Research On The Scalable Synthesis Of α,β-Difluoro-γ-Amino Acid And 2-fluoro Digitoxose

It has become evident that fluorine has a remarkable influence on fluorinated compounds and often imparts organic molecules with desired properties,such as lipophilicity,conformational changes and metabolic stability.Development of novel and efficient routes to synthesize fluorinated bioactive is thus highly desirable.This dissertation describes the study towards the scalable synthesis of α,β-difluoro-γ-amino acid and the development of de novo synthesis of 2-fluoro-digitoxose.The synthetic efforts are following:Firstly,we have investigated three different strategies,using either α-fluorination of aldehyde,allylic fluorination,or benzylic fluorination as the key step for the construction of vicinal difluoro-substructure of syn-α,β-difluoro-γ-amino acid.Our study shows that a fluorine atom greatly decreases the reactivity of the vicinal carbon,which resulted in the failure of the former two strategies.However,we successfully introduced the second fluorine via a benzylic fluorination through extensive experimentation,and realized the scalable synthesis of syn-α,β-difluoro-γ-amino acid.Secondly,we have developed the de novo synthesis of 2-fluoro-digitoxose employing α-fluorination of aldehydes as key step.The approach developed in this work has the features,such as mild conditions,safe fluorination reagents and high stereoselectivity controlled by catalyst.We believe the evaluation and optimization of different methods for benzylic C-H fluorination and α-fluorination of aldehydes would provide valuable information for chemists who want to use them for target synthesis in future.