Studies On Minisci Reaction Of Cyclopropanol Oxalates With Heterocycles

The cyclopropane motif is widely distributed in bioactive natural products and clinical drugs.Although effective methods,such as Simmons-Smith cyclopropanation,transition metal-catalyzed diazo compound decomposition,Michael addition-initiated cyclization reaction,C-H insertion,and ring isomerization,have been developed toward the construction of cyclopropane skeleton,those methods suffer from drawbacks including tedious operation procedure,employment of expensive transition metals and hazardous diazo compounds.Because heterocyclic structure is widespread in natural products and clinical drugs,development of new methods for introducing cyclopropane motif on hetereocycles is of high value and has broad application in drug discovery.In this thesis,an unprecedented method of radical addition of cyclopropanol oxalate to a series of pyridine molecules including quinine has been developed,providing several representative heterocyclic compounds with a cyclopropane motif in good yields.This is the first study on Minisci reaction of heterocyclic compounds with cyclopropanol as precursor of the cyclopropane motif.Cyclopropanols can be conveniently prepared by Kulinkovich reaction from esters,and cyclopropanol used as the precursor of the cyclopropane motif is unknown.Therefore,this method not only provides a new and efficient protocol to introduce cyclopropane motif to heterocycles but also enriches the cyclopropanol chemistry.