Synlett 2020; 31(07): 713-717
DOI: 10.1055/s-0039-1691590
letter
© Georg Thieme Verlag Stuttgart · New York

Difluorocarbene-Based Cyanation of Aryl Iodides

Yin-Xiang Zhang
a  Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, P. R. of China   Email: guoyuhy@126.com   Email: yaoyao19840415@126.com   Email: zhengxing9166@sohu.com
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: jlin@sioc.ac.cn   Email: jchxiao@sioc.ac.cn
,
Xuan Xiao
a  Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, P. R. of China   Email: guoyuhy@126.com   Email: yaoyao19840415@126.com   Email: zhengxing9166@sohu.com
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: jlin@sioc.ac.cn   Email: jchxiao@sioc.ac.cn
,
Zhi-Hong Fu
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: jlin@sioc.ac.cn   Email: jchxiao@sioc.ac.cn
c  School of Materials Science and Engineering, Southwest Petroleum University, Xindu, Chengdu 610500, P. R. of China
,
Jin-Hong Lin
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: jlin@sioc.ac.cn   Email: jchxiao@sioc.ac.cn
,
Yu Guo
a  Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, P. R. of China   Email: guoyuhy@126.com   Email: yaoyao19840415@126.com   Email: zhengxing9166@sohu.com
,
Xu Yao
a  Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, P. R. of China   Email: guoyuhy@126.com   Email: yaoyao19840415@126.com   Email: zhengxing9166@sohu.com
,
Yu-Cai Cao
d  State Key Laboratory of Polyolefins and Catalysis, Shanghai Key Laboratory of Catalysis Technology for Polyolefins, Shanghai Research Institute of Chemical Industry Co. Ltd., Shanghai, P. R. of China
,
Ruo-Bing Du
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: jlin@sioc.ac.cn   Email: jchxiao@sioc.ac.cn
,
Xing Zheng
a  Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, P. R. of China   Email: guoyuhy@126.com   Email: yaoyao19840415@126.com   Email: zhengxing9166@sohu.com
,
Ji-Chang Xiao
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: jlin@sioc.ac.cn   Email: jchxiao@sioc.ac.cn
› Author Affiliations
The authors thank the National Natural Science Foundation (21421002, 21672242, 21971252), the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS) (QYZDJSSW-SLH049), the Youth Innovation Promotion Association CAS (2019256), the Fujian Institute of Innovation, CAS (FJCXY18040102), the Shanghai Research Institute of Chemical Industry Co., Ltd. (SKL-LCTP-201802), the Hunan Provincial Hengyang City Joint Fund Project (2018JJ4036), the general project of the University of South China (18C0438), the Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study (0223-0007-000004), and the Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, CAS (2018-10) for financial support.
Further Information

Publication History

Received: 15 January 2020

Accepted after revision: 15 January 2020

Publication Date:
03 February 2020 (online)


These authors contributed equally to this work.

Abstract

A large number of efficient cyanation methods have been developed because of the wide range of applications of nitriles, but conventional methods usually suffer from the need for a toxic cyanation reagent. Although difluorocarbene chemistry has received increasing attention, the use of difluorocarbene as a sources of the nitrile carbon for nitrile groups remains largely unexplored. We describe a difluorocarbene-based cyanation of aryl iodides promoted by a cheap copper source, Cu(NO3)2·2.5H2O, under an air atmosphere. Ph3P+CF2CO2 , an easily available and shelf-stable difluorocarbene reagent, and NaNH2 are used as the carbon source and the nitrogen source for the nitrile group, respectively. The cyanation protocol is attractive because no toxic reagent is used and performing the reactions under an air atmosphere is operationally convenient.

Supporting Information

 
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  • 31 Cyanation of Aryl Iodides 1; General Procedure Under air atmosphere, a reaction tube was charged with the appropriate aryl iodide 1 (0.5 mmol), Ph3P+CF2CO2 (268 mg, 0.75 mmol, 1.5 equiv), ligand L4 (6.3 mg, 5 mol%), Cu(NO3)2·2.5 H2O (143 mg, 0.65 mmol, 1.3 equiv), NaNH2 (39 mg, 1.0 mmol, 2.0 equiv), and anhyd DMF (4 mL). The mixture was stirred at 130 °C for 15 h, then cooled to rt and filtered through a pad of Celite that was washed with CH2Cl2. The combined organic phase was washed with H2O (3 × 15 mL), and the organic layer was further washed with sat. aq Na2SO3 and sat. brine, then dried (Na2SO4) and concentrated under vacuum. The residue was purified by flash column chromatography. 9,9-Dimethyl-9H-fluorene-3-carbonitrile (2k) The reaction was performed on a 0.6 mmol scale. Yellow oil; yield: 85 mg (65%). IR (neat): 3062, 2962, 2924, 2866, 2223, 1609, 1485, 1471, 1447, 1416, 1302, 1283, 1219, 1077, 1023, 893, 835, 783, 759, 737 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.80–7.72 (m, 2 H), 7.69 (s, 1 H), 7.62 (d, J = 7.9 Hz, 1 H), 7.46 (d, J = 7.1 Hz, 1 H), 7.43–7.34 (m, 2 H), 1.48 (s, 6 H). 13C NMR (101 MHz, CDCl3): δ = 154.19, 154.16, 143.8, 137.2, 131.4, 129.1, 127.5, 126.4, 122.9, 121.1, 120.5, 119.7, 110.1, 47.1, 26.8. HRMS (EI); m/z [M]+ calcd for C16H13N: 219.1048; found: 219.1054.
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