Lewis Base-Boryl Radical Promoted Carbon-heteroatom Bond Activation Via Spin-Center Shift:Functionalization Of N-Heterocycles

Nitrogen-containing heterocyclic compounds have valuable applications in pharmaceuticals,agrochemicals,and functional materials.Although numerous methods and strategies have been established,synthetic methods used for the direct activation of carbon-heteroatom bonds in N-heterocycles are relatively less explored.In this thesis,we have described a series of activation and functionalization methods of N-heterocycles,wherein the carbon-heteroatom bond activation involves the spin-center shift mechanism.The first chapter describes the concept and applications of a spin-center shift in carbon-heteroatom bond activations in different conditions.The second chapter introduces 4-dimethylamminopyridine-boryl radical-promoted monodefluorinative alkylation of 3,3-difluoroxindoles.In this work,a range of 3,3-difluorooxindoles have been successfully employed in selective defluorinative alkylation reactions with the cleavage of only one C-F bond,providing a diverse range of structurally new 3-alkyl-3-fluorooxindoles in moderate to good chemical yields.The synthetic utility of the method is also showcased through the modification of bioactive molecules.A radical clock experiment revealed the involvement of the C3-radical intermediate resulting from the cleavage of single C-F bonds by the spin center shift process.Chapter three introduces 4-dimethylamminopyridine-boryl radical-promoted C-O bond activation and subsequent alkylation reactions of 3-hydroxyoxindole derivatives.Two reaction conditions have been established for the dehydoxylative alkylation of Boc-activated 3-hydroxy-oxindoles(condition-Ⅰ)and non-activated 3-hydroxy-oxindoles(condition Ⅱ),respectively,for the synthesis of 3-alkyl oxindoles in moderate to good yields.A wide range of new C-3 alkylated oxindole products,including the ones containing all-carbon quaternary centers,were synthesized.In chapter four,we described a new application of the spin-center shift that involves the activation of C=N/C=C bonds in quionoxalinones and quinolinones N-heterocycles.The reaction procceds through the attack of a boryl radical to the amide oxygen atom to trigger the C=N or C=C n-bond activation by the spin-center shift mechanism along with a two-electron ionic movement.The ensuing C-3 radicals are then captured by a wide range of alkenes to furnish 3,3-disubstituted 3,4-dihydroquinoxalin-2(1H)-ones,which feature an all-carbon quaternary center.In conclusion,we have developed a series of functionalization reactions of N-heterocycles through the activation of C-F,C-O,C=N,and C=C bonds by strategic application of spin-center shift mechanism.Following the activation,radical addition with a wide range of alkenes provided access to assemble the challenging C-C bonds onto the N-heterocycle framework.The methods are efficient entries to modify N-heterocycles.