An easily removable pyrimidine-based auxiliary has been employed for the remote meta-C-H cyanation of arenes. The scope of this Pd-catalyzed cyanation reaction using copper(I) cyanide as the cyanating agent was demonstrated with benzylsilanes, benzylsulfonates, benzylphophonates, phenethylsulfonates, and phenethyl ether derivatives. The method was utilized for the synthesis of pharmaceutically valuable precursors.

Arenes containing conformationally flexible long alkyl chains have been successfully functionalized at the meta-position. Good to excellent meta selectivity is achieved for systems with up to 20 atoms between the target C-H bond and the coordinating heteroatom of the directing group. The palladium-catalyzed functionalization reactions include alkylation, cyanation, olefination, and acetoxylation. The meta selectivity is exclusively governed by the design of flexible pyrimidine-based scaffolds.

Rhodium-catalyzed ortho-C-H functionalization is well known in the literature. Described herein is the Xphos-supported rhodium catalysis of meta-C-H olefination of benzylsulfonic acid and phenyl acetic acid frameworks with the assistance of a para-methoxy-substituted cyano phenol as the directing group. Complete mono-selectivity is observed for both scaffolds. A wide range of olefins and functional groups attached to arene are tolerated in this protocol.

Selective meta-C−H activation of arenes to date has met with a limited number of functionalizations. Expanding the horizon of meta-C−H functionalization, herein we disclose an unprecedented meta-silylation and -germanylation protocol by employing a simple nitrile-based directing template. Longer linkers between the target site and the directing template were successfully explored for meta-silylation (sp 2 -ε and sp 2 -ζ). Additionally, synthetic utility was demonstrated with several postsynthetic elaborations and with a formal synthesis of TAC101, a promising drug for the treatment of lung cancer.

Photoexcited dihydronicotinamides like NADH and analogues have been found to generate alkyl radicals upon reductive decarboxylation of redox-active esters without auxiliary photocatalysts. This principle allowed aliphatic photocoupling between redox-active carboxylate derivatives and electron-poor olefins, displaying surprising water and air-tolerance and unusually high coupling rates in dilute conditions. The orthogonality of the reaction in the presence of other carboxylic acids and its utility in the functionalization of DNA is presented, notably using visible light in combination with NADH, the ubiquitous reductant of life.