Synthesis Of Four-membered Heterocyclic Compounds Using A Fluorocyclization Strategy

Saturated four-membered heterocycles occur as raw materials and intermediates in organic synthesis,and chiral catalysts in asymmetric catalytic reactions.Besides,they are often observed in pharmaceuticals,bioactive natural products.Its synthesis and application have attracted great attention.The cyclization by intramolecular nucleophilic displacement and [2 + 2] cycloaddition represent classical approach to access saturated four-membered ring frameworks.Rearrangement reaction,electrophilic cyclization reaction,cyclization through C-C bond formation,conversion of heterocyclic-containing building blocks are also effective ways to construct four-membered heterocycles.Although the traditional synthesis methods are mature and widely used,current methods to access these heterocycles suffer from limitations such as multiple steps to access cyclization precursors,typically required pre-formed heterocycles,poor kinetics of cyclization.Therefore,novel and practical methods for the facile synthesis of such heterocycle frameworks are highly appealing.Recently,oxidative fluoro-functionalization reactions of alkenes based on aryl iodine(Ⅰ-Ⅲ)catalysis have been emerging as a useful means to construct the fluorine-containing heterocycles compounds.The application of this strategy in the construction of fluorine-containing heterocycles has achieved great progress.However,such a state-of-the-art strategy has not been applied to the construction of saturated fluorinated oxetanes and azetidines.In order to solve the above problems,we validate a new method to prepare 3-functionalized oxetanes and azetidines by fluorocyclization of readily available 2-azidoallyl alcohols and amines.The pendant azido group plays a crucial role in polarizing the C=C double bond and facilitating the cyclization process,as verified by DFT and experimental studies.Moreover,the practicality of this method has been highlighted by the direct use of ketones as the starting materials in a multiple-step operation,as well as the late-stage functionalization of natural products.In addition,the feasibility of the synthesis of Bradyoxetin,a natural product,was also studied.