Photocatalytic Diphenyl Sulfide-Promoted Coupling Reaction Of Aromatic Acids With Terminally Unsaturated Hydrocarbons

Photoredox catalysis is more and more used in organic synthesis,but photocatalytic acylation coupling reaction of carboxylic acid has not been widely studied.As acylation reagents,carboxylic acids generally require pre-activation into chlorinated acids,amides and anhydrides to participate in the reaction,which greatly destroys the tolerance and regional selectivity of functional groups.Carboxylic acids are the most potential raw materials for organic synthesis due to their inexpensive,readily available and and diverse structure.Therefore,it is of great significance to develop a photocatalytic direct acylation coupling strategy for carboxylic acids.In this paper,photocatalytic diphenyl sulfide-promoted coupling acylations of aromatic carboxylic acids with terminal alkenes and terminal alkynes were developed,which were used to synthesize dihydrochalcone and flavonoids,respectively.Firstly,the coupling reaction of aryl formic acid derivatives as acylation reagents with terminal olefins was studied to synthesize dihydrochalcones,and the photocatalytic coupling strategy for synthesis of dihydrochalcones was developed by using benzoic acid and styrene as template substrates.The optimal conditions were determined by screening photocatalysts,oxygen transfer reagents,bases and solvents:diphenyl sulfide as oxygen transfer reagent,Mes-Acr-Me Cl O₄ as photocatalyst,sodium carbonate as base,under blue light irradiation in（DMF）/H₂O（4:1）.Under these conditions,the scope of application of the method was studied,and 29 substituted dihydrochalcone products were obtained and their structures were characterized.The reaction mechanism was explored by controlled experiments and the reaction mechanism of its free radicals was proposed.Then,the coupling cyclization reaction of salicylic acid derivatives as acylating reagents with terminal alkynes to synthesize flavonoids was studied.Using salicylic acid and phenylacetylene as substrates,the photocatalytic coupling cyclization for synthesis of flavonoids was developed.The optimal conditions were determined by screening photocatalysts,oxygen transfer reagents,bases and solvents:diphenyl sulfide as oxygen transfer reagent,Mes-Acr-Me Cl O₄ as photocatalyst,potassium carbonate as base,under blue light irradiation in DMSO)/H₂O（4:1）.Under this condition,the applicable scope of the method was studied,and 45 flavonoid derivatives were obtained and their structures were characterized.To further verify the practicability of this method,six bioactive flavonoid natural products were synthesized.Through a series of controlled experiments,the reaction mechanism was explored and the reaction mechanism of its free radical was proposed.