Copper-catalyzed Remote Functionalization Of Unactivated Csp~3-H Bonds

The direct functionalization of the alkyl Csp~3-H bond simplifies the existing chemical synthesis process and enables simpler and more efficient organic reactions.Therefore,in recent years,the direct catalytic activation of Csp~3-H bonds for functionalization has attracted more and more attention.In this text,copper catalysts are used to catalyze N-fluorosulfonamide compounds to generate nitrogen radicals,and then 1,5-HAT process is performed to generate remote carbon radicals.Finally,the Csp~3-H bond remote functionalization of aliphatic sulfonamides is realized.-Lcffler-Freytag(HLF)reaction has been expanded.The main content of this text includes the following two aspects:Firstly,N-fluorosulfonamide compounds are catalyzed by copper,and then reacted with p-toluenesulfonyl cyanide to realize the cyanide functionalization of the remote Csp~3-H bond.This reaction is a free radical reaction.In the reaction process,copper catalyzes the N-fluorosulfonamide substrate to generate nitrogen radicals,and then the carbon radicals generated by the 1,5 hydrogen atom transfer react with p-toluenesulfonyl cyanide.Generate cyanide products.This reaction overcomes the limitations of the classic HLF reaction intramolecular amination by optimizing the selection of various conditions,and realizes the direct activation and functionalization of the remote site-selective Csp~3-H bond,which simplifies the chemical synthesis process,and is realized for the first time the copper-catalyzed nitrogen radical-directed remote unactivated Csp~3-H bond cyanidation reaction.Through experiments on more than thirty kinds of substrates,it is found that the yields are mostly between 50%and 80%.Secondly,the seven-membered ring urea compound is synthesized by catalyzing N-fluorosulfonamide compounds and then performing isocyanate reaction.This reaction is also a free radical reaction.The generated carbon free radicals are combined with a copper catalyst and trimethylsilyl isocyanate(TMSNCO)to produce a seven-membered ring urea product.This reaction developed a new method for site-selective isocyanate synthesis of seven-membered ring urea compounds by N-fluorosulfonamide,which overcomes the traditional shortcomings of noble metal catalysis or toxic reagents required for the synthesis of seven-membered ring urea compounds.For the first time,the HLF reaction of N-fluorosulfonamide to prepare seven-membered urea compound is realized.The reaction yields are mostly between45%-75%,and the applicability is good.