Single-Electron-Transfer Reduction-Based Synthesis Of Allenes And Radical Addition Toward Carbonyl Group

The single-electron transfer-based radical-polar crossover(RPC)process can transform radical intermediates into ionic intermediates,so that the radical and ionic reactions can be carried out in the same system.This strategy has been widely used in organic synthesis and the construction of natural drug molecules because of its dual characteristics of radical-ion reaction and ionic reaction.In this thesis,to further extend the application of the RPC process,we attempt to apply this strategy to the construction of multi-substituted allenes and carbonyl reduction addition reactions.The thesis consists of two main parts.In the first part,the nickel-catalyzed synthesis of di-and trisubstituted allenes from 1,3-enyne was realized.N-(alkylcarbonyloxy)phthalimide(NHPI)esters was used as the radical precursor,with Nickel(II)acetate tetrahydrateas as the catalyst and zinc as the reducing agent,various alkyl radicals derived from alkyl NHPI esters could react with 1,3-enynes to give trisubstituted allenes.With 1,3-enynes bearing ethynyl or trimethylsilylethynyl group as the radical acceptors,disubstituted allenes was achieved.NHPI esters containing fragments of drug molecules could be used for the preparation of 1,1-disubstituted allenes.In addition to broad substrate scope,this protocol features great functional group tolerance,the use of a simple and readily available nickel catalyst,and the absence of ligands or additives.The formation of alkyl intermediates was confirmed by free radical clock experiments.The presence of allenyl carbanion or analogue was verified by deuteration experiments.Finally,the conversion from an allene to a furan could be realized under palladium catalysis.This protocol provides a new strategy for the synthesis of polysubstituted allenes.The second part is a research on the coupling reaction of photocatalytically reduced carbonyl and radicals.The coupling reaction of the electron-deficient carbonyl and alkyl radicals was realized to obtain carbonyl addition products by using Ir[III] complexes as photocatalysts in the presence of visible light.In the presence of potassium carbonate or cesium carbonate,the addition/cyclization reactions with various carbonyl compounds were achieved under the same catalytic conditions to obtain tetrahydrofuran spirocyclic compounds.When chloropropyl alkyl silicate was used as the radical precursor.Under acidic conditions,the carbonyl addition products obtained are prone to intramolecular dehydration,thus introducing double bonds containing high activity on the isoindolinone backbone.This method uses alkyl silicate as a radical precursor,and achieves not only the coupling of non-activated primary carbon radicals and carbonyl groups,but also the radical coupling/cyclization tandem reaction of chloropropyl radicals and carbonyl compounds.