Selective Aminofluorination Of 1,3-dienes Via Silver/Copper Dual Catalysis

Allylic fluorides,prevalent motifs in bioactive molecules,are an important class of fluorinated building blocks,and the double bonds in the allylic fluorides can also be further transformed.Meanwhile,allylic fluorides can also be used as an important precursor for the synthesis of other fluorine-containing compounds.Therefore,the construction of allylic fluorides has always been a hotspot in organic chemistry.Traditional synthetic methods include nucleophilic substitution and electrophilic substitution,however,leaving groups need to be pre-installed on the substrate,and the atomic utilization is low.In recent years,other methods for constructing allylic fluorides have also been developed,including allylic C-H fluorination reaction,which directly converts C-H into C-F and improves the atomic utilization,however,its substrate scope limited;In addition,allylic fluorides with special structure has been constructed using fluorinated building blocks.In comparison,the intermolecular fluorodifunctionalization of 1,3-dienes can start from a simple substrate and introduce other functional groups while constructing allylic fluorides,which represents an appealing strategy for the rapid preparation of highly functionalized allylic fluorides.There are two double bonds in the 1,3-dienes,one significant challenge for intermolecular difunctionalization of 1,3-dienes lies in the control of regio-,site-,and stereoselectivities.By now,most of the reported fluorodifunctionalization of 1,3-dienes need to use 1,3-butadiene or 1,3-dienes with special structure as the reaction substrate.The fluorodifunctionalization of alkyl-1,3-dienes has not been studied.In this paper,we report an intermolecular three-component 1,2-aminofluorination of1,3-dienes via silver/copper dual catalysis.N-Bromodialkylamines and Ag F serve as alkylamino and nucleophilic fluoride sources,respectively,delivering the corresponding allylic β-aminofluorides with high regio-,site-and stereoselectivities.This protocol is compatible with challenging alkyl-1,3-dienes,as well as common aryl-1,3-dienes.The E/Z-mixed 1,3-dienes are allowed to be processed to single E-products,providing a convenience for the substrate preparation.Detailed mechanistic studies illustrate a reaction sequence involving ARC generation,aziridinium formation,and identify the distinct roles of dual catalysis,wherein the silver complex initiates a singleelectron transfer(SET)to generate electrophilic ARC while the copper complex dramatically enhances the 1,2-regioselectivity through aziridinium intermediates.The 1,3-dienes aminofluorination provides a new scheme for the construction of allylic fluorides.This paper mainly studies from the following two aspects:1.The construction methods of allylic fluorides were summarized,including the nucleophilic substitution,electrophilic substitution,allylic C-H fluorination and the construction of fluorinated building blocks.The research progress of halogenated bifunctional reactions of 1,3-dienes is reviewed.2.The reaction conditions of intermolecular 1,2-aminofluorination of 1,3-dienes was screened and the substrate was expanded.Further mechanistic studies reveal the pivotal role of silver/copper dual catalysis.