Photocatalytic Cascade Sulfonylative Cyclization Of Alkynyl Aldehydes

As fundamental scaffolds,carbonyl groups widely exist in natural products,functional materials,and pharmaceuticals.As such,seeking efficient methods for the synthesis of these motifs is highly desirable in synthetic chemistry.Along this line,we have recently developed a radical-mediated methodology for direct transforamtion of aldehydes to ketones,thus providing an effective access to carbonyl compounds.Despite the success,the previous reports are restricted to aryl or alkenyl aldehydes,and direct transformation of alkyl aldehydes has not been achieved yet.Herein,this dissertation focuses on the investigation of cyclization of alkyl aldehydes triggered by radical addition to alkynes,which leads to the divergent synthesis of cyclopentenones and dihydropyranols under mild reaction conditions.The main contents are divided into two parts:First,a facile synthesis of sulfonyl cyclopentenones has been realized via the visible light-induced sulfonyl-acetylation of alkynes.By usingγ-alkynyl aliphatic aldehydes as the starting material,aryl sulfonyl chorides as the sulfonylation reagent,fac-Ir（ppy）₃ as the photocatalyst,Na₂CO₃ as the base,and DMA as the solvent,various polysubstituted cyclopentenones are assembled in moderate to excellent yields with good functional group tolerance at room temperature.Preliminary mechanistic studies and DFT calculations imply an unprecedented DMA-assisted1,2-HAT of alkoxy radicals,thus accounting for the selective formation of cyclopentenones.Subsequently,a new method for the direct construction of dihydropyranols fromγ-alkynyl aliphatic aldehydes has been developed.With aryl sulfonyl chorides as the sulfonylation reagent,fac-Ir（ppy）₃ as the photocatalyst,Na₂CO₃ as the base,and Me CN,instead of DMA,as the solvent,a vairety of dihydropyranols are efficiently synthesized at 50 ^oC.Four new chemical bonds are concurrently constructed under mild reaction conditions,thus highlighting the high efficiency of this method.The ¹⁸O isotope labeling experiments indicate that the hydroxy group of dihydropyranols is originated from water.DFT calculations suggest that aβC-C cleavage followed by6-endo radical cyclization to formyl group accounts for the generation of dihydropyranols in Me CN.Additionally,the one-pot synthesis of dihydropyrones was realized by directly treating the photocatalytic reaction with Jones reagent.The divergent synthesis of cyclopentenones and dihydropyranols from the same starting material makes it a highly attractive method for organic synthesis.Tuning the reaction pathways of alkoxy radicals,such as 1,2-HAT andβ-fragmentation,by solvent is unprecedented,which represents a novel and valuable strategy for the selective activation of inert C-H and C-C bonds.