Regioselective Umpolung Para-C-H Functionalization Of Arylhydroxylamines

The regioselective C-H bond functionalization of arene is not only used in the field of synthetic chemistry,but also in material science and pharmaceutical industry.Different from the well-developed ortho-and meta-C-H bond functionalization reactions of arene,the paraC-H bond functionalization of arene is less studied and more challenging because these C-H bonds are relatively far away from the directing group.At present,the para-selective C-H functionalization of arene is mainly achieved by a special directing group-assisted C-H bond activation strategy,and this strategy often requires the use of expensive transition metal catalysts or ligands.Arylhydroxylamines as the very useful class of small molecules,the fragile N-O bonds are their main react sites.Previous studies have used this feature to achieve the construction of many organic functional molecules,such as indoles,biaryl compounds and functionalized aromatic amines.Among them,the most is focus on the ortho-functionalization reaction of anilines,and the examples of para-functionalization are much less.Therefore,it is still of great significance to seek a broad-spectrum,metal-free,oxidant-free and easy-to-operate new organic synthesis method to realize the para-functionalization of anilines.After continuous attempts,we have found a simple,practical,rapid and effective method for the divergent synthesis of para-functionalized anilines from a wide range of N-arylhydroxylamines and various types of nucleophiles in the presence of fluorosulfuryl imidazolium triflates.In this paper,we will focus on this strategy,and research on its substrate range,reaction mechanism and application prospects.This paper is divided into the following three parts:In the first part,the research progress and common strategies of para-functionalization of arene are introduced.The para-functionalization of arene mainly includes the conversion of halogen atoms of halogenated aromatic hydrocarbons and the direct para-C-H bond functionalization reaction.This chapter will focus on the common strategies of direct paraC-H bond functionalization of arene:using the electronic effect of the substrate itself to regulate the position selectivity;using the directing group to precisely achieve the C-H bond activation;using the substrate itself or the large steric hindrance of the catalyst or ligand to achieve para-selectivity;using non-covalent bonds such as hydrogen bonds to regulate regioselectivity.In the second part,the synthesis of phenols,the reaction mode of aryl hydroxylamines and the para-hydroxylation of arylamines mediated by fluorosulfuryl imidazolium triflates were introduced.According to our design,the O-fluorosulfonylation of aryl hydroxylamines was first achieved by the reaction of aryl hydroxylamines with the electrophilic activation reagent fluorosulfonyl imidazolium salt,followed by the cleavage of the N-O bond and the attack of the external nucleophile(water),then the para-hydroxylated anilide derivatives were obtained.We proposed a polarity reversal reaction mode,which has been verified by control experiments and theoretical calculations.The transformation can be carried out smoothly at low temperature in air without the participation of metal or oxidant,and para-hydroxylated anilide derivatives can be obtained with good yield and excellent para-selectivity.By rapidly converting the product into a series of structurally diverse functional molecules,the synthesis significance of the method was further demonstrated.In the third part,the author extended the umpolung strategy for the para-functionalization of anilide derivatives to the reaction with alcohols and thiols nucleophiles,and finally realized the efficient synthesis of a series of para-functionalized anilide derivatives with diverse structures.This type of reaction mode shows excellent yield,broad substrate range and specific site selectivity in various functionalizations.