Mechanism of the Arene-Limited Nondirected C-H Activation of Arenes with Palladium*.

Recently palladium catalysts have been discovered that enable the directing-group-free C-H activation of arenes without requiring an excess of the arene substrate, thereby enabling methods for the late-stage modification of complex organic molecules. The key to success has been the use of two complementary ligands, an N-acyl amino acid and an N-heterocycle. Detailed experimental and computational mechanistic studies on the dual-ligand-enabled C-H activation of arenes have led us to identify the catalytically active species and a transition state model that explains the exceptional activity and selectivity of these catalysts.

Ligand-Enabled γ-C(sp )-H Olefination of Free Carboxylic Acids.

We report the ligand-enabled C-H activation/olefination of free carboxylic acids in the γ-position. Through an intramolecular Michael addition, δ-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the γ-position.

Sterically Controlled Late-Stage C-H Alkynylation of Arenes.

Phenylacetylenes are key structural motifs in organic chemistry, which find widespread applications in bioactive molecules, synthetic intermediates, functional materials, and reagents. These molecules are typically prepared from prefunctionalized starting materials, e.g.

Arene-Limited Nondirected C-H Activation of Arenes.

The nondirected C(sp )-H activation of simple arenes has advanced significantly in recent years through the discovery of new catalyst systems that are able to perform transformations with the arene as the limiting reagent. Important developments in catalyst and ligand design that have improved reactivity and selectivity are reviewed.

Dual Ligand-Enabled Nondirected C-H Olefination of Arenes.

The application of the Pd-catalyzed oxidative C-H olefination of arenes, also known as the Fujiwara-Moritani reaction, has traditionally been limited by the requirement for directing groups on the substrate or the need to use the arene in large excess, typically as a (co)solvent. Herein the development of a catalytic system is described that, through the combined action of two complementary ligands, makes it possible to use directing-group-free arenes as limiting reagents for the first time. The reactions proceed under a combination of both steric and electronic control and enable the application of this powerful reaction to valuable arenes, which cannot be utilized in excess.