Recent Advances in External-Directing-Group-Free C–H Functionalization of Carboxylic Acids without Decarboxylation

Abstract

The selective functionalization of C–H bonds is an extremely important topic in present-day organic synthesis, as it utilizes the most abundant portion of a molecule as a tool for synthetic manipulations. Despite the great progress over the past decade, the major limitation remains the use of an equivalent amount of a directing group to generate the product. The utilization of a native carboxylate group for the same purpose has come up as a better alternative to perform C–H activation, as no exogenous directing group is required to perform the reaction. In this Perspective, we intend to provide a broader picture of transformations that have been carried out by assistance from the carboxylate group and could be applied routinely in the synthesis of complex molecules. The intact carboxylic group in the substrate could be further transformed into different functional moieties, which increases the diversity of such reactions. Extensive coverage of the topic of carboxylate-aided functionalizations of organic molecules without decarboxylation is expected to make this Perspective unique and extremely beneficial to researchers in academia and industry.

Transition‐Metal‐Catalyzed Selective Alkynylation of C−H Bonds

“…Although directing groups play a significant role in C−H activation methods, the steps involving the pre‐installation [49] and removal [50] of DGs reduce the practical utility of the procedures. To overcome this drawback, recent studies were performed focusing on utilizing weakly coordinating intrinsic functional groups, instead of externally tethered directing groups, to carry out similar reactions [51] . The use of a highly electrophilic metal catalyst and a proper oxidative system is expected to compromise the weak interaction offered by functional groups which in turn destabilize the active intermediate.…”

Traditional and sustainable approaches for the construction of C–C bonds by harnessing C–H arylation

“…A suitably designed directing group can coordinate with the transition metal to form a cyclometallated intermediate, thus reaching in the vicinity of the target C–H bond to avail a successful functionalization 15 . Directing groups known so for primarily can be classified into two types, i.e., strong co-ordinating like pyridine 16 , pyrimidine 17 and weakly co-ordinating like acid 18 , amide 19 , nitrile 20 . The initial study was commenced with strong directing groups.…”

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).…”