A para-C–H Functionalization of Aniline Derivatives via In situ Generated Bulky Hypervalent Iodinium Reagents

Article abstract of DOI:10.1002/ejoc.201801058

A practical para-C-H functionalization of aniline derivatives has been developed using an in situ generated bulky hypervalent iodinium reagent. Para-iodo, bromo, chloro, nitro, trifluormethyl aniline derivatives can be obtained efficiently, in many cases in 10 min in a transition metal-free manner. Medicinal chemicals or intermediates can be purified without column chromatography or recrystallization, which significantly reduces the waste and simplifies the work-up process.

Full text of DOI:10.1002/ejoc.201801058

A Journal of
Accepted Article
Title: A para-C-H functionalization of aniline derivatives via in-situ
generated bulky hypervalent iodinium reagents
Authors: Chao Tian, Xu Yao, Weizhe Ji, Qian Wang, Guanghui An, and
Guangming Li
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801058
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801058
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10.1002/ejoc.201801058
European Journal of Organic Chemistry
FULL PAPER
A para-C-H functionalization of aniline derivatives via in-situ
generated bulky hypervalent iodinium reagents
Chao Tian,[a] Xu Yao,[a] Weizhe Ji,[a] Qian Wang,[a] Guanghui An*[a,b] and Guangming Li*[a]
Abstract:
A
practical para-C-H functionalization of aniline
derivatives has been developed using an in-situ generated bulky
hypervalent iodinium reagent. Para-iodo, bromo, chloro, nitro,
trifluormethyl aniline derivatives can be obtained efficiently, in many
cases in 10 mins in a transition metal-free manner. Medicinal
chemicals or intermediates can be purified without column
chromatography or recrystallization, which significantly reduces the
waste and simplifies the work-up process.
Introduction
During the past decades, the para-selective C–H
functionalization of arenes has attracted considerable attention
owing to its utility in the construction of challenging and
important structural motifs.[1] The groups of Gaunt[2] and Ritter[3]
reported electronic controlled C-H functionalization at the para-
position of electron-rich arenes (Scheme 1a). Maiti et al. have
applied extended template strategies in the remote para-C-H
olefination of arenes and phenols.[4] The groups of Itami[5] and
Nakao[6] reported para-C-H borylation and alkylation using
designed bulky iridium (I) catalysts and manipulation of steric
effects. Zhao and Lan employed a ruthenium-catalyzed σ-
activation strategy via strongly bound ruthenacycles for
electronic activation of remote positions, and developed radical
para-selective difluoromethylation.[7] Although great progress
has been achieved, the scope of para-C-H functionalization
process however is still limited.
Anilides, ubiquitous in pharmaceuticals and agrochemical
compounds have been widely used as templates for C-H
functionalization. para-Substituted anilides are important building
blocks for many pharmaceutical agents, such as SB-245570
(antidepressive),[8] Apixaban (anticoagulant),[9] Rivaroxaban
(antithrombotics),[10] and Cilostazol (antiplatelet)[11] (Figure 1).
Electronic control strategies[12] and bidentate cyclometalates
protocol[13,14] have been widely applied to the para-
functionalization of 8-aminoquinolines (Scheme 1b).
[a]
C. Tian, X. Yao, W.Z. Ji, Q. Wang, Associate Prof. Dr. G.H. An,
Prof. Dr. G.M. Li
Key Laboratory of Functional Inorganic Material Chemistry (MOE)
School of Chemistry and Materials Science
Heilongjiang University
Scheme 1. Previous reports on para-selective catalytic C-H functionalization
in the context of this work.
No. 74, Xuefu Road, Nangang District, Harbin 150080 (P.R. China)
E-mail: chemagh@163.com
gmli@hlju.edu.cn
Associate Prof. Dr. G.H. An
College of Materials Science and Chemical Engineering
Harbin Engineering University
Harbin, 150001 (P.R. China)
Coordinating activation strategy via bidentate cyclometalates
has been utilized by Weng et al. in the para-C-H
functionalization of naphthylamides.[15] However, owing to the
lack of an ortho sterically hindering group, control of the
regioselectivity for para-functionalization of common aniline
derivatives is difficult, and only a few examples have been
[b]
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201801058
European Journal of Organic Chemistry
FULL PAPER
reported.[12d,16] Consequently,
a general protocol to install
Table 1. Optimization of para-bromination conditions.[a]
various para-substituents on anilides remains highly desirable.
Recently, a ruthenium-catalyzed σ-activation strategy has been
applied to para-selective alkylation and difluoromethylation of
aniline derivatives by Frost’s group[17] and Zhao and Lan et al.[18]
Despite these progresses and works on C5-functionalization of
8-acylamino quinolines,[19]
a
general transition-metal-free[20]
Entry
1
Catalyst
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeBr3
CuCl2
none
Oxidant
Time
7 h
Yield [%][b]
30
para-functionalziation of aniline derivatives with reduced toxicity
has scarcely been reported. Herein, we disclose a general steric
control strategy employing in-situ generated bulky hypervalent
iodinium reagents[21] for the para-selective C-H functionalization
of anilides to form C-X (X= Cl, Br, I), C-N or C-C bonds. The
protocol uses readily available reagents in an environmentally
benign solvent and proceeds in a transition-metal-free manner
(Scheme 1c).[22] Medicinally related compounds can be obtained
with a simple work-up procedure.
PhI(OAc)2 (2a)
PhI(OPiv)2 (2b)
PhI(OCOPh)2 (2c)
DMP (2d)
2
7 h
35
3
7 h
40
4
7 h
32
5
Na2S2O8 (2e)
K2S2O8 (2f)
7 h
trace
trace
74
6
7 h
7
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
PhI(TFA)2 (2g)
7 h
8
7 h
72[c]
61
9
7 h
10
11
12
13
14
15
7 h
80
7 h
80
none
7 h
70[d]
89[e]
90[e]
90[e]
none
7 h
none
2 h
none
10 min
[a] Unless otherwise specified, the reactions were carried out in the presence
of 1 (0.2 mmol), NaBr (2 equiv), oxidant (1.5 equiv), catalyst (10 mol%), and
MeOH (2 mL) at 25 °C under air. [b] Isolated yield. [c] 3 equiv PhI(TFA)2 was
added. [d] MeCN instead of MeOH. [e] EtOH instead of MeOH. DMP = Dess-
Martin periodinane.
entry 7 vs entries 1-3). Na2S2O8 and K2S2O8 (Table 1, entries 5-
6), which have been commonly used in C5-functionalization of 8-
acylamino quinolines,[13a-e,14c-d] delivered no desired products.
Moreover, the reaction failed in the absence of an oxidant,
indicating that the hypervalent iodinium reagent is indispensable
and crucial in the process. Increasing the amount of oxidants
didn’t elevate the reaction efficiency (Table 1, entry 8). A series
of metal salts as catalysts were subjected to the halogenation
conditions and showed no significant improvement in reaction
efficiency (Table 1, entries 9-10; for details, see SI Table S1,
entries 10-17). With these preliminary results (Scheme 1b), we
speculated that the catalyst may not be necessary, and a
catalyst-free reaction indeed was found to proceed smoothly
without any loss of reactivity (Table 1, entries 9-10 vs entry 11).
Thus, the reaction could not be an electrophilic aromatic
substitution catalyzed by Lewis acids. Further screening of
solvents revealed that the environmentally benign solvent, EtOH
Figure 1. Representative bioactive para-substituted anilines.
Results and Discussion
We selected
a
halogenation reaction for optimization
experiments and commenced our studies with the para-
halogenation of N-phenylacetamide with NaBr, employing
various hypervalent iodinium reagents and other oxidants (Table
1, entries 1-7). In our hypothesis for the reaction, we envisioned
that the hypervalent iodium reagent would afford the active
species PhI(TFA)X (Scheme 1c) via ligand exchange and
phenyliodo bis(trifluoroacetate) (PhI(TFA)2) (2g) was reported to
faciliate the process with a fast reaction rate.[21] Indeed,
PhI(TFA)2 (2g) exhibited the best efficiency among various
hypervalent iodium reagents, producing 3 in 74% yield (Table 1,
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10.1002/ejoc.201801058
European Journal of Organic Chemistry
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Scheme 2. Substrate scope with respect to bromination. [a] Reactions were carried out in the presence of anilides (0.2 mmol), NaBr (2 equiv), PhI(TFA)2 (1.5
equiv), and EtOH (2 mL) at 25 °C under air. [b] Reactions were carried out in the presence of anilides (0.1 mmol), NaBr (4 equiv), PhI(TFA)2 (3 equiv), and EtOH
(2 mL) at 25 °C under air. [c] Isolated yield.
can promote the para-bromination producing higher chemical
yields (Table 1, entry 13). Surprisingly, reaction is effectively
complete within 10 minutes with 90% yield (Table 1, entry 15).
With the optimal conditions in hand, we explored the scope
of para-C-H bromination with respect to substituted acetanilides
(Scheme 2A). The method showed good tolerance to a broad
scope of aniline derivatives with different substituents including
methyl (4, 5), methoxyl (6, 7), F (8, 9) Cl (10, 11), Br (12), and a
2,5-methoxy compound (13). Electron-donating groups on the
aromatic rings accelerate the reaction and most of the
substituents at the ortho- or meta-position have little effect on
the regioselectivity. Interestingly, m-methoxyacetanilide under-
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10.1002/ejoc.201801058
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goes a dibromination process, generating 7 in 69% yield. This
may be attributed to the strong electron donating nature of
methoxyl group. When the substrates with strong electron-
withdrawing groups, NO2 and CN, in ortho-position of aromatic
ring were subjected to the reaction, the para-bromo products
were not obtained. N-(quinolin-8-yl)acetamide, which was
previously employed in a metal-catalyzed halogenation,[13j] was
also viable under the current reaction conditions. A range of
carboxylic anilides were examined (Scheme 2B). Aromatic
carboxylic anilides require a longer reaction time. N-Phenyl-
benzamide[16i] and N-phenylpicolinamide[16k] which have been
studied previously, afforded the corresponding products (19-20),
and
a
previously reported substrate, N-(naphthalen-1-
yl)picolinamide[15] was also compatible with these reaction
conditions, delivering 21 in a satisfactory yield. In addition to
carboxylic anilides, N-Boc aniline and N-sulfonylaniline also
gave novel bromination products (22-23).[16i] We continued to
explore the versatility of this protocol, examining the para-
bromination of synthetically useful secondary anilides. As shown
in Scheme 2C,
a variety of building blocks related to
pharmaceutical compounds,[23] such as indoline-2,3-dione,
dihydroquinolinone and phenanthridin-6(5H)-one, underwent this
para-selective reaction smoothly, delivering the corresponding
para-bromo anilides (24-27) in moderate to good yields.
Chlorzoxazone, a muscle relaxant also reacted under these
conditions, affording a disubstituted product (28). The absence
of any need for a catalyst in the reaction suggests that the N-H
group was not required for coordination, and so tertiary amides
may be accessible to the reaction. Hence, we subjected the
normally unreactive N-methyl-N-phenylacetamide to the reaction
(Scheme 2D), and obtained the para-brominated product (29).
This had been reported only rarely in previous research,[16i] and
suggests that an unsubstituted N−H group is not a prerequisite
for this transformation. Given the importance of para-
halogenated cyclic tertiary anilides as important precusors for
various bioactive and medicinal compounds (Figure 1),[24] we
were delighted to observe that the para-bromination proceeded
with excellent positional selectivity and the purification of
corresponding products required no column chromatography or
recrystallization (30-32).[25] A single substituted brominated
product (33) was obtained from 1-phenylindoline-2,3-dione,
indicating that the fused ring structure in anilides such as
oxindole was more likely to promote para-bromination than a
tertiary cyclic anilide. The bromination of 1 was also successfully
performed on a gram scale (7.4 mmol, 1 g) under the same
reaction conditions, producing 3 in 69% yield (Scheme 3).
Scheme 4. Control Experiments.
To gain insights into the mechanism of the reaction, a
series of control experiments were carried out (Scheme 4). The
radical scavenger, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO),
can readily inhibit the bromination process and allows 95%
recovery of the starting materials, implying a single electron
transfer (SET) process for the reaction (Scheme 4a). Ortho-
bromination of compound 3 gave yields of less than 5%
(Scheme 4b), indicating that the steric effect with an innate
electronic nature could be the key factor governing the control of
regioselectivity. The halogen radical was trapped using 1,1-
diphenylethylene in the presence of NaBr, and the coupling
product (34) was obtained in 28% yield (Scheme 4c). A similar
radical coupling reaction was observed with 1-phenyl-1H-
Scheme 3. Gram-scale synthesis.
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10.1002/ejoc.201801058
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Scheme 5. Proposed Mechanism.
Scheme 7. Substrate scope with respect to Iodination. [a] Reactions were
carried out in the presence of anilides (0.1 mmol), NaI (4 equiv), PhI(TFA)2 (3
equiv), and EtOH (2 mL) at 25 °C under air. [b] Isolated yield.
pyrrole-2,5-dione, providing a single product (35) (Scheme 4d).
This compound (35) was utilized as conjugate acceptor for
bioconjugation,[26] and precursor for synthesis of natural
products[27] and electronic communication materials.[28]
Interestingly, 35 could be purified without use of chromatography
and recrystallization,[25] which further shows the value of this
protocol. Further investigation into the origin of the bromo radical
and the regioselectivity revealed that the proposed in situ
generated intermediate (36) derived from dichlorophenyl-λ3-
iodane and AgTFA readily afforded the para-product (37) in a
reasonable yield (Scheme 4e). Therefore, an in situ generated
bulky hypervalent iodinium reagent could be responsible for the
generation of bromo radical and the outcome in terms of the
regioselectivity. In addition, no deuterium was incorporated into
the recovered starting material when MeOH-d4, was used as the
solvent. This indicates that an irreversible C–H cleavage event
occurred during the reaction (Scheme 4f).The kinetic isotope
effect factor of 1.02 suggests that the C-H activation is not the
rate-determining step (Scheme 4g). After completion of the
reaction, iodobenzene was detected and acidity of reaction
mixture had increased. Therefore, we rationalized that the
intermediate 36 as a bulky halogen source would direct the
attack on the para-position of anilides in a SET process.
With this bulky hypervalent iodium reagent protocol formed
in situ, other moieties, which previously were reported to be
inaccessible to para C-H functionalization of anilides, can be
successfully introduced to the para position. Para-chlorination
and para-nitration were examined by reacting N-
phenylacetamide with NaCl and NaNO2 (Scheme 6), delivering
37 and 39. Para-trifluoromethylation, which was mainly
investigated on 8-amino quinoline derivatives,[12c] can be
Scheme 6. Versatile para-C−H functionalization of N-phenylacetamide.
Conditions: (a) 1 (0.2 mmol), NaCl (2 equiv), PhI(TFA)2 (1.5 equiv), and EtOH
(2 mL), air, 25 °C, 1 h; (b) 1 (0.2 mmol), CF3SO2Na (2 equiv), PhI(TFA)2 (1.5
equiv), and MeCN (2 mL), air, 25 °C, 24 h; (c) 1 (0.1 mmol), NaNO2 (4 equiv),
PhI(TFA)2 (3 equiv), and MeCN (2 mL), air, 25 °C, 7 h; (d) 1 (0.1 mmol), NaI (4
equiv), PhI(TFA)2 (3 equiv), and EtOH (2 mL), air, 25 °C, 10 min.
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10.1002/ejoc.201801058
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evaporated in vacuo and the residue was purified by column
chromatography on silica gel to give the pure product.
successfuly achieved on anilides. These results not only
demonstrate an easy route to para-substituted aniline
derivatives under relatively mild conditions, but also support our
proposed mechanism.
General experimental procedure for the synthesis of compounds 8-
12 and 15-27
We found that iodinated products, which are widely used
as coupling reagents, can also be obtained through this reaction
(Scheme 7) and various carboxylic anilides can efficiently
complete the para-iodination reaction. Interestingly, all
iodoanilides can be obtained without chromatography or
recrystallization. The heterocylic amide, N-(quinolin-8-yl)acet-
amide, can also participate in the reaction, affording 44 in 86%
yield. N-Boc-para-iodo-anilides (50) can be readily accessed
satisfactory yields by this protocol. Furthermore, a cyclic
secondary amide was also tolerated in the reaction system (51).
To a mixture of aniline derivatives (0.2 mmol, 1 equiv), NaBr (0.4 mmol, 2
equiv), and PhI(TFA)2 (0.3 mmol, 1.5 equiv) in EtOH (2 mL) was added
and reaction mixture was stirred at 25 °C. After completion of reaction,
the solvent was evaporated under reduced pressure and the residue was
diluted with EtOAc, and washed with brine. The aqueous phase was
extracted with EtOAc (2 × 30 mL) and the combined organic phase was
dried over Na2SO4. The solvent was evaporated in vacuo and the residue
was purified by column chromatography on silica gel to give the pure
product.
Experimental procedure for the synthesis of 28
Conclusions
Chlorzoxazone (0.2 mmol, 1 equiv) and PhI(TFA)2 (0.3 mmol, 1.5 equiv)
were dissolved in EtOH (2 mL) and stirred for 5 min. NaBr (0.4 mmol, 2
equiv) was added and reaction mixture was stirred at 25 °C for 12 h.
After completion of reaction, the solvent was evaporated under reduced
pressure and the residue was diluted with EtOAc, and washed with brine.
The aqueous phase was extracted with EtOAc (2 × 30 mL) and the
combined organic phase was dried over Na2SO4. The solvent was
evaporated in vacuo and the residue was washed with petroleum ether,
and then the product was obtained by filtration.
In summary, we have developed a general sterically controlled
strategy via in-situ generated bulky hypervalent iodinium
reagents to access various para-substituted aniline derivatives.
The protocol can be performed by using a combination of readily
available reagents and environmentally benign solvents in a
manner free of transition metals. A variety of anilides, including
challenging tertiary amides undergo this reaction smoothly.
Products related to medicinal chemicals can be obtained without
purification by column chromatography or recrystallization. A
mechanistic investigation revealed that the in situ generated
bulky hypervalent iodinium reagents together with the innate
electronic nature of anilines work to control the regioselectivity.
General experimental procedure for the synthesis of compounds
29-33
To a mixture of aniline derivatives (0.1 mmol, 1 equiv), NaBr (0.4 mmol, 4
equiv) was added a solution in EtOH of PhI(TFA)2 (0.3 mmol, 3 equiv) (2
mL) and reaction mixture was stirred at 25 °C. After completion of
reaction, the solvent was evaporated under reduced pressure and the
residue was diluted with EtOAc, and washed with brine. The aqueous
phase was extracted with EtOAc (2 × 30 mL) and the combined organic
phase was dried over Na2SO4. The solvent was evaporated in vacuo, the
residue was washed with petroleum ether, and the product was obtained
by filtration.
Experimental Section
General information
Unless otherwise noted, all reagents were obtained from commercial
suppliers and used without further purification. The reaction product was
isolated by column chromatography on a silica gel (236–400 mesh)
column using petroleum ether (PE) with a boiling range from 60 to 90 °C
and EtOAc. 1H, 13C and 19F NMR spectra were recorded on 400, 101,
376 MHz NMR spectrometers using DMSO or CDCl3 as solvent. In
Experimental procedure for the synthesis of 37
To a mixture of N-phenylacetamide (0.2 mmol, 1 equiv), NaCl (0.4 mmol,
2 equiv) was added a solution in EtOH of PhI(TFA)2 (0.3 mmol, 1.5 equiv)
(2 mL) and reaction mixture was stirred at 25 °C. After completion of
reaction, the solvent was evaporated under reduced pressure and the
residue was diluted with EtOAc, and washed with brine. The aqueous
phase was extracted with EtOAc (2 × 30 mL) and the combined organic
phase was dried over Na2SO4. The solvent was evaporated in vacuo and
the residue was purified by column chromatography on silica gel to give
the pure product.
1
addition, H and 13C NMR spectra used tetramethylsilane as the internal
standard and the 19F NMR spectra used trifluoroacetic acid as the
internal standard. HRMS were made by means of ESI. Unless otherwise
noted, all reagents were weighed and handled in air, and all reactions
were carried out in air.
General experimental procedure for the synthesis of compounds 3-
7, and 13-14
Experimental procedure for the synthesis of 38
To a mixture of aniline derivatives (0.2 mmol, 1 equiv) and NaBr (0.4
mmol, 2 equiv) was added a solution in EtOH of PhI(TFA)2 (0.3 mmol, 1.5
equiv) (2 mL) and the reaction mixture was stirred at 25 °C. After
completion of reaction, the solvent was evaporated under reduced
pressure and the residue was diluted with EtOAc, and washed with brine.
The water phase was extracted with EtOAc (2 × 30 mL) and the
combined organic phase was dried over Na2SO4. The solvent was
To a mixture of N-phenylacetamide (0.2 mmol, 1 equiv), CF3SO2Na (0.4
mmol, 2 equiv) was added a solution in MeCN of PhI(TFA)2 (0.3 mmol,
1.5 equiv) (2 mL) and the reaction mixture was stirred at 25 °C. After
completion of reaction, the solvent was evaporated under reduced
pressure and the residue was diluted with EtOAc, and washed with brine.
The aqueous phase was extracted with EtOAc (2 × 30 mL) and the
combined organic phase was dried over Na2SO4. The solvent was
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10.1002/ejoc.201801058
European Journal of Organic Chemistry
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evaporated in vacuo and the residue was purified by column
chromatography on silica gel to give the pure product.
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Experimental procedure for the synthesis of 39
To a mixture of N-phenylacetamide (0.2 mmol, 1 equiv), NaNO2 (0.4
mmol, 4 equiv) was added a solution in MeCN of PhI(TFA)2 (0.3 mmol, 3
equiv) (2 mL) and the reaction mixture was stirred at 25 °C. After
completion of reaction, the solvent was evaporated under reduced
pressure and the residue was diluted with EtOAc, and washed with brine.
The water phase was extracted with EtOAc (2 × 30 mL) and the
combined organic phase was dried over Na2SO4. The solvent was
evaporated in vacuo and the residue was purified by column
chromatography on silica gel to give the pure product.
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General experimental procedure for the synthesis of compounds
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To a mixture of aniline derivatives (0.1 mmol, 1 equiv), NaI (0.4 mmol, 4
equiv) was added a solution in EtOH of PhI(TFA)2 (0.3 mmol, 3 equiv) (2
mL) and reaction mixture was stirred at 25 °C. After completion of
reaction, the solvent was evaporated under reduced pressure and the
residue was diluted with EtOAc, and washed with brine. The water phase
was extracted with EtOAc (2 × 30 mL) and the combined organic phase
was dried over Na2SO4. The solvent was evaporated in vacuo and the
residue was washed with petroleum ether, and then the product was
obtained by filtration.
[5]
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4935.
Gram-scale reaction
To a mixture of N-phenylacetamide (7.4 mmol, 1 equiv), NaBr (14.8
mmol, 2 equiv), and PhI(TFA)2 (11.1 mmol, 1.5 equiv) was added EtOH
(74 mL) and reaction mixture was stirred at 25 °C. After completion of
reaction, the solvent was evaporated under reduced pressure and the
residue was diluted with EtOAc, and washed with brine. The water phase
was extracted with EtOAc (3 × 30 mL) and the combined organic phase
was dried over Na2SO4. The solvent was evaporated in vacuo and the
residue was purified by column chromatography on silica gel to give the
pure product.
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The authors gratefully acknowledge support from National
Natural Science Foundation of China (21502046), Natural
Science Foundation of Heilongjiang Province (B2016008) and
the University Nursing Program for Young Scholars with
Creative Talents in Heilongjiang Province (UNPYSCT-2017124).
The Fundamental Research Funds for the Central Universities
from
Harbin
Engineering
University
(HEUCFD1412,
HEUCFJ161002, HEUCFJ 171006, and HEUCFJ181008) were
also acknowledged. Dr. Guijie Mao was acknowledged for her
help in the NMR spectrum.
Conflicts of interest
There are no conflicts to declare.
Keywords: arenes • C-H activation • hypervalent iodinium
reagents • reaction mechanisms • steric control
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801058
European Journal of Organic Chemistry
FULL PAPER
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10.1002/ejoc.201801058
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Entry for the Table of Contents
FULL PAPER
C-H functionalization*
Chao Tian, Xu Yao, Weizhe Ji, Qian
Wang, Associate Prof. Dr. Guanghui An*
and Prof. Dr. Guangming Li*
Page No. – Page No.
A general para-selective C-H functionalization was achieved via a steric control
strategy. Para-iodo, bromo, chloro, nitro, and trifluormethyl aniline derivatives can
be efficiently accessed via in-situ generated, bulky hypervalent iodinium reagents in
as little as 10 min. Medicinal chemicals or intermediates can be purified without
column chromatography or recrystallization, which significantly reduces the waste
and simplifies the work-up.
A para-C-H functionalization of
aniline derivatives via in-situ
generated bulky hypervalent iodinium
reagents
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