This article reports the first example of a 2‐pyridone accelerated non‐directed C−H cyanation with an arene as the limiting reagent. This protocol is compatible with a broad scope of arenes, including advanced intermediates, drug molecules, and natural products. A kinetic isotope experiment (kH/kD=4.40) indicates that the C−H bond cleavage is the rate‐limiting step. Also, the reaction is readily scalable, further showcasing the synthetic utility of this method.

Transition-metal-catalyzed alkene hydrosilylation is one of the most important homogeneous catalytic reactions, and the development of methods that use base metals, especially iron, as catalysts for this transformation is a growing area of research. However, the limited number of ligand scaffolds applicable for base-metal-catalyzed alkene hydrosilylation has seriously hindered advances in this area. Herein, we report the use of 1,10-phenanthroline ligands in base-metal catalysts for alkene hydrosilylation. In particular, iron catalysts with 2,9-diaryl-1,10-phenanthroline ligands exhibit unexpected reactivity and selectivity for hydrosilylation of alkenes, including unique benzylic selectivity with internal alkenes, Markovnikov selectivity with terminal styrenes and 1,3-dienes, and excellent activity toward aliphatic terminal alkenes. According to the mechanistic studies, the unusual benzylic selectivity of this hydrosilylation initiates from π–π interaction between the phenyl of the alkene and the phenanthroline of the ligand. This ligand scaffold and its unique catalytic model will open possibilities for base-metal-catalyzed hydrosilylation reactions.

Controlling site selectivity of C–H activation without using a directing group remains a significant challenge. While Pd­(II) catalysts modulated by a mutually repulsive pyridine-type ligand have been shown to favor the relatively electron-rich carbon centers of arenes, reversing the selectivity to favor palladation at the relatively electron-deficient positions has not been possible. Herein we report the first catalytic system that effectively performs meta C–H arylation of a variety of alkoxy aromatics including 2,3-dihydrobenzofuran and chromane with exclusive meta site selectivity, thus reversing the conventional site selectivity governed by native electronic effects. The identification of an effective ligand and modified norbornene (NBE-CO2Me), as well as taking advantage of the statistics, are essential for achieving the exclusive meta selectivity.

One of the core challenges in developing C-H activation reactions is to distinguish multiple C-H bonds that are nearly identical in terms of electronic properties and bond strengths. Through recognition of distance and molecular geometry, remote C(sp 2)-H bonds have been selectively activated in the presence of proximate ones 1-2. Yet achieving such unconventional site selectivity with C(sp 3)-H bonds remains a paramount challenge. Here we report a combination of a simple pyruvic acid derived directing group and a 2-pyridione ligand that enables the preferential activation of the distal γ-C(sp 3)-H bond over the proximate β-C(sp 3)-H bonds for a wide range of alcohol derived substrates. Competition experiment of five-and six-membered cyclopalladation step as well as kinetic experiments demonstrate the feasibility of using geometric strain to reverse the conventional site selectivity in C(sp 3)-H activation. Developing C-H activation reactions as new retrosynthetic disconnections could offer a multitude of novel synthetic strategies due to the abundance of positionally diverse C-H bonds 3-4. On the other hand, the great resemblance between these C-H bonds in terms of bond strength and electronic properties presents a tremendous challenge for achieving regioselectivity. This difficulty escalates with metalation chemistry because in such processes, the numerous primary or secondary C-H bonds are nearly indistinguishable by the metal. For example, despite the recent advances in developing a wide range of Pdcatalyzed C(sp 3)-H activation reactions, their regioselectivity is largely restricted to the cleavage of the C-H bond that will result in five-membered cyclopalladation 5-12. Therefore, it is fundamentally important to develop strategies to switch the selectivity of the key metalation step from five-membered to six-membered cyclopalladation (Fig. 1b). Such Reprints and permissions information is available at www.nature.com/reprints.