Visible Light-Induced Transition-Metal-Catalyzed Transformation Of Carboxylic Acid Esters

Carboxylic acids and their derivatives are widely used in organic synthesis due to the fact that they are most abundant,readily available,and inexpensive feedstocks.In recent years,cross-coupling reactions using carboxylic acids derivatives as acyl electrophiles have been developed.However,most studies are constrained to the coupling of aromatic carboxylic acids or their derivatives with high temperature.Recently,the strategy of photocatalytic generation of radicals is gradually adopted in chemical synthesis because of its mild reaction conditions and high efficiency.Moreover,the emergence of metal/photoredox dual catalysis provides a powerful platform for the construction of sp~3 C–C as well as C–X(X=N,O,S,P,etc.)bonds.This means has also been applied in the acylation coupling reactions.In this vein,active acyl electrophiles such as alkyl acyl chlorides,anhydrides coupling with alkyl radical precursors to form ketones.However,these electrophiles are sensitive to air and difficult to preserve.Thus,the acylation coupling reactions with stable esters as electrophiles will broaden the methods for ketone synthesis.As an important part of esters,N-(acyloxy)phthalimides(NHPI esters)are predisposed to undergo reductive fragmentation via a single-electron transfer(SET)event to afford free radicals that participate in a multitude of transformations.Above all,carboxylic esters can be seen as both good acyl sources and desirable alkyl donors.In this thesis,we mainly studied the selective transformation of esters catalyzed by visible light/transition metals through decarboxylation coupling reactions.(1)A nickel catalyzed cross-electrophile coupling of two different carboxylic acid esters towards ketones synthesis via a photoredox-assisted reductive acyl cross-coupling(PARAC)strategy is developed.This strategy provides an alternative and reliable way to synthesize various sterically congested ketones under mild and highly unified conditions,which have been otherwise difficult to access.The combined experimental and computational studies identified a Ni(0)/Ni(I)/Ni(III)pathway for ketone formation.(2)An electron-donor-acceptor complex enabled,nickel-catalyzed three-component net-reductive 1,2-alkylacylation of alkenes is developed.This intermolecular conjunctive reductive acyl cross-coupling process obviates the need for exogenous photocatalyst and stoichiometric metal-based reductant,affording various synthetically useful 1,3-dicarbonyl compounds and ketones in good yields with broad substrate scope and excellent functional group tolerance.Both alky and acyl electrophiles are derived from the highly abundant and readily accessible carboxylic acids,the acyl electrophilics are 2-pyridyl esters and the radical precursors are NHPI esters.This method enables a modular synthetic platform for1,3-dicarbonyl compounds and ketones.(3)An electron-donor-acceptor(EDA)complex enabled copper catalyzed decarboxylative cyanation of N-(acyloxy)phthalimides(NHPI esters)is developed.Thanks to the dual catalysis of catalytic amount EDA complex and copper,the reaction obviates the need for photocatalysts.Cu(I)is oxidized by the phosphine/iodine radical to form Cu(II)species,which traps the alkyl radicals to produce the Cu(III),followed by reductive elimination to give the desired compounds.A series of primary,secondary,and tertiary alkylnitriles are obtained in good yields with broad substrate scope and excellent functional group tolerance under mild conditions.