Pd^II-Catalyzed γ-C(sp³)-H (Hetero)Arylation of Ketones Enabled by Transient Directing Groups.

ABSTRACT: Pd(II)-catalyzed γ-C(sp³)-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(sp³)-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.

SUBMITTER: Li YH 

PROVIDER: S-EPMC10249709 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature