Oxidative Kinetic Resolution Of NOBIN Based On N-O Bond Formation

Axial chirality is a special form of chirality,which has a crucial impact on the pharmacological activity and efficacy of drug molecules,with wide application in asymmetric synthesis.Axially chiral biaryls are an important source of structure for many biologically active molecules,and are widely used as chiral catalysts in organic synthesis.[1,1 ’-binaphthalene]-2,2’-diol(BINOL),[1,1’-binaphthalene]-2,2’-diamine(BINAM)and 2’-amino-[1,1’-binaphthalene]-2-ol(NOBIN)is the most representative axial chiral biaryl compound.NOBIN is an analog of the BINOL and BINAM backbones with excellent stereoselectivity and outstanding biological activity.A variety of chiral ligands can be converted from NOBIN by simple synthetic methods,thus,NOBIN becomes a special framework for the construction of various chiral ligands in asymmetric catalysis,for example,via diethylzinc addition of aldehydes,allylation of aldehydes,allyl substitution,Diels-Alder and Suzuki coupling reactions,etc.Since the synthesis of NOBIN was first reported by Kocovsky,the modification,synthesis and application of NOBIN have been widely studied and important progress has been made,but the asymmetric synthesis of 2-amino-[1,1’-binaphthyl]-2-ol(NOBIN)still faces challenges.This article summarizes various methods for obtaining optically pure NOBIN,including the asymmetric oxidative cross-coupling reaction of 2-naphthol and 2-naphthylamine,and the kinetic resolution of NOBIN.Most of the asymmetric synthesis methods such as oxidative cross-coupling and direct aromatization have limitations such as complex synthesis steps and low optical purity of the final NOBIN.Kinetic resolution of NOBIN is one of the main methods to obtain optically pure NOBIN,especially the kinetic resolution of amine compounds has always been the focus of scientists.At present,kinetic resolution of racemic NOBIN is an effective method to obtain optically pure biaryl amino alcohol derivatives,which has the characteristics of wide substrate range,simple operation,etc.,and can rapidly construct high enantioselective NOBIN with good yields,but catalytic kinetic resolution examples of NOBIN are rare.In previous studies,our group has developed a catalytic kinetic resolution method through the asymmetric oxidization of indolines.Therefore,this subject uses the difference in the oxidation kinetics of the two enantiomeric amino groups to study the catalytic kinetic resolution of NOBIN by asymmetric oxidation.With NOBIN as the reaction substrate,the catalyst and reaction solvent,temperature were screened to determine the optimal reaction conditions,and a catalytic oxidation kinetic resolution method of NOBIN was developed with salalen-Ti as the catalyst and hydrogen peroxide as the oxidant.This method performs asymmetric oxidation of the amine group of NOBIN to obtain NOBIN and nitroso-like NOBIN derivatives with high enantioselectivity.The substrate range of oxidized NOBIN was expanded.When most of the substrates were converted to 50%,the recovered NOBIN and nitroso products had good stereoselectivity with the over 90%ee value.In conclusion,we obtained optically pure NOBIN and nitroso products with high enantioselectivity by catalytic kinetic resolution of oxidative racemic NOBIN.Structurally diverse NOBIN molecules are expected to be used in drug development,synthesis of natural products and their derivatives,and research on chiral catalysts or ligands.