Palladium-catalyzed Ugi-type reaction of 2-iodoanilines with isocyanides and carboxylic acids affording N-acyl anthranilamides.

The first palladium-catalyzed Ugi-type multicomponent reaction for the synthesis of N-acyl anthranilamides from isocyanides, 2-iodoanilines and carboxylic acids has been developed. This method provides expeditious and highly efficient access to structurally diverse N-acyl anthranilamides from readily available starting materials with good functional group compatibility. The utility of this method has been demonstrated by the late stage functionalization of two commercial drugs: Flurbiprofen and Loxoprofen.

Synthesis of imides via palladium-catalyzed three-component coupling of aryl halides, isocyanides and carboxylic acids.

A palladium-catalyzed three-component synthesis of acyclic imides from feedstock aryl halides, carboxylic acids and isocyanides through the intermediacy of isoimides has been developed. The key to the success of this approach was controlled isocyanide slow addition and organic/aqueous biphasic conditions. This transition-metal-catalyzed approach features readily available starting materials, atom- and step-economy, good functional group compatibility and gram-scale synthetic capability. Utilization of this new method is illustrated in the late-stage functionalization of drugs Carprofen, Loxoprofen and Flurbiprofen. This strategy has also been successfully applied in the synthesis of cyclic imides including phthalimide, homophthalimide, and 2H-2-benzazepine-1,3-dione derivatives.

Highly Selective Synthesis of Dihydrobenzo[d]isoxazoles and Dihydrobenzo[d]oxazoles from Oximes and Arynes via in Situ Generation of Nitrones.

An efficient method for the synthesis of dihydrobenzo[d]isoxazoles and dihydrobenzo[d]oxazoles bearing a quaternary carbon center has been developed. The reaction involves generation of a ketonitrone intermediate in situ from a ketoxime and an aryne. A novel thermal rearrangement of the dihydrobenzo[d]isoxazole products to the corresponding dihydrobenzo[d]oxazoles has been observed. These transformations tolerate a variety of functional groups and offer a rapid and efficient way to diverse dihydrobenzo[d]isoxazoles and dihydrobenzo[d]oxazoles under mild transition-metal-free conditions.