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.

Site-selective C-H functionalization has emerged as an attractive tool for derivatizing complex synthetic intermediates, but its use for late-stage diversification is limited by the functional groups that can be introduced, especially at unactivated sp(3)-hybridized positions. To overcome this, we introduce a strategy that directly installs a sulfonyloxy group at a β-C-H bond of a masked alcohol and subsequently employs nucleophilic substitution reactions to prepare various derivatives. Hydroxyl groups are widely found in bioactive molecules and are thus readily available as synthetic handles. A directing group is easily added (and subsequently removed) from the alcohols such that a formal site-selective β-C-H sulfonyloxylation of these alcohols is achieved. Substitution reactions with carbon, nitrogen, oxygen and other nucleophiles then lead to diverse functionalizations that may help to streamline the synthesis of complex analogues for drug discovery.

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General procedures for metathesis reactions…………………………………………………………….20 X-Ray crystallography data for 3c……………………………………………………………...……21-22 X-Ray crystallography data for 3d……………………………………………………………..…….23-24 References…………………………………………………………….………………..…………….…..25 S2 General considerations. Unless otherwise stated, all manipulations were carried out in dry solvents under an atmosphere of argon, using either standard Schlenk techniques or a glovebox. Pentane, toluene, benzene, and diethyl ether were dried using a custom solvent purification system. 4-iodo-2-methylbut-1-ene, 1 1a 2 , and 1b 2 were prepared by literature procedures or slight modifications thereof. Compounds S1,

The efficient Z-selective cross-metathesis between acrylamides and common terminal olefins has been developed by the use of novel cyclometalated ruthenium catalysts with bulky N-heterocyclic carbene (NHC) ligands. Superior reactivity and stereoselectivity are realized for the first time in this challenging transformation, allowing streamlined access to an important class of cis-Michael acceptors from readily available feedstocks. The kinetic preference for cross-metathesis is enabled by a pivalate anionic ligand, and the origin of this effect is elucidated by density functional theory calculations.