Copper Acetate Aerobic Oxidative Synthesis of Pyrido[1,2-a]benzimidazoles from Aminopyridines and Phenylboronic Acids

Hao Yan; Hui Guo; Xiaoqiang Zhou; Zhenyu Zuo; Jingli Liu; Guanghui Zhang; Shuan Zhang

doi:10.1055/s-0037-1611847

Synlett, Table of Contents

Synlett 2019; 30(12): 1469-1473
DOI: 10.1055/s-0037-1611847

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Copper Acetate Aerobic Oxidative Synthesis of Pyrido[1,2-a]benzimidazoles from Aminopyridines and Phenylboronic Acids

Authors

Hao Yan*

^aCollege of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China Email: yanhao@sntcm.edu.cn

^bState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. of China
Hui Guo

^aCollege of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China Email: yanhao@sntcm.edu.cn
Xiaoqiang Zhou

^bState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. of China

^cCollege of Chemistry and Materials, Weinan Normal University, Chaoyang Road, Weinan 714099, P. R. of China
Zhenyu Zuo

^aCollege of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China Email: yanhao@sntcm.edu.cn
Jingli Liu

^aCollege of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China Email: yanhao@sntcm.edu.cn
Guanghui Zhang

^aCollege of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China Email: yanhao@sntcm.edu.cn
Shuan Zhang

^aCollege of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China Email: yanhao@sntcm.edu.cn

Abstract

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Abstract

Pyrido[1,2-a]benzimidazoles, which show interesting and potentially useful biological activities, have drawn extensive attention from chemists. A straightforward copper acetate-oxidative one-pot synthesis of these compounds from 2-aminopyridines and phenylboronic acids through C–N bond formation and C–H bond activation was developed as a simple and convenient method.

Key words

oxidation - cyclization - N–H coupling - C–H activation - pyridobenzimidazoles

Full Text

References

References and Notes
1 Bagdi AK, Santra S, Monir K, Hajra A. Chem. Commun. 2015; 51: 1555

2a Rupert KC, Henry JR, Dodd JH, Wadsworth SA, Cavender DE, Olini GC, Fahmy B, Siekierka J. Bioorg. Med. Chem. Lett. 2003; 13: 347
2b Moraski GC, Markley LD, Hipskind PA, Boshoff H, Cho S, Franzblau SG, Miller MJ. ACS Med. Chem. Lett. 2011; 2: 466

3 Bae J.-S, Lee D.-W, Lee D.-H, Jeong D.-S. WO 2007011163, 2007
4 Takeshita H, Watanabe J, Kimura Y, Kawakami K, Takahashi H, Takemura M, Kitamura A, Someya K, Nakajima R. Bioorg. Med. Chem. Lett. 2010; 20: 3893
5 Refaat HM. Med. Chem. Res. 2012; 21: 1253
6 Ndakala AJ, Gessner RK, Gitari PW, October N, White KL, Hudson A, Fakorede F, Shackleford DM, Kaiser M, Yeates C, Charman SA, Chibale K. J. Med. Chem. 2011; 54: 4581
7 Jardosh HH, Sangani CB, Patel MP, Patel RG. Chin. Chem. Lett. 2013; 24: 123
8 Rasheed S, Rao DN, Das P. J. Org. Chem. 2015; 80: 9321

9a Qian G, Liu B, Tan Q, Zhang S, Xu B. Eur. J. Org. Chem. 2014; 4837
9b Rao DN, Rasheed S, Vishwakarma RA, Ras P. RSC Adv. 2014; 4: 25600

10 Yan CG, Wang QF, Song XK, Sun J. J. Org. Chem. 2009; 74: 710
11 Wu Z, Huang Q, Zhou X, Yu L, Yu L, Li Z, Wu D. Eur. J. Org. Chem. 2011; 5242
12 Barolo SM, Wang Y, Rossi RA, Cuny GD. Tetrahedron 2013; 69: 5487
13 Panda K, Suresh JR, Ila H, Junjappa H. J. Org. Chem. 2003; 68: 3498
14 Liang D, He Y, Liu L, Zhu Q. Org. Lett. 2013; 15: 3476
15 Ibrahim MA. Tetrahedron 2013; 69: 6861
16 Chen J, Natte K, Man NY. T, Stewart SG, Wu X.-F. Tetrahedron Lett. 2015; 56: 4843
17 Wang H, Wang Y, Peng C, Zhang J, Zhu Q. J. Am. Chem. Soc. 2010; 132: 13217
18 Masters K.-S, Rauws TR. M, Yadav AK, Herrebout WA, Van der Veken B, Maes BU. W. Chem. Eur. J. 2011; 17: 6315

19a Yan H, Yang SZ, Gao XA, Zhou K, Ma C, Yan RL, Huang GS. Synlett 2012; 2961
19b Yan H, Yan R, Yang S, Gao X, Wang Y, Huang G, Liang Y. Chem. Asian J. 2012; 7: 2028
19c Yan R.-L, Yan H, Ma C, Ren Z.-Y, Gao X.-A, Huang G.-S, Liang Y.-M. J. Org. Chem. 2012; 77: 2024
19d Yan H, Ma Y, Sun Y, Ma C, Wang Y, Ren X, Huang G. Tetrahedron 2014; 70: 2761
19e Yan H, Wang Y, Pan C, Zhang H, Yang S, Ren X, Li J, Huang G. Eur. J. Org. Chem. 2014; 2754
19f Hu T, Yan H, Liu X, Wu C, Fan Y, Huang J, Huang G. Synlett 2015; 26: 2866
19g Zhou X, Yan H, Ma C, He Y, Li Y, Cao J, Yan R, Huang G. J. Org. Chem. 2016; 81: 25

20 Pyrido[1,2-a ]benzimidazole (3aa); Typical Procedure An oven-dried Schlenk tube was charged with 2-aminopyridine (1a; 0.32 mmol), PhB(OH)₂ (2a; 0.38 mmol), and Cu(OAc)₂ (29 mg, 0.16 mmol). The Schlenk tube was sealed and then evacuated and backfilled with O₂ (three cycles). DMSO (2 mL) was added, and the mixture was stirred at 120 °C for 36 h then cooled to r.t. The solvent was diluted with EtOAc (10 mL), and the mixture was washed with brine (5 mL) then dried (Na₂SO₄) and concentrated under vacuum. The residue was purified by column chromatography (silica gel, PE–EtOAc) to give a yellow solid; yield: 43 mg (80%); mp 174–176 °C. IR (neat): 3057, 3018, 1641, 1502, 1466, 1356, 1258, 1226, 1144, 756, 723 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.42 (dd, J = 6.8, 1.2 Hz, 1 H), 7.94 (d, J = 8.4 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 1 H), 7.68 (dd, J = 9.2, 0.8 Hz, 1 H), 7.54–7.51 (m, 1 H), 7.42–7.34 (m, 2 H), 6.82 (t, J = 6.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 148.4, 144.5, 129.2, 128.6, 125.6, 125.1, 120.9, 119.9, 118.0, 110.3, 110.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₁H₉N₂: 169.0760; found: 169.0757.
21 Han Y, Zhang M, Zhang Y.-Q, Zhang Z.-H. Green Chem. 2018; 20: 4891

22a Ley SV, Thoms AW. Angew. Chem. Int. Ed. 2003; 42: 5400
22b Zhang M. Appl. Organomet. Chem. 2010; 24: 269
22c King AE, Huffman LM, Casitas A, Costas M, Ribas X, Stahl SS. J. Am. Chem. Soc. 2010; 132: 12068

Supplementary Material

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