Pd[II]-Catalyzed γ-C(sp)-H (Hetero)Arylation of Ketones Enabled by Transient Directing Groups.ACS Catal. 2022 Sep 02; 12(17):10581-10586.AC
Pd(II)-catalyzed γ-C(sp)-H (hetero)arylation of aliphatic ketones is developed using α-amino acid as transient directing groups (TDG). A variety of aliphatic ketones were (hetero)arylated at the γ-position via a 5,6-membered fused cyclopalladation intermediate to afford the remotely arylated products in up to 88% yield. The crucial ligand effect of 2-pyridone is further enhanced by reducing the loading of acid additives. Consequentially, the improved reactivity of this catalytic system has also made possible the cyclic γ-methylene C(sp)-H arylation of ketones. Mechanistic investigtigation and comparison to the γ-C-H arylation of aldehydes revealed a structural insight for designing site selective TDG.