Cp*Co(III)-catalyzed C[sbnd]H amidation of azines with dioxazolones

Article abstract of DOI:10.1016/j.cclet.2020.08.046

Cp*Co(III)-catalyzed direct C[sbnd]H amidation of azines has been developed. This conversion could proceed smoothly in the absence of external oxidants, acids or bases, with excellent regioselectivity and broad functional group tolerance. CO₂ w

Full text of DOI:10.1016/j.cclet.2020.08.046

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CCLET 5823 No. of Pages 4
Chinese Chemical Letters xxx (2019) xxx–xxx
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Chinese Chemical Letters
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Communication
Cp*Co(III)-catalyzed CÀÀH amidation of azines with dioxazolones
*
*
Yanzhen Huang, Chao Pi , Zhen Tang, Yangjie Wu, Xiuling Cui
Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, College of Chemistry, Green
Catalysis Center, Zhengzhou University, Zhengzhou 450052, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 3 July 2020
Received in revised form 6 August 2020
Accepted 26 August 2020
Available online xxx
Cp*Co(III)-catalyzed direct CÀÀH amidation of azines has been developed. This conversion could proceed
smoothly in the absence of external oxidants, acids or bases, with excellent regioselectivity and broad
functional group tolerance. CO2 was released as the sole byproduct, thus providing an environmentally
benign amidation process. The products obtained are important intermediates in organic synthesis.
© 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Cp*Co(III)-catalyzed
Azines
Amidation
Dioxazolone
Nitrogen-containing compounds are widely existed in many
natural products, pharmaceutics, and functional materials [1,2]. So
far, the main methods for the construction of the CÀÀN bond have
been represented by Ullmann and Buchwald–Hartwig amination,
using copper or palladium as catalyst [3–6]. Despite the fact that
these means are well developed and widely applied, aryl halides or
complex ligands are required in most cases. Recently, the direct
CÀÀH amination of the aromatic ring and the redox amine source
has been developed. The common redox amine sources [7–9],
include imidoiodine [10,11], organic azide [12–21], hydroxamate
[22–24], heterocyclic amines [25–33]. Among which, dioxazolones
are used as effective amidation reagents to construct CÀÀN bonds
due to their high efficiency, safety, and ease of preparation
[28,33,34].
Azine is an important nitrogen-containing compound, which is
widely used in pesticides, medicine, functional materials and other
fields [35–40]. Nowadays, direct CÀÀH bond functionalization has
been established to build various azine derivatives. Rh(III)-
catalyzed ortho-alkenylation [41], ortho-thioetherification and
ortho-allylation [42,43], ortho-alkylation [44] of azines have been
respectively developed by Huang, Zhu and our group (Scheme 1,
i–v). Bhanage’s group [45] utilized a relatively inexpensive cobalt
as a catalyst to achieve the cyclization reaction of azines with two
molecules of alkyne through NÀÀN bond cleavage, to synthesize a
series of polysubstituted isoquinolines (Scheme 1, i). Subsequently,
Shi [46] first developed rhodium-catalyzed ortho-CÀÀH sulfami-
dation of azines and obtained the corresponding sulfamidated
products with high regioselectivity. Nevertheless, equivalent
oxidant was required (Scheme 1, v). Based on the relevant reports
[47–52] and the importance of azines, cobalt-catalyzed directed
CÀÀH amidation of azines should be attractive and feasible. In
continuation of our ongoing exploration of redox CÀÀH amidation
[26,30,53], herein, we report Co-catalyzed amidation of azines
with dioxazolones via direct CÀÀH activation. This transformation
could be carried out smoothly without additional oxidant, acid or
base. And, CO2 is released as the sole byproduct, thus providing an
environmentally benign amidation process.
First, we investigated the direct CÀÀH amination with aceto-
phenazine 1a and dioxazolone 2a as the model substrates (Table 1).
In an initial set of experiment, the expected ortho-amided product
3a was obtained in 25% isolated yield in the presence of [Cp*Co(CO)
I2] (10 mol%), AgSbF6 (20 mol%), and Cu(OAc)2 (20 mol%) in DCE at
80 ꢀC for 12 h (entry 1). Due to the solubility of the substrates, we
initiated our studies by examining the effects of the solvent. And
DCM was found to be optimal (entries 1ÀÀ7). The yield was almost
unaffected under air, N2, O2, respectively. So we decided to conduct
the reaction at air atmosphere (entry 8). Considering the redox
property of dioxazolone, we tried to avoid the use of Cu(OAc)2 as
oxidant. Surprisingly, the yield was increased from 55% to 72%
(entry 9). Afterward, the effect of silver salt was investigated (such
as AgSbF6, AgNTf2, AgBF4, AgOAc) (entries 9–12), and AgSbF6 gave
the better result. However, the corresponding product was not
obtained when the silver salt was replaced with KPF6 (entry 13).
Subsequently, some additives were screened (entries 14–18), and
yield was slightly reduced compared to the yield in the absence of
any additives. It was noting that the desired product 3a could be
obtained in 84% yield when the reaction time was decreased to 8 h
because the formation of di-substituted amination as by-product
* Corresponding authors.
E-mail addresses: pichao@zzu.edu.cn (C. Pi), cuixl@zzu.edu.cn (X. Cui).
https://doi.org/10.1016/j.cclet.2020.08.046
1001-8417/© 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Y. Huang, et al., Cp*Co(III)-catalyzed CÀÀH amidation of azines with dioxazolones, Chin. Chem. Lett. (2020),
https://doi.org/10.1016/j.cclet.2020.08.046

G Model
CCLET 5823 No. of Pages 4
2
Y. Huang et al. / Chinese Chemical Letters xxx (2019) xxx–xxx
para-substituted azines 1b–1c with electron-donating groups (-Me
and -OMe) was found to react smoothly more than para-
substituted azines 1h with electron withdrawing groups (COOMe).
The 4-halo azines (1d-1g) reacted with the dioxazolone to give the
target products in moderate to good yields, significantly better
than 3-halo azines (1i-1k). For the same substituent, the overall
yields of 4-substituted products (3b-3f, 58%–81%) were signifi-
cantly higher than that of 3-substituted products (3i-3 m, 48%–
62%). The reaction of 1p was sluggish and only 18% product 3p was
obtained. Surprisingly, 3n was afforded in 76% yield with good
regioselectivity. In a similar fashion, 1,2-bis((E)-3,4-dihydronaph-
thalen-1(2H)-ylidene) hydrazine 1o and bis(ferrocenyl acetone)
hydrazine 1p were also tolerated. Moreover, dibenzaldehyde
hydrazine provided the amidated product 3q in 56% yield.
To further examine the substrate scope of this procedure, a
series of dioxazolones (2a-2t) were screened for coupling with
acetophenazine 1a (Scheme 3). Both electron-donating (e.g., Me,
MeO) and electron-withdrawing groups (e.g., F, Cl, Br, CF3, 3,5-di-
Cl) in benzene were compatible with this reaction protocol.
Dioxazolones bearing electron-withdrawing substituents on the
aromatic ring were generally more efficient, giving the desired
amidated product in relatively higher yields. Importantly, halides,
such as chloride (4d, 4h, 4m and 4n), bromide (4i), could survive
under the optimized conditions, giving the desired products in
58%–85% yields. Furthermore, thiophene- and naphthalene-
functionalized dioxazolones also reacted smoothly to afford
products 4o and 4p in 70% and 75% yields, respectively.
Nevertheless, aliphatic dioxazolone, such as 2r, was not amenable
to this protocol. The yield of the corresponding products (4t, 62%;
4q, 41%; 4s, 28%) decreased along with increasing the steric
hindrance for aliphatic-dioxazolone (2t, 2q, 2s).
Scheme 1. Direct functionalization of azines by transition metal catalysis.
Table 1
Optimization of direct amidation conditionsa.
To demonstrate the practical application of the amidation
reaction, a scaling up experiment was carried out with 1 mmol
scale of acetophenazine 1a, which successfully afforded the
aminated product 3a in 75% under the optimal reaction conditions
(Scheme 4). The product 3a could be hydrolyzed, treated by 1
equiv. of sodium hydroxide in methanol, to obtain 6a in 98% yield.
Similarly, 3a was stirred in 4 mol/L hydrochloric acid solution in
DCM at room temperature to give the hydrolysis product 5a in 96%
yield. According to the literature, 5a could be easily transformed to
the corresponding biologically active 2-phenyl-4-quinolinone (6b)
[54–57] and 3-methyl-2-phenylindole (6c) [58–60].
Entry
Ag+
Additives
Solvent
3a Yield (%)b
1
2
3
4
5
6
7
8
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgNTf2
AgBF4
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
–
DCE
25
29
trace
10
16
Toluene
MeOH
THF
TFE
HFIP
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
17
55
56
c/d
9
72
67
Trace
Trace
Trace
38
47
61
14
57
10
11
12
13
14
15
16
17
18
19e
20e,f
–
–
AgOAc
KPF6
–
–
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
PivOH
NaOAc
KOAc
CsOAc
NaOPiv
–
Á
H2O
84
54
–
DCE: 1,2-dichloroethane; THF: Tetrahydrofuran; TFE: 2,2,2-trifluoroethanol; HFIP:
hexafluoro isopropanol; DCM: 1,2-dichloromethane.
a
Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), [Cp*Co(CO)I2] (10 mol%),
Ag+ (20 mol%), additives (20 mol%), solvent (1 mL), 12 h, under air, 100 ꢀC, sealed.
b
Isolated yields.
O2.
N2.
8 h.
c
d
e
f
[Cp*Co(CO)I2] (5 mol%), AgSbF6 (10 mol%).
3aa was reduced (entry 19). Reducing the amount of catalyst to
5 mol%, only 54% of product 3a was obtained (entry 20). Finally, the
optimal reaction conditions were determined as follows: [Cp*Co
(CO)I2] (10 mol%), AgSbF6 (20 mol%), in 1 mL DCM under air
atmosphere at 100 ꢀC for 8 h.
Scheme 2. Scope of azines. Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol),
[Cp*Co(CO)I2] (10 mol%), AgSbF6 (20 mol%), DCM (1 mL), 8 h, 100 ꢀC, sealed. Isolated
yields.
With the optimized conditions in hand, the scope of azines was
next examined (Scheme 2). The coupling of dioxazolone (2a) and
Please cite this article in press as: Y. Huang, et al., Cp*Co(III)-catalyzed CÀÀH amidation of azines with dioxazolones, Chin. Chem. Lett. (2020),
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3
Scheme 5. Proposed reaction mechanism.
Scheme 3. Scope of dioxazolones. Reaction conditions: 1a (0.1 mmol), 2a
(0.2 mmol), [Cp*Co(CO)I2] (10 mol%), AgSbF6 (20 mol%), DCM (1 mL), 8 h, under
air, 100 ꢀC, sealed. Isolated yields.
anti-infection, anti-tumor, anti-inflammatory and other biological
activities.
Declaration of competing interest
No conflict of interest exits in the submission of this
manuscript, and manuscript is approved by all authors.
Acknowledgments
This work was financially supported by the Ministry of Science
and Technology of China (No. 2016YFE0132600), Henan Center for
Outstanding Overseas Scientists (No. GZS2020001).
Appendix A. Supplementary data
Supplementary material related to this article can be
found, in the online version, at doi:https://doi.org/10.1016/j.
cclet.2020.08.046.
References
Scheme 4. Scale-up experiment and transformations of the amidated product.
[1] T. Naito, Chem. Pharm. Bull. 56 (2008) 1367–1383.
[2] Y. Wu, B. Tian, C. Hu, et al., Org. Biomol. Chem. 17 (2019) 5505–5508.
[3] C. Sambiagio, S.P. Marsden, A.J. Blacker, P.C. McGowan, Chem. Soc. Rev. 43
(2014) 3525–3550.
[4] S. Bhunia, G.G. Pawar, S.V. Kumar, Y. Jiang, D. Ma, Angew. Chem. Int. Ed. 56
(2017) 16136–16179.
Based on the above results and previous reports [61,62], a
plausible reaction mechanism was proposed (Scheme 5). Firstly,
the reactive cationic Cp*CoIII species I was generated with the
assistance of AgSbF6. Subsequently, Cp*CoIII species I coordinated
to nitrogen atom of the substrate 1a, and formed cobaltacycle II
through CÀÀH bond cleavage. Cobaltacycle II subsequently
coordinated with nitrogen atom of 2a to form intermediate III.
Next, nitrogen carbine intermediate IV was afforded by extrusion
of CO2 as a single byproduct. Subsequently, migratory insertion of
intermediate IV provided the intermediate V. Finally, proton-
demetallization of intermediate V liberated the desired product 3a
along with the regeneration of the active catalyst into the next
cycle.
In summary, we have developed an efficient and convenient
cobalt(III)-catalyzed CÀÀH amidation of azines with dioxazolones.
The method could be scalable and compatible with a broad range of
functional groups. The results have paved the way toward
construction of 2-phenyl-4-quinolinone and 3-methyl-2-phenyl-
indole derivatives, which exist in drug molecule with broad
[5] C. Torborg, M. Beller, Adv. Synth. Catal. 351 (2009) 3027–3043.
[6] F. Monnier, M. Taillefer, Angew. Chem. Int. Ed. 48 (2009) 6954–6971.
[7] Y. Park, Y. Kim, S. Chang, Chem. Rev. 117 (2017) 9247–9301.
[8] Y. Park, K.T. Park, J.G. Kim, S. Chang, J. Am. Chem. Soc. 137 (2015) 4534–4542.
[9] Y. Park, S. Jee, J.G. Kim, S. Chang, Org. Process Res. Dev. 19 (2015) 1024–1029.
[10] J.A. Souto, P. Becker, Á. Iglesias, K. Muñiz, J. Am. Chem. Soc. 134 (2012) 15505–
15511.
[11] C. You, T. Yuan, Y. Huang, et al., Org. Biomol. Chem. 16 (2018) 4728–4733.
[12] K. Shin, H. Kim, S. Chang, Acc. Chem. Res. 48 (2015) 1040–1052.
[13] C. Pi, X. Cui, Y. Wu, J. Org. Chem. 80 (2015) 7333–7339.
[14] J.Y. Kim, S.H. Park, J. Ryu, et al., J. Am. Chem. Soc. 134 (2012) 9110–9113.
[15] S.H. Park, J. Kwak, K. Shin, et al., J. Am. Chem. Soc. 136 (2014) 2492–2502.
[16] L. Jie, L. Wang, D. Xiong, et al., J. Org. Chem. 83 (2018) 10974–10984.
[17] Y. Feng, Y. Li, Y. Yu, L. Wang, X. Cui, RSC Adv. 8 (2018) 8450–8454.
[18] L. Xu, L. Wang, Y. Feng, et al., Org. Lett. 19 (2017) 4343–4346.
[19] Y. Li, Y. Feng, L. Xu, L. Wang, X. Cui, Org. Lett. 18 (2016) 4924–4927.
[20] B. Zhu, X. Cui, C. Pi, D. Chen, Y. Wu, Adv. Synth. Catal. 358 (2016) 326–332.
[21] Y. Feng, Z. Zhang, Q. Fu, et al., Chin. Chem. Lett. 31 (2020) 58–60.
[22] H. Jung, H. Keum, J. Kweon, S. Chang, J. Am. Chem. Soc. 142 (2020) 5811–5818.
[23] D. Dev, N.B. Palakurthy, K. Thalluri, J. Chandra, B. Mandal, J. Org. Chem. 79
(2014) 5420–5431.
[24] J. Senger, J. Melesina, M. Marek, et al., J. Med. Chem. 59 (2016) 1545–1555.
Please cite this article in press as: Y. Huang, et al., Cp*Co(III)-catalyzed CÀÀH amidation of azines with dioxazolones, Chin. Chem. Lett. (2020),
https://doi.org/10.1016/j.cclet.2020.08.046

G Model
CCLET 5823 No. of Pages 4
4
Y. Huang et al. / Chinese Chemical Letters xxx (2019) xxx–xxx
[25] S. Huang, H. Li, X. Sun, L. Xu, L. Wang, X. Cui, Org. Lett. 21 (2019) 5570–5574.
[26] L. Xu, T. Li, L. Wang, X. Cui, J. Org. Chem. 84 (2019) 560–567.
[27] X.H. Hu, X.F. Yang, T.P. Loh, ACS Catal. 6 (2016) 5930–5934.
[28] J. Park, S. Chang, Angew. Chem. Int. Ed. 54 (2015) 14103–14107.
[29] Y. Park, K.T. Park, J.G. Kim, S. Chang, J. Am. Chem. Soc. 137 (2015) 4534–4542.
[30] X. Mi, W. Feng, C. Pi, X. Cui, J. Org. Chem. 84 (2019) 5305–5312.
[31] Y. He, C. Pi, Y. Wu, X. Cui, Chin. Chem. Lett. 31 (2020) 396–400.
[32] J. Ren, C. Pi, Y. Wu, X. Cui, Org. Lett. 21 (2019) 4067–4071.
[33] N.K. Mishra, Y. Oh, M. Jeon, et al., Eur. J. Org. Chem. 2016 (2016) 4976–4980.
[34] K.M. van Vliet, B. de Bruin, ACS Catal. 10 (2020) 4751–4769.
[35] G. Le Goff, J. Ouazzani, Bioorg. Med. Chem. 22 (2014) 6529–6544.
[36] L.M. Blair, J. Sperry, J. Nat. Prod. 76 (2013) 794–812.
[46] H.M. Vu, J.Y. Yong, F.W. Chen, X.Q. Li, G.Q. Shi, J. Org. Chem. 85 (2020) 4963–
4972.
[47] P.W. Tan, A.M. Mak, M.B. Sullivan, D.J. Dixon, J. Seayad, Angew. Chem. Int. Ed. 56
(2017) 16550–16554.
[48] J.S. Sun, M. Liu, J. Zhang, L. Dong, J. Org. Chem. 83 (2018) 10555–10563.
[49] J. Park, S. Chang, Angew. Chem. Int. Ed. 54 (2015) 14103–14107.
[50] Y. Liu, F. Xie, A.Q. Jia, X. Li, Chem. Commun. (Camb.) 54 (2018) 4345–4348.
[51] B. Khan, V. Dwivedi, B. Sundararaju, Adv. Synth. Catal. 362 (2020) 1195–1200.
[52] J. Huang, J. Ding, T.M. Ding, et al., Org. Lett. 21 (2019) 7342–7345.
[53] D.-G. Yu, M. Suri, F. Glorius, J. Am. Chem. Soc. 135 (2013) 8802–8805.
[54] C. Brouwer, K. Jenko, S.S. Zoghbi, R.B. Innis, V.W. Pike, J. Med. Chem. 57 (2014)
6240–6251.
[37] Y. Zhu, H. Jin, Y. Huang, Chem. Commun. (Camb.) 55 (2019) 10135–10137.
[38] W. Tang, Y. Xiang, A. Tong, J. Org. Chem. 74 (2009) 2163–2166.
[39] C. Chakravarty, B. Mandal, P. Sarkar, J. Phys. Chem. C 122 (2018) 3245–3255.
[40] M.X. Wu, Y.W. Yang, Chin. Chem. Lett. 28 (2017) 1135–1143.
[41] W. Han, G. Zhang, G. Li, H. Huang, Org. Lett. 16 (2014) 3532–3535.
[42] J. Wen, A. Wu, M. Wang, J. Zhu, J. Org, Chem. 80 (2015) 10457–10463.
[43] J. Wen, A. Wu, Y. Miao, J. Zhu, Tetrahedron Lett. 56 (2015) 5512–5516.
[44] Y. Yu, C. Kuai, R. Chauvin, et al., J. Org. Chem. 82 (2017) 8611–8616.
[45] D.S. Deshmukh, P.A. Yadav, B.M. Bhanage, Org. Biomol. Chem. 17 (2019) 3489–
3496.
[55] C.P. Jones, K.W. Anderson, S.L. Buchwald, J. Org. Chem. 72 (2007) 7968–7973.
[56] J. Huang, Y. Chen, A.O. King, et al., Org. Lett. 10 (2008) 2609–2612.
[57] C. Eidamshaus, T. Triemer, H.U. Reissig, Synthesis 2011 (2011) 3261–3266.
[58] A. Fuerstner, A. Hupperts, A. Ptock, E. Janssen, J. Org. Chem. 59 (1994) 5215–
5229.
[59] A. Fuerstner, A. Hupperts, J. Am. Chem. Soc. 117 (1995) 4468–4475.
[60] A. Fürstner, D.N. Jumbam, Tetrahedron 48 (1992) 5991–6010.
[61] Y. Liang, Y.F. Liang, C. Tang, Y. Yuan, N. Jiao, Chem. Eur. J. 21 (2015) 16395–
16399.
[62] P. Shi, L. Wang, K. Chen, J. Wang, J. Zhu, Org. Lett. 19 (2017) 2418–2421.
Please cite this article in press as: Y. Huang, et al., Cp*Co(III)-catalyzed CÀÀH amidation of azines with dioxazolones, Chin. Chem. Lett. (2020),
https://doi.org/10.1016/j.cclet.2020.08.046