Ligand-Promoted Rhodium(III)-Catalyzed ortho-C?H Amination with Free Amines

Article abstract of DOI:10.1002/anie.201703300

Ligand development for rhodium(III)-catalyzed C?H activation reactions has largely been limited to cyclopentadienyl (Cp) based scaffolds. 2-Methylquinoline has now been identified as a feasible ligand that can coordinate to the metal center of Cp*RhCl to accelerate the cleavage of the C?H bond of N-pentafluorophenylbenzamides, providing a new structural lead for ligand design. The compatibility of this reaction with secondary free amines and anilines also overcomes the limitations of palladium(II)-catalyzed C?H amination reactions.

Full text of DOI:10.1002/anie.201703300

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Accepted Article
Title: Ligand-Promoted Rhodium(III)-Catalyzed ortho-C-H Amination
with Free Amines
Authors: Huai-Wei Wang, Yi Lu, Bing Zhang, Jian He, Hua-Jin Xu,
Yan-Shang Kang, Wei-Yin Sun, and Jin-Quan Yu
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201703300
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Angewandte Chemie International Edition
DOI: 10.1002/anie.201((will be filled in by the editorial staff))
C–H Amination
Ligand-Promoted Rhodium(III)-Catalyzed ortho-C–H Amination with
Free Amines
Huai-Wei Wang, Yi Lu,* Bing Zhang, Jian He, Hua-Jin Xu, Yan-Shang Kang, Wei-Yin Sun,* Jin-Quan Yu*
Abstract: Ligand development for Rh(III)-catalyzed C–H activation
reactions are largely limited to Cp based scaffolds. 2-
Methylquinoline is identified as a feasible ligand which can
coordinate to the metal center of Cp*RhCl to accelerate the
cleavage of C–H bond of N-pentafluorophenylbenzamides,
providing a new structural lead for ligand design. The compatibility
of this reaction with secondary free amines and anilines also
overcomes the limitations of Pd(II)-catalyzed C–H amination
reactions.
hydroxycarbamates, O-acylhydroxylamines, nitrosobenzenes, azides,
and 1,4,2-dioxazol-5-one) has been extensively explored with
Pd(II),[3,4] Ir(III),[5] Rh(III),[6] Ru(II),[7] Cu(II),[8] Co(II)[9] and
Fe(II)[10] catalysts (Scheme 1a). While these reactions establish the
feasibility of the C–H insertion and C–N reductive elimination steps
with a number of synthetically useful directing groups, the use of a
chalcogenide type amino electrophiles is not ideal due to the costs
and limited scope of amino groups that can be introduced. Thus, the
development of the direct intermolecular coupling of arenes with
free amines as nucleophiles is a significant task.
A
ryl amines are privileged structural fragments in modern drug
Although the Pd(II)-catalyzed C–H coupling with organometallic
carbon nucleophiles via Pd(II)/Pd(0) catalysis has been
demonstrated,[11] analogous coupling using strongly coordinative
free amines remains an unmet challenge. On the other hand, C–H
amination with secondary and primary amines has been made
possible with Cu(II), Ni(II) and Co(III) catalysts (Scheme 1b).[12]
Although the use of bidentate directing groups containing quinoline
or oxazoline moieties substantially improved the scope of amine
coupling partners, anilines, especially are poor coupling partners in
general, with N-alkyl anilines being completely inactive. Significant
progress has also been made with Ir(III) catalyst to enable ortho-C–
H amination of benzamides using simple anilines and alkylamines
as coupling partners. However, the involvement of a nitrene
insertion pathway excluded secondary amines (Scheme 1b).[13]
Moreover, Rh(III)-catalyzed intermolecular C–H amination is
uniformly limited to pre-activated amine coupling partners.[6] Such
limitations point to the need of development of new ligands for
Rh(III) catalysts. Herein, we report the identification of a new
quinoline ligand to promote Rh(III)-catalyzed ortho-C–H amination
with free amines. Notably, both secondary amines and primary
anilines are compatible with this newly developed catalytic system.
The combination of mono-dentate weakly coordinating amide
substrates and ligands has enabled a great number of Pd(II)-
catalyzed C–H activation reactions. The synthetic utility and
practicality of our N-pentafluorophenylbenzamide directing group
has been demonstrated by an elegant synthetic route developed by a
Novartis process team.[14] Inspired by the aforementioned progress
on C–H amination, we began to investigate the possibility of
achieving Rh(III)-catalyzed C–H amination with morpholine using a
simple mono-dentate amide directing group, anticipating potential
ligand development. We commenced our investigation with N-
arylamide substrate 1a and morpholine 2a using [RhCp*Cl2]2 as the
catalyst (Table S1). We found that the addition of Ag2CO3 and
NaOAc in MeCN afforded the aminated product 3a in 8% yield
(Table S1, entry 1). We further optimized reaction parameters by
carrying out the screening of oxidants, solvents, and bases to obtain
the optimum yield and found that the presence of PhCO2Na
increased the yield to 34% (Table S1, entry 7).
discovery.[1]
Recently, transition-metal-catalyzed C–H
activation/amination of arenes via an organometallic metal insertion
approach has emerged as a significant area of research towards
developing new methods for the synthesis of aryl amines.[2] A redox
catalytic cycle proceeding via metal insertion and subsequent
oxidation with chalcogenide type N–O or N-halogen amino donors
(such as N-benzoate alkylamines, N-chloroamines, N-
Scheme 1. Transition-Metal-Catalyzed C–H Amination Reactions
[*]
Mr. H.-W. Wang, Prof. Dr. Y.Lu, Mr. B. Zhang, Mr. H.-J. Xu, Mr. Y.-S.
Kang, Prof. Dr. W.-Y. Sun
Coordination Chemistry Institute, State Key Laboratory of Coordination
Chemistry, School of Chemistry and Chemical Engineering, Nanjing
National Laboratory of Microstructures, Collaborative Innovation Center
of Advanced Microstructures, Nanjing University, Nanjing 210023, China.
E-mail: luyi@nju.edu.cn; sunwy@nju.edu.cn
Dr. J. He, Prof. Dr. J.-Q. Yu
Department of Chemistry, The Scripps Research Institute (TSRI)
10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
E-mail: yu200@scripps.edu
Based on the impact of ligand development in Pd(II)-catalyzed
C–H amination reactions,[3c,3d] it is reasonable to assume that the use
of proper ligands could accelerate C(sp2)–H cleavage and promote
subsequent the C–N formation step by potentially tuning the steric
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/anie.201xxxxxx.
1
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10.1002/anie.201703300
Angewandte Chemie International Edition
and electronic properties of the active catalyst. Notably, ligand
scaffolds for Rh(III) catalysts are largely limited to Cp-based ligand
scaffolds. To identify new ligand scaffolds for Rh(III) catalysts, a
series of simple pyridine-based ligands were tested for their
efficiency of promoting amination (Table 1). Encouragingly,
pyridine (L1) gave the desired product in 54% yield. Further ligand
screening showed that an electron-withdrawing substituent (L2) had
a slightly negative impact on the reaction, while the electron-
donating ones (L3–L7) significantly improved the yield of the
desired product (46–79%). We further investigated quinoline-based
ligands (L8–L19) and found that 2-methylquinoline (L9) possessed
an optimal balance of steric and electronic properties to provide 3a
in the highest yield (82%). Reducing catalyst loading to 2.5 and 5
mol% decreased the yields to 45 and 67% respectively. To elucidate
the role of the ligand, we examined the influence of L9 on the rate
profile (Figure S2), which revealed that the ligand significantly
accelerates the rate of this C–H amination reaction. The mono-N-
protected amino acid (MPAA) and phosphine ligands had been
studied for this reaction as well, and we found that MPAA could
also accelerate this C(sp2)–H amination reaction to some extent
(Table S2).
in moderate to good yields (56–88%). In general, the reactivity of
electron-rich substrates (1a–1h) was more efficient compared to that
of electron-deficient substrates (1k–1r). Nonsubstituted benzamide
substrate 1i afforded the desired product in good yield (77%).
Notably, only monoaminated products were formed in all cases.
Moreover, for meta-substituted benzamides (1b, 1d, and 1l),
selective C–H functionalization occurred exclusively at the less
hindered position, showing good regioselectivity in this reaction
system. Gratifyingly, 2-naphthamide 1j was also applicable under
the standard conditions, affording the desired product 3j in
reasonable yield. Noteworthy, this transformation also well tolerated
halogenated substituents, especially the iodo group, which was apt
to participate in cross-coupling reactions. In addition, we were
pleased to find that heterocyclic amides, including furan 1s and
thiophene 1t, are competent substrates and could also be aminated in
moderate yields (3s and 3t, 56% and 68%, respectively). We also
prepared 3g on a gram scale in order to demonstrate the preparative
utility of this transformation. After treatment of the aminated
products with BF3•Et2O in methanol, the auxiliary can be readily
removed and converted to methyl esters in good yields (Supporting
Information).
Table 1. Screening of Ligands.[a,b]
Table 2. Scope of Benzamide Substrates.[a,b]
[a] Conditions: 1a (0.1 mmol), 2a (0.2 mmol), [RhCp*Cl2]2 (5 mol %), Ag2CO3 (0.2
mmol), ligand (20 mol %), PhCO2Na (0.2 mmol) and dry toluene (2 mL) under N2, 16 h,
90 °C. [b] The yield was determined by 1H NMR analysis of the crude product using
CH2Br2 as the internal standard.
With the optimized conditions in hand, we examined the scope of
N-pentafluoroarylbenzamides (1b–1t) with morpholine 2a (Table 2).
To our delight, the substrates bearing various substituents were
compatible with the reaction system, affording the desired products
[a] Conditions: 1a–1t (0.1 mmol), 2a (0.2 mmol), [RhCp*Cl2]2 (5 mol %), Ag2CO3 (0.2
mmol), L9 (20 mol %), PhCO2Na (0.2 mmol) and dry toluene (2 mL) under N2, 16 h,
90 °C. [b] Isolated yield. [c] The reaction was performed on a 3 mmol scale.
2
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10.1002/anie.201703300
Angewandte Chemie International Edition
To further explore the scope of the amination reaction, various
secondary amines had been tested. As shown in Table 3, the reaction
of substrate 1a with a series of six-membered cyclic secondary
amines, such as piperidine, 4-methylpiperidine, ethylisonipecotate,
4-cyanopiperidine, 1,4-dioxa-8-azaspiro[4.5]decane and Boc-
protected 4-aminopiperidine under the optimized conditions
afforded the corresponding aminated products in 62–80% yields
(4b–4g). Moreover, the coupling of 1a with some simple secondary
amines, such as N-methylpropan-1-amine and N-ethylethanamine
also gave the aminated products 4h and 4i in 72% and 52% yields,
respectively. Notably, with respect to 1a, 4-tert-butyl benzamide 1g
afforded a higher yield (4i vs 4j). Meanwhile, the reaction of
substrate 1g with N-methylbenzylamine afforded the desired product
4k in moderate yield. The reaction conditions are also applicable for
amination with N-substituted aniline. To the best of our knowledge,
no examples of arenes with N-substituted aniline as the coupling
partners were demonstrated before. Gratifyingly, we found that the
coupling of 1g with N-substituted anilines, such as N-methylaniline
and N-ethylaniline could afford the corresponding products 4l and
4m in excellent yields (89% and 80%, respectively).
with a wide range of anilines in the reaction of 1a (Table 4).
Anilines bearing electron-withdrawing substituents, such as nitro,
nitrile, trifluromethyl, and halogen groups, afforded the desired
products 5a–5f in moderate yields (44–63%). Interestingly, 1-
naphthylamine also reacted to furnish the corresponding aminated
product 5g in a moderate yield (56%). Gratifyingly, reactivity of
aniline or its derivatives bearing electron-donating functional groups
was observed to be good under present conditions. Simple aniline
also reacted with 1a, providing the desired product 5h in moderate
yield (54%). Anilines possessing a methyl substituent afforded the
aminated products 5i–5k in good yields (60–65%). 3,5-
Dimethylaniline gave 5l in the highest yield of 70%. Importantly,
anilines possessing electron-donating substituents, such as methoxy
and tert-butyl groups, also furnished the desired products 5m–5o in
good yields (62–67%).
We next carried out extensive mechanistic investigations to gain
further understanding of this ligand-promoted C–H amination
reaction. To test the possibility of in situ conversion of the amines to
some electrophilic/reactive amines, we monitored the quantity of the
free aniline (4-methoxyaniline) and the corresponding amination
product 5m by NMR throughout the reaction course. Only unreacted
anilines were observed. Although we observed that large proportion
of free aniline was oxidized to diazene species (see the Supporting
Information) in the absence of the substrate, control experiment
showed that such diazene species are not reactive for this amination
reaction. Competition experiments using free anilines (4-
(trifluoromethyl)aniline and p-toluidine) also revealed that the
electron-rich aniline with the stronger nucleophilic property was
more reactive in this reaction (see the Supporting Information).
To probe whether C-H activation is rate-determining step in this
catalytic cycle, we performed a series of experiments to determine
the kinetic isotope effect (KIE). The observed intermolecular KIE of
1.87 and parallel KIE of 1.70 revealed that the ortho-C-H bond
cleavage may be the rate-determining step (see the Supporting
Information). The key C–H insertion intermediate is also
characterized (cyclorhodacyclic complex 7’, see the Supporting
Information), and transformed into the desired product 5m in
isolated yield of 46% under the standard reaction conditions (see the
Supporting Information), supporting the involvement of this
intermediate. Based on the reaction conditions, a plausible reaction
mechanism for this transformation is proposed in Scheme 2. The
reaction process is initiated by the coordination of amide 1i to Rh(III)
bound to the quinoline ligand (L), which is followed by C–H
activation to give the corresponding five-membered rhodacycle
intermediate 7. Subsequent ligand exchange at Rh(III) center leads
to intermediate 8, which undergoes C–N reductive elimination to
give the ortho-aminated product 3i and Rh(I) species. The ligand
exchange process has also been observed with phosphine ligands.[15]
The oxidation of Rh(I) by Ag2CO3 completes the catalytic cycle.
Table 3. Scope of Secondary Amines.[a,b]
[a] Conditions: 1a or 1g (0.1 mmol), 2 (0.2 mmol), [RhCp*Cl2]2 (5 mol %), Ag2CO3
(0.2 mmol), L9 (20 mol %), PhCO2Na (0.2 mmol) and dry toluene (2 mL) under N2, 16
h, 90 °C. [b] Isolated yield. [c] 4 equiv of alkylamines were used.
In summary, we have developed a ligand-promoted Rh(III)-
catalyzed amination reaction of aryl C–H bonds with free secondary
alkyl amines as well as a variety of anilines using a readily
removable N-pentafluorophenylamide auxiliary. This transformation
exhibits a broad substrate scope and tolerates various functional
groups. The significant enhancing effect with quinolines also
provides a new lead for ligand design in Rh(III)-catalyzed C–H
activation reactions.
The successful use of N-alkyl anilines prompted us to examine
the compatibility of this reaction with free anilines. Transition-
metal-catalyzed amination of arenes with primary amines has been
developed using several systems.[12k,12l,13] However, few examples
of electron-rich anilines were demonstrated. Daugulis[12k] and
Jana[12l] recently disclosed copper-mediated, bidentate auxiliary-
directed amination with electron-donating anilines. We were pleased
to observe that the present amination conditions were compatible
3
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10.1002/anie.201703300
Angewandte Chemie International Edition
Table 4. Scope of Primary Amines.[a,b]
Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff))
Acknowledgement
We gratefully acknowledge the National Natural Science Foundation
of China (grant no. 21671097, 21331002 and 21201100), the National
Science Foundation (CHE-1465292) and the Fundamental Research
Funds for the Central Universities (020514380071) for financial
support.
Keywords: ligand-promoted · amination ·free amines · quinoline
ligand
[1] a) R. Hili, A. K. Yudin, Nat. Chem. Biol. 2006, 2, 284; b) A. Ricci,
Amino Group Chemistry: From Synthesis to the Life Sciences; Wiley-
VCH: Weinheim, 2008; c) J. Yamaguchi, A. D. Yamaguchi, K. Itami,
Angew. Chem. Int. Ed. 2012, 51, 8960; Angew. Chem. 2012, 124,
9092.
[2] For selected reviews of C–H amination, see: a) M.-L. Louillat, F. W.
Patureau, Chem. Soc. Rev. 2014, 43, 901; b) V. S. Thirunavukkarasu, S. I.
Kozhushkov, L. Ackermann, Chem. Commun. 2014, 50, 29; c) N.
Yoshikai, ChemCatChem 2015, 7, 732; d) N. Moselage, J. Li, L.
Ackermann, ACS Catal. 2016, 6, 498; e) Y. R. Zhou, J. J. Yuan, Q. Yang,
Q. Xiao, Y. Y. Peng, ChemCatChem 2016, 8, 2178.
[3] a) E. J. Yoo, S.; Ma, T.-S. Mei, K. S. L. Chan, J.-Q. Yu, J. Am. Chem. Soc.
2011, 133, 7652; b) M. Anand, R. B. Sunoj, H. F. Schaefer, III. J. Am.
Chem. Soc. 2014, 136, 5535; c) D. J. Zhu, G. Q. Yang, J. He, L. Chu, G.
Chen, W. Gong, M. D. Eastgate, J.-Q. Yu, Angew. Chem. Int. Ed. 2015, 54,
2497; Angew. Chem. 2015, 127, 2527; d) J. He, T. Shigenari, J.-Q. Yu,
Angew. Chem. Int. Ed. 2015, 54, 6545; Angew. Chem. 2015, 127, 6645; e)
Q. Gou, G. Liu, Z.-N. Liu, J. Qin, Chem. - Eur. J. 2015, 21, 15491; f) M.
Anand, R. B. Sunoj, H. F. Schaefer, III. ACS Catal. 2016, 6, 696.
[4] For Pd-catalyzed C–N bond formation via a plausible nitrene insertion
mechanism, see: a) K.-H. Ng, A. S. C. Chan, W.-Y. Yu, J. Am. Chem. Soc.
2010, 132, 12862; b) K.-H. Ng, F.-N. Ng, W.-Y. Yu, Chem. Commun.
2012, 48, 11680.
[5] a) D. Lee, Y. Kim, S. Chang, J. Org. Chem. 2013, 78, 11102; b) J. Ryu, J.
Kwak, K. Shin, D. Lee, S. Chang, J. Am. Chem. Soc. 2013, 135, 12861; c)
T. M. Figg, S. Park, J. Park, S. Chang, D. G. Musaev, Organometallics
2014, 33, 4076; d) H. Hwang, J. Kim, J. Jeong, S. Chang, J. Am. Chem.
Soc. 2014, 136, 10770; e) J. Kim, S. Chang, Angew. Chem. Int. Ed. 2014,
53, 2203; Angew. Chem. 2014, 126, 2235; f) H. Chen, M. P. Huestis,
ChemCatChem 2015, 7, 743. g) P. Becker, R. Pirwerdjan, C. Bolm, Angew.
Chem. Int. Ed. 2015, 54, 15493; Angew. Chem. 2015, 127, 15713; h) B. F.
Zhu, X. L. Cui, C. Pi, D. Chen, Y. J. Wu, Adv. Synth. Catal. 2016, 358,
326; i) G. N. Hermann, P. Becker, C. Bolm, Angew. Chem. Int. Ed. 2016,
55, 3781; Angew. Chem. 2016, 128. 3845; j) J.-B. Liu, X.-H. Sheng, C.-Z.
Sun, F. Huang, D.-Z. Chen, ACS Catal. 2016, 6, 2452.
[6] a) C. Grohmann, H. G. Wang, F. Glorius, Org. Lett. 2012, 14, 656; b) K.-
H. Ng, Z. Y. Zhou, W.-Y. Yu, Org. Lett. 2012, 14, 272; c) J. Y. Kim, S. H.
Park, J. Ryu, S. H. Cho, S. H. Kim, S. Chang, J. Am. Chem. Soc. 2012,
134, 9110; d) J. Ryu, K. Shin, S. H. Park, J. Y. Kim, S. Chang, Angew.
Chem. Int. Ed. 2012, 51, 9904; Angew. Chem. 2012, 124. 10042; e) K.
Shin, Y. Baek, S. Chang, Angew. Chem. Int. Ed. 2013, 52, 8031; Angew.
Chem. 2013, 125. 8189; f) D.-G. Yu, M. Suri, F. Glorius, J. Am. Chem.
Soc. 2013, 135, 8802; g) Y. Lian, J. R. Hummel, R. G. Bergman, J. A.
Ellman, J. Am. Chem. Soc. 2013, 135, 12548; h) S. J. Yu, B. S. Wan, X. W.
Li, Org. Lett. 2013, 15, 3706; i) R.-J. Tang, C.-P. Luo, L. Yang, C.-J. Li,
Adv. Synth. Catal. 2013, 355, 869; j) B. Zhou, J. J. Du, Y. X. Yang, H. J.
Feng, Y. C. Li, Org. Lett. 2013, 15, 6302; k) C. H. Tang, Y. Z. Yuan, Y. X.
Cui, N. Jiao, Eur. J. Org. Chem. 2013, 7480; l) H. J. Kim, M. J. Ajitha, Y.
Lee, J. Ryu, J. Kim, Y. Lee, Y. Jung, S. Chang, J. Am. Chem. Soc. 2014,
136, 1132; m) F.-N. Ng, Z. Y. Zhou, W.-Y. Yu, Chem. - Eur. J. 2014, 20.
4474; n) K. Wu, Z. L. Fan, Y. Xue, Q. Z. Yao, A. Zhang, Org. Lett. 2014,
16, 42; o) B. Zhou, J. J. Du, Y. X. Yang, H. J. Feng, Y. C. Li, Org. Lett.
2014, 16, 592; p) W. Yang, J. Q. Sun, X. X. Xu, Q. Zhang, Q. Liu, Chem.
Commun. 2014, 50, 4420; q) Y. Park, K. T. Park, J. G. Kim, S. Chang, J.
Am. Chem. Soc. 2015, 137, 4534.
[a] Conditions: 1a (0.1 mmol), 3 (0.2 mmol), [RhCp*Cl2]2 (5 mol %), Ag2CO3 (0.2
mmol), L9 (20 mol %), PhCO2Na (0.2 mmol) and dry toluene (2 mL) under N2, 16 h,
90 °C. [b] Isolated yield. [c] 4 equiv of primary amines were used.
[7] a) M. Bhanuchandra, M. R. Yadav, R. K. Rit, M. R. Kuram, A. K. Sahoo,
Chem. Commun. 2013, 49, 5225; b) Q.-Z. Zheng, Y.-F. Liang, C. Qin, N.
Jiao, Chem. Commun. 2013, 49, 5654; c) M. Shang, S.-H. Zeng, S.-Z. Sun,
H.-X. Dai, J.-Q. Yu, Org. Lett. 2013, 15, 5286; d) V. S. Thirunavukkarasu,
K. Raghuvanshi, L. Ackermann, Org. Lett. 2013, 15, 3286; e) L-L. Zhang,
L.-H. Li, Y.-Q. Wang, Y.-F. Yang, X.-Y. Liu, Y.-M. Liang,
Organometallics 2014, 33, 1905; f) K. Shin, J. Ryu, S. Chang, Org. Lett.
Scheme 2. Proposed Reaction Mechanism.
4
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10.1002/anie.201703300
Angewandte Chemie International Edition
2014, 16, 2022; g) M. R. Yadav, M. Shankar, E. Ramesh, K. Ghosh, A. K.
Sahoo, Org. Lett. 2015, 17, 1886.
[8] a) J. L. Peng, Z. Q. Xie, M. Chen, J. Wang, Q. Zhu, Org. Lett. 2014, 16,
4702; b) J. L. Peng, M. Chen, Z. Q. Xie, S. Luo, Q. Zhu, Org. Chem.
Front. 2014, 1, 777.
[9] a) B. Sun, T. Yoshino, S. Matsunaga, M. Kanai, Adv. Synth. Catal. 2014,
356, 1491; b) B. Sun, T. Yoshino, S. Matsunaga, M. Kanai, Chem.
Commun. 2015, 51, 4659; c) P. Patel, S. Chang, ACS Catal. 2015, 5, 853;
d) J. Park, S. Chang, Angew. Chem. Int. Ed. 2015, 54, 14103; Angew.
Chem. 2015, 127, 14309; e) Y. J. Liang, Y.-F. Liang, C. H. Tang, Y. Z.
Yuan, N. Jiao, Chem. - Eur. J. 2015, 21, 16395; f) R. H. Mei, J. Loup, L.
Ackermann, ACS Catal. 2016, 6, 793; g) F. Wang, H. Wang, Q. Wang, S.
J. Yu, X. W. Li, Org. Lett. 2016, 18, 1306.
2013, 125, 6159; e) A. M. Martínez, N. Rodríguez, R. G. Arrayas, J. C.
Carretero, Chem. Commun. 2014, 50, 2801; f) Q. Li, S.-Y. Zhang, G. He,
Z. Ai, W. Nack, G. Chen, Org. Lett. 2014, 16, 1764; g) M. Shang, S.-Z.
Sun, H.-X. Dai, J.-Q. Yu, J. Am. Chem. Soc. 2014, 136, 3354; h) L. Wang,
D. L. Priebbenow, W. R. Dong, C. Bolm, Org. Lett. 2014, 16, 2661; i) Q.
Q. Yan, Z. K. Chen, W. L. Yu, H. Yin, Z. X. Liu, Y. H. Zhang, Org. Lett.
2015, 17, 2482; j) P. Sadhu, T. Punniyamurthy, Chem. Commun. 2016, 52,
2803; k) J. Roane, O. Daugulis, J. Am. Chem. Soc. 2016, 138, 4601; l) K.
B. Singh, A. Polley, R. Jana, J. Org. Chem. 2016, 81, 4295; m) L. B.
Zhang, S. K. Zhang, D. H. Wei, X. J. Zhu, X. Q. Hao, J. H. Su, J. L. Niu,
M. P. Song, Org. Lett. 2016, 18, 1318.
[13] a) H. Kim, K. Shin, S. Chang, J. Am. Chem. Soc. 2014, 136, 5904; b) H.
Kim, S. Chang, ACS Catal. 2015, 5, 6665.
[10] T. Matsubara, S. Asako, L. Ilies, E. Nakamura, J. Am. Chem. Soc. 2014,
136, 646.
[11] a) X. Chen, J.-J. Li, X.-S. Hao, C. E. Goodhue, J.-Q. Yu, J. Am. Chem. Soc.
2006, 128, 78; b) X. Chen, C. E. Goodhue, J.-Q. Yu, J. Am. Chem. Soc.
2006, 128, 12634.
[14] M. H. Daniels, J. R. Armand, K. L. Tan, Org. Lett. 2016, 18, 3310.
[15] a) X. Yu, Y. Dian, W. Guo, T. Wang, Q. Xie, S. Wu, C. Jiang, Z. Fan, J.
Wang, G. Liu, Organometallics 2017, 36, 1027; b) S. Y. Hong, J. Jeong, S.
Chang, Angew. Chem. Int. Ed. 2017, 56, 2408; Angew. Chem. 2017, 129,
2448.
[12] a) X. Chen, X.-S. Hao, C. E. Goodhue, J.-Q. Yu, J. Am. Chem. Soc. 2006,
128, 6790; b) T. Uemura, S. Imoto, N. Chatani, Chem. Lett. 2006, 35, 842;
c) A. John, K. M. Nicholas, J. Org. Chem. 2011, 76, 4158. d) L. D. Tran, J.
Roane, O. Daugulis, Angew. Chem. Int. Ed. 2013, 52, 6043; Angew. Chem.
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10.1002/anie.201703300
Angewandte Chemie International Edition
C–H Amination
Huai-Wei Wang, Yi Lu,* Bing Zhang,
Jian He, Hua-Jin Xu, Yan-Shang
Kang, Wei-Yin Sun,* Jin-Quan Yu*
__________ Page – Page
Ligand-Promoted Rhodium(III)-
Catalyzed ortho-C–H Amination with
Free Amines
2-Methylquinoline is identified as an efficient ligand for promoting rhodium(III)-
catalyzed directed C–H amination of N-pentafluorophenylbenzamides, providing a
new structural lead for ligand design in Rh(III)-catalyzed C–H activation reactions.
Both secondary amines and primary anilines are compatible, thus significantly
expanding the scope of C–H amination reaction with free amines.
6
This article is protected by copyright. All rights reserved.