Search

Palladium(II)‐catalyzed C(alkenyl)−H alkenylation enabled by a transient directing group (TDG) strategy is described. The dual catalytic process takes advantage of reversible condensation between an alkenyl aldehyde substrate and an amino acid TDG to facilitate coordination of the metal catalyst and subsequent C(alkenyl)−H activation by a tailored carboxylate base. The resulting palladacycle then engages an acceptor alkene, furnishing a 1,3‐diene with high regio‐ and E/Z‐selectivity. The reaction enables the synthesis of enantioenriched atropoisomeric 2‐aryl‐substituted 1,3‐dienes, which have seldom been examined in previous literature. Catalytically relevant alkenyl palladacycles were synthesized and characterized by X‐ray crystallography, and the energy profiles of the C(alkenyl)−H activation step and the stereoinduction model were elucidated by density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

In this study, we systematically evaluate different ambiphilic organohalides for their ability to participate in anti‐selective carbo‐ or heteroannulation with non‐conjugated alkenyl amides under PdII/PdIV catalysis. Detailed optimization of the reaction conditions has led to protocols for synthesizing tetrahydropyridines, tetralins, pyrrolidines, and other carbo/heterocyclic cores via [n+2] (n=3–5) (hetero)annulation. Expansion of scope to otherwise unreactive ambiphilic haloketones through PdII/amine co‐catalysis is also demonstrated. Compared to other annulation processes, this method proceeds via a distinct PdII/PdIV mechanism involving Wacker‐type directed nucleopalladation. This difference results in unique reactivity and selectivity patterns, as revealed through assessment of reaction scope and competition experiments. [ABSTRACT FROM AUTHOR]

Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel‐catalyzed monofluoromethylation of unactivated alkyl halides using a low‐cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross‐coupling of two alkyl halides. Results with 1‐bromo‐1‐fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp3)‐C(sp3) cross‐coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional‐group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first‐order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate‐determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides. [ABSTRACT FROM AUTHOR]