Iodine-Mediated Oxidative Annulation of ß,γ-Unsaturated Hydrazones in Dimethyl Sulfoxide: A Strategy to Build 1,6-Dihydropyridazines and Pyrroles.

Simple, commercially available iodine was successfully employed as a highly efficient and chemoselective catalyst for the oxidative annulation of ß,γ-unsaturated hydrazones to produce 1,6-dihydropyridazines under mild conditions for the first time. Interestingly, when active ß,γ-unsaturated hydrazone compounds containing electron-donating groups, such as furyl, thienyl, and cycloalkyl, were used, pyrroles were obtained. A gram-scale preparation experiment and further derivatization of pyridazines demonstrated the potential applicability of our synthesis method. Experimental studies and density functional theory calculations unveiled the origin of the chemoselectivity determining the formation of different products.

Pd-Catalyzed Approach for Assembling 9-Arylacridines via a Cascade Tandem Reaction of 2-(Arylamino)benzonitrile with Arylboronic Acids in Water.

A novel palladium-catalyzed protocol for the synthesis of 9-arylacridines via tandem reaction of 2-(arylamino)benzonitrile with arylboronic acids in water has been developed with good functional group tolerance. The present synthetic route could be readily scaled up to gram quantity without difficulty. This methodology was further extended to the synthesis of a 4'-OH derivative, which showed estrogenic biological activity. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular Friedel-Crafts acylation and dehydration to acridines.

Synthesis of Imidazoles and Oxazoles via a Palladium-Catalyzed Decarboxylative Addition/Cyclization Reaction Sequence of Aromatic Carboxylic Acids with Functionalized Aliphatic Nitriles.

We herein report an efficient approach for the assembly of multiply substituted imidazoles and oxazoles in a single-step manner. These transformations are based on a decarboxylation addition and annulation of readily accessible aromatic carboxylic acids and aliphatic nitriles and exhibit good functional group compatibility and a high step economy. The reaction is scalable, and as-prepared products could be transformed into practical skeletons. Importantly, the late-stage derivatization of Momelotinib highlights the potential utility of this methodology.

Homoleptic Bis(trimethylsilyl)amides of Yttrium Complexes Catalyzed Hydroboration Reduction of Amides to Amines.

Homoleptic lanthanide complex Y[N(TMS)2]3 is an efficient homogeneous catalyst for the hydroboration reduction of secondary amides and tertiary amides to corresponding amines. A series of amides containing different functional groups such as cyano, nitro, and vinyl groups were found to be well-tolerated. This transformation has also been nicely applied to the synthesis of indoles and piribedil. Detailed isotopic labeling experiments, control experiments, and kinetic studies provided cumulative evidence to elucidate the reaction mechanism.