Cover Picture: Site‐Selective Pyridylic C−H Functionalization by Photocatalytic Radical Cascades (Angew. Chem. Int. Ed. 29/2022)

Abstract

The selective installation of functional groups at the pyridylic position is of significant interest in synthetic and medicinal chemistry. In their Research Article (e202204217), Sungwoo Hong et al. report the successful C−H functionalization of the heterobenzylic site of pyridines and quinolines by orchestrating cascade reactions on a modular photochemical platform. This reaction offers a powerful synthetic tool for the rational modification of heterobenzylic C−H bonds in complex settings under mild conditions.

A photoinduced transient activating strategy for late-stage chemoselective C(sp3)–H trifluoromethylation of azines

“…The selective introduction of functionality at the heterobenzylic site of azines is of significant interest for modification of drugs. 5–9 However, due to the strong basicity of most common azines, namely pyridine, pyrimidine, quinoline, etc. , the late-stage functionalization of alkylated azines exhibits inevitable difficulties and often requires harsh conditions.…”

“…, the late-stage functionalization of alkylated azines exhibits inevitable difficulties and often requires harsh conditions. Recent advances in the activation of C(sp 3 )–H bonds using pyridinium salts as precursors have found success in transformations such as fluoroalkylation 7,8 and alkylation 9 (Fig. 1a, left).…”

“…Considering the significance of fluorine-containing moieties in medicine, 10–17 the introduction of trifluoromethyl groups into organic molecules has attracted considerable attention, and significant progress has been achieved in this field in the past few decades. 18–28 The fluoroalkyl modification of pyridylic C–H bonds to regulate the metabolism is particularly appealing, 29–31 In order to introduce fluoroalkyl groups into heterocyclic scaffolds, the trifluoromethylation of pyridylic C–H bonds has been achieved using prefunctionalized N -oxides 7 and N -amido pyridinium salts 8 via alkylidene dihydropyridine intermediates followed by nucleophilic or radical addition. However, the formation of the new C(sp 3 )–CF 3 bond through azinylic C(sp 3 )–H fluoroalkylation was limited by tedious substrate preparation and hazardous procedures.…”

Visible-Light-Photoexcited Palladium-Catalyzed Silylmethylation of Benzyl Alcohol Derivatives

“…To evaluate the possibility of a radical-cyclization pathway, we conducted the same reaction with the photoredox catalyst Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 , which does not form a covalent bond with the substrate. 19 As a result, the same cyclized product was obtained under blue LED irradiation. Although these results do not constitute direct evidence for a Pd-catalyzed reaction, we consider that they provide supporting data for a radical-cyclization pathway.…”

Visible‐Light‐Active Coumarin‐ and Quinolinone‐Based Photocatalysts and Their Applications in Chemical Transformations

“…conditions. [38] In this system, the alkylidene dihydropyridine intermediate can be reversibly generated from an alkyl Namidopyridinium salt without the requirement for an external base. This intermediate serves as a radical acceptor by trapping fluoroalkyl or alkylsulfonyl radicals, which provide fluoroalkylated or β-fluoroalkylsulfonated products at the pyridylic site.…”