Direct Dehydrogenative Arylation Of Benzaldehydes With Arenes Using Transient Directing Groups

Aldehyde is a ubiquitous structural unit in biologically active compounds and organic functional materials,and the key intermediate in chemical synthesis.Therefore,aldehyde groups are highly desirable directing groups for direct C-H functionalization.Currently,however,only a handful of reports describe aldehyde directed C-H functionalization with transition-metal catalysts,due to the aldehyde's weak coordinating ability.In order to address this issue,several groups have reported C-H functionalization methods using pre-installed imine or oxime directing groups.However,the practicality of this strategy is compromised by additional steps required for installation/removal of the directing group.However,recently,a significant transient directing group?TDG?strategy was exploited.There is a reagent that can be reversibly linked to the substrate and can serve as a directing group.Upon C–H activation and subsequent functionalization,this reagent would dissociate from the product and transiently link to another substrate so that only a catalytic quantity of the directing group would be needed.The utilization of the transient directing strategy into the direct oxidative dehydrogenative arylation of aldehydes with arenes was reported for the first time.The reaction conditions were used as follows:Pd?OAc?₂?10 mol%?,TFA?8.0 equiv?,K₂S₂O₈?2.0 equiv?,amino acid A6?40 mol%?,at 60°C.Featured by mild reaction conditions,good functional group compatibility,and great regioselectivity,the method should find broad applications in new medicine and material development and discovery processes.