Studies On Radical-Participated Remote Functional Group Migration

Structurally novel and disverse compound libraries are of paramount importance for rapid and efficicient screening in the process of developing new drugs,agrochemicals,and materials.This thesis focuses on the use of highly reactive radicals for inducing selective C–C and C–H bond cleavages under energetic driving forces,thus realizing remote functional group migrations and facile and efficient molecular reconstruction.Our aim is to develop a series of novel functionalization methods,which would provide not only assistance for overcoming related chanlleges in organic chemistry but also expedient and practical synthetic tools for researches in the areas of medicine,agrochemical,and material sciences.The cyano group exists widely in many natural products and bioactive molecules as well as synthetic intermediates,and thus is very important in organic chemistry.We initiated our study by employing copper(I)to reduce Togni’s reagent for generating trifluoromethyl radical,which subsequently added to an alkene substrate and induced intramolecular 1,4/5-cyano migration.In this way,we have achieved a series of 1,2-cyanotrifluoromethylation of unactived alkene(16 examples,40–92% yield).Next,we capitalized on the similar copper catalytic system or visible-light catalytic system for forming different radicals,i.e.,azido,phosphonyl,sulfonyl,and fluoroalkyl ones,the addition of which to alkene substates elicited corresponding intramolecular cyano migrations and ultimately furnished a panel of 1,2-cyanofunctionalization of unactivated alkene,such as 1,2-cyanoazidation(3 examples,58–83% yield),1,2-cyanophosphonylation(3 examples,67–86% yield),1,2-cyanosufonylation(3 examples,82–92% yield),and 1,2-cyanofluoroalkylation(4 examples,85–90% yield).Finally,we proposed a possible mechanism for the reaction on the basis of literature and our mechanistic results.Oximes are another family of important synthetic intermediates similar to cyano compounds.However,the oximination of alkene has long been underdeveloped.We took use of similar copper catalytic systems for implementing a variety of 1,2-oximinotrifluoromethylation of linear unactivated alkene with the Togni’s reagent as a radical precursor for inducing corresponding intramolecular 1,4/5-oximino migration(16 examples,25–84% yield).Besides,we have also accomplished the highly efficient preparation of four 8–10-membered medium-sized cyclic compounds from cyclic substrates via a ring-expansion strategy(67–82% yield).In addition,we transformed a medium-sized cyclic product to a compound featuring the core structure of bioactive benzazepinones(40% yield).On the basis of the two types of 1,2-difunctionalization of unactivated alkene mentioned above,we used similar methods for formation of sulfonyl,phosphonyl,and malonate-derived alkyl radicals to achieve 1,2-hydrosulfonylation(4 examples,31–82% yield),1,2-hydrophosphonylation(13 examples,47–90% yield),and 1,2-hydroalkylation(7 examples,35–57% yield)of unactivated alkene via alkene addition and intramolecular 1,5/6-hydrogen migrations.We found no loss of efficiency of the reaction when it was performed on large scales,indicating the practicability of this method.Besides,we have carried out mechanistic experiments using radical inbihitors and deuterated substrates,which proved the proposed radical mechanism.Medium-sized lactams(8–11-membered)are essential motifs in numerous natural products and bioactive molecules.Inspired by the ring-expansion reaction via the oximino migration aforementioned,we utilized visible-light catalysis to oxidize amide to amidyl radical,which added to intramolecular aryl or heteroaryl moieties and brought about 1,4-(hetero)aryl migration from C to N.As such,we established a new ring-expansion reaction and forged a number of medium-sized lactams(26 examples,20–89% yield)at the same time.In addition,we converted the thus-obtained medium-sized lactams to eight useful compound skeletons,demonstrating the important application potential of these molecules.At the end,we carried out radical inhibition,electrochemical characterization,and luminescence quenching experiments,and proposed detailed reaction mechanism thereafter.