Pd<sup>II</sup>-Catalyzed γ-C(sp<sup>3</sup>)–H (Hetero)arylation of Ketones Enabled by Transient Directing Groups
Yi-Hao Li, Yuxin Ouyang, Nikita Chekshin, Jin‐Quan Yu
Abstract
Pd(II)-catalyzed γ-C(sp3)–H (hetero)arylation of aliphatic ketones is developed using α-amino acids 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(sp3)–H arylation of ketones. Mechanistic investigation and comparison to the γ-C–H arylation of aldehydes revealed a structural insight for designing site-selective TDG.