Metal-free tandem reactions of 2-iodoaryl ynones with sodium azide for the synthesis of benzoisoxazole containing 1,2,3-triazoles

Article abstract of DOI:10.1039/d0ob02608e

A metal-free approach has been developed for the synthesis of benzo[c]isoxazole (anthranils) containing 1,2,3-triazoles. The reaction proceeded efficiently through a [3 + 2] azide-alkyne cycloaddition, S_NAr azidation and denitrogenative cyclization sequence. The metal-free protocol enabled effective construction of one N-O and three C-N bonds in one pot. In addition, the synthetic utility of the current methodology was further demonstrated by late stage modification of the obtained products.

Full text of DOI:10.1039/d0ob02608e

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
Metal-free tandem reactions of 2-iodoaryl ynones
with sodium azide for the synthesis of
benzoisoxazole containing 1,2,3-triazoles†
a
Cite this: Org. Biomol. Chem., 2021,
19, 3707
Kashif Majeed,a Fengtao Zhou*b and Qiuyu Zhang
*
A metal-free approach has been developed for the synthesis of benzo[c]isoxazole (anthranils) containing
1,2,3-triazoles. The reaction proceeded efficiently through a [3 + 2] azide–alkyne cycloaddition, SNAr azi-
dation and denitrogenative cyclization sequence. The metal-free protocol enabled effective construction
of one N–O and three C–N bonds in one pot. In addition, the synthetic utility of the current methodology
was further demonstrated by late stage modification of the obtained products.
Received 31st December 2020,
Accepted 29th March 2021
DOI: 10.1039/d0ob02608e
rsc.li/obc
ing Lewis acid (BF3·Et2O) based cyclization using nitroso-
benzene and condensation of nitrobenzenes with phenylaceto-
Introduction
Heteroatom–heteroatom N–X (X = N, O, S) bond formation, in nitriles were also employed successfully.10 Recently, another
particular N–O bond formation, is a long-standing challenge photochemical cyclization approach for the efficient synthesis
in organic synthesis1,2 and remains less explored as compared of benzo[c]isoxazoles from 2-azidobenzoic acids was also
to other C–C and C–X bond formations. Even though the reported.11 In addition, Peters showed that 2,1-benzisoxazoles
importance of the N–O bond in biologically active molecules can also be obtained by the electrochemical reduction of
and natural products can’t be denied, so far only a few o-nitrobenzaldehyde and ketones using stable electrodes.12
approaches have been reported for the direct construction of Another similar electrochemical approach was reported for the
the N–O bond.2 For example, the benzo[c]isoxazole scaffold is synthesis of both benzo[c]isoxazoles and quinoline N-oxides
an important class of heterocycles because of its extensive bio- from o-nitrobenzaldehyde.13 Various other studies have also
logical and pharmacological activities3 (Fig. 1), and is widely reported the synthesis of 1,2,3-triazoles fused with other
used as an intermediate in the preparation of other biologi- heterocyclic moieties.14 However, lengthy procedures, harsh
cally active compounds such as benzodiazepines, quinazo- reagents/conditions and the use of expensive metal salts are
lines, quinolines and acridines.4,5
some of the disadvantages. In view of the high cost and cyto-
Several diverse approaches for the construction of benzo[c] toxicity associated with heavy metal usage, the development of
isoxazoles have been reported to date. The key to the synthesis novel biocompatible and eco-friendly protocols to construct
of benzo[c]isoxazoles lies in how efficiently the N–O bond can benzo[c]isoxazole and its derivatives is extremely desirable.
be constructed. Ortho-substituted compounds such as ani-
There is only one study that reported the copper catalyzed
lines, aryl azides, nitroso and nitroarenes are frequently used synthesis of 2,1-benzoisoxazole-containing 1,2,3-triazoles.15
as substrates because of their unusual ability to form cyclized
products. These approaches have been used to increase the
electrophilicity or nucleophilicity of ortho substituents or other
substrates. Based on the annulation strategies used, they can
be grouped into four main categories, (1) oxidative cyclization6
(2) reductive cyclization7 (3) metal-assisted cyclization8 (4)
thermal cyclization9 (Scheme 1). Several other methods includ-
aXi’an Key Laboratory of Functional Organic Porous Materials, Department of
Applied Chemistry, School of Chemistry and Chemical Engineering, Northwestern
Polytechnical University, Xi’an, Shaanxi, 710072, PR China.
E-mail: qyzhang@nwpu.edu.cn
bSchool of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, P.R. China
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
d0ob02608e
Fig. 1 Selected examples of bioactive 2,1-benzoisoxazole derivatives.
Org. Biomol. Chem., 2021, 19, 3707–3716 | 3707
This journal is © The Royal Society of Chemistry 2021

View Article Online
Paper
Organic & Biomolecular Chemistry
ing 1,2,3-triazoles from 1-(2-iodoaryl)-2-yn-1-ones and sodium
azide.
Results and discussion
1-(2-Iodophenyl)-3-phenylprop-2-yn-1-one (1a) and sodium
azide were chosen as model substrates for the initial investi-
gation, and the results are summarized in Table 1. Based on
the previous methodology,16 we carried out the reaction of 1a
and sodium azide (2.0 equiv.) in dimethyl sulfoxide (DMSO) at
130 °C. Unfortunately, the reaction failed to give the expected
product. The only product obtained was 3-(5-phenyl-1H-1,2,3-
triazol-4-yl)benzo[c]isoxazole (2a) in 45% isolated yield
(Table 1, entry 1). Encouraged by the exciting discovery of
metal-free transformation, subsequent optimization studies
were carried out to improve the yield of 2a. To our delight,
with 3.0 equivalents of sodium azide, the desired product 2a
was successfully isolated in 79% yield (Table 1, entry 3).
Among the other screened solvents such as tetrehydrofuran
(THF), N,N-dimethylformamide (DMF), N-methyl pyrrolidone
(NMP), toluene and 1,4-dioxane, DMSO was the most optimal
solvent for the reaction, giving rise to the desired product in
79% yield (Table 1, entries 6–11). Additionally, there is no
product 2a formed at room temperature (only the [3 + 2] cyclo-
addition product 3a was obtained in 100 mg, 53% yield)
(Table 1, entry 12). However, the product 2a was obtained only
in 32% yield at 100 °C.
Scheme 1 Different approaches towards 2,1-benzoisoxazole synthesis.
Hence, novel, efficient and metal-free synthetic routes that can
provide a direct access to 2,1-benzoisoxazole-containing 1,2,3-
triazoles are still extremely desirable. In this context, tandem
reactions based on C–X bond formation reactions have
emerged as a powerful tool for the construction of biologically
active and structurally complex heterocycles in a single step.
The individual biological and therapeutic importance of benzo
[c]isoxazoles and 1,2,3-triazoles has prompted us to develop
such a metal-free reaction. Keeping in mind our previous data
for developing a metal-free reaction for the synthesis of [1,2,3]
triazolo-[1,5-a]quinoxalin-4(5H)-ones,16 we assume that our
metal-free protocol may also work for the substrate (1-(2-iodo-
phenyl)-3-phenylprop-2-yn-1-one) used in previous studies.
Unexpectedly, when we conducted the experiment with 1-(2-
iodophenyl)-3-phenylprop-2-yn-1-one (1a) instead of N-(2-
haloaryl)propionamides, triazolo benzisoxazole (2a) was
obtained (Scheme 2). Herein, we disclosed a metal-free
tandem protocol for the synthesis of benzo[c]isoxazole-contain-
With the optimized reaction conditions in hand, the sub-
strate scope was explored, and the results are shown in
Table 2. In most cases, the tandem reactions of sodium azide
Table 1 Screening of reaction conditionsa
Entry
Substrate
Solvent
t (°C)
Yield 2a (%)b
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
DMSO
DMSO
DMSO
DMSO
DMSO
THF
130
130
130
130
130
130
130
130
130
130
130
Rt
45d
66e
79
69 f
71g
<10
34
DMF
1,4-Dioxane
MeCN
Toluene
NMP
DMSO
DMSO
Trace
40
9
10
11
12
13
n.d.c
<10
n.d.c
32
100
a Reagents and reaction conditions: 1a (0.5 mmol, 1.0 equiv.), NaN3
(1.5 mmol, 3.0 equiv.), solvent (3.0 mL). b Isolated yields. c No desired
product was detected. d NaN3 (1.0 mmol, 2.0 equiv.). e NaN3
(1.25 mmol, 2.5 equiv.). f NaN3 (1.75 mmol, 3.5 equiv.). g NaN3
(2.0 mmol, 4.0 equiv.).
Scheme 2 Our previous and current work.
3708 | Org. Biomol. Chem., 2021, 19, 3707–3716
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 2 Reaction scopea,b
Table 3 Reaction scopea,b
a Reagents and reaction conditions: 1 (0.5 mmol, 1.0 equiv.) and NaN3
(1.5 mmol, 3.0 equiv.) in DMSO (4.0 mL) at 130 °C for 12 h b Isolated
yields.
iodophenyl ring bearing electron-withdrawing and electron
donating substituents was successfully converted to the
desired products in good yields (68–71%; 2ab–2af).
To illustrate the synthetic utility and demonstrate the appli-
cation prospects of this cascade reaction, further modifi-
cations and functionalization of the obtained products were
conducted. For example, 2a efficiently underwent a ring
opening reaction of benzisoxazole in the presence of CuI and
CF3COOH to give (2-aminophenyl) (5-phenyl-1H-1,2,3-triazol-4-
yl)methanone 4 (Scheme 3). In the following experiment, 2a
was easily converted into 3-(2-benzyl-5-phenyl-2H-1,2,3-triazol-
4-yl)benzo[c]isoxazole (5) via nucleophilic substitution with
benzyl bromide. In addition, the synthetic utility of this proto-
col was further demonstrated by carrying out a gram-scale
experiment. Gratifyingly, this cascade reaction could be easily
scaled up to 4.0 mmol, affording the desired product 2a in
71% isolated yield (Scheme 3).
a Reagents and reaction conditions: 1 (0.5 mmol, 1.0 equiv.) and NaN3
(1.5 mmol, 3.0 equiv.) in DMSO (4.0 mL) at 130 °C for 12 h. b Isolated
yields.
with 1-(2-iodoaryl)ynones afforded the desired products in
moderate or good yields. Both the alkyl and aryl substituents
on the alkyne moieties of the alkynyl ketones 1 were well toler-
ated, and the corresponding tandem reaction products were
obtained in high yields. When aryl substituents on the alkyne
moiety were phenyl or phenyl substituted with an electron-
donating group (such as –Me, –Et, –nPr and –OMe), the corres-
ponding products were obtained in good yields (2a–2e). While
electron-withdrawing groups (such as, –F, –Cl, –Br, and –NO2)
on the aryl substituents were also well tolerated and the
desired products were obtained in moderate to excellent yields
(2f–2n). When substituents on the alkyne moiety were alkyl
groups such as –cyclopropyl, –nButyl, and –nPentyl, the corres-
ponding products (2o–2q) were obtained in good yields.
Fortunately, aromatic heterocyclic substituents such as
3-thienyl and 3-pyridinyl were also tolerated in this reaction,
delivering the product 2r in 75% yield; however, 2s was
obtained in poor yield. In addition, polycyclic aromatic substi-
tuents such as 2-naphthalene and 9-phenanthrene were toler-
ated smoothly to give products (2t and 2u) in 77 and 83%
yields, respectively.
To gain insight into the mechanistic details of this metal-
free reaction, various control experiments were performed
(Scheme 4). Initially, we tried to convert intermediate 3b into
the desired product under the optimized conditions; unfortu-
nately, we could not obtain the target product (Scheme 4-1). In
Subsequently, the substrate scope with regard to the iodo-
phenyl ring moiety was examined (Table 3). To our delight, the Scheme 3 Follow-up transformations and gram-scale experiments.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 3707–3716 | 3709

View Article Online
Paper
Organic & Biomolecular Chemistry
were involved in this tandem process. Further research and
applications of this metal-free strategy for the synthesis of
structurally novel heterocyclic compounds is currently under-
way in our laboratory.
Experimental
General
Unless otherwise stated, all starting materials were obtained
from commercial suppliers and used without further purifi-
cation. All reactions were carried out in 10 mL tubes. All new
compounds were fully characterized. TLC analysis was per-
formed using precoated glass plates. Visualization of spots on
a TLC plate was accomplished with UV light (254 nm) and
staining over the I2 chamber. Column chromatography was
performed using silica gel (200–300 mesh). 1H NMR spectra
were recorded in CDCl3 on 400 MHz NMR spectrometers, and
resonances (δ) are given in parts per million relative to tetra-
methylsilane (internal standard). Data are reported as follows:
chemical shift, multiplicity (s = singlet, d = doublet, t = triplet,
m = multiplet, q = quadruple), coupling constants (Hz), and
integration. 13C spectra were recorded in CDCl3 on 100 MHz
NMR spectrometers, and resonances (δ) are given in ppm.
High-resolution mass spectra were recorded with a q-TOF elec-
trospray mass spectrometer.
Scheme 4 Control experiments.
Scheme 5 A possible mechanism.
General procedure for the synthesis of substrates. The syn-
thesis of substrates 1a–1w and 1ab–1af is described below. The
substrates 1a–1w and 1ab–1af were prepared from the acety-
lene derivative and 2-iodobenzaldehyde derivatives according
to general procedure A.
the following experiment, intermediate 3a was tested under
the standard conditions; luckily, the desired product 2a was
obtained in 81% yield (Scheme 4-2). These results indicated
that intermediate 3a might be the key intermediate in this
transformation process.
1-(2-Iodophenyl)-3-phenylprop-2-yn-1-one (1a). General pro-
cedure A. n-BuLi (2.5 M in hexane, 1.3 equiv., 1.6 mL) was
slowly added through a syringe to a stirring solution of phenyl
acetylene (1.1 equiv., 3.3 mmol) in freshly prepared dry THF
(30 mL) at −78 °C, and the resulting reaction mixture was
stirred for another 30 min at the same temperature. To this,
2-iodobenzaldehyde (3.0 mmol) in THF (5 mL) was added
dropwise and the reaction mixture was allowed to warm to
room temperature overnight. After complete consumption of
the starting material (monitored by TLC), the reaction mixture
was quenched by dropwise addition of a saturated solution of
NH4Cl (10 mL) and diluted with H2O (40 mL) and EtOAc
(20 mL). The organic layer was separated and the aqueous
phases were extracted three times with ethyl acetate/diethyl
ether. The extract was washed with brine, dried over anhydrous
Na2SO4 and concentrated under reduced pressure to obtain
Although the mechanistic details have not been fully
obtained, based on the experimental observations and litera-
ture precedence,8c,9,11,17 a possible mechanism was proposed,
which is shown in Scheme 5. We reasoned that the formal [3 +
2] cycloaddition of 1-(2-iodophenyl)-3-phenylprop-2-yn-1-one
(1a) and sodium azide would occur first to produce the inter-
mediate (2-iodophenyl)(5-phenyl-1H-1,2,3-triazol-4-yl)metha-
none A. Intermediate A could then undergo a SNAr with NaN3
to afford intermediate B. Finally, by thermal and intra-
molecular denitrogenative cyclization of intermediate C, the
target product 3-(5-phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxa-
zole (2a) was formed.
Conclusions
In summary, a novel metal-free tandem approach for the syn- the crude product, which was purified by column chromato-
thesis of various 2,1-benzoisoxazole-containing 1,2,3-triazole graphy (EtOAc/hexane, 1 : 5) to furnish propargyl alcohol. To a
derivatives has been developed. A wide range of substrates stirred solution of propargyl alcohol in dry DCM (20 mL) at
were tolerated in the reaction, giving the corresponding pro- room temperature was added MnO2 (11.5 equiv. 12 mmol) and
ducts in moderate to high yields. Furthermore, the utility of the reaction mixture was stirred for 4–5 hours. After the reac-
this protocol was demonstrated by scale-up synthesis and tion was completed, the mixture was filtered and the filtrate
further functionalization of the benzoisoxazole core. was concentrated and purified by silica gel column chromato-
Mechanism investigation demonstrated that a [3 + 2] cyclo- graphy using the eluent petroleum ether/EtOAc = 5/1 to afford
addition, SNAr and the subsequent denitrogenation cyclization the desired product 1a as yellow oil (0.895 g, 90%). 1H NMR
3710 | Org. Biomol. Chem., 2021, 19, 3707–3716
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
(400 MHz, CDCl3) δ 8.13 (dd, J = 7.8, 1.7 Hz, 1H), 8.04 (dd, J = (td, J = 7.5, 1.3 Hz, 1H), 7.21 (td, J = 7.6, 1.7 Hz, 1H). 13C{1H}
7.8, 1.2 Hz, 1H), 7.69–7.60 (m, 2H), 7.55–7.44 (m, 2H), NMR (101 MHz, CDCl3) δ 177.1, 142.2, 138.3, 137.4, 134.8,
7.44–7.37 (m, 2H), 7.20 (td, J = 7.6, 1.7 Hz, 1H). 13C{1H} NMR 133.8, 133.5, 131.8, 129.5, 127.9, 126.7, 120.1, 92.7, 90.8, 89.8.
(101 MHz, CDCl3) δ 177.8, 141.9, 139.1, 133.3, 132.9, 130.8, HRMS (ESI) m/z: [M + H]+ calcd for C15H8ClIO 366.9381, found
128.5, 127.9, 119.7, 94.2, 92.6, 87.0. HRMS (ESI) m/z: [M + H]+ 366.9383.
calcd for C15H9IO 332.9771, found 332.9774.
3-(3-Fluorophenyl)-1-(2-iodophenyl)prop-2-yn-1-one
(1h).
1-(2-Iodophenyl)-3-(p-tolyl)prop-2-yn-1-one (1b). The title The title compound was obtained as a yellow solid in 96%
compound was obtained as a yellow solid in 88% yield yield (1.01 g). 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 7.8, 1.7
1
(0.875 g). H NMR (400 MHaz, CDCl3) δ 8.13 (dd, J = 7.8, 1.7 Hz, 1H), 8.04 (dd, J = 7.9, 1.2 Hz, 1H), 7.50 (td, J = 7.5, 1.1 Hz,
Hz, 1H), 8.09–8.01 (m, 1H), 7.59–7.45 (m, 3H), 7.25–7.16 (m, 1H), 7.45–7.34 (m, 2H), 7.34–7.29 (m, 1H), 7.24–7.14 (m, 2H).
1
3H), 2.40 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 178.0, 13C{1H} NMR (101 MHz, CDCl3) δ 177.5, 162.0 (C–F, JC–F
=
=
=
3
141.9, 141.7, 139.4, 133.2, 133.0, 132.8, 129.4, 127.9, 116.6, 246.0 Hz), 160.8, 142.0, 138.9, 133.4, 132.9, 130.3 (C–F, JC–F
4
3
95.0, 92.7, 87.0, 21.7. HRMS (ESI) m/z: [M + H]+ calcd for 8.0 Hz), 128.7 (C–F, JC–F = 4.0 Hz), 128.0, 121.5 (C–F, JC–F
2
2
C16H11IO 346.9927, found 346.9928.
9.0 Hz), 119.4 (C–F, JC–F = 23.0 Hz), 118.2 (C–F, JC–F = 21.0
3-(4-Ethylphenyl)-1-(2-iodophenyl)prop-2-yn-1-one (1c). The Hz), 92.7, 92.1 (C–F, 4JC–F = 3.3 Hz), 87.1. HRMS (ESI) m/z: [M +
title compound was obtained as a yellow solid in 79% yield H]+ calcd for C15H8FIO 350.9677, found 350.9678.
(0.850 g). 1H NMR (400 MHz, CDCl3) δ 8.12 (dd, J = 7.7, 1.7 Hz,
3-(3-Chlorophenyl)-1-(2-iodophenyl)prop-2-yn-1-one (1i). The
1H), 8.03 (dd, J = 7.9, 1.2 Hz, 1H), 7.56 (d, J = 8.3 Hz, 2H), 7.49 title compound was obtained as a yellow solid in 93% yield
1
(td, J = 7.6, 1.2 Hz, 1H), 7.25–7.16 (m, 3H), 2.68 (q, J = 7.6 Hz, (1.02 g). H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 7.8, 1.7 Hz,
2H), 1.24 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 1H), 8.05 (dd, J = 7.9, 1.2 Hz, 1H), 7.60 (t, J = 1.8 Hz, 1H),
177.9, 147.8, 141.9, 139.3, 133.2, 133.1, 132.8, 128.1, 127.7, 7.55–7.47 (m, 2H), 7.47–7.42 (m, 1H), 7.34 (t, J = 7.9 Hz, 1H),
116.8, 95.0, 92.6, 86.9, 28.8, 15.0. HRMS (ESI) m/z: [M + H]+ 7.21 (td, J = 7.6, 1.7 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
calcd for C17H13IO 361.0084, found 361.0088.
1-(2-Iodophenyl)-3-(4-propylphenyl)prop-2-yn-1-one
177.4, 142.0, 138.8, 134.4, 133.4, 132.9, 132.4, 131.0, 130.9,
(1d). 129.8, 127.9, 121.4, 92.7, 91.9, 87.3. HRMS (ESI) m/z: [M + H]+
The title compound was obtained as a yellow solid in 51% calcd for C15H8ClIO 366.9381, found 366.9383.
yield (0.570 g). 1H NMR (400 MHz, CDCl3) δ 8.16–8.09 (m, 1H),
3-(4-Fluorophenyl)-1-(2-iodophenyl)prop-2-yn-1-one (1j). The
8.04 (d, J = 7.9 Hz, 1H), 7.56 (d, J = 7.9 Hz, 2H), 7.49 (t, J = 7.6 title compound was obtained as a yellow solid in 84% yield
Hz, 1H), 7.25–7.15 (m, 3H), 2.62 (t, J = 7.6 Hz, 2H), 1.69–1.59 (0.880 g). 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 7.8, 1.7 Hz,
(m, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, 1H), 8.05 (dd, J = 7.9, 1.2 Hz, 1H), 7.69–7.60 (m, 2H), 7.50 (td, J
CDCl3) δ 177.9, 146.3, 141.9, 139.3, 133.2, 133.0, 132.8, 128.7, = 7.5, 1.2 Hz, 1H), 7.21 (td, J = 7.6, 1.7 Hz, 1H), 7.16–7.05 (m,
127.9, 116.8, 95.0, 92.6, 86.9, 37.9, 24.0, 13.6. HRMS (ESI) m/z: 2H). 13C{1H} NMR (100 MHz, CDCl3) for major isomer: δ 177.8,
1
3
[M + H]+ calcd for C18H15IO 375.0240, found 375.0243.
163.9 (C–F, JC–F = 252 Hz), 141.9, 135.3 (C–F, JC–F = 9.0 Hz),
1-(2-Iodophenyl)-3-(4-methoxyphenyl)prop-2-yn-1-one (1e). 133.3, 132.8, 127.9, 116.1 (C–F, JC–F = 22.0), 115.8 (C–F, 4JC–F
=
2
The title compound was obtained as a light yellow solid in 3.0), 93.1, 92.6, 86.9 (C–F, 3JC–F = 1.0 Hz). HRMS (ESI) m/z: [M +
80% yield (0.870 g). H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = H]+ calcd for C15H8FIO 350.9677, found 350.9678.
1
7.8, 1.7 Hz, 1H), 8.04 (dd, J = 7.8, 1.2 Hz, 1H), 7.65–7.56 (m,
3-(4-Chlorophenyl)-1-(2-iodophenyl)prop-2-yn-1-one
(1k).
2H), 7.49 (td, J = 7.6, 1.2 Hz, 1H), 7.19 (td, J = 7.6, 1.7 Hz, 1H), The title compound was obtained as a brown solid in 68%
1
6.97–6.87 (m, 2H), 3.85 (s, 3H). 13C{1H} NMR (101 MHz, yield (0.750 g). H NMR (400 MHz, CDCl3) δ 8.10 (dd, J = 7.8,
CDCl3) δ 178.1, 161.7, 141.8, 139.6, 135.1, 133.1, 132.6, 127.9, 1.7 Hz, 1H), 8.07–8.00 (m, 1H), 7.61–7.53 (m, 2H), 7.53–7.46
114.3, 111.5, 95.6, 92.6, 87.2, 55.3. HRMS (ESI) m/z: [M + H]+ (m, 1H), 7.41–7.33 (m, 2H), 7.24–7.16 (m, 1H). 13C{1H} NMR
calcd for C16H11IO2 362.9877, found 362.9879.
(101 MHz, CDCl3) δ 177.5, 141.9, 138.8, 137.1, 134.0, 133.3,
3-(2-Fluorophenyl)-1-(2-iodophenyl)prop-2-yn-1-one (1f). The 132.8, 128.9, 127.9, 118.1, 92.6, 92.6, 87.6. HRMS (ESI) m/z: [M
title compound was obtained as a yellow solid in 94% yield + H]+ calcd for C15H8ClIO 366.9381, found 366.9384.
1
(0.99 g). H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 7.7, 1.7 Hz,
3-(4-Bromophenyl)-1-(2-iodophenyl)prop-2-yn-1-one (1l). The
1H), 8.05 (dd, J = 7.9, 1.2 Hz, 1H), 7.66–7.58 (m, 1H), 7.55–7.42 title compound was obtained as a yellow solid in 28% yield
(m, 2H), 7.25–7.10 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ (350 mg). 1H NMR (400 MHz, CDCl3) δ 8.13–8.03 (m, 2H),
177.1, 163.6 (C–F, 1JC–F = 251 Hz), 142.1, 138.4, 134.5, 133.5 (C– 7.61–7.46 (m, 5H), 7.22 (td, J = 7.6, 1.7 Hz, 1H). 13C{1H} NMR
4
3
F, JC–F = 4.0 Hz), 132.8 (C–F, JC–F = 8.0), 127.9, 124.3 (C–F, (101 MHz, CDCl3) δ 177.7, 142.0, 139.1, 134.2, 133.4, 132.8,
4JC–F = 4.0 Hz), 115.7 (C–F, 2JC–F = 20 Hz), 108.7 (C–F, 2JC–F = 15 131.9, 127.9, 125.7, 118.7, 92.8, 92.7, 87.7. HRMS (ESI) m/z: [M
Hz), 92.7, 91.2 (C–F, 4JC–F = 3.0 Hz), 87.1 ppm. HRMS (ESI) m/z: + H]+ calcd for C15H8BrIO 410.8876, found 410.8875.
[M + H]+ calcd for C15H8FIO 350.9677, found 350.9677.
1-(2-Iodophenyl)-3-(3-nitrophenyl)prop-2-yn-1-one (1m). The
3-(2-Chlorophenyl)-1-(2-iodophenyl)prop-2-yn-1-one
(1g). title compound was obtained as a light yellow solid in 37%
1
The title compound was obtained as yellow oil in 95% yield yield (0.419 g). H NMR (400 MHz, CDCl3) δ 8.48 (t, J = 1.9 Hz,
1
(1.05 g, 95%). H NMR (400 MHz, CDCl3) δ 8.33 (dd, J = 7.8, 1H), 8.35–8.30 (m, 1H), 8.15–8.05 (m, 2H), 7.95 (dt, J = 7.7, 1.3
1.7 Hz, 1H), 8.06 (dd, J = 7.9, 1.2 Hz, 1H), 7.67 (dd, J = 7.7, 1.7 Hz, 1H), 7.63 (t, J = 8.0 Hz, 1H), 7.54 (td, J = 7.6, 1.2 Hz, 1H),
Hz, 1H), 7.56–7.44 (m, 2H), 7.40 (td, J = 7.8, 1.7 Hz, 1H), 7.30 7.28–7.22 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 177.2,
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 3707–3716 | 3711

View Article Online
Paper
Organic & Biomolecular Chemistry
148.0, 142.2, 138.6, 138.2, 133.7, 133.0, 129.7, 128.0, 127.4,
1-(2-Iodophenyl)-3-(naphthalen-2-yl)prop-2-yn-1-one
(1t).
125.2, 121.7, 92.8, 90.0, 87.9. HRMS (ESI) m/z: [M + H]+ calcd The title compound was obtained as a light-yellow solid in
for C15H8INO3 377.9622, found 377.9624.
96% yield (1.1 g). 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H),
1-(2-Iodophenyl)-3-(4-nitrophenyl)prop-2-yn-1-one (1n). The 8.19 (d, J = 7.7 Hz, 1H), 8.08 (d, J = 7.9 Hz, 1H), 7.87 (d, J = 8.0
title compound was obtained as a brown solid in 35% yield Hz, 3H), 7.64 (d, J = 8.6 Hz, 1H), 7.62–7.49 (m, 3H), 7.25–7.18
(0.4 g). 1H NMR (400 MHz, CDCl3) δ 8.33–8.23 (m, 2H), (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 177.9, 142.0, 139.3,
8.15–8.05 (m, 2H), 7.86–7.77 (m, 2H), 7.57–7.49 (m, 1H), 134.3, 133.8, 133.2, 132.9, 132.5, 128.4, 128.1, 128.1, 128.0,
7.29–7.21 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 177.2, 127.9, 127.8, 126.9, 116.9, 94.8, 92.7, 87.3. HRMS (ESI) m/z: [M
148.4, 142.2, 138.6, 133.7, 133.5, 133.0, 128.0, 126.4, 123.6, + H]+ calcd for C19H11IO 382.9927, found 382.9925.
92.8, 90.2, 89.7. HRMS (ESI) m/z: [M + H]+ calcd for C15H8INO3
1-(2-Iodophenyl)-3-(phenanthren-9-yl)prop-2-yn-1-one (1u).
377.9622, found 377.9619.
The title compound was obtained as a yellow solid in 76%
3-Cyclopropyl-1-(2-iodophenyl)prop-2-yn-1-one (1o). The title yield (0.990 g). 1H NMR (400 MHz, CDCl3) δ 8.64–8.54 (m, 2H),
compound was obtained as yellow oil in 68% yield (0.600 g). 8.42–8.33 (m, 1H), 8.31–8.20 (m, 1H), 8.15 (s, 1H), 8.08 (d, J =
1H NMR (400 MHz, CDCl3) δ 8.04–7.90 (m, 2H), 7.43 (td, J = 7.9 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.74–7.63 (m, 3H),
7.6, 1.2 Hz, 1H), 7.14 (td, J = 7.6, 1.7 Hz, 1H), 1.56–1.45 (m, 7.63–7.48 (m, 2H), 7.25–7.16 (m, 1H). 13C{1H} NMR (101 MHz,
1H), 1.07–0.95 (m, 4H). 13C{1H} NMR (101 MHz, CDCl3) δ CDCl3) δ 177.6, 141.9, 139.1, 135.6, 133.2, 132.9, 131.0, 130.3,
177.7, 141.6, 139.3, 132.9, 132.6, 127.7, 102.4, 92.3, 75.7, 9.7, 130.2, 129.7, 128.9, 128.7, 127.9, 127.3, 127.3, 127.0, 126.2,
−0.09. HRMS (ESI) m/z: [M + H]+ calcd for C12H9IO 296.9771, 122.6, 122.4, 116.0, 92.8, 92.7, 91.1. HRMS (ESI) m/z: [M + H]+
found 296.9772.
calcd for C23H13IO 433.0084, found 433.0085.
1-(2-Iodophenyl)hept-2-yn-1-one (1p). The title compound
4-(Benzyloxy)-1-(2-iodophenyl)but-2-yn-1-one (1v). The title
was obtained as yellow oil in 69% yield (0.650 g). 1H NMR compound was obtained as dark yellow oil in 78% yield
1
(400 MHz, CDCl3) δ 8.04 (dd, J = 7.8, 1.7 Hz, 1H), 8.00 (dd, J = (0.880 g). H NMR (400 MHz, CDCl3) δ 8.11–8.07 (m, 1H), 8.04
7.8, 1.1 Hz, 1H), 7.44 (td, J = 7.6, 1.2 Hz, 1H), 7.16 (td, J = 7.6, (d, J = 7.9 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.40–7.31 (m, 5H),
1.7 Hz, 1H), 2.46 (t, J = 7.1 Hz, 2H), 1.67–1.55 (m, 2H), 7.23–7.17 (m, 1H), 4.67 (s, 2H), 4.44 (s, 2H). 13C{1H} NMR
1.53–1.40 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 176.8, 142.0, 138.0, 136.4, 133.5, 133.3,
(101 MHz, CDCl3) δ 177.8, 141.8, 139.0, 133.0, 132.9, 127.7, 128.3, 127.9, 127.9, 127.8, 92.5, 91.0, 84.0, 72.0, 56.9. HRMS
98.0, 92.4, 79.7, 29.4, 21.8, 18.7, 13.3. HRMS (ESI) m/z: [M + (ESI) m/z: [M + H]+ calcd for C17H13IO2 398.9852, found
H]+ calcd for C13H13IO 313.0084, found 313.0086.
398.9859.
1-(2-Iodophenyl)oct-2-yn-1-one (1q). The title compound was
1-(5-Bromo-2-iodophenyl)-3-phenylprop-2-yn-1-one
(1ab).
obtained as yellow oil in 71% yield (0.693 g). 1H NMR The title compound was obtained as a yellow solid in 52%
(400 MHz, CDCl3) δ 8.08–8.02 (m, 1H), 7.99 (d, J = 7.9 Hz, 1H), yield (0.640 g). 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 2.4 Hz,
7.44 (t, J = 7.5 Hz, 1H), 7.20–7.11 (m, 1H), 2.45 (t, J = 7.1 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.70–7.63 (m, 2H), 7.55–7.47 (m,
2H), 1.67–1.59 (m, 2H), 1.45–1.28 (m, 4H), 0.89 (t, J = 7.1 Hz, 1H), 7.47–7.38 (m, 2H), 7.32 (dd, J = 8.4, 2.4 Hz, 1H). 13C{1H}
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 177.8, 141.8, 138.9, NMR (101 MHz, CDCl3) δ 176.5, 143.0, 140.8, 136.1, 135.3,
133.0, 132.9, 127.7, 98.0, 92.4, 79.7, 30.8, 27.1, 21.8, 19.0, 13.7. 133.0, 131.1, 128.5, 122.2, 119.3, 95.2, 90.6, 86.6. HRMS (ESI)
HRMS (ESI) m/z: [M + H]+ calcd for C14H15IO 327.0240, found m/z: [M + H]+ calcd for C15H8BrIO 410.8876, found 410.8876.
327.0243.
1-(5-Bromo-2-iodophenyl)-3-(p-tolyl)prop-2-yn-1-one
(1ac).
1-(2-Iodophenyl)-3-(thiophen-3-yl)prop-2-yn-1-one (1r). The The title compound was obtained as a yellow solid in 86%
1
title compound was obtained as brown oil in 77% yield yield (1.1 g). H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 2.4 Hz,
1
(0.777 g). H NMR (400 MHz, CDCl3) δ 8.15–8.06 (m, 1H), 8.02 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.59–7.52 (m, 2H), 7.32 (dd, J =
(d, J = 7.9 Hz, 1H), 7.86–7.80 (m, 1H), 7.49 (t, J = 7.6 Hz, 1H), 8.3, 2.4 Hz, 1H), 7.23 (d, J = 7.9 Hz, 2H), 2.41 (s, 3H). 13C{1H}
7.40–7.32 (m, 1H), 7.27 (d, J = 5.1 Hz, 1H), 7.24–7.14 (m, 1H). NMR (101 MHz, CDCl3) δ 176.6, 143.0, 142.0, 141.0, 135.9,
13C{1H} NMR (101 MHz, CDCl3) δ 177.6, 141.7, 138.8, 134.0, 135.2, 133.1, 129.4, 122.1, 116.2, 96.1, 90.6, 86.6, 21.7. HRMS
133.1, 132.7, 129.8, 127.8, 126.1, 118.8, 92.5, 89.6, 87.1. HRMS (ESI) m/z: [M + H]+ calcd for C16H10BrIO 424.9032, found
(ESI) m/z: [M + H]+ calcd for C13H7IOS 338.9335, found 424.9026.
338.9334.
1-(5-Chloro-2-iodophenyl)-3-phenylprop-2-yn-1-one
(1ad).
1-(2-Iodophenyl)-3-(pyridin-3-yl)prop-2-yn-1-one (1s). The The title compound was obtained as a light yellow solid in
1
title compound was obtained as a light yellow solid in 72% 77% yield (0.843 g). H NMR (400 MHz, CDCl3) δ 8.04 (d, J =
yield (0.715 g). 1H NMR (400 MHz, CDCl3) δ 8.89–8.83 (m, 1H), 2.5 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 7.5 Hz, 2H),
8.68 (dd, J = 4.9, 1.7 Hz, 1H), 8.12 (dd, J = 7.8, 1.7 Hz, 1H), 8.06 7.54–7.46 (m, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.18 (dd, J = 8.4, 2.5
(dd, J = 7.9, 1.2 Hz, 1H), 7.93 (dt, J = 7.9, 2.0 Hz, 1H), 7.51 (td, J Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 176.5, 142.8, 140.4,
= 7.6, 1.2 Hz, 1H), 7.40–7.33 (m, 1H), 7.22 (td, J = 7.6, 1.7 Hz, 134.4, 133.1, 133.0, 132.4, 131.0, 128.5, 119.3, 95.1, 89.7, 86.5.
1H). 13C{1H} NMR (101 MHz, CDCl3) δ 177.3, 153.1, 150.7, HRMS (ESI) m/z: [M + H]+ calcd for C15H8ClIO 366.9381, found
142.1, 139.7, 138.6, 133.5, 133.0, 128.0, 123.1, 117.1, 92.7, 90.0, 366.9381.
89.3. HRMS (ESI) m/z: [M + H]+ calcd for C14H8INO 333.9723,
1-(2-Iodo-5-methylphenyl)-3-phenylprop-2-yn-1-one
(1ae).
found 333.9723.
The title compound was obtained as a yellow solid in 82%
3712 | Org. Biomol. Chem., 2021, 19, 3707–3716
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
yield (0.850 g). 1H NMR (400 MHz, CDCl3) δ 7.94–7.86 (m, 2H), J = 8.8 Hz, 1H), 7.67–7.60 (m, 3H), 7.47–7.40 (m, 1H), 7.34 (d, J
7.69–7.61 (m, 2H), 7.53–7.45 (m, 1H), 7.45–7.37 (m, 2H), = 7.8 Hz, 2H), 7.15–7.08 (m, 1H), 2.60 (t, J = 7.6 Hz, 2H),
7.07–6.99 (m, 1H), 2.39 (s, 3H). 13C{1H} NMR (101 MHz, 1.66–1.56 (m, 2H), 0.89 (t, J = 7.3 Hz, 3H). 13C{1H} NMR
CDCl3) δ 178.1, 141.6, 139.1, 138.1, 134.3, 133.5, 132.9, 130.7, (101 MHz, DMSO-d6) δ 157.2, 155.9, 143.2, 131.1, 128.0, 127.8,
128.5, 119.8, 94.1, 88.6, 87.0, 20.7. HRMS (ESI) m/z: [M + H]+ 124.2, 120.8, 114.6, 113.7, 36.4, 23.3, 13.0. HRMS (ESI) m/z: [M
calcd for C16H11IO 346.9927, found 346.9928.
+ H]+ calcd for C18H16N4O 305.1396, found 305.1375.
1-(2-Iodo-4-methylphenyl)-3-phenylprop-2-yn-1-one
(1af).
3-(5-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxa-
The title compound was obtained as a yellow solid in 30% zole (2e). The title compound was obtained as a light yellow
1
yield (0.330 g). 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 7.9 Hz, solid in 69% yield (100 mg). H NMR (400 MHz, DMSO-d6) δ
1H), 7.88 (s, 1H), 7.67–7.61 (m, 2H), 7.51–7.44 (m, 1H), 7.94 (d, J = 8.6 Hz, 1H), 7.70–7.63 (m, 3H), 7.50–7.42 (m, 1H),
7.44–7.38 (m, 2H), 7.29 (d, J = 8.1 Hz, 1H), 2.36 (s, 3H). 13C{1H} 7.18–7.09 (m, 3H), 3.84 (s, 3H). 13C{1H} NMR (101 MHz,
NMR (101 MHz, CDCl3) δ 176.9, 144.5, 142.6, 135.8, 133.2, DMSO-d6) δ 159.7, 157.4, 155.9, 131.56, 131.2, 129.4, 124.2,
132.7, 130.5, 128.5, 128.3, 119.6, 93.3, 92.8, 86.8, 20.7. HRMS 120.9, 114.6, 113.7, 113.6, 54.7. HRMS (ESI) m/z: [M + H]+ calcd
(ESI) m/z: [M + H]+ calcd for C16H11IO 346.9927, found for C16H12N4O2 293.1033, found 293.1035.
346.9928.
3-(5-(2-Fluorophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
(2f). The title compound was obtained as a yellow solid in 34%
yield (47 mg). H NMR (400 MHz, DMSO-d6) δ 7.92 (d, J = 8.7
General procedure for the synthesis of products 2
1
General procedure B. A mixture of 1-(2-iodophenyl)-3-phenyl- Hz, 1H), 7.72 (t, J = 7.6 Hz, 1H), 7.68–7.58 (m, 2H), 7.51–7.37
prop-2-yn-1-one 1a (166 mg, 0.5 mmol, 1.0 equiv.), NaN3 (m, 3H), 7.21–7.11 (m, 1H). 13C{1H} NMR (100 MHz, DMSO-d6)
1
(97.0 mg, 1.5 mmol, 3.0 equiv.) and dry DMSO (4.0 mL) was for the major isomer: δ 158.9 (C–F, JC–F = 247 Hz), 156.8,
added in a closed vessel and then the reaction mixture was 155.8, 135.6, 131.5 (C–F, 3JC–F = 8.0 Hz), 131.3, 131.1 (C–F, 4JC–F
allowed to stir overnight at 130 °C. After the disappearance of = 3.0), 124.6, 124.3 (C–F, 4JC–F = 4.0 Hz), 120.4, 115.4 (C–F, 2JC–F
the reactant (monitored by TLC), 3.0 mL of ammonia solution = 21.0 Hz), 114.4, 113.9 ppm. HRMS (ESI) m/z: [M + H]+ calcd
was added to the mixture, washed with water and extracted for C15H9N4OF 281.0833, found 281.0803.
with EtOAc three times (3 × 25 mL). The extract was washed
3-(5-(2-Chlorophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
with brine, dried over anhydrous Na2SO4 and concentrated (2g). The title compound was obtained as a yellow solid in
1
under reduced pressure. The residue was purified by silica gel 47% yield (69 mg). H NMR (400 MHz, DMSO-d6) δ 7.89 (d, J =
column chromatography using the eluent petroleum ether/ 9.0 Hz, 1H), 7.74–7.51 (m, 5H), 7.49–7.41 (m, 1H), 7.20–7.12
EtOAc = 3/1 to afford the desired product 2a as a yellow solid.
(m, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 155.8, 132.4,
3-(5-Phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2a). The 131.6, 131.2, 130.9, 129.1, 126.8, 124.5, 120.3, 114.2, 113.8.
title compound was obtained as a yellow solid in 79% yield HRMS (ESI) m/z: [M + H]+ calcd for C15H9N4OCl 297.0538,
1
(103 mg). H NMR (400 MHz, DMSO-d6) δ 7.90 (d, J = 8.9 Hz, found 297.0508.
1H), 7.55–7.65 (m, 7H), 7.14 (t, J = 7.6 Hz, 1H). 13C{1H} NMR
3-(5-(3-Fluorophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
(101 MHz, DMSO-d6) δ 157.1, 155.9, 131.2, 128.9, 128.1, 128.0, (2h). The title compound was obtained as a yellow solid in
1
124.3, 120.7, 114.7, 113.8. HRMS (ESI) m/z: [M + H]+ calcd for 52% yield (73 mg). H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J =
C15H10N4O 263.0927, found 263.0932.
9.1 Hz, 1H), 7.67 (d, J = 9.1 Hz, 1H), 7.63–7.54 (m, 3H),
3-(5-(p-Tolyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
(2b). 7.50–7.43 (m, 1H), 7.43–7.33 (m, 1H), 7.20–7.12 (m, 1H). 13C
The title compound was obtained as a light yellow solid in {1H} NMR (100 MHz, DMSO-d6) for the major isomer: δ 161.4
1
1
3
74% yield (100 mg). H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J (C–F, JC–F = 242.0 Hz), 156.8, 156.1, 131.3, 130.2 (C–F, JC–F
=
=
= 9.2 Hz, 1H), 7.70–7.54 (m, 3H), 7.48–7.42 (m, 1H), 7.35 (d, J = 8.0 Hz), 124.6, 124.2 (C–F, 4JC–F = 3.0), 120.7, 115.7 (C–F, 2JC–F
7.8 Hz, 2H), 7.18–7.10 (m, 1H), 2.39 (s, 3H). 13C{1H} NMR 21.0 Hz), 114.9, 114.8 (C–F, JC–F = 8.0 Hz), 113.9 ppm. HRMS
(101 MHz, DMSO-d6) δ 157.3, 155.9, 138.6, 131.7, 131.2, 128.7, (ESI) m/z: [M + H]+ calcd for C15H9N4OF 281.0833, found
127.8, 124.3, 120.8, 114.6, 113.8, 20.3. HRMS (ESI) m/z: [M + 281.0802.
3
H]+ calcd for C16H12N4O 277.1084, found 277.1087.
3-(5-(3-Chlorophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
3-(5-(4-Ethylphenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2i). The title compound was obtained as a light yellow solid in
1
(2c). The title compound was obtained as a light yellow solid 51% yield (76 mg). H NMR (400 MHz, DMSO-d6) δ 7.92 (d, J =
1
in 76% yield (110 mg). H NMR (400 MHz, CD2Cl2) δ 7.94 (d, J 8.8 Hz, 1H), 7.82 (s, 1H), 7.74–7.63 (m, 2H), 7.63–7.54 (m, 2H),
= 8.8 Hz, 1H), 7.71–7.54 (m, 3H), 7.41–7.25 (m, 3H), 7.05 (t, J = 7.51–7.42 (m, 1H), 7.22–7.13 (m, 1H). 13C{1H} NMR (101 MHz,
7.6 Hz, 1H), 2.69 (d, J = 7.7 Hz, 2H), 1.24 (t, J = 7.8 Hz, 3H). 13
C
DMSO-d6) δ 156.7, 156.0, 132.7, 131.3, 130.0, 128.7, 127.7,
{1H} NMR (101 MHz, CD2Cl2) δ 157.7, 157.1, 146.4, 133.5, 126.7, 124.6, 120.6, 114.8, 113.8. HRMS (ESI) m/z: [M + H]+
131.4, 128.6, 128.3, 125.0, 124.7, 121.64, 116.2, 114.5, 28.7, calcd for C15H9N4OCl 297.0538, found 297.0505.
15.1. HRMS (ESI) m/z: [M + H]+ calcd for C17H14N4O 291.1240,
3-(5-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
found 291.1243.
(2j). The title compound was obtained as a light yellow solid in
1
3-(5-(4-Propylphenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole 46% yield (64 mg). H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J =
(2d). The title compound was obtained as a light yellow solid 8.6 Hz, 1H), 7.83–7.75 (m, 2H), 7.64 (d, J = 9.0 Hz, 1H),
in 89% yield (136 mg). 1H NMR (400 MHz, DMSO-d6) δ 7.91 (d, 7.47–7.35 (m, 3H), 7.18–7.10 (m, 1H). 13C{1H} NMR (100 MHz,
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 3707–3716 | 3713

View Article Online
Paper
Organic & Biomolecular Chemistry
DMSO-d6) for the major isomer: δ 162.2 (C–F, 1JC–F = 246.0 Hz),
3-(5-Pentyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2q). The
3
157.0, 155.9, 131.2, 130.4 (C–F, JC–F = 8.0 Hz), 124.4, 120.7, title compound was obtained as a yellow solid in 74% yield
2
4
115.2 (C–F, JC–F = 22.0), 115.0, 114.7 (C–F, JC–F = 5.0 Hz), (95 mg). 1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.8 Hz,
113.8 ppm. HRMS (ESI) m/z: [M + H]+ calcd for C15H9N4OF 1H), 7.64 (d, J = 9.1 Hz, 1H), 7.51–7.40 (m, 1H), 7.21–7.11 (m,
281.0833, found 281.0819.
1H), 3.07 (t, J = 7.6 Hz, 2H), 1.77–1.66 (m, 2H), 1.37–1.24 (m,
3-(5-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole 4H), 0.88–0.79 (m, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ
(2k). The title compound was obtained as a yellow solid in 158.0, 155.9, 132.8, 131.2, 124.0, 120.9, 113.7, 113.5, 30.0, 27.3,
1
34% yield (50 mg). H NMR (400 MHz, DMSO-d6) δ 7.94–7.89 23.0, 21.0, 13.1. HRMS (ESI) m/z: [M + H]+ calcd for C14H16N4O
(m, 1H), 7.80–7.71 (m, 2H), 7.69–7.57 (m, 3H), 7.49–7.42 (m, 257.1397, found 257.1374.
1H), 7.19–7.12 (m, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ
3-(5-(Thiophen-3-yl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2r).
156.8, 155.9, 133.6, 131.2, 129.7, 128.1, 124.5, 120.6, 114.7, The title compound was obtained as a yellow solid in 75%
1
113.8. HRMS (ESI) m/z: [M + H]+ calcd for C15H9N4OCl yield (100 mg). H NMR (400 MHz, DMSO-d6) δ 8.12 (d, J = 2.9
297.0538, found 297.0520.
Hz, 1H), 7.97 (d, J = 8.9 Hz, 1H), 7.77 (t, J = 4.1 Hz, 1H), 7.67
(d, J = 9.1 Hz, 1H), 7.56 (d, J = 5.1 Hz, 1H), 7.51–7.43 (m, 1H),
3-(5-(4-Bromophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
(2l). The title compound was obtained as a light yellow solid in 7.21–7.12 (m, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 157.0,
1
64% yield (109 mg). H NMR (400 MHz, DMSO-d6) δ 7.92 (d, J 156.0, 131.2, 126.9, 126.6, 125.6, 124.3, 120.8, 114.7, 113.7.
= 8.6 Hz, 1H), 7.81–7.72 (m, 2H), 7.72–7.63 (m, 3H), 7.50–7.43 HRMS (ESI) m/z: [M + H]+ calcd for C13H8N4OS 269.0491,
(m, 1H), 7.17 (dd, J = 8.8, 6.3 Hz, 1H). 13C{1H} NMR (101 MHz, found 269.0471.
DMSO-d6) δ 156.8, 156.0, 131.3, 131.1, 130.8, 130.0, 127.2,
3-(5-(Pyridin-3-yl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2s).
124.5, 122.3, 120.6, 114.7, 113.8. HRMS (ESI) m/z: [M + H]+ The title compound was obtained as a light orange solid in
1
calcd for C15H9N4OBr 341.0033, found 340.9989.
3-(5-(3-Nitrophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
<10% yield (15 mg). H NMR (400 MHz, DMSO-d6) δ 8.99–8.90
(m, 1H), 8.78–8.70 (m, 1H), 8.21–8.13 (m, 1H), 8.01–7.93 (m,
(2m). The title compound was obtained as a light yellow solid 1H), 7.70–7.65 (m, 1H), 7.64–7.58 (m, 1H), 7.51–7.43 (m, 1H),
1
in 64% yield (98 mg). H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 7.23–7.15 (m, 1H).13C{1H} NMR (101 MHz, DMSO-d6) δ 156.7,
1H), 8.43–8.35 (m, 1H), 8.22 (d, J = 7.7 Hz, 1H), 7.98–7.92 (m, 156.0, 149.6, 148.4, 138.4, 135.6, 135.5, 131.3, 128.4, 127.2,
1H), 7.85 (t, J = 8.1 Hz, 1H), 7.69 (d, J = 9.1 Hz, 1H), 7.52–7.45 124.6, 123.1, 120.6, 114.7, 113.9. HRMS (ESI) m/z: [M + H]+
(m, 1H), 7.20 (t, J = 7.6 Hz, 1H). 13C{1H} NMR (101 MHz, calcd for C14H9N5O 264.0880, found 264.0863.
DMSO-d6) δ 156.0, 147.2, 134.4, 131.4, 129.8, 124.7, 123.4,
122.5, 120.6, 114.8, 113.9. HRMS (ESI) m/z: [M + H]+ calcd for (2t). The title compound was obtained as a yellow solid in 77%
C15H9N5O3 308.0778, found 308.0737.
yield (120 mg). 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H),
3-(5-(Naphthalen-2-yl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
3-(5-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2n). 8.08 (d, J = 8.6 Hz, 1H), 8.04–7.97 (m, 2H), 7.94 (d, J = 8.7 Hz,
The title compound was obtained as a light yellow solid in 1H), 7.81 (d, J = 8.5 Hz, 1H), 7.67 (d, J = 9.1 Hz, 1H), 7.64–7.57
1
57% yield (87 mg). H NMR (400 MHz, DMSO-d6) δ 8.42–8.36 (m, 2H), 7.49–7.42 (m, 1H), 7.19–7.10 (m, 1H). 13C{1H} NMR
(m, 2H), 8.07–7.99 (m, 2H), 7.95–7.89 (m, 1H), 7.73–7.66 (m, (101 MHz, DMSO-d6) δ 157.1, 156.0, 132.4, 131.9, 131.2, 127.6,
1H), 7.52–7.45 (m, 1H), 7.23–7.15 (m, 1H). 13C{1H} NMR 127.6, 127.5, 127.1, 126.5, 126.2, 125.3, 124.4, 120.7, 114.7,
(101 MHz, DMSO-d6) δ 156.3, 156.0, 147.1, 131.3, 129.2, 129.2, 113.8. HRMS (ESI) m/z: [M + H]+ calcd for C19H12N4O
124.8, 123.2, 123.0, 120.5, 115.0, 113.9. HRMS (ESI) m/z: [M + 313.1084, found 313.1056.
H]+ calcd for C15H9N5O3 308.0778, found 308.0737.
3-(5-(Phenanthren-9-yl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
3-(5-Cyclopropyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2o). (2u). The title compound was obtained as a light yellow solid
The title compound was obtained as a light yellow solid in in 83% yield (150 mg). 1H NMR (400 MHz, DMSO-d6) δ
1
56% yield (63 mg). H NMR (400 MHz, DMSO-d6) δ 8.08 (d, J = 9.06–8.92 (m, 2H), 8.15 (s, 1H), 8.08 (d, J = 7.9 Hz, 1H),
8.8 Hz, 1H), 7.67 (d, J = 9.1 Hz, 1H), 7.50–7.45 (m, 1H), 8.04–7.95 (m, 1H), 7.83 (t, J = 7.7 Hz, 1H), 7.75 (q, J = 8.0 Hz,
7.20–7.12 (m, 1H), 2.58–2.52 (m, 1H), 1.21–1.15 (m, 2H), 2H), 7.65–7.52 (m, 3H), 7.45–7.36 (m, 1H), 7.19–7.08 (m, 1H).
1.01–0.96 (m, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 158.6, 13C{1H} NMR (101 MHz, DMSO-d6) δ 155.7, 131.2, 129.8, 129.6,
156.5, 134.0, 131.9, 124.6, 121.5, 114.4, 114.2, 8.8, 5.7. HRMS 129.3, 128.4, 127.5, 126.8, 126.7, 124.9, 124.4, 122.9, 122.4,
(ESI) m/z: [M + H]+ calcd for C12H10N4O 277.0927, found 120.6, 114.3, 113.7. HRMS (ESI) m/z: [M + H]+ calcd for
277.0910.
C23H14N4O 363.1240, found 363.1211.
3-(5-Butyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2p). The
3-(5-((Benzyloxy)methyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxa-
title compound was obtained as yellow oil in 65% yield zole (2v). The title compound was obtained as a brown solid in
1
(79 mg). 1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.7 Hz, 26% yield (40 mg). H NMR (400 MHz, DMSO-d6) δ 8.07 (d, J =
1H), 7.62 (d, J = 9.1 Hz, 1H), 7.47–7.40 (m, 1H), 7.17–7.10 (m, 8.8 Hz, 1H), 7.69 (d, J = 9.1 Hz, 1H), 7.53–7.45 (m, 1H),
1H), 3.06 (t, J = 7.6 Hz, 2H), 1.74–1.63 (m, 2H), 1.40–1.29 (m, 7.39–7.25 (m, 5H), 7.19 (dd, J = 8.8, 6.3 Hz, 1H), 4.99 (s, 2H),
2H), 0.88 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) 4.64 (s, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 155.9, 137.1,
δ 158.0, 155.9, 132.8, 131.2, 126.0, 125.2, 123.9, 120.9, 113.7, 131.3, 127.6, 127.0, 124.4, 120.5, 114.1, 113.7, 71.3, 60.9.
113.5, 29.8, 22.8, 21.0, 12.9. HRMS (ESI) m/z: [M + H]+ calcd for HRMS (ESI) m/z: [M + H]+ calcd for C17H14N4O2 307.1189,
C13H14N4O 243.1240, found 243.1227.
found 307.1152.
3714 | Org. Biomol. Chem., 2021, 19, 3707–3716
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
5-Bromo-3-(5-phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2ab). Experimental procedure for the synthesis of compound 4
The title compound was obtained as a yellow solid in 47%
The
3-(5-phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
2a
yield (80 mg). 1H NMR (400 MHz, DMSO-d6) δ 8.11–8.05 (m,
1H), 7.75–7.71 (m, 2H), 7.68–7.64 (m, 1H), 7.58–7.54 (m, 3H),
7.53–7.50 (m, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 156.9,
154.4, 140.1, 134.5, 129.0, 128.1, 128.0, 127.8, 122.6, 116.9,
116.2, 115.5. HRMS (ESI) m/z: [M + H]+ calcd for C15H9N4OBr
341.0033, found 341.0012.
(131.0 mg, 0.50 mmol) and CuI (10 mg, 0.05 mmol) were dis-
solved in degassed DMF (3 mL) in a Schlenk tube under a N2
atmosphere. CF3COOH (114 mg, 1.00 mmol) was added by
injection. The mixture was stirred in an oil bath at 110 °C.
After 12 h, the reaction was completed (monitored by TLC,
eluent = 3 : 1 PE/EA). Then 50 mL of water was introduced and
extracted with EtOAc 3 times (3 × 50 mL). The extract was
washed with 30% NaCl solution (v/v), dried over
anhydrous Na2SO4 and concentrated under reduced
pressure. The residue was purified by column chromatography
on silica gel (eluent: PE/EA = 3/1) to afford the desired
product 4.
(2-Aminophenyl)(5-phenyl-1H-1,2,3-triazol-4-yl)methanone (4).
The title compound was obtained as a yellow solid in 67%
yield (88 mg). 1H NMR (400 MHz, DMSO-d6) δ 7.66–7.59 (m,
2H), 7.59–7.32 (m, 6H), 7.32–7.26 (m, 1H), 6.85 (d, J = 8.4 Hz,
1H), 6.46 (t, J = 7.5 Hz, 1H). 13C{1H} NMR (101 MHz, DMSO-d6)
δ 190.5, 152.3, 135.1, 134.1, 128.7, 128.3, 128.0, 127.5, 116.8,
116.7, 114.3. HRMS (ESI) m/z: [M + H]+ calcd for C15H12N4O
265.1084, found 265.1056.
5-Bromo-3-(5-(p-tolyl)-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
(2ac). The title compound was obtained as a light yellow solid
1
in 79% yield (140 mg). H NMR (400 MHz, DMSO-d6) δ 8.09 (s,
1H), 7.69–7.58 (m, 3H), 7.51 (dd, J = 9.4, 1.8 Hz, 1H), 7.39–7.33
(m, 2H), 2.40 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ
157.1, 154.3, 140.1, 138.8, 134.4, 128.7, 128.4, 128.0, 127.9,
122.6, 116.8, 116.1, 115.4, 20.3. HRMS (ESI) m/z: [M + H]+ calcd
for C16H11N4OBr 355.0189, found 355.0165.
5-Chloro-3-(5-phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole (2ad).
The title compound was obtained as a light yellow solid in
68% yield (102 mg). 1H NMR (400 MHz, DMSO-d6) δ 7.88 (s,
1H), 7.78–7.66 (m, 3H), 7.60–7.50 (m, 3H), 7.41 (d, J = 9.4 Hz,
1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 157.1, 154.4, 132.4,
129.0, 128.6, 128.1, 128.0, 119.1, 116.2, 114.7. HRMS (ESI) m/z:
[M + H]+ calcd for C15H9N4OCl 297.0538, found 297.0509.
5-Methyl-3-(5-phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
(2ae). The title compound was obtained as an off-white solid Experimental procedure for the synthesis of compound 5
in 62% yield (86 mg). 1H NMR (400 MHz, DMSO-d6) δ
To a solution of 3-(5-phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxa-
7.75–7.67 (m, 2H), 7.64–7.49 (m, 5H), 7.29 (d, J = 9.2 Hz, 1H),
zole 2a (105.0 mg, 0.40 mmol) in THF was added NaH (32 mg,
2.33 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 155.6, 155.3,
0.80 mmol, 2.0 equiv.) at
0
°C in an ice bath.
134.4, 133.7, 128.8, 128.1, 128.0, 117.7, 115.0, 113.6, 20.6.
HRMS (ESI) m/z: [M + H]+ calcd for C16H12N4O 277.1084,
found 277.1059.
After10 minutes, benzyl bromide (103 mg, 0.60 mmol, 1.5
equiv.) was added to the reaction mixture. Then the ice bath
was removed and the reaction mixture was stirred at room
temperature for 12 h. After the disappearance of the reactant
(monitored by TLC), 50 mL of water was introduced, and the
mixture was extracted with EtOAc 3 times (3 × 50 mL). The
extract was then washed with 30% NaCl solution (v/v), dried
over anhydrous Na2SO4 and concentrated under reduced
pressure. The obtained residue was purified by column chrom-
atography on silica gel (eluent: PE/EA = 8/1) to afford the
desired product 5.
3-(2-Benzyl-5-phenyl-2H-1,2,3-triazol-4-yl)benzo[c]isoxazole (5).
The title compound was obtained as a brown solid in 57%
yield (80 mg). 1H NMR (400 MHz, chloroform-d) δ 7.85–7.76
(m, 3H), 7.60 (dt, J = 9.1, 1.0 Hz, 1H), 7.51–7.43 (m, 5H),
7.43–7.30 (m, 4H), 7.05–7.00 (m, 1H), 5.74 (s, 2H). 13C{1H}
NMR (101 MHz, CDCl3) δ 157.2, 157.0, 147.1, 134.3, 134.2,
131.0, 129.4, 129.0, 128.7, 128.5, 128.5, 128.4, 128.1, 124.5,
121.4, 116.1, 114.7, 59.2. HRMS (ESI) m/z: [M + H]+ calcd for
C22H16N4O 353.1396, found 353.1334.
6-Methyl-3-(5-phenyl-1H-1,2,3-triazol-4-yl)benzo[c]isoxazole
(2af). The title compound was obtained as a brown solid in
1
38% yield (53 mg). H NMR (400 MHz, DMSO-d6) δ 7.77 (d, J =
9.0 Hz, 1H), 7.74–7.67 (m, 2H), 7.59–7.50 (m, 3H), 7.39 (s, 1H),
6.98 (d, J = 9.0 Hz, 1H), 2.38 (s, 3H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 156.5, 141.3, 128.9, 128.12, 127.9, 127.6, 120.1,
113.5, 111.1, 21.2. HRMS (ESI) m/z: [M + H]+ calcd for
C16H12N4O 277.1084, found 277.1058.
(2-Iodophenyl)(5-phenyl-1H-1,2,3-triazol-4-yl)methanone (3a).
The title compound was obtained as a white solid in 53% yield
1
(100 mg). H NMR (400 MHz, DMSO-d6) δ 7.98–7.84 (m, 3H),
7.57–7.45 (m, 5H), 7.29–7.22 (m, 1H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 189.8, 144.0, 138.4, 130.9, 129.1, 128.3, 128.1,
127.8, 127.2, 92.4. HRMS (ESI) m/z: [M + H]+ calcd for
C15H10N3OI 375.9941, found 375.9910.
(1-Benzyl-5-phenyl-1H-1,2,3-triazol-4-yl)(2-iodophenyl)metha-
none (3b). The title compound was obtained as a yellow solid
1
in 40% yield (94 mg). H NMR (400 MHz, CDCl3) δ 7.61 (d, J =
7.8 Hz, 1H), 7.39 (d, J = 7.3 Hz, 2H), 7.35–7.20 (m, 5H),
7.18–7.05 (m, 3H), 7.01 (t, J = 7.5 Hz, 1H), 6.96–6.82 (m, 2H),
5.95 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 187.0,
151.1, 141.0, 140.1, 134.5, 132.4, 130.2, 129.4, 129.1, 128.9,
Author contributions
128.6, 128.4, 128.4, 128.3, 127.6, 127.38, 93.24, 53.79. HRMS Kashif Majeed carried out the experiments, and wrote the
(ESI) m/z: [M + H]+ calcd for C22H16N3OI 466.0410, found manuscript with support from Fengtao Zhou, and Qiuyu
466.0385.
Zhang supervised the project.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 3707–3716 | 3715

View Article Online
Paper
Organic & Biomolecular Chemistry
M. Chiarini, L. Del Vecchio, F. Marinelli and V. Michelet,
Eur. J. Org. Chem., 2017, 2017, 2214.
Conflicts of interest
There are no conflicts to declare.
7 (a) K. Y. Lee, J. M. Kim and J. N. Kim, Bull. Korean Chem.
Soc., 2002, 23, 1493; (b) J. Chauhan and S. Fletcher,
Tetrahedron Lett., 2012, 53, 4951; (c) J. L. Serrano,
P. F. Soeiro, M. A. Reis, R. E. F. Boto, S. Silvestre and
P. Almeida, Mol. Divers., 2020, 24, 155.
Acknowledgements
The authors are grateful for the support and funding from the
National Natural Science Foundation of China (no. 21702165
and 51673156) and the Natural Science Foundation of Shaanxi
province China (no. 2018JQ2018). The support by the
Fundamental Research Funds for the Central Universities (no.
3102017jc01001) is acknowledged.
8 (a) N. Asao, K. Sato and Y. Yamamoto, Tetrahedron Lett.,
2003, 44, 5675; (b) X. Li, C. D. Incarvito, T. Vogel and
R. H. Crabtree, Organometallics, 2005, 9, 3066;
(c) B. J. Stokes, C. V. Vogel, L. K. Urnezis, M. Pan and
T. G. Driver, Org. Lett., 2010, 12, 2884; (d) P. Patel and
C. V. Ramana, Org. Biomol. Chem., 2011, 9, 7327;
(e) X. A. Gao, R. L. Yan, X. X. Wang, H. Yan, J. Li, H. Guo
and G. S. Huang, J. Org. Chem., 2012, 77, 7700.
9 (a) P. A. S. Smith, B. B. Brown, R. K. Putney and
R. F. Reinisch, J. Am. Chem. Soc., 1953, 75, 6335;
(b) L. K. Dyall, Aust. J. Chem., 1977, 30, 2669;
(c) V. V. Mezhnev, M. D. Dutov and S. A. Shevelev, Russ.
Chem. Bull., Int. Ed., 2009, 58, 476; (d) A. S. Golubev,
A. F. Shidlovskii, A. S. Peregudov and N. D. Kagramanov,
Russ. Chem. Bull., Int. Ed., 2014, 63, 2264;
(e) A. V. Odinokov, S. D. Plekhovich and A. V. Budruev,
Russ. Chem. Bull., Int. Ed., 2019, 68, 1298.
10 (a) K. D. Otley and J. A. Ellman, J. Org. Chem., 2014, 79,
8296; (b) M. WiÈ©cław, M. Bobin, A. Kwast, R. Bujok,
Z. Wróbel and K. Wojciechowski, Mol. Divers., 2015, 19,
807; (c) P. Beier and T. Pastýříková, Beilstein J. Org. Chem.,
2013, 9, 411; (d) J. S. Baum, M. E. Condon and D. A. Shook,
J. Org. Chem., 1987, 52, 2983.
Notes and references
1 (a) P. Nimnual, J. Tummatorn, C. Thongsornkleeb and
S. Ruchirawat, J. Org. Chem., 2015, 80, 8657; (b) X. Zhang,
R. Huang, J. Marrot, V. Coeffard and Y. Xiong, Tetrahedron,
2015, 71, 700.
2 (a) E. Whiting, M. E. Lanning, J. A. Scheenstra and
S. Fletcher, J. Org. Chem., 2015, 80, 1229;
(b) R. G. Kalkhambkar and H. Yuvaraj, Synth. Commun.,
2014, 44, 547; (c) T. J. Dale, A. C. Sather and J. Rebek,
Tetrahedron Lett., 2009, 50, 6173; (d) A. J. Boulton,
P. B. Ghosh and A. R. Katritzky, Angew. Chem., Int. Ed.
Engl., 1964, 3, 693; (e) P. A. S. Smith, B. B. Brown,
R. K. Putney and R. F. Reinisch, J. Am. Chem. Soc., 1953, 75,
6335.
11 D. Y. Dzhons and A. V. Budruev, Beilstein J. Org. Chem.,
2016, 12, 874.
12 S. Hosseini, S. A. Bawel, M. S. Mubarak and D. G. Peters,
ChemElectroChem, 2019, 6, 4318.
13 E. Rodrigo, H. Baunis, E. Suna and S. R. Waldvogel, Chem.
Commun., 2019, 55, 12255.
3 (a) A. C. Pierce, M. Jacobs and C. Stuver-Moody, J. Med.
Chem., 2008, 51, 1972; (b) Y. Tong, K. D. Stewart,
S. Thomas, M. Przytulinska, E. F. Johnson, V. Klinghofer,
J. Leverson, O. McCall, N. B. Soni, Y. Luo, N.-h. Lin,
T. J. Sowin, V. L. Giranda and T. D. Penning, Bioorg. Med.
Chem. Lett., 2008, 18, 5206.
14 (a) W. Wang, S. Huang, S. Yan, X. Sun, C. H. Tung and
Z. Xu, Chin. J. Chem., 2020, 38, 445–448; (b) W. Wang,
X. Peng, F. Wei, C. H. Tung and Z. Xu, Angew. Chem., Int.
Ed., 2016, 55, 649–653.
4 J. L. Serrano, E. Cavalheiro, S. Barroso, M. J. Romão,
S. Silvestre and P. Almeida, C. R. Chim., 2017, 20, 990.
5 M. WiÈ©cław, M. Bobin, A. Kwast, R. Bujok, Z. Wróbel and
K. Wojciechowski, Mol. Divers., 2015, 19, 807.
15 Y. Wang, P. Yu, Q. Ren, F. Jia, Y. Chen and A. Wu, J. Org.
Chem., 2020, 85, 2688.
16 K. Majeed, L. Wang, B. Liu, Z. Guo, F. Zhou and Q. Zhang,
J. Org. Chem., 2021, 86, 207–222.
6 (a) D. Sulikowski and M. Makosza, Acta Chim. Slov., 2009,
56, 680; (b) D. Anand, O. P. S. Patel, R. K. Maurya, R. Kant
and P. P. Yadav, J. Org. Chem., 2015, 80, 12410;
(c) M. Chiarini, L. Del Vecchio, F. Marinelli, L. Rossi and
A. Arcadi, Synthesis, 2016, 48, 3017; (d) A. Arcadi,
17 J. Li, Q. Zhang and L. Zhou, J. Org. Chem., 2012, 77, 2566.
3716 | Org. Biomol. Chem., 2021, 19, 3707–3716
This journal is © The Royal Society of Chemistry 2021