Regioselective Gem-difluorenylation And Alkynylation Of Aliphatic Amine By 1,5-hydrogen Atom Transfer

Nitrogen radical-mediated 1,5-hydrogen atom transfer reaction enables highly selective functionalization of amines with distal inactive C(sp~3)-H bonds.It is of great synthetic value and scientific significance to develop more innovative ways to trap nitrogen radicals and introduce different functional groups into nitrogen-containing compounds to enhance the practicality of this efficient synthetic strategy.At the same time,this is also a huge challenge facing the field.Considering the strategy of generating nitrogen-centered radicals by direct cleavage of N-H bonds,it has the advantages of easy availability of starting materials,high step economy,and atom economy.We devised a protocol for the selective functionalization of aliphatic amines with remote inactive C(sp~3)-H bonds to introduce geminal difluorovinyl groups and alkynyl groups into such compounds.The first part of this work introduces the selective geminal difluoroalkenylation of aliphatic amines based on a 1,5-hydrogen atom transfer.Under mild photocatalytic conditions,geminal difluorovinyl groups were introduced into aliphatic amines with high selectivity using trifluoroacetyl-protected aliphatic amines and?-trifluoromethyl olefins as substrates.The reaction conditions are simple and mild and have good substrate versatility for both aliphatic amines and?-trifluoromethyl olefins.When a variety of?-trifluoromethyl olefins with different functional groups participate in the reaction The target product was obtained in high yield,and it also showed good reactivity to the primary,secondary and tertiary?-C(sp~3)-H bonds in aliphatic amines.In addition,late-stage modification of bioactive molecules can also yield the desired products in satisfactory yields.The second part of the work introduces the selective alkynylation of aliphatic amines based on the 1,5-hydrogen atom transfer.Under photocatalysis,the selective alkynylation of unactivated C(sp~3)-H bonds at the distal end of aliphatic amines was achieved using aliphatic amines and alkynyl sulfones as substrates.Under standard conditions,this reaction is compatible with a variety of sulfonylated alkynes and aliphatic amines,and yields long-range alkynylation products in high yields.In addition,this reaction can also achieve allylation and thioetherification of the remote unactivated C(sp~3)-H bond.And this reaction also has the advantages of mild conditions and high regioselectivity.