Site-Selective Palladium-Catalyzed 1,1-Arylamination of Terminal Alkenes

Many of the commonly used pharmaceuticals and biologically active natural products are nitrogen-containing compounds. Recently, the transitionmetal-catalyzed or the radical-mediated 1,2-carboamination of alkenes has been well explored to access amine scaffolds. However, synthetic strategies toward the 1,1-carboamination of alkenes are severely limited. Herein, we describe a method to achieve the 1,1arylamination using readily available building blocks enabled by palladium catalysis. This sequential three step-Heck arylation, metal migration, followed by aza-1,6-Micheal addition process exhibits excellent chemo- and regioselectivity. To showcase the potential as a method for diversity-oriented drug discovery, the modification of numerous structurally complex bioactive molecules was also successfully performed. [GRAPHICS] .

Automated summary

Many pharmaceuticals and natural products contain nitrogen compounds. The 1,2-carboamination of alkenes has been extensively studied, but the 1,1-carboamination is limited. In this study, a method using palladium catalysis was developed to achieve 1,1-arylamination, demonstrating excellent selectivity.