多功能氧酰胺导向基在碳氢键活化反应中的研究进展

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

近年来,通过导向基团进行碳氢键活化构建C―C键及C―X键的方法得到了快速发展,已成为有机合成的重要手段之一。在碳氢键活化中,作为多功能导向基团之一的氧酰胺,由于其独特的性质,引起了科学家们的广泛关注。氧酰胺中O―N键的氧化性替代外部氧化剂,使反应处于氧化还原中性。加入化学计量的外部氧化剂,通常可以使O―N键得到保留。在不同的溶剂中,能够表现出不同的区域选择性和立体选择性;皆体现了氧酰胺作为导向基团的独特之处。本文综述了N-苯氧基酰胺作为底物进行碳氢键活化的研究进展,同时根据现有的实验和理论研究结果对不同反应的机理进行了探讨。

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 orα,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 Rhand 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.