Studies On Free Radical Asymmetric Desymmetrization Of Alkenyl 1,3-Diols

Difunctionalization of unactivated alkenes is an important research area in organic synthesis chemistry.Due to the short steps of synthesis,high atom economy and easy availability of olefin raw materials,the difunctionalization reaction of unactivated alkenes has attracted the attention of many researchers.Free radical reaction is characterized by mild reaction conditions,high tolerance of functional groups and insensitivity to moisture.In recent years,great progress has been made in the construction of heterocyclic compounds by generating free radical to attack olefin,there-by triggering the intramolecular difunctionalization of olefin.However,as free radicals act as unstable active intermediates,their reactivity is very high,so such reactions have very strong background reactio ns,and it is difficult to control their enantioselectivity through chiral catalysts.Therefore,it is very challenging to construct chiral heterocyclic compounds by catalytic enantioselective radical difunctionalization of unactivated olefin.At the same time,the synthesis of chiral compounds by catalytic asymmetric desymmetrization of prochiral and meso compounds has always been the focus of chemistry researchers.At present,the enzymatic,metal-catalyzed and organocatalyzed asymmetric reactions have been well developed.However,the catalytic asymmetric radical desymmetrization reactions have not been reported.In this paper,prochiral olefinic 1,3-diol was used as the substrate to react with Togni's reagent under the dual catalysis of copper(I)and chiral phosphoric acid to obtain tetrahydrofuran skeleton compound containing two chiral centers.On this basis,the core skeleton and its analogues of posaconazole were further derived.The reaction has the advantages of mild reaction conditions,high yield and good compatibility o f substrates.On the basis of the previous work of the research group,the present study achieved the radical asymmetric desymmetrization of the prochiral olefinic 1,3-dio l through the dual catalytic system of copper(I)and chiral phosphoric acid.By screening copper salt,chiral phosphoric acid,achiral ligand,base,solvent and temperature,Tetrahydrofuran compounds with two chiral centers were synthesized with high diastereoselectivity and enantioselectivity.Tetrahydrofuran comp ounds with two chiral centers were synthesized and further derivated in order to build a library of tetrahydrofuran compounds with two chiral centers.In this paper,the catalytic asymmetric radical desymmetrization reaction has been r e a l i z e d fo r t h e f i r s t t i m e,a n d t h e r a d i c a l a s y m m e t r ic i n t r a mo l e c u l a r difunctionalization of unactivated alkenes has been further enriched and developed.