Alkylation reactions represent an important organic transformation to form C-C bonds. In addition to conventional approaches with alkyl halides or sulfonates as alkylating agents, the use of unactivated olefins for alkylations has become attractive from both cost and sustainability viewpoints. This Review summarizes transition-metal-catalyzed alkylations of various carbon-hydrogen bonds (addition of C-H bonds across olefins) using regular olefins or 1,3-dienes up to May 2016. According to the mode of activation, the Review is divided into two sections: alkylation via C-H activation and alkylation via olefin activation.

Herein, we report the palladium-catalyzed direct arylation of unactivated aliphatic C-H bonds in free primary amines. This method takes advantage of an exo-imine-type directing group (DG) that can be generated and removed in situ. A range of unprotected aliphatic amines are suitable substrates, undergoing site-selective arylation at the γ-position. Methyl as well as cyclic and acyclic methylene groups can be activated. Furthermore, when aniline-derived substrates were used, preliminary success with δ-C-H arylation was achieved. The feasibility of using the DG component in a catalytic fashion was also demonstrated.

Carbon−hydrogen (C−H) and carbon−carbon (C−C) bonds are the main constituents of organic matter. The recent advancement of C−H functionalization technology has vastly expanded our toolbox for organic synthesis1. In contrast, C−C activation methods that allow for editing the molecular skeleton remain limited2–7. To date, a number of methods have appeared for catalytic C−C activation, particularly with ketone substrates, which are typically promoted either by ring-strain release as a thermodynamic driving force4,6 or using directing groups5,7 (DGs) to control the reaction outcome. While effective, these strategies require highly strained ketone substrates or those containing a preinstalled DG, or are limited to more specialist substrate classes5. Here, we report a general C−C activation mode driven by aromatization of an in situ-formed pre-aromatic intermediate. This reaction suitable for various ketone substrates, is catalyzed by an iridium/phosphine combination, and is promoted by a hydrazine reagent and 1,3-dienes. Specifically, the acyl group is removed from the ketone, transformed to a pyrazole, and the resulting alkyl fragment undergoes various transformations. These include the deacetylation of methyl ketones, carbenoid-free formal homologation of aliphatic linear ketones, and deconstructive pyrazole synthesis from cyclic ketones. Given that ketones are prevalent in feedstock chemicals, natural products and pharmaceuticals, these transformations could offer new strategic bond disconnections in the synthesis of complex bioactive molecules.

The application of exo-type directing groups (DGs) has led to the discovery of a wide range of novel C(sp3)–H activation methods, which allow efficient and site-selective functionalization of alcohol and amide derivatives.