Silver-catalyzed Oxidative Radical Addition Of Cycloalkanols To Aldehydes And Imines

The radical reaction has become a highly attractive and powerful method for the construction of carbon-carbon and carbon-heteroatom bonds,due to its features such as mild reaction conditions and broad substrate scope.So far,the C-C double or triple bonds are common acceptors for radical addition reactions,while the radical addition to C-O and C-N double bonds has attracted much less attention.The oxidative radical addition reaction of aldehyde groups as acceptors has yet to be developed.This paper first carried out research in this area.On the other hand,the reductive radical addition to C-N double bonds has been developed for the synthesis of secondary amines.In contrast,the oxidative radical addition to C-N double bonds,especially the readily available imines,has not been achieved because of its high electronegativity of nitrogen atom.At the same time,pyrroles are important building blocks in organic synthesis and they are widely existed in drugs and natural products.The main content of the thesis is described below.1.Silver-Catalyzed oxidative radical addition of cycloalkanols to aldehydes.The aromatic aldehyde was used,AgNO₃ as catalyst,Na₂S₂O₈ as oxidant,by oxidative radical addition reaction of the aromatic aldehydes and the 1,4 or 1,5-dicarbonyl compound was synthesized in one step.Mechanistic studies including DFT calculations suggest the involvement of an uncommon water-assisted 1,2-HAT process,which is strongly exothermic and thus promotes addition of carbon radicals to aldehydes.In contrast to traditional reductive radical addition protocols,this work represents the first example of the intermolecular oxidative radical addition to aldehydes,thus offering a novel strategy for the direct synthesis of acyclic ketones from readily accessible aldehydes.2.A silver-catalyzed formal[3+2]cycloaddition between cyclopropanols and imines has been developed providing multisubstituted pyrroles in good to excellent yields.The reaction takes place at mild reaction conditions and tolerates a wide range of functional groups such as F,Cl,Br,OMe,Ac,CO₂Me,Ms,CN,amide,epoxide,alkene,and pyridine,which offers an operationally simple and highly efficient for the access to polysubstituted pyrroles.Preliminary studies on mechanistic investigations indicate that the reaction proceeds via a cascade Ag-catalyzed ring-opening of cyclopropanols,radical addition to imines,1,2-HAT,SET oxidation,deprotonation and intramolecular cyclization.The reaction described here constitutes the first example of oxidative radical addition to imines,thus offering a novel strategy for the radical transformation of imines.