Visible-Light Photoredox Catalyzed Acyl Radical Michael Addition And Its Application In The Synthesis Of Haloperidol

In this article,visible-light photoredox catalysis which represents a green,environmental catalytic mode was exploited to realize an acyl radical Michael addition of aryl carboxylic anhydrides to electron-deficient alkenes.A series of 1,4-dicarbonyl compounds were synthesized by this novel method.The research is mainly about two aspects.Firstly,symmetric aryl anhydrides were used as acyl radical source in Michael addition.Secondly,aryl acids were directly used in Michael addition as radical source by the transient generation of more active mixed anhydrides.Firstly,we developed an efficient acyl Michael addition using symmetric aryl anhydrides as acyl radical source.Under this condition,with only 1 mol%photocatalyst,a wide range of substrates are amenable to this new type of acyl Michael addition under mild conditions with broad functional group tolerance.TEMPO radical-trapping experiments proved the existence of acyl radical in this reaction.Moreover,luminescence quenching experiments indicated that photocatalyst undergoes a reductive quenching way,and a possible reaction mechanism was proposed.In the second part,we utilized carboxylic acids as acyl radical sources via transient generation of mixed anhydride intermediates.This is a novel method for constructing 1,4-dicarbonyl compounds.As an application,a novel four-step synthesis of medicinal agent haloperidol with 45%overall yield is also presented in this part.