Substrate‐Directed C‐H Functionalization of 2‐Aryl Pyridines by Transition Metal Complexes

Abstract

Transition metal mediated CÀH activation is a powerful synthetic tool for the total synthesis of complex natural products and biologically active molecules. The strategy involves mainly CÀH activation, nucleophilic addition and regeneration of the catalyst. It proceeds through a CÀH bond cleavage by ligand coordination to transition metal. Transition metals like Pd, Rh, Ru, Co, and Ir are the most often used catalysts, which form a complex with 2-aryl pyridine and facilitates the functionalization of various CÀH bonds to generate diverse CÀC and CÀX bonds under typically mild reaction conditions with low catalyst loading. In particular, the chelation-assisted cleavage of CÀH bonds at ortho-position of the pyridine directing group has been recognized as one of the most powerful strategies for the functionalization of unreactive CÀH bonds. Recently, transition metal catalyzed CÀH bond activation has received significant interest because it does not require the prefunctionalization of the substrate. Therefore, the metal-catalyzed CÀH activation and functionalization is currently considered as atom economy and simplified procedure in comparison with the traditional strategies.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Metal catalysed C–H functionalisation chemistry is a rapidly expanding field with research going into many different directions. 1 – 21 Due to the ubiquity of C–H bonds in organic molecules, selective functionalisation of a specific C–H bond is highly challenging. In aromatic heterocycles, the heteroatoms usually guide the regioselectivity of C–H functionalisation reactions due to their influence on the electron density of the different C–H positions.…”

No Making Without Breaking: Nitrogen-Centered Carbonylation Reactions

“…Pyridine and its derivatives are important motifs in materials and medicinal chemistry, which also act as an efficient directing group for the transition-metal catalyzed functionalization of unreactive C−H bonds. 88 Recently, transition-metal catalyzed carbonylation of C−H bonds using pyridine as the directing group has attracted much attention because of their high efficiency in incorporating carbonyl groups into their parent compounds. In 2014, Zhu and co-workers developed a Pdcatalyzed carbonylative annulation of N-aryl-2-aminopyridines.…”

Ir-Catalyzed Atroposelective Desymmetrization of Heterobiaryls: Hydroarylation of Vinyl Ethers and Bicycloalkenes

“…There is a plethora of catalysts based on different transition metals that have been used for the functionalization of 2-phenylpryridine and related heterobiaryls. 9 A closer analysis, however, reveals that the vast majority of these systems are not useful to our purpose. First, high temperatures are usually required, compromising the configurational lability of the products.…”

“…A more appealing strategy exploits the ortho -directing effect of the heterobiaryl N atom to perform regioselective asymmetric C–H functionalization reactions (Scheme A). There is a plethora of catalysts based on different transition metals that have been used for the functionalization of 2-phenylpryridine and related heterobiaryls . A closer analysis, however, reveals that the vast majority of these systems are not useful to our purpose.…”