The Emergence of Palladium‐Catalyzed C(sp³)−H Functionalization of Free Carboxylic Acids

Abstract

Palladium‐catalyzed directing group assisted C−H bond activation has emerged as a powerful tool in synthetic organic chemistry. However, only recently, among various directing groups, widely available carboxylate moiety is recognized as a versatile candidate for the regioselective transformations. Notably, palladium‐catalyzed carboxylate directed C(sp3)−H bond activation and diverse functionalization is highly challenging and has gained huge attention for its versatile applications. Mono‐ and bidentate ligands have proven to be useful for accelerating the C(sp3)−H bond activation step, which helps to control reactivity and selectivity (including enantioselectivity). In this Minireview, we discuss the recent progress made in palladium‐catalyzed C(sp3)−H bond functionalization reactions for the construction of C−C and C−Heteroatom bonds with the direction of free carboxylic acid.

Pd-catalysed C–H functionalisation of free carboxylic acids

“…While prior reviews have predominantly focused on the scope 15,16,[21][22][23][24][25][26] and mechanistic understanding [27][28][29][30][31][32][33][34] of carboxylic acids, this review highlights the multifaceted roles of carboxylic acids as well as the developments in this area including recent studies and other important aspects. In this context, it is important to mention that free or mono-N-protected amino acids also utilize their carboxylic acid parts for coordination, but those substrates are not included here because they are a different class of substrates (or ligands).…”

Amide-Directed Rhodium-Catalyzed Chain-Walking Hydrothiolation of Internal Alkenes

“…Given the ubiquitous existence of sp 3 -hybridized backbones in organic molecules, direct C­(sp 3 )–H functionalization has emerged as a crucial strategy for the formation of C­(sp 3 )–C or C­(sp 3 )–heteroatom bonds with minimal reaction steps. − This method has been profoundly developed through transition-metal-mediated C­(sp 3 )–H bond cleavage, presenting an effective alternative to traditional cross-coupling reactions. However, this approach often requires an oxidant to modulate the redox level of the reaction process upon introducing nucleophiles, − which diminish atom economy.…”

The Direct β-C(sp3)–H Fluorination of Carboxylic Acids

“…Most of these studies focused on developing new C-C bond forming reactions. [26][27][28] Amongst the C-heteroatom bond forming reactions, the C-O bond formation received significant attention. [29][30][31][32] Very recently, Yu and co-workers have reported the bromination and chlorination of free carboxylic acids.…”