3-Amino-1-methyl-1H-pyridin-2-one-Directed Pd^II Catalysis: C(sp³)–H Activated Diverse Arylation Reaction

Abstract

A new bidentate directing group, 3-amino-1-methyl-1 H-pyridin-2-one, is introduced to achieve a powerful Pd metallacycle for selective γ-C(sp)-H activation and arylation of aromatic and aliphatic carboxylic acid derivatives. The versatility of the directing group is validated for remote arylation of β-C(sp)-H, β-C(sp)-H, and γ-C(sp)-H to achieve therapeutically important 2-pyridone analogues and arylated acid synthons. The traceless removal of the directing group to retrieve the directing element and carboxylic acids makes this method more interesting.

Transition-Metal-Catalyzed, Coordination-Assisted Functionalization of Nonactivated C(sp3)–H Bonds

“…Notably, the glycine dimethylamide bidentate DG could promote a subsequent intramolecular C­(sp 2 )–H amination to prepare 2-quinolinones through seven-membered palladation (Scheme c) . In 2018, Maiti and co-workers used 3-amino-1-methyl-1 H -pyridin-2-one as an N , O -bidentate DG for both β- and γ-C­(sp 3 )–H arylation of carboxylic acid derivatives (Scheme d) . This protocol is efficient for direct arylation of both β-methylene and γ-methyl C­(sp 3 )–H bonds.…”

“…Although a range of bidentate DGs have been developed for the effective C(sp 3 )−H activation 87d). 260 This protocol is efficient for direct arylation of both βmethylene and γ-methyl C(sp 3 )−H bonds.…”

Diverse strategies for transition metal catalyzed distal C(sp3)–H functionalizations

“…Later Maiti and coworkers came up with another approach for g-C(sp 3 )-H arylation of b-quaternary aliphatic acids. 48 Instead of 8-amino quinoline, they developed a new 2-pyridonebased N,O-bidentate directing group that enables monoselective g-C(sp 3 )-H arylation without requiring excess acid substrate (Scheme 46). The usage of aryl iodides were a little limited with electron decient aryl iodides majorly provided better yields.…”

Quinoline-Fused Lactones via Tandem Oxidation Cyclization: Metal-Free sp3 C–H Functionalization

“…Therefore, seeking efficient, atom economical, and mild strategies for synthesizing heteroaryl-fused lactones is highly desirable. Direct sp 3 C–H functionalization has emerged as a powerful tool for construction of C–C, C–N, and C–O bonds . Because of the inertness of the C­(sp 3 )–H bond, its late-stage functionalization is challenging, though attractive.…”