Harnessing the radical reactivity of cationic salts for the site-selective C-H functionalisation of organic molecules

The late-stage functionalization (LSF) of complex biorelevant compounds is a powerful tool to speed up the identification of structure-activity relationships (SARs) and to optimize absorption-distribution-metabolism-excretion (ADME) profiles. The direct C-H in LSF represents an ideal strategy, reducing processes mass intensity, and streamlining synthetic routes for more sustainable chemical routes. Indeed, the conversion of a C-H bond into new C-C bonds involves the displacement of the lightest element, namely hydrogen, establishing an ideal scenario in terms of atom economy. An emerging powerful synthetic method for chemoselective C-H functionalization is visible light photoredox catalysis, which allows the formation of new C-C bonds under extraordinarily mild conditions, exploiting the remarkable potential of light as a traceless, mild, and safe reagent in organic chemistry.
Recently, photoredox catalysis has been used in combination whit vinyl phosphonium and vinyl sulfonium salts in decarboxylative radical reactions. This allowed the development of a general methodology for the rapid structural diversification of bioactive molecules and natural products in native form, without installing exogenous activating groups or protecting strategies
Despite the remarkable potential of the methodologies presented above, due to the underlying decarboxylative mechanism, a relevant functional group is lost as a result of the reaction, while the application in C-H functionalization is still limited in direct systems (i.e., exclusively at the alpha position for alcohols). Furthermore, a significant challenge in this approach would be the selective manipulation of C-H bonds, ubiquitous in organic molecules.