Acta Physico-Chimica Sinica ›› 2019, Vol. 35 ›› Issue (9): 989-1004.doi: 10.3866/PKU.WHXB201812016

Special Issue: 碳氢键活化

• Review • Previous Articles     Next Articles

Research Advances in C―H Bond Activation of Multitasking N-Phenoxyamides

Yuelu ZHU1,Xinyang ZHAO1,Qian WU2,Ying CHEN2,Jing ZHAO1,*()   

  1. 1 State Key Laboratory of Coordination Chemistry, Institute of Chemistry and BioMedical Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. China
    2 Guangdong Key Lab of Nano-Micro Material Research, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, Guangdong Province, P. R. China
  • Received:2018-12-05 Accepted:2019-01-15 Published:2019-01-21
  • Contact: Jing ZHAO E-mail:jingzhao@nju.edu.cn
  • Supported by:
    the National Science Foundation of China(21622103);the National Science Foundation of China(21571098);the National Science Foundation of China(91753121);Natural Science Foundation of Jiangsu Province, China(BK20160022);Shenzhen Basic Research Program, China(JCYJ20170413150538897);Fundamental Research Funds for the Central Universities, China(020514380139)

Abstract:

Transition-metal-catalyzed C―H functionalization reactions, assisted by directing groups (DGs), have become some of the most powerful strategies to form C―C and C―X (X = O, N, S, etc.) bonds. It has brought about a revolution in the synthesis of drugs and natural products, and the method is widely applicable in the fields of material chemistry and pharmaceutical industry. This strategy has mainly focused on regioselective C―H functionalization of amides, esters, carbamates, and enamides with DGs to form C―C and C―X bonds. Since these DGs are relatively stable, they must be removed by other methods when the reaction is completed. Therefore, the use of a traceless DG is one of the important challenges for transition-metal-catalyzed C―H functionalization. Recently, N-phenoxyamide has been attracting significant research attention as a versatile DG. Oxyacetamide (O―NHAc) is one of the most versatile functionalities for directed C―H functionalization cascades, such as the internal oxidation with N―O bond cleavage. The O―NHAc has been reported as a superb DG for redox-neutral C―H activation/annulation cascade reactions to synthesize phenol and complex heterocyclic scaffolds by coupling with alkynes, alkenes, heteroarenes, and diazo compounds. However, for the external oxidation with preservation of the N―O bond, e.g. when a stoichiometric external oxidant is present, N-phenoxyamides could react with aldehydes or α, β-unsaturated aldehydes. In addition, the solvent can control the chemoselectivity. In this minireview, the C―H bond functionalization of N-phenoxyamide is divided into five categories according to the different substrates, viz. alkenes, alkynes, diazo, and other compounds and intramolecular C―H bond activation reactions. Based on experimental and theoretical research results, the reaction mechanism was discussed. In the first part, we summarize the ortho-alkylation, alkenylation, and cyclization of N-phenoxyamide with olefins. In the second part, we present the Rh- and Ir-catalyzed C―H activation or cyclization of N-phenoxyamide with alkanes to synthesize phenol or benzofuran compounds. In the third part, we describe the synthesis of phenolic compounds functionalized by Rh-catalyzed diazo compounds by carbene intermediates and N-phenoxyamides. The forth part summarizes the C―H activation/annulation reaction using aldehydes, heterocyclic aromatic, and sulfur reagents as substrates. The last part of the paper generalizes the intramolecular ortho-hydroxylation and ortho, para-amidation reactions.

Key words: C―H activation, N-phenoxyamides, Multitasking, Phenols, Selenium

MSC2000: 

  • O643