Synlett, Table of Contents Synlett 2022; 33(10): 973-976DOI: 10.1055/s-0037-1610795 letter Copper-Mediated Direct Aromatic ortho-C–H Cyanation by AIBN Aijun Zhou , Zhenlian Wang , Fan Chen , Peng-Cheng Qian∗ , Jiang Cheng∗ Recommend Article Abstract Buy Article All articles of this category Abstract We have developed a copper-mediated chelation-assisted direct aromatic ortho-C–H cyanation that uses AIBN as a safe cyanation reagent. The substrate scope included indoles, pyrroles, a carbazole, and a thiophene. Key words Key wordscopper catalysis - cyanation - C–H bond activation - AIBN - radical reaction - safety Full Text References References and Notes 1a Hao E, Jiang X, Fu D, Wang D, Xie M, Qu G, Guo H. Youji Huaxue 2016; 36: 2746 1b Saranya S, Neetha M, Aneeja T, Anilkumar G. Adv. Synth. Catal. 2020; 362: 4543 1c Cui J, Song J, Liu Q, Liu H, Dong Y. Chem. Asian J. 2018; 13: 482 1d Yan G, Zhang Y, Wang J. Adv. Synth. Catal. 2017; 359: 4068 2a Wen Q, Jin J, Zhang L, Luo Y, Lu P, Wang Y. Tetrahedron Lett. 2014; 55: 1271 2b Kanchana US, Mathew TV, Anilkumar G. J. Organomet. Chem. 2020; 920: 121337 3 Ahmad MS, Indra NP, Li C. New J. Chem. 2020; 44: 17177 4a Neetha M, Afsina CM. A, Aneeja T, Anilkumar G. RSC Adv. 2020; 10: 33683 4b Hosseinian A, Ahmadi S, Monfared A, Kheirollahi Nezhad PD, Vessally E. Curr. Org. Chem. 2018; 22: 1862 5a Ping Y, Ding Q, Peng Y. ACS Catal. 2016; 6: 5989 5b Wang L, Shao Y, Cheng J. Org. Biomol. Chem. 2021; 19: 8646 6a Mishra NK, Jeong T, Sharma S, Shin Y, Han S, Park J, Oh JS, Kwak JH, Jung YH, Kim IS. Adv. Synth. Catal. 2015; 357: 1293 6b Yu D.-G, Gensch T, de Azambuja F, Vásquez-Céspedes S, Glorius F. J. Am. Chem. Soc. 2014; 136: 17722 6c Lv S, Li Y, Yao T, Yu X, Zhang C, Hai L, Wu Y. Org. Lett. 2018; 20: 4994 6d Liu W, Richter SC, Mei R, Feldt M, Ackermann L. Chem. Eur. J. 2016; 22: 17958 6e Liu M, You E, Cao W, Shi J. Asian J. Org. Chem. 2019; 8: 1850 7a Xu S, Huang X, Hong X, Xu B. Org. Lett. 2012; 14: 4614 7b Hong X, Wang H, Qian G, Tan Q, Xu B. J. Org. Chem. 2014; 79: 3228 8 Qi C, Hu X, Jiang H. Chem. Commun. 2017; 53: 7994 9a Kou X, Zhao M, Qiao X, Zhu Y, Tong X, Shen Z. Chem. Eur. J. 2013; 19: 16880 9b Pan C, Jin H, Xu P, Liu X, Cheng Y, Zhu C. J. Org. Chem. 2013; 78: 9494 10 Pawar AB, Chang S. Org. Lett. 2015; 17: 660 11 Xu S, Teng J, Yu J.-T, Sun S, Cheng J. Org. Lett. 2019; 21: 9919 12a Liu P.-Y, Zhang C, Zhao S.-C, Yu F, Li F, He Y.-P. J. Org. Chem. 2017; 82: 12786 12b Liu L, Wang Z, Fu X, Yan C.-H. Org. Lett. 2012; 14: 5692 13 Rong G, Mao J, Zheng Y, Yao R, Xu X. Chem. Commun. 2015; 51: 13822 14 Teng F, Yu J.-T, Yang H, Jiang Y, Cheng J. Chem. Commun. 2014; 50: 12139 15 Teng F, Yu J.-T, Zhou Z, Chu H, Cheng J. J. Org. Chem. 2015; 80: 2822 16 Xu H, Liu P.-T, Li Y.-H, Han F.-S. Org. Lett. 2013; 15: 3354 17 Heterocyclic Nitriles 2a–s; General ProcedureAn oven-dried Schlenk tube equipped with a magnetic stirring bar was charged sequentially with the appropriate heterocycle 1a–s (0.1 mmol), AIBN (82.1 mg, 0.5 mmol), Cu(OAc)2 (27.2 mg, 0.15 mmol), DMF (0.5 mL), and MeCN (1.5 mL). After evacuation and backfilling with O2 three times, the Schlenk tube was attached to an O2 balloon, and the mixture was stirred at 135 °C (oil bath) for 48 hours then cooled to r.t. The resultant mixture was poured into H2O (10 mL) and extracted with EtOAc (3 × 5 mL). The combined organic phase was dried (Na2SO4; White solid; yield: 15.5 mg (85%), Rf = 0.5 (PE–EtOAc, 5:1). 1H NMR (400 MHz, CDCl3)), filtered, and concentrated under reduced pressure to give a residue that was purified by flash column chromatography [silica gel, PE–EtOAc (10:1)].1-Pyrimidin-2-yl-1H-indole-2-carbonitrile (2a) 11White solid; yield: 15.5 mg (85%), Rf = 0.5 (PE–EtOAc, 5:1). 1H NMR (400 MHz, CDCl3): δ = 8.83 (d, J = 4.8 Hz, 2 H), 8.68 (d, J = 8.6 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.52–7.46 (m, 2 H), 7.34–7.30 (m, 1 H), 7.24–7.21 (m, 1 H). 13C NMR (101 MHz, CDCl3): δ = 158.4, 156.6, 136.6, 127.8, 127.6, 123.6, 122.0, 121.0, 118.0, 116.2, 114.3, 108.9 Supplementary Material Supplementary Material Supporting Information
