Rh(iii)-catalyzed C–H activation/β-F elimination/Michael addition: diastereoselective access to dihydroisoquinolinones featuring β-amino α-fluorocarbonyl motif

Abstract

The β-amino α-fluorocarbonyl motif is a privileged scaffold in medicinal chemistry, yet its efficient synthesis from readily available precursors remains challenging. Herein, we report a Rh(III)-catalyzed cascade reaction that constructs 3,4-dihydroisoquinolin-1(2H)-ones featuring this motif via C–H activation/β-F elimination/Michael addition. Using gem-difluorobut-3-en-1-ones as versatile fluorinated building blocks, the reaction proceeds under mild conditions with broad substrate scope and high diastereoselectivity.