Polyfunctionalized biaryls accessed by a one-pot nucleophilic aromatic substitution and sigmatropic rearrangement reaction cascade under mild conditions

Article abstract of DOI:10.1016/j.tet.2021.131966

A practical synthetic method has been developed for polyfunctionalized biaryls based on a facile one-pot nucleophilic aromatic substitution (S_NAr) reaction and [5,5]- or [3,3]-sigmatropic rearrangement reaction cascade. Under mild basic conditions, N-arylhydroxylamines reacted with o-activated fluoro (het)arenes to form N,O-diarylhydroxylamine intermediates which underwent spontaneously selective [5,5]-sigmatropic rearrangement reaction to produce diverse functionalized 4-amino-4′-hydroxy-1,1′-biaryls. A sequential S_NAr reaction and [3,3]-sigmatropic rearrangement took place between N-arylhydroxylamines and 2-fluoropyridine derivatives or 4-fluorobenzonitrile to afford functionalized 2-amino-2′-hydroxy-1,1′-biaryls. As invaluable and unique building blocks, the resulting biaryls were applied in the straightforward synthesis of N₂,O₂-coronarene, carbazole, aza- and diaza carbazole derivatives.

Full text of DOI:10.1016/j.tet.2021.131966

Tetrahedron 83 (2021) 131966
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Polyfunctionalized biaryls accessed by a one-pot nucleophilic
aromatic substitution and sigmatropic rearrangement reaction
cascade under mild conditions
Dong-Dong Liang, Shen-Yi Guo, Shuo Tong**, Mei-Xiang Wang*
MOE Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A practical synthetic method has been developed for polyfunctionalized biaryls based on a facile one-pot
nucleophilic aromatic substitution (SNAr) reaction and [5,5]- or [3,3]-sigmatropic rearrangement reaction
cascade. Under mild basic conditions, N-arylhydroxylamines reacted with o-activated fluoro (het)arenes
to form N,O-diarylhydroxylamine intermediates which underwent spontaneously selective [5,5]-
sigmatropic rearrangement reaction to produce diverse functionalized 4-amino-40-hydroxy-1,10-biaryls.
A sequential SNAr reaction and [3,3]-sigmatropic rearrangement took place between N-arylhydroxyl-
amines and 2-fluoropyridine derivatives or 4-fluorobenzonitrile to afford functionalized 2-amino-20-
hydroxy-1,10-biaryls. As invaluable and unique building blocks, the resulting biaryls were applied in the
straightforward synthesis of N2,O2-coronarene, carbazole, aza- and diaza carbazole derivatives.
© 2021 Elsevier Ltd. All rights reserved.
Received 27 December 2020
Received in revised form
16 January 2021
Accepted 23 January 2021
Available online 29 January 2021
Keywords:
N,O-diarylhydroxylamine
SNAr reaction
[5,5]-sigmatropic rearrangement
[3,3]-sigmatropic rearrangement
Biaryl
1. Introduction
Suzuki reaction of 1-bromo-4-nitrobenzene [5,6] or from the
nitration of [1,10-biphenyl]-4-ol derivatives [4]. Diels-Alder reaction
Polyfunctionalized biaryls such as 4-amino-40-hydroxy-1,10-
biaryls are useful structural scaffolds in synthetic organic chemis-
try, drug design and discovery [1e3], and functional materials [4].
4-Amino-40-hydroxy-1,10-biphenyl, for example, constitutes the
core of novel necroptosis inducers [1] while 5-(4-aminophenyl)
pyridin-2-ol derivatives are potent carboxylic acid diacyglycerol
acyltransferase 1 inhibitors [3]. 4-Amino-40-hydroxy-1,10-biphenyl
has also been used as a building block in the fabrication of liquid
crystalline materials [4]. Among the methods [1e3,5e8] reported
for the synthesis of 4-amino-40-hydroxy-1,10-biaryl compounds, the
most frequently used one is the palladium-catalyzed cross coupling
reaction between pre-functionalized aryl halides and arylboronic
acids or esters (Suzuki reaction) [1e3,5,6]. Functional group
transformations such as reduction of the nitro group of 40-nitro-
[1,10-biphenyl]-4-ol derivatives also provide a synthetic route to 4-
amino-40-hydroxy-1,10-biaryl compounds [4]. In this regard, 40-
nitro-[1,10-biphenyl]-4-ol derivatives are obtained either from the
of 1-ethynyl-4-nitrobenzene with (cyclohexa-1,5-dien-1-yloxy)
trimethylsilane followed by aromatization at 140 ꢀC has also been
reported to afford 40-nitro-[1,10-biphenyl]-4-ol in 40% yield [7].
Heteracalixaromatics [9e11] and coronarenes [12e16] are
composed of meta- and para-(het)arylenes, respectively, with het-
eroatom linkages alternatively in a macrocyclic manner. Both types
of macrocycles are versatile synthetic host molecules to recognize
various cations, anions and charge-neutral guest species [9e16]. To
enrich the structure diversity and to exploit application of heter-
acalixaromatics and coronarenes, we became interested in 4-
amino-40-hydroxy-1,10-biaryl derivatives which are invaluable
building blocks for the fabrication of functional and giant cavities.
To obtain primary materials used in the construction of macro-
cycles for supramolecular applications,
a synthetic method
featuring (a) the avoidance of transition metal catalysts, (b) the use
of cheap and easily available reactants, (c) the tolerance to various
functional groups, and (d) simple operation procedures such as a
reaction cascade in one-pot is highly desired. We report herein the
synthesis of polyfunctionalized biaryls from the nucleophilic aro-
matic substitution reaction (SNAr) of N-arylhydroxylamines and
halo (het)arenes via the sigmatropic rearrangements of N,O-dia-
rylhydroxylamine intermediates. Synthetic applications of the
* Corresponding author.
** Corresponding author.
E-mail addresses: tongshuo@mail.tsinghua.edu.cn (S. Tong), wangmx@mail.
tsinghua.edu.cn (M.-X. Wang).
https://doi.org/10.1016/j.tet.2021.131966
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
resulting products will also be demonstrated.
temperature. The resulting transient N,O-diarylhydroxylamines
undergoes rapid [3,3]-sigmatropic rearrangement to afford mainly
2-amino-20-hydroxy-1,10-biaryls in moderate yields. Intriguingly,
the reaction does not take place when the o-halo substituent was
replaced by other groups [23].
A literature survey shows, in comparison with benzidine rear-
rangement [17], examples of rearrangement reactions of N,O-dia-
rylhydroxylamines are limited and the mechanism remains largely
unexplored although the first report of [5,5]-sigmatropic rear-
rangement may date back to early 1960s [18]. When reacting N-
acetyl-N-phenylhydroxylamine or N-hydroxy-N-phenylacetamide
with a diphenyliodonium salt to prepare N-acetyl-N,O-diphe-
nylhydroxylamine, Cox and Dunn [18] reported in 1963 the isola-
tion of N-(40-hydroxy-[1,10-biphenyl]-4-yl)acetamide in 33% yield.
Later in 1970s, Sheradsky [19e21] studied the reaction of benzyl N-
hydroxy-N-phenylcarbamate with several nitrated halo (het)arenes
in ethanolic potassium hydroxide demonstrating the synthesis of 4-
amino-40-hydroxy-biaryl products. It should be addressed that, in
addition to Refs. [5,5]-sigmatropic rearrangement, N,O-diary-
lhydroxylamines are able to undergo other reactions [18,20,22e25].
One overlooked but synthetically useful reaction is [3,3]-sigma-
tropic rearrangement [22e24]. Very recently, Kürti and co-workers
[23] reported the addition of ArMgX to o-halonitrobenzenes at low
2. Results and discussion
We embarked our study with the examination of SNAr reaction
between N-benzyl-N-phenylhydroxylamine 1a and 1-fluoro-2-
nitrobenzene 2a with the initial attempt to synthesize N,O-diary-
lhydroxylamine, a potential building unit for the construction of all
heteroatom-linked homo calixaromatics [26,27] and coronarenes
[28]. In the presence of Cs2CO3 as a base, the reaction proceeded
smoothly at 50 ꢀC in DMSO. Instead of N,O-diarylhydroxylamine A,
the reaction afforded straightforwardly nitro-bearing 4-
benzylamino-40-hydroxy-1,10-biphenyl 3a,
a
[5,5]-sigmatropic
rearrangement product of A, as the major product in 54% yield in
5 h (Scheme 1). 1-Chloro-2-nitrobenzene 2a′ reacted similarly as 2a
Scheme 1. Synthesis of polyfunctionalized biaryls 3 from the reaction of 1 with 2. [a] Yield from the reaction using 1-chloro-2-nitrobenzene 2a’. [b] 4a was also isolated in 34%.
2

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
to give the same product 3a in a slightly decreased yield (48%)
because of the diminished reactivity of 2a′ in comparison to 2a.
Upon further optimization of reaction conditions, we found that
polar aprotic solvent DMSO afforded highest yield compared with
other less polar solvents such as CH3CN and THF. Only trace amount
of 3a were obtained by using CH3CN or THF as solvent. Temperature
also plays an important role. Yields dropped a little bit when the
reaction was carried out at r. t. - 40 ꢀC (5e10% falling range) while
too high temperature gave a messy mixture. Besides Cs2CO3, K2CO3
could also serve as a base in spite of lower yields. The reaction gave
an inseparable mixture when other bases such as NaOAc and
NaOtBu were used. The reaction was extended readily to other
fluorobenzene substrates which contain other electron-
withdrawing functional groups. Cyano-bearing biaryl analog 3b
was obtained for example from the same reaction using 2-
fluorobenzonitrile 2b. Methyl 2-fluorobenzoate 2c underwent
similar reaction with 1a to form the corresponding product 3c
albeit in a lower yield due to the saponification of the methyl ester
group under the reaction conditions. In order to introduce pyridine
nucleus into the biaryl scaffolds, 2,6-difluoropyridine 2d was
employed. The reaction of 1a with 2d went to completion with 5 h,
resulting in the desired biaryl compound, namely, 5-(4-(benzyla-
mino)phenyl)-6-fluoropyridin-2-ol 3d in 29% yield. Notably, from
the same reaction mixture, 3-(2-(benzylamino)phenyl)-6-
fluoropyridin-2-ol 4a, which is derived from Refs. [3,3]-sigma-
tropic rearrangement of N,O-diarylhydroxylamine intermediate A,
was also isolated in 34% yield (Scheme 2). We will discuss this issue
later.
The substituent effect on the reactivity of arylhydroxylamine
was then examined. To our delight, results illustrated in Scheme 1
show that N-arylhydroxylamines substituted with either electron-
donation (1b) or electron-withdrawing (1c) groups on phenyl
acted as excellent substrates. They reacted efficiently with 1-fluoro-
2-nitrobenzene 2a to produce 4-amino-40-hydroxy-1,10-biphenyl
derivatives 3e and 3f in the yield of 86% and 67%, respectively.
Heterocyclic hydroxylamine such as N-(6-fluoropyridin-2-yl)-N-
methylhydroxylamine 1d, which was quantitatively prepared from
the reaction of 2,6-difluoropyridine 2d with N-methylhydroxyl-
amine (3 equiv.) within in 1 h, was also capable of reacting with
fluorobenzenes 2a-c. The chemical yields of the 4-amino-40-hy-
droxy-1,10-biaryl products 3g-i were only moderate owing to the
decreased nucleophilicity of hydroxylamine 1d. In the synthesis of
3g, its isomer, 4g, which is derived from Refs. [3,3]-sigmatropic
rearrangement of N,O-diarylhydroxylamine intermediate A, was
also isolated in 30% yield (Scheme 2). In these cases, there were also
side-reactions forming quite
a few polar and inseparable
Scheme 2. Synthesis of polyfunctionalized biaryls 4 from the reaction of 1 with 2. [a] 3d was also isolated in 29%. [b] 3g was also isolated in 42%.
3

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
compounds based on thin layer chromatography (TLC) analysis of
the reaction mixture. From the reaction of 1d with 2a, for instance,
we managed to isolate a small amount of 2-((6-fluoropyridin-2-yl)
(methyl)amino)-6-nitrophenol (8%) (see Supporting Information).
Finally, N-Boc-N-phenylhydroxylamine 1e was found to be a good
substrate. The reaction of 1e with activated fluorobenzenes 2a-b,
2d proceeded efficiently to furnish products 3j-l in 67e71% yields.
The outcomes summarized in Scheme 1 show clearly that N-
arylhydroxylamines 1a-e acted as O-nucleophiles to react with halo
(het)arenes 2a-d to form N,O-diarylhydroxylamine intermediates A
which are highly reactive to undergo spontaneously and predom-
inantly [5,5]-sigmatropic rearrangement producing functionalized
4-amino-40-hydroxy-1,10-biaryls 3a-l. However, in the case of the
reaction between 2,6-difluoropyridine 2d and 1a or 1g, formation
of both [5,5]- and [3,3]-sigmatropic rearrangement products 3a,g
and 4a,g were observed. This promoted us to further investigate the
reaction of N-arylhydroxylamines that bear an N-(para-substituted
phenyl) moiety as the presence of a para-substituent would block
the pathway of [5,5]-sigmatropic rearrangement, enabling [3,3]-
sigmatropic rearrangement and therefore the selective synthesis of
2-amino-20-hydroxy-1,10-biaryl compounds (Scheme 2). In accor-
dance to our expectation, reaction of N-(p-methylphenyl)- and N-
(p-methoxyphenyl)-hydroxylamines 1f and 1g with 2,6-
difluoropyridine 2d yielded indeed 2-amino-20-hydroxy-1,10-biar-
yls 4b and 4c, respectively. When 5-cyano-2-fluoropyridine 2e was
utilized to react with 1a or 1d, a sequential SNAr and [3,3]-sigma-
tropic rearrangement reactions took place similarly. Evidenced by
spectroscopic data and X-ray diffraction analysis, products 4d and
4e adopt pyridin-2(1H)-one tautomeric structure. It is worth noting
that the reaction between 1d and 2d resulted in the formation of
[3,3]-sigmatropic rearrangement product 6,60-difluoro-2’-(meth-
ylamino)-[3,30-bipyridin]-2-ol 4f in 63%. 6-Fluoro-3-((6-
fluoropyridin-2-yl) (methyl)amino)pyridin-2-ol (10%) was also
isolated as a by-product (see Supporting Information). Intriguingly,
no formation of 2,20-difluoro-6’-(methylamino)-[3,30-bipyridin]-6-
ol product, which is derived from Refs. [5,5]-sigmatropic rear-
rangement of N,O-dipyridylhydroxylamine intermediate A, was
observed. Finally, the reaction between 4-fluorobenzonitrile 2f and
N-Boc-N-(p-methylphenyl)-hydroxylamine 1h or N-Boc-N-(p-
methoxyphenyl)-hydroxylamine 1i afforded the corresponding
biphenyl 4h or 4i in the yield of 53% or 49%, respectively [29]
(Scheme 2).
Scheme 3. One-pot synthesis of 3,30-bipyridine derivatives 4f and 4j.
Scheme 4. Synthesis of macrocycle 6.
2,4-dichloro-6-methoxy-1,3,5-triazine and 3a (2 equiv) afforded
intermediate 5 which underwent macrocyclic condensation with
cyanuric acid chloride to produce macrocyclic compound 6. The
enlarged cavity and functional groups would render the macrocycle
6 useful in supramolecular applications [10,11,16]. 2-Amino-20-
hydorxy-1,10-biaryls, on the other hand, were easily and efficiently
converted, through a consecutive process of O-triflation and
intramolecular palladium-catalyzed CeN bond forming reaction,
into functionalized 9H-carbazole, aza-9H-carbazole and diaza-9H-
carbazole compounds 8 which are the privileged scaffolds for the
discovery of drugs [30] and functional materials [31] (Scheme 5).
Since N-(6-fluoropyridin-2-yl)-N-methylhydroxylamine 1d was
prepared nearly quantitatively from the reaction of N-methylhy-
droxylamine hydrochloride with equimolar 2,6-difluoropyridine 2d
under mild conditions, the synthesis of 3,30-bipyridine 4f was then
attempted from the reaction of 2d and N-methylhydroxylamine
hydrochloride in 2:1 stoichiometry. Gratifyingly, a tandem one-pot
reaction comprising two directional N- and O-nucleophilic re-
actions of hydroxylamine with 2d followed by Refs. [3,3]-sigma-
tropic rearrangement resulted in the production of 4f in 72% yield
(Scheme 3). An overall yield of 72% for a three-step cascade echoes
the efficiency of every bond forming reaction is as high as to 90%.
Moreover, the one-pot tandem method was readily extended to the
synthesis of tetrafluorinated 6’-(methylamino)-[3,30-bipyridin]-6-
ol 4j from the [5,5]-rearrangement reaction of N-methylhydroxyl-
amine with 2,3,6-trifluoropyridine (Scheme 3).
3. Conclusion
In conclusion, we have developed a practical cascade nucleo-
philic aromatic substitution and sigmatropic rearrangement
method for the synthesis of polyfunctionalized biaryls which are
hardly accessible by other means. We have revealed that N,O-dia-
rylhydroxylamines generated in situ underwent [5,5]-sigmatropic
rearrangement reaction predominantly, yielding 4-amino-40-hy-
droxy-1,10-biaryls. The reaction was steered away by the presence
of a para-substituent on the aryl moiety to Refs. [3,3]-sigmatropic
rearrangement to produce 2-amino-20-hydroxy-1,10-biaryls. The
easy availability of starting materials, transition metal-free and
mild one-pot reaction conditions, incorporation of multiple func-
tionalities and tunable reaction pathways would render this
Condensed functionalities confer the resulting biaryl products 3
and
4 invaluable platforms in organic synthesis because of
conceivable diverse functional group transformations. To demon-
strate the synthetic utility of the method, 4-amino-40-hydroxy-1,10-
biphenyl 3a was employed as a building block to construct N2,O2-
corona [2]biphenyl [2]triazine analog 6 by means of a fragment
coupling protocol. As depicted in Scheme 4, SNAr reaction between
4

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
solvents, the residue was purified by column chromatography on
silica gel to give 3.
4.1. 4’-(Benzylamino)-3-nitro-[1,10-biphenyl]-4-ol (3a)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (173 mg, 54%
yield): yellow solid, m. p. 107e108 ꢀC; 1H NMR (400 MHz,
DMSO‑d6)
d
10.80 (s, 1H), 7.95 (d, J ¼ 2.7 Hz, 1H), 7.73 (dd, J ¼ 8.7,
2.3 Hz, 1H), 7.45e7.28 (m, 6H), 7.22 (t, J ¼ 7.1 Hz, 1H), 7.13 (d,
J ¼ 8.7 Hz, 1H), 6.65 (d, J ¼ 8.7 Hz, 2H), 6.47 (t, J ¼ 6.2 Hz, 1H), 4.31
(d, J ¼ 6.4 Hz, 2H); 13C NMR (100 MHz, DMSO‑d6)
d 150.6, 148.7,
140.6,137.3,133.1,132.9,128.9,127.6,127.4, 127.3,125.8,121.3,120.0,
113.4, 46.7; IR (KBr, cmꢁ1
) n 3218, 3030, 1612, 1519, 1488. HRMS
(ESI-ion trap) calcd. for C19H15N2Oꢁ3 [M ꢁ H]- 319.1088. Found:
319.1087.
4.2. 4’-(Benzylamino)-4-hydroxy-[1,10-biphenyl]-3-carbonitrile
(3b)
Scheme 5. Synthesis of 9H-carbazole, aza-9H-carbazole and diaza-9H-carbazole
compounds 8.
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 15/1) (169 mg, 56%
yield): white solid, m. p. 196e197 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
method highly attractive and useful in organic synthesis.
d
10.91 (s, 1H), 7.71 (d, J ¼ 2.3 Hz, 1H), 7.66 (d, J ¼ 8.7 Hz, 1H),
7.44e7.27 (m, 6H), 7.22 (t, J ¼ 7.2 Hz, 1H), 7.01 (d, J ¼ 8.7 Hz, 1H),
6.62 (d, J ¼ 8.7 Hz, 2H), 6.42 (t, J ¼ 6.0 Hz, 1H), 4.30 (d, J ¼ 6.0 Hz,
4. Experimental section
2H); 13C NMR (100 MHz, DMSO‑d6)
d 158.4,148.1,140.2,132.4,131.8,
General. Reagents and solvents were purchased from com-
mercial sources and preserved under argon. More sensitive com-
pounds were stored in a desiccator or glove-box if required.
Reagents were used without further purification unless otherwise
noted. All reactions were performed under argon (or nitrogen) and
stirring unless otherwise noted. When needed oven dried glass-
ware was used (Tꢀ>100 ꢀC) or under vacuum with a heat gun
(Tꢀ>200 ꢀC). Anhydrous solvents were purified and dried following
standard procedures. Flash column chromatography was per-
formed using Silicycle SiliaFlash® P60 230e400 mesh. TLC analysis
was performed on pre-coated, glass-backed silica gel plates. TLC’s
were revealed by UV fluorescence (254 nm) then one of the
following: KMnO4, phosphomolybdic acid, ninhydrin, pancaldi, p-
anisaldehyde, vanillin. Melting points were uncorrected. The 1H
NMR, 13C NMR and 19F NMR spectra were recorded on a JEOL ECX-
400 400 MHz spectrometers, 1H frequency is at 400.13 MHz, 13C
frequency is at 100.62 MHz, 19F frequency is at 376.31 MHz.
129.3, 128.3, 127.2, 126.74, 126.66, 125.7, 117.2, 116.6, 112.7, 99.2,
46.3; IR (KBr, cmꢁ1
) n 3219, 2243, 1611, 1500. HRMS (ESI-ion trap)
calcd. for C20H15N2Oꢁ [M ꢁ H]- 299.1190. Found: 299.1190.
4.3. Methyl 4’-(benzylamino)-4-hydroxy-[1,10-biphenyl]-3-
carboxylate (3c)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (81 mg, 24%
yield): white solid, m. p. 107e108 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
d
10.38 (s, 1H), 7.87 (d, J ¼ 2.3 Hz, 1H), 7.69 (dd, J ¼ 8.7, 2.3 Hz, 1H),
7.45e7.27 (m, 6H), 7.22 (t, J ¼ 7.1 Hz, 1H), 6.99 (d, J ¼ 8.2 Hz, 1H),
6.65 (d, J ¼ 8.7 Hz, 2H), 6.41 (t, J ¼ 6.0 Hz, 1H), 4.30 (d, J ¼ 6.0 Hz,
2H), 3.90 (s, 3H); 13C NMR (100 MHz, DMSO‑d6)
d 169.4,158.3,148.1,
140.3, 133.0, 132.3, 128.5, 127.3, 126.85, 126.80, 126.5, 126.3, 117.9,
113.3, 112.9, 52.6, 46.4; IR (KBr, cmꢁ1
) n 3379, 3027, 2679, 1612,
1490. HRMS (ESI-ion trap) calcd. for C21H18NO3- [M ꢁ H]- 332.1292.
Chemical shifts (
d
) were reported in parts per million (ppm) relative
Found: 332.1292.
to residual solvent peaks rounded to the nearest 0.01 for proton and
0.1 for carbon (ref: DMSO [dH ¼ 2.50; dC ¼ 39.52] and CHCl3
4.4. 5-(4-(Benzylamino)phenyl)-6-fluoropyridin-2-ol (3d)
[
dH ¼ 7.26, dC ¼ 77.16]). Coupling constants (J) were reported in Hz
to the nearest 0.1 Hz. Peak multiplicity was indicated as follows s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and br
(broad). Attribution of peaks was done using the multiplicities and
integrals of the peaks. The high resolution mass spectra (HRMS)
were recorded on a GCT-MS Micromass UK spectrometer or a
microTOF-Q spectrometer. Infrared spectra were recorded using a
PerkinElmer Spectrum 100 FT-IR spectrometer with KBr pellets in
the 4000-400 cmꢁ1 region.
General procedure for the synthesis of [5,5]-rearrangement
product 3. To a 25 mL Schlenk tube were charged with N-arylhy-
droxylamines 1 (1 mmol), aryl fluoride 2 (1 mmol), and Cs2CO3
(489 mg, 1.5 mmol, 1.5 equiv). The reaction mixture was purged
three times with Ar. DMSO (2 mL) was injected to the Schlenk tube
and the resulting mixture was stirring at 50 ꢀC for 5 h. The reaction
mixture was quenched with water, neutralized with 1 N HCl to
pH ¼ 7. The resulting mixture was extracted with ethyl acetate
(3 ꢂ 10 mL) and dried over anhydrous Na2SO4. After removal of
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (86 mg, 29%
yield): white solid, m. p. 210e211 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
d
11.20 (s, 1H), 7.79 (dd, J ¼ 10.8, 8.0 Hz, 1H), 7.45e7.27 (m, 4H),
7.25e7.18 (m, 3H), 6.64 (d, J ¼ 8.7 Hz, 2H), 6.59 (d, J ¼ 7.8 Hz, 1H),
6.48 (t, J ¼ 6.0 Hz, 1H), 4.30 (d, J ¼ 6.0 Hz, 2H); 19F NMR (376 MHz,
DMSO‑d6)
d
d
ꢁ74.60 (d, J ¼ 11.7); 13C NMR (100 MHz, DMSO‑d6)
160.9 (d, J ¼ 15.3 Hz), 158.1 (d, J ¼ 236.4 Hz), 148.4, 143.5, 140.6,
129.4, 128.9, 127.6, 127.2, 121.4, 113.9 (d, J ¼ 26.7 Hz), 112.9, 107.2,
46.6; IR (KBr, cme1)
n 3392, 3031, 1612, 1489. HRMS (ESI-ion trap)
calcd. for C18H14FN2Oꢁ [M ꢁ H]- 293.1096. Found: 293.1095.
4.5. 4’-(Benzylamino)-20,60-dimethyl-3-nitro-[1,10-biphenyl]-4-ol
(3e)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 15/1) (300 mg, 86%
5

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
yield): white solid, m. p. 131e132 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
4.10. tert-Butyl (40-hydroxy-30-nitro-[1,10-biphenyl]-4-yl)
d
10.90 (s, 1H), 7.52 (d, J ¼ 2.3 Hz, 1H), 7.38e7.20 (m, 6H), 7.13 (d,
J ¼ 8.2 Hz, 1H), 6.34 (s, 2H), 6.18 (t, J ¼ 6.2 Hz, 1H), 4.26 (d, J ¼ 6.2 Hz
2H), 1.85 (s, 6H); 13C NMR (100 MHz, DMSO‑d6)
150.8, 148.1, 140.9,
137.7, 136.7136.5, 132.5128.7, 127.52, 127.47, 127.1, 126.2, 119.3, 111.8,
carbamate (3j)
d
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (221 mg, 67%
yield): orange solid, m. p. 147e149 ꢀC; 1H NMR (400 MHz,
46.6, 21.3; IR (KBr, cmꢁ1
) n 3402, 3237, 2859,1610,1529,1427. HRMS
(ESI-ion trap) calcd. for C21H19N2Oꢁ3 [M ꢁ H]- 347.1401. Found:
DMSO‑d6)
7.82 (dd, J ¼ 8.7, 2.4 Hz, 1H), 7.58e7.53 (m, 4H), 7.19 (d, J ¼ 8.7 Hz,
1H), 1.48 (s, 9H); 13C NMR (100 MHz, DMSO‑d6)
152.7, 150.8, 139.1,
137.2, 132.7, 131.4, 131.2, 126.5, 121.9, 119.6, 118.5, 79.1, 28.1; IR (KBr,
d
10.98 (br s, 1H), 9.46 (br s, 1H), 8.07 (d, J ¼ 2.4 Hz, 1H),
347.1399.
d
4.6. 4’-(Benzylamino)-20,60-dichloro-3-nitro-[1,10-biphenyl]-4-ol
(3f)
cmꢁ1
) n 3367, 3181, 2968, 1702, 1511, 1427, 1322, 1231, 1157, 823;
HRMS (ESI) Calcd. for C17H17O5Nꢁ2 [M ꢁ H]- 329.1143. Found:
329.1142.
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 20/1) (261 mg, 67%
yield): yellow solid, m. p. 114e115 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
4.11. tert-Butyl (30-cyano-40-hydroxy-[1,10-biphenyl]-4-yl)
carbamate (3k)
d
11.15 (s, 1H), 7.68 (s, 1H), 7.50e6.80 (m, 8H), 6.73 (br s, 2H), 4.33 (s,
2H); 13C NMR (100 MHz, DMSO‑d6)
151.4, 149.6, 139.1, 137.4, 136.5,
134.3, 128.5, 127.7, 127.2, 127.0, 126.8, 122.9, 118.7, 111.3, 45.9; IR
d
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (220 mg, 71%
yield): light yellow solid, m. p. 200e202 ꢀC; 1H NMR (400 MHz,
(KBr, cmꢁ1
) n 3417, 3203, 1604, 1538. HRMS (ESI-ion trap) calcd. for
C
19H13Cl2N2O3- [M ꢁ H]- 387.0309. Found: 387.0307.
DMSO‑d6)
7.76 (dd, J ¼ 8.8, 2.4 Hz, 1H), 7.55e7.50 (m, 4H), 7.07 (d, J ¼ 8.7 Hz,
1H), 1.48 (s, 9H); 13C NMR (100 MHz, DMSO‑d6)
159.2, 152.7, 138.9,
132.4, 131.8, 131.4, 130.3, 126.4, 118.4, 117.0, 116.7, 99.4, 79.1, 28.1; IR
d
11.11 (br s, 1H), 9.42 (br s, 1H), 7.85 (d, J ¼ 2.4 Hz, 1H),
4.7. 4-(2-Fluoro-6-(methylamino)pyridin-3-yl)-2-nitrophenol (3g)
d
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (110 mg, 42%
yield): yellow solid, m. p.169e170 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
(KBr, cmꢁ1
) n 3292, 2236, 1693, 1531, 1427, 1283, 1248, 1156, 819;
HRMS (ESI) Calcd. for C18H17N2Oꢁ3 [M ꢁ H]- 309.1245. Found:
309.1243.
d
11.03 (s, 1H), 7.94 (d, J ¼ 2.3 Hz, 1H), 7.80e7.58 (m, 2H), 7.17 (d,
J ¼ 8.7 Hz, 1H), 7.08 (d, J ¼ 4.6 Hz, 1H), 6.43 (d, J ¼ 6.4 Hz, 1H), 2.77
4.12. tert-Butyl (4-(2-fluoro-6-hydroxypyridin-3-yl)phenyl)
carbamate (3l)
(d, J ¼ 5.0 Hz, 3H); 19F NMR (376 MHz, DMSO‑d6)
d
ꢁ73.99 (d,
J ¼ 9.0 Hz); 13C NMR (100 MHz, DMSO‑d6)
159.1 (d, J ¼ 232.6 Hz),
d
158.2 (d, J ¼ 18.2 Hz), 150.7, 140.7, 136.8, 134.5, 126.0 (d, J ¼ 5.7 Hz),
123.7 (d, J ¼ 3.8 Hz), 119.3, 105.0 (d, J ¼ 36.2 Hz), 104.5 27.9; IR (KBr,
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (204 mg, 67%
yield): white solid, m. p. 210e211 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
cmꢁ1
) n 3283, 3131, 1638, 1539, 1457. HRMS (ESI-ion trap) calcd. for
C
12H9FN3Oꢁ3 [M ꢁ H]- 262.0633. Found: 262.0632.
d
11.35 (s, 1H), 9.44 (s, 1H), 7.88 (t, J ¼ 9.4 Hz, 1H), 7.53 (d, J ¼ 8.7 Hz,
2H), 7.41 (d, J ¼ 8.2 Hz, 2H), 6.64 (d, J ¼ 8.2 Hz, 1H), 1.48 (s, 9H); 19
F
4.8. 5-(2-Fluoro-6-(methylamino)pyridin-3-yl)-2-
hydroxybenzonitrile (3h)
NMR (376 MHz, DMSO‑d6)
d
ꢁ74.29 (d, J ¼ 8.6 Hz); 13C NMR
(100 MHz, DMSO‑d6)
d
161.5 (d, J ¼ 16.2 Hz), 157.7 (d, J ¼ 237.4 Hz),
152.7, 143.4 (d, J ¼ 4.8 Hz), 138.9, 128.5, 127.4 (d, J ¼ 4.8 Hz), 118.1,
112.5 (d, J ¼ 26.7 Hz), 106.9, 79.1, 28.1; IR (KBr, cmꢁ1
) n 3391, 2981,
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (71 mg, 29%
yield): white solid, m. p. 193e195 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
1704, 1589, 1508. HRMS (ESI-ion trap) calcd. for C16H16FN2O3:
[M ꢁ H]- 303.1150. Found: 303.1150.
d
11.16 (s, 1H), 7.76e7.63 (m, 2H), 7.60 (d, J ¼ 8.7 Hz, 1H), 7.05 (d,
General procedure for the synthesis of [3,3]-rearrangement
product 4. To a 25 mL Schlenk tube were charged with N-arylhy-
droxylamines 1 (1 mmol), aryl fluoride 2 (1 mmol), and Cs2CO3
(489 mg, 1.5 mmol, 1.5 equiv). The reaction mixture was purged
three times with Ar. DMSO (2 mL) was injected to the Schlenk tube
and the resulting mixture was stirring at 50 ꢀC for 5 h. The reaction
mixture was quenched with water, neutralized with 1 N HCl to
pH ¼ 7. The resulting mixture was extracted with ethyl acetate
(3 ꢂ 10 mL) and dried over anhydrous Na2SO4. After removal of
solvents, the residue was purified by column chromatography on
silica gel to give 4.
J ¼ 8.7 Hz, 2H), 6.41 (d, J ¼ 6.4 Hz, 1H), 2.76 (d, J ¼ 4.6 Hz, 3H); 19
F
NMR (376 MHz, DMSO‑d6)
d
ꢁ74.28 (d, J ¼ 8.6 Hz); 13C NMR
(100 MHz, DMSO‑d6)
d
159.1 (d, J ¼ 232.6 Hz), 158.9, 158.1 (d,
J ¼ 17.1 Hz), 140.9, 134.4, 134.3, 132.0, 126.4 (d, J ¼ 4.7 Hz), 117.0,
116.5, 105.2 (d, J ¼ 27.7 Hz), 99.2 28.0; IR (KBr, cmꢁ1
) n 3250, 2237,
1627, 1572, 1427. HRMS (ESI-ion trap) calcd. for C13H9FN3Oꢁ
[M ꢁ H]- 242.0735. Found: 242.0733.
4.9. Methyl 5-(2-fluoro-6-(methylamino)pyridin-3-yl)-2-
hydroxybenzoate (3i)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 8/1) (67 mg, 24%
yield): white solid, m. p. 157e158 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
4.13. 3-(2-(Benzylamino)phenyl)-6-fluoropyridin-2-ol (4a)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (101 mg, 34%
yield): white solid, m. p. 150e151 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
d
10.48 (s, 1H), 7.84 (s, 1H), 7.75e7.54 (m, 2H), 7.12e6.92 (m, 2H),
6.43 (dd, J ¼ 8.2, 1.4 Hz, 1H), 3.90 (s, 3H), 2.77 (d, J ¼ 4.6 Hz, 3H); 19
F
NMR (376 MHz, DMSO‑d6)
(100 MHz, DMSO‑d6)
d
ꢁ74.47 (d, J ¼ 11.7 Hz); 13C NMR
d
11.52 (s, 1H), 7.69 (t, J ¼ 8.2 Hz, 1H), 7.34 (d, J ¼ 7.3 Hz, 2H), 7.28 (t,
d
169.0, 159.1 (d, J ¼ 235.5 Hz), 158.6, 158.0 (d,
J ¼ 7.6 Hz, 2H), 7.19 (t, J ¼ 7.1 Hz, 1H), 7.06e7.00 (m, 1H), 6.91 (dd,
J ¼ 7.6, 1.6 Hz, 1H), 6.67 (dd, J ¼ 7.8, 2.7 Hz, 1H), 6.57 (t, J ¼ 7.1 Hz,
1H), 6.42 (d, J ¼ 8.2 Hz, 1H), 5.29 (br, 1H), 4.28 (s, 2H); 19F NMR
J ¼ 17.2 Hz), 140.8, 135.0, 128.9, 126.1 (d, J ¼ 4.7 Hz), 117.8, 113.2,
105.7, 105.3 (d, J ¼ 39.1 Hz), 52.6, 27.9; IR (KBr, cmꢁ1
) n 3289, 1686,
1637, 1439. HRMS (ESI-ion trap) calcd. for C14H12FN2Oꢁ3 [M ꢁ H]-
(376 MHz, DMSO‑d6)
d
d
ꢁ73.08; 13C NMR (100 MHz, DMSO‑d6)
275.0837. Found: 275.0839.
161.5 (d, J ¼ 235.5 Hz), 160.3 (d, J ¼ 14.3 Hz), 146.2, 146.1, 140.7,
6

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
131.3, 129.3, 129.1, 127.5, 127.3, 122.5, 118.0, 116.8, 111.3, 100.4 (d,
4.18. 6,60-Difluoro-2’-(methylamino)-[3,30-bipyridin]-2-ol (4f)
J ¼ 35.3 Hz), 46.9; IR (KBr, cmꢁ1
) n 3446, 3026, 1600, 1578, 1442.
HRMS (ESI-ion trap) calcd. for C18H14FN2Oꢁ [M ꢁ H]- 293.1096.
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (151 mg, 63%
yield): white solid, m. p. 212 ꢀC, sublimation; 1H NMR (400 MHz,
Found: 293.1094.
4.14. 3-(2-(Benzylamino)-5-methylphenyl)-6-fluoropyridin-2-ol
(4b)
DMSO‑d6)
d
11.47 (s, 1H), 7.64 (t, J ¼ 8.2 Hz, 1H), 7.30 (t, J ¼ 8.2 Hz,
1H), 6.64 (dd, J ¼ 8.0, 2.5 Hz, 1H), 6.15 (dd, J ¼ 7.8, 2.7 Hz, 1H), 6.04
(s, 1H), 2.70 (d, J ¼ 4.1 Hz, 3H); 19F NMR (376 MHz, DMSO‑d6)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 8/1) (170 mg, 55%
yield): white solid, m. p. 148e150 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
d
d
ꢁ71.63 (d, J ¼ 8.6 Hz), ꢁ72.39; 13C NMR (100 MHz, DMSO‑d6)
162.4 (d, J ¼ 230.7 Hz),161.1 (d, J ¼ 235.5 Hz),160.3 (d, J ¼ 15.3 Hz),
156.1 (d, J ¼ 18.1 Hz), 145.4 (d, J ¼ 8.6 Hz), 142.4 (d, J ¼ 9.5 Hz), 114.9
(d, J ¼ 4.8 Hz), 113.3 (d, J ¼ 4.8 Hz), 99.8 (d, J ¼ 36.2 Hz), 92.6 (d,
d
11.51 (br, 1H), 7.68 (t, J ¼ 8.2 Hz, 1H), 7.33e7.23 (m, 4H), 7.18 (t,
J ¼ 7.0 Hz, 1H), 6.85 (d, J ¼ 8.5 Hz, 1H), 6.75 (s, 1H), 6.66 (dd, J ¼ 7.9,
2.4 Hz, 1H), 6.36 (d, J ¼ 7.9 Hz, 1H), 5.06 (br, 1H), 4.25 (s, 2H), 2.14 (s,
J ¼ 37.2 Hz), 28.3; IR (KBr, cmꢁ1
) n 3437, 2942, 1619, 1588. HRMS
(ESI-ion trap) calcd. for C11H8F2N3Oꢁ [M ꢁ H]- 236.0641. Found:
3H); 19F NMR (376 MHz, DMSO‑d6)
d
ꢁ73.15; 13C NMR (100 MHz,
236.0637.
DMSO‑d6)
d
160.8 (d, J ¼ 235.5 Hz), 160.0 (d, J ¼ 16.2 Hz), 145.3 (d,
J ¼ 8.6 Hz), 143.4, 140.4, 131.2, 128.9, 128.2, 126.8, 126.4, 124.1, 122.0,
117.6 (d, J ¼ 4.8 Hz), 110.7, 99.3 (d, J ¼ 35.2 Hz), 46.6, 19.9; IR (KBr,
4.19. 2-(6-Fluoro-2-(methylamino)pyridin-3-yl)-6-nitrophenol
(4g)
cmꢁ1
) n 3419, 3026, 1592, 1519, 1472. HRMS (ESI-ion trap) calcd. for
C
19H16FN2Oꢁ [M ꢁ H]- 307.1252. Found: 307.1252.
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (79 mg, 30%
yield): orange solid, m. p. 177e179 ꢀC; 1H NMR (400 MHz,
4.15. 3-(2-(Benzylamino)-5-methoxyphenyl)-6-fluoropyridin-2-ol
(4c)
DMSO‑d6)
d
10.49 (br s, 1H), 8.07 (dd, J ¼ 8.4, 1.7 Hz, 1H), 7.52 (dd,
J ¼ 7.4, 1.7 Hz, 1H), 7.36 (dd, J ¼ 8.4, 7.8 Hz, 1H), 7.10 (dd, J ¼ 8.4,
7.4 Hz, 1H), 6.20 (dd, J ¼ 7.7, 2.8 Hz, 1H), 6.05 (br s, 1H), 2.71 (s, 3H);
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (159 mg, 49%
yield): white solid, m. p. 173e174 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
13C NMR (100 MHz, DMSO‑d6)
d
162.6 (d, J ¼ 231 Hz), 155.9 (d,
J ¼ 18 Hz), 151.4, 142.2 (d, J ¼ 9 Hz), 138.7, 135.9, 128.2, 124.9, 119.9,
d
11.30 (br, 1H), 7.72 (t, J ¼ 8.2 Hz, 1H), 7.33e7.16 (m, 5H), 6.73e6.58
113.5 (d, J ¼ 4 Hz), 92.8 (d, J ¼ 37 Hz), 28.2; IR (KBr, cmꢁ1
) n 3457,
(m, 3H), 6.44 (d, J ¼ 8.7 Hz, 1H), 5.20 (br, 1H), 4.21 (s, 2H), 3.63 (s,
3161, 3079, 1619, 1597, 1531, 1444, 1398, 1316, 1266, 1216, 746;
HRMS (ESI-ion trap) Calcd. for C12H9O3N3Fꢁ [M ꢁ H]- 262.0633;
Found: 262.0631.
3H); 19F NMR (376 MHz, DMSO‑d6)
DMSO‑d6)
d
ꢁ72.78; 13C NMR (100 MHz,
d
160.9 (d, J ¼ 234.6 Hz), 159.9 (d, J ¼ 15.2 Hz), 150.6,
145.3 (d, J ¼ 8.5 Hz), 140.4, 139.8, 128.2, 126.9, 126.5, 123.3, 117.4 (d,
J ¼ 5.7 Hz), 116.9, 113.8, 112.0, 99.3 (d, J ¼ 36.2 Hz), 55.3, 47.2; IR
4.20. tert-Butyl (50-cyano-20-hydroxy-5-methyl-[1,10-biphenyl]-2-
yl)carbamate (4h)
(KBr, cmꢁ1
)
n
3380, 3030, 1620, 1519, 1472. HRMS (ESI-ion trap)
calcd. for C19H16FN2Oꢁ2 [M ꢁ H]- 323.1201. Found: 323.1201.
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 4/1) (172 mg, 53%
yield): white solid, m. p. 205e207 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
4.16. 5-(2-(Benzylamino)phenyl)-6-oxo-1,6-dihydropyridine-3-
carbonitrile (4d)
d
10.82 (br s, 1H), 7.91 (br s, 1H), 7.63 (dd, J ¼ 8.5, 2,2 Hz,1H), 7.50 (d,
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (166 mg, 55%
yield): white solid, m. p. 161e162 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
J ¼ 2.1 Hz, 1H), 7.31 (d, J ¼ 8.1 Hz, 1H), 7.14 (dd, J ¼ 8.2, 1.6 Hz, 1H),
7.08e7.06 (m, 2H), 2.29 (s, 3H), 1.31 (s, 9H); 13C NMR (100 MHz,
DMSO‑d6)
d 158.6,153.3,135.5,133.7,133.4,133.0,131.5,131.3,128.6,
d
12.60 (s,1H), 8.32 (d, J ¼ 2.4 Hz,1H), 7.64 (d, J ¼ 2.4 Hz,1H), 7.37 (d,
127.4, 125.2, 119.4, 116.6, 101.2, 78.6, 27.9, 20.4; IR (KBr, cmꢁ1
) n
J ¼ 7.3 Hz, 2H), 7.29 (t, J ¼ 7.3 Hz, 2H), 7.19 (t, J ¼ 7.0 Hz, 1H),
7.14e7.00 (m, 1H), 6.96 (dd, J ¼ 7.6, 1.5 Hz, 1H), 6.57 (t, J ¼ 7.3 Hz,
3377, 3183, 2229, 1682, 1603, 1504, 1280, 1159, 841; HRMS (ESI-ion
trap) Calcd. for C19H19N2O3ꢁ [M ꢁ H]- 323.1401; Found: 323.1399.
1H), 6.42 (d, J ¼ 7.9 Hz, 1H), 5.60 (s, 1H), 4.28 (d, J ¼ 4.3 Hz, 2H); 13
C
NMR (100 MHz, DMSO‑d6)
d
160.6, 146.1, 143.4, 140.2, 140.1, 131.9,
4.21. tert-Butyl (50-cyano-20-hydroxy-5-methoxy-[1,10-biphenyl]-2-
130.6, 129.0, 128.2, 126.8, 126.5, 121.8, 117.3, 115.6, 110.5, 89.9, 46.3.
yl)carbamate (4i)
IR (KBr, cmꢁ1
) n 3295, 3061, 2229, 1642. HRMS (ESI-ion trap) calcd.
for C19H14N3Oꢁ [M ꢁ H]- 300.1142. Found: 300.1142.
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 4/1) (167 mg, 49%
yield): white solid, m. p. 189e191 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
4.17. 60-Fluoro-2’-(methylamino)-2-oxo-1,2-dihydro-[3,30-
bipyridine]-5-carbonitrile (4e)
d
10.83 (br s,1H), 7.93 (br s, 1H), 7.63 (dd, J ¼ 8.5, 2.2 Hz, 1H), 7.53 (d,
J ¼ 2.1 Hz, 1H), 7.26 (d, J ¼ 8.6 Hz, 1H), 7.07 (d, J ¼ 8.5 Hz, 1H), 6.91
(dd, J ¼ 8.8, 3.0 Hz, 1H), 6.82 (d, J ¼ 2.9 Hz, 1H), 3.75 (s, 3H), 1.29 (s,
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (91 mg, 37%
yield): white solid, m. p. 198e199 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
9H); 13C NMR (100 MHz, DMSO‑d6)
d 158.7,156.4,153.7, 135.4,133.7,
133.0, 128.9, 127.5, 127.3, 119.5, 116.7, 115.8, 113.6, 101.0, 78.4, 55.3,
d
10.62 (d, J ¼ 5.5 Hz, 1H), 7.60 (t, J ¼ 7.6 Hz, 1H), 7.48 (d, J ¼ 6.0 Hz,
28.0; IR (KBr, cmꢁ1
) n
3393, 3147, 2969, 2230, 1675, 1603, 1504,
1H), 6.24 (d, J ¼ 7.8 Hz, 1H), 4.55 (d, J ¼ 10.5 Hz, 1H), 4.31 (d,
1285, 1161, 1032, 874, 838; HRMS (ESI-ion trap) Calcd. for
J ¼ 10.5 Hz, 1H), 2.94 (s, 3H); 19F NMR (376 MHz, DMSO‑d6)
d
ꢁ74.14
C
19H19N2Oꢁ4 [M ꢁ H]- 339.1350; Found: 339.1347.
(d, J ¼ 8.6 Hz); 13C NMR (100 MHz, DMSO‑d6)
d
167.0, 164.0 (d,
One-pot synthesis of 3,3′-bipyridine derivatives 4f and 4j. To a
J ¼ 233.6 Hz), 160.9 (d, J ¼ 18.1 Hz), 142.6, 137.4 (d, J ¼ 8.6 Hz), 119.5,
25 mL Schlenk tube were charged with N-methylhydroxylamine
hydrochloride (83.5 mg, 1 mmol), Cs2CO3 (978 mg, 3 mmol). The
reaction mixture was purged three times with Ar. DMSO (2 mL) was
injected and the resulting mixture was stirring at room
115.8 (d, J ¼ 3.8 Hz), 95.3 (d, J ¼ 37.1 Hz), 82.9, 60.8, 41.9, 31.3; IR
(KBr, cmꢁ1
) n 3293, 2870, 2218, 1702, 1661. HRMS (ESI-ion trap)
calcd. for C12H8FN4Oꢁ [M ꢁ H]- 243.0688. Found: 243.0685.
7

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
temperature for 30 min. Aryl fluoride 2 (2 mmol) was added and
the resulting mixture was stirring at 80 ꢀC for 24 h. The reaction
mixture was quenched with water, neutralized with 1 N HCl to
pH ¼ 7. The resulting mixture was extracted with ethyl acetate
(3 ꢂ 10 mL) and dried over anhydrous Na2SO4. After removal of
solvents, the residue was purified by column chromatography on
silica gel to give 4.
Synthesis of 7. To a solution of 4 (2 mmol) in dry pyridine (4 mL)
was added Tf2O (0.42 mL, 2.5 mmol, 1.25 equiv) dropwise at 0 ꢀC.
The resulting solution was stirred at room temperature overnight.
Dilute hydrochloric acid (1 N) was added to the mixture to pH ¼ 3
to quench the reaction. Than resulting mixture was diluted with
water (20 mL) and extracted with CH2Cl2 (3 ꢂ 10 mL). The com-
bined organic layers were washed with brine, dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (petroleum ether
and ethyl acetate) to give compound 7.
4.22. 5,50,6,60-Tetrafluoro-2’-(methylamino)-[3,30-bipyridin]-2-ol
(4j)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 3/1) (164 mg, 60%
yield): white solid, m. p. 268e270 ꢀC; 1H NMR (400 MHz, DMSO‑d6,
4.23. 3-(2-(Benzylamino)phenyl)-6-fluoropyridin-2-yl
trifluoromethanesulfonate (7a)
60 ꢀC)
d
12.25 (br s, 1H), 7.82e7.78 (m, 1H), 7.60e7.55 (m, 1H), 7.10
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (478 mg, 56%
(br s, 1H), 2.85 (d, J ¼ 4.6 Hz, 3H); 13C NMR (100 MHz, DMSO‑d6,
60 ꢀC)
d
154.1 (d, J ¼ 232 Hz),152.2 (d, J ¼ 237 Hz),150.5,147.3,145.8
yield): colorless oil; 1H NMR (400 MHz, CDCl3)
d
8.02 (t, J ¼ 7.8 Hz,
(d, J ¼ 247 Hz), 143.3 (d, J ¼ 247 Hz), 128.8e128.7 (m, 1C),
1H), 7.34e7.23 (m, 6H), 7.12 (dd, J ¼ 8.2, 3.0 Hz, 1H), 7.04 (dd, J ¼ 7.5,
124.8e124.7 (m, 1C), 105.3e105.0 (m, 1C), 97.8e97.5 (m, 1C), 27.2;
1.5 Hz, 1H), 6.82 (td, J ¼ 7.5, 1.0 Hz, 1H), 6.74 (d, J ¼ 8.3 Hz, 1H), 4.33
IR (KBr, cmꢁ1
)
n
3278, 3129, 1634, 1573, 1509, 1470, 1429, 1231, 1178,
(s, 2H), 3.71 (br s, 1H); 13C NMR (100 MHz, CDCl3)
d 160.8 (d,
1073, 910, 789, 738; HRMS (ESI-ion trap) Calcd. for C11H6N3OF4ꢁ
[M ꢁ H]- 272.0453; Found: 272.0451.
J ¼ 249 Hz),151.0 (d, J ¼ 14 Hz), 147.7 (d, J ¼ 7 Hz),145.5,138.9,130.9
(d, J ¼ 7 Hz), 128.8, 127.5, 127.4, 124.5 (d, J ¼ 6 Hz), 118.9 (q,
J ¼ 319 Hz), 117.81, 117.76, 111.9, 110.7 (d, J ¼ 34 Hz), 100.1, 48.4; IR
Synthesis of 5. To a solution of 3a (128 mg, 0.4 mmol) and DIPEA
(65 mg, 0.5 mmol) in dry acetonitrile (2 mL) which was pre-heated
(KBr, cmꢁ1
) n 3437, 2921, 2850, 1602, 1576, 1511, 1474, 1422, 1213,
to 60 ꢀC,
a
solution of 2,4-dichloro-6-methoxy-1,3,5-triazine
1134, 975, 844; HRMS (ESI-ion trap) Calcd. for C19H13N2O3F4Sꢁ
(36 mg, 0.2 mmol) in acetonitrile (1.5 mL) was added dropwise
during 4 h. The resulting solution was stirred at 60 ꢀC for 3 h until
3a was consumed. The mixture was then cooled gradually to room
temperature, a saturated ammonium chloride was added to pH ¼ 7
to quench the reaction. The resulting mixture was extracted with
dichloromethane (3 ꢂ 50 mL). The combined organic layers were
washed with brine (50 mL), and dried over anhydrous Na2SO4. After
removal of solvent, the residue was chromatographed on a silica gel
column with a mixture of petroleum ether and acetone as the
mobile phase to give pure product 5 (115 mg, 77% yield): yellow
[M ꢁ H]- 425.0589; Found: 425.0589.
4.24. 3-(2-(Benzylamino)-5-methylphenyl)-6-fluoropyridin-2-yl
trifluoromethanesulfonate (7b)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (362 mg, 41%
yield): light yellow soild, m. p. 89e91 ꢀC; 1H NMR (400 MHz,
DMSO‑d6)
d
8.26 (t, J ¼ 8.0 Hz, 1H), 7.55 (dd, J ¼ 8.2, 2.5 Hz, 1H),
7.32e7.24 (m, 4H), 7.20e7.16 (m, 1H), 6.94 (dd, J ¼ 8.4, 1.8 Hz, 1H),
6.79 (d, J ¼ 1.8 Hz,1H), 6.39 (d, J ¼ 8.4 Hz,1H), 5.58 (t, J ¼ 6.0 Hz,1H),
4.24 (d, J ¼ 5.9 Hz, 2H), 2.15 (s, 3H); 13C NMR (100 MHz, DMSO‑d6)
solid, m. p. 137e139 ꢀC; 1H NMR (400 MHz, Acetone-d6)
d 8.15 (d,
J ¼ 2.4 Hz, 2H), 7.92 (dd, J ¼ 8.4, 2.4 Hz, 2H), 7.46e7.40 (m,10H), 7.32
(t, J ¼ 7.6 Hz, 4H), 7.23 (t, J ¼ 8.2 Hz, 2H), 6.75 (d, J ¼ 8.7 Hz, 4H), 5.83
(t, J ¼ 5.2 Hz, 1H), 4.42 (s, 4H), 3.93 (s, 3H); 13C NMR (100 MHz,
d
159.4 (d, J ¼ 245 Hz), 149.9 (d, J ¼ 13 Hz), 149.2 (d, J ¼ 8 Hz), 143.4,
140.2, 130.8, 130.5, 128.1, 126.6, 126.4, 124.7 (d, J ¼ 5 Hz), 124.1, 117.8
Acetone-d6)
d
174.4, 173.1, 149.47, 142.3, 141.9, 140.8, 140.0, 131.8,
(q, J ¼ 319 Hz), 117.1, 111.3, 111.0, 46.2, 19.7; IR (KBr, cmꢁ1
) n 3427,
128.5,127.8, 127.3, 126.9,125.4,125.2,122.0,113.1, 55.5, 47.1; IR (KBr,
3030, 2920, 1606, 1519, 1473, 1413, 1212, 977, 839, 606; HRMS (ESI-
ion trap) Calcd. for C20H15N2O3F4Sꢁ [M ꢁ H]- 439.0745; Found:
439.0745.
cmꢁ1
) n 3512, 3421, 3028, 1609, 1523, 1489, 1364, 1223, 1117, 816.
HRMS (ESI-ion trap) calcd. for C42H33N7O7Clꢁ [MþCl]- 782.2136.
Found: 782.2142.
Synthesis of 6. To a solution of DIPEA (32 mg, 0.25 mmol) in dry
acetonitrile (20 mL), which was pre-heated to reflux, a solution of 5
(75 mg, 0.1 mmol) and cyanuric chloride (20 mg, 0.11 mmol) in
acetonitrile (20 mL) was added dropwise during 12 h. The resulting
solution was stirred for 12 h until 5 was consumed. The mixture
was then cooled gradually to room temperature, a saturated
ammonium chloride was added to pH ¼ 7 to quench the reaction.
The resulting mixture was extracted with dichloromethane
(3 ꢂ 50 mL). The combined organic phase was washed with brine
(50 mL), and dried over anhydrous Na2SO4. After removal of sol-
vent, the residue was chromatographed on a silica gel column with
a mixture of petroleum ether and acetone as the mobile phase to
give pure product 6 (29 mg, 34% yield): white or pale yellow solid,
4.25. 2-(6-Fluoro-2-(methylamino)pyridin-3-yl)-6-nitrophenyl
trifluoromethanesulfonate (7c)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 10/1) (680 mg, 86%
yield): yellow oil; 1H NMR (400 MHz, DMSO‑d6)
d
8.33 (dd, J ¼ 8.1,
1.8 Hz, 1H), 7.90 (dd, J ¼ 7.8, 1.8 Hz, 1H), 7.83e7.79 (m, 1H), 7.55 (t,
J ¼ 8.1 Hz, 1H), 6.54e6.52 (m, 1H), 6.29 (dd, J ¼ 7.9, 2.8 Hz, 1H), 2.73
(d, J ¼ 4.5 Hz, 3H); 13C NMR (100 MHz, DMSO‑d6)
d 163.3 (d,
J ¼ 234 Hz), 155.8 (d, J ¼ 18 Hz), 144.2 (d, J ¼ 9 Hz), 142.3, 138.9,
138.7,133.0,130.3,126.4,117.5 (q, J ¼ 319 Hz),110.1 (d, J ¼ 5 Hz), 93.4
(d, J ¼ 38 Hz), 28.1; IR (KBr, cmꢁ1
) n 3425, 2962, 1580, 1541, 1511,
1428, 1395, 1363, 1229, 1218, 1133, 799, 756; HRMS (ESI-ion trap)
m. p. > 300 ꢀC; 1H NMR (400 MHz, Acetone-d6)
d
8.09 (d, J ¼ 2.0 Hz,
Calcd. for C13H8N3O5F4Sꢁ [M ꢁ H]- 394.0126; Found: 394.0124.
2H), 7.87 (dd, J ¼ 8.4, 2.4 Hz, 2H), 7.52 (t, J ¼ 2.0 Hz, 2H), 7.50 (t,
J ¼ 2.2 Hz, 2H), 7.32e7.20 (m, 16H), 5.26 (s, 4H), 4.14 (s, 3H); 13C
4.26. 6,60-Difluoro-2’-(methylamino)-[3,30-bipyridin]-2-yl
trifluoromethanesulfonate (7d)
NMR (100 MHz, Acetone-d6) d 175.4,172.8,169.9,165.5,143.6,142.6,
141.7, 139.2, 137.8, 135.0, 132.5, 128.5, 128.2, 127.9, 127.4, 125.4,
122.9, 55.9, 52.3; IR (KBr, cmꢁ1
)
n
3033, 2953,1600,1563,1541, 1361,
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (605 mg, 82%
yield): white solid, m. p. 140e141 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
1219, 1115, 824, 733. HRMS (MALDI) calcd. for C45H32ClN10Oþ
[MþH]þ 859.2139. Found: 859.2134.
8

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
d
8.27 (t, J ¼ 8.0 Hz, 1H), 7.57 (q, J ¼ 7.6 Hz 2 Hz, 1H), 7.47 (t,
column (petroleum ether and ethyl acetate ¼ 5/1) (237 mg, 97%
yield): yellow solid, m. p. 203e205 ꢀC; 1H NMR (400 MHz,
J ¼ 8.4 Hz, 1H), 6.47 (d, J ¼ 4.6 Hz, 1H), 6.27 (dd, J ¼ 7.8, 2.7 Hz, 1H),
2.71 (d, J ¼ 4.6 Hz, 3H); 19F NMR (376 MHz, DMSO‑d6)
d
ꢁ68.97 (d,
DMSO‑d6, 60 ꢀC)
d
8.83e8.79 (m, 1H), 8.56e8.54 (m, 1H), 8.07 (d,
J ¼ 5.6 Hz), ꢁ69.38 (d, J ¼ 5.6 Hz), ꢁ73.73; 13C NMR (100 MHz,
J ¼ 7.9 Hz, 1H), 7.44 (t, J ¼ 7.5 Hz, 1H), 7.10 (d, J ¼ 8.3 Hz, 1H), 3.81 (s,
13
DMSO‑d6)
d
163.3 (d, J ¼ 233.6 Hz), 160.5 (d, J ¼ 245.0 Hz), 155.9 (d,
3H); C NMR (100 MHz, DMSO‑d6, 60 ꢀC)
d
162.0 (d, J ¼ 238 Hz),
J ¼ 18.1 Hz), 149.9 (d, J ¼ 14.3 Hz), 149.4 (d, J ¼ 8.6 Hz), 143.2 (d,
J ¼ 8.6 Hz), 122.2 (d, J ¼ 4.8 Hz), 117.8 (q, J ¼ 318.5 Hz), 111.4 (d,
J ¼ 34.3 Hz), 108.9 (d, J ¼ 3.8 Hz), 93.3 (d, J ¼ 38.1 Hz), 28.0; IR (KBr,
150.1 (d, J ¼ 18 Hz), 135.7, 134.5 (d, J ¼ 10 Hz), 130.8, 126.0, 123.8,
122.5, 119.7, 111.7, 101.7 (d, J ¼ 38 Hz), 30.7; IR (KBr, cmꢁ1
) n 3083,
1600, 1586, 1516, 1477, 1423, 1351, 1289, 1221, 1146, 974, 805, 736;
HRMS (ESI-ion trap) Calcd. for C12H9N3O2Fþ [MþH]þ 246.0673;
Found: 246.0673.
cmꢁ1
) n 3444, 2946, 1621, 1587. HRMS (ESI-ion trap) calcd. for
C
12H9F5N3O3Sþ [MþH]þ 370.0279. Found: 370.0277.
4.27. 2’-((tert-Butoxycarbonyl)amino)-5-cyano-50-methoxy-[1,10-
biphenyl]-2-yl trifluoromethanesulfonate (7e)
4.31. 2,7-Difluoro-9-methyl-9H-pyrrolo[2,3-b:5,4-b’]dipyridine
(8d)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 8/1) (728 mg, 77%
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 20/1) (215 mg, 98%
yield): white solid, m. p. 234e236 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
yield): colorless oil; 1H NMR (400 MHz, CDCl3)
d 7.79e7.76 (m, 2H),
d
8.65 (t, J ¼ 7.8 Hz, 2H), 7.01 (d, J ¼ 8.2 Hz, 2H), 3.83 (s, 3H); 19F NMR
7.54e7.49 (m, 2H), 7.00 (dd, J ¼ 8.9, 2.9 Hz, 1H), 6.75 (d, J ¼ 2.9 Hz,
1H), 5.87 (br s, 1H), 3.80 (s, 3H), 1.30 (s, 9H); 13C NMR (100 MHz,
(376 MHz, DMSO‑d6)
d
ꢁ70.35; 13C NMR (100 MHz, DMSO‑d6)
CDCl3)
d 157.4, 153.8, 149.6, 136.8, 134.8, 133.6, 129.3, 128.5, 127.5,
d
161.1 (d, J ¼ 237.4 Hz), 148.3 (d, J ¼ 18.1 Hz), 133.6 (d, J ¼ 9.6 Hz),
110.4, 100.6 (d, J ¼ 38.1 Hz), 26.0; IR (KBr, cmꢁ1
) n 1581, 1498, 1409.
123.3, 118.4 (q, J ¼ 319 Hz), 117.0, 116.1, 115.7, 113.2, 80.8, 55.8, 28.3;
IR (KBr, cmꢁ1
) n 3346, 2980, 2235, 1715, 1515, 1485, 1426, 1218, 1160,
HRMS (ESI-ion trap) calcd. for C11H8F2Nþ3 [MþH]þ 220.0681. Found:
870, 616; HRMS (ESI-ion trap) Calcd. for C20H18N2O6F3Sꢁ [M ꢁ H]-
220.0677.
471.0838; Found: 471.0839.
Synthesis of 8. To a Schlenk tube were charged with 7 (1 mmol),
Pd (dba)2 (29 mg, 0.05 mmol), dppf (55 mg, 0.1 mmol), K2CO3
(152 mg, 1.1 mmol) at room temperature. The reaction mixture was
purged three times with Ar. To the reaction mixture was injected
anhydrous 1,4-dioxane (2 mL) and heated to reflux. After 2 h, The
resulting mixture was cooled to room temperature and filtered
with Celite. The filtrate was concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel
(petroleum ether and ethyl acetate) to give compound 8.
4.32. tert-Butyl 3-cyano-6-methoxy-9H-carbazole-9-carboxylate
(8e)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (319 mg, 99%
yield): white solid, m. p. 162e163 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
d
8.69 (d, J ¼ 1.4 Hz, 1H), 8.27 (d, J ¼ 8.7 Hz, 1H), 8.06 (d, J ¼ 9.1 Hz,
1H), 7.86 (dd, J ¼ 8.7, 1.7 Hz, 1H), 7.82 (d, J ¼ 2.6 Hz, 1H), 7.15 (dd,
J ¼ 9.1, 2.7 Hz, 1H), 3.86 (s, 3H), 1.70 (s, 9H); 13C NMR (100 MHz,
DMSO‑d6) d 156.1,149.7,140.2,132.4,130.4,125.6,125.0,124.6,119.3,
116.7,116.6,116.5,105.1,103.9, 84.9, 55.6, 27.7; IR (KBr, cmꢁ1
) n 2981,
4.28. 9-Benzyl-2-fluoro-9H-pyrido[2,3-b]indole (8a)
2228, 1734, 1493, 1359, 1220, 1158, 1139, 816; HRMS (ESI-ion trap)
Calcd. for C19H19N2Oþ3 [MþH]þ 323.1390; Found: 323.1391.
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (260 mg, 94%
yield): colorless oil; 1H NMR (400 MHz, DMSO‑d6)
d 8.69 (t,
Declaration of competing interest
J ¼ 8.0 Hz, 1H), 8.18 (d, J ¼ 7.4 Hz, 1H), 7.62 (d, J ¼ 8.2 Hz, 1H), 7.45
(ddd, J ¼ 8.3, 7.2, 1.2 Hz, 1H), 7.30e7.19 (m, 6H), 6.98 (dd, J ¼ 8.2,
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
1.0 Hz, 1H), 5.62 (s, 2H); 13C NMR (100 MHz, DMSO‑d6)
d 161.6 (d,
J ¼ 236 Hz), 148.7 (d, J ¼ 18 Hz), 138.9, 137.1, 133.8 (d, J ¼ 10 Hz),
128.5,127.3,127.0,126.2,120.8,120.5,119.8,112.8 (d, J ¼ 3 Hz),110.3,
100.0 (d, J ¼ 38 Hz), 44.3; IR (KBr, cmꢁ1
) n 1599, 1573, 1485, 1354,
Acknowledgments
1199, 803, 701; HRMS (ESI-ion trap) Calcd. for C18H14N2Fþ [MþH]þ
277.1136; Found: 277.1138.
We thank the National Natural Science Foundation of China
(21732004, 21901137) and Tsinghua University Initiative Scientific
Research Program for financial support. S. Tong also thanks the
Thousand Young Talents Program for support.
4.29. 9-Benzyl-2-fluoro-6-methyl-9H-carbazole (8b)
Purification: Flash column chromatographed on a silica gel
column (petroleum ether and ethyl acetate ¼ 5/1) (267 mg, 92%
yield): white solid, m. p. 115e117 ꢀC; 1H NMR (400 MHz, DMSO‑d6)
Appendix A. Supplementary data
d
8.87 (t, J ¼ 8.0 Hz, 1H), 8.60 (d, J ¼ 7.4 Hz, 1H), 8.11 (d, J ¼ 8.7 Hz,
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.131966.
1H), 7.47 (t, J ¼ 7.9 Hz, 1H), 7.15 (d, J ¼ 8.0 Hz, 1H), 3.83 (s, 3H); 13
C
NMR (100 MHz, DMSO‑d6)
d
161.5 (d, J ¼ 235 Hz), 148.8 (d,
J ¼ 17 Hz), 137.2, 133.7 (d, J ¼ 9 Hz), 129.5, 128.5, 127.5, 127.3, 127.0,
120.7, 119.9, 112.7 (d, J ¼ 3 Hz), 110.1, 99.7 (d, J ¼ 38 Hz), 44.3, 20.9;
References
IR (KBr, cmꢁ1
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9

D.-D. Liang, S.-Y. Guo, S. Tong et al.
Tetrahedron 83 (2021) 131966
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10