(500 MHz, CDCl3) δ 9.70 (s, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.53
(d, J = 8.0 Hz, 1H), 7.47–7.34 (m, 6H), 7.28–7.26 (m, 2H),
7.22–7.17 (m, 3H), 7.12–7.11 (m, 3H); 13C NMR (125 MHz,
CDCl3) δ 189.2, 144.3, 140.3, 136.6, 136.4, 133.9, 131.2, 131.0,
130.1, 128.8, 128.0, 127.9, 127.8, 127.2, 126.8, 126.6, 126.3,
125.4, 122.2, 121.2. HRMS (ESI) calcd for C21H14FNONa
[M + Na]+: 396.1365, found 396.1371.
Conflicts of interest
There are no conflicts of interest to declare.
Org. Biomol. Chem.
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