Carbopalladation/Suzuki Coupling Cascade for the Generation of Quaternary Centers. Access to Pyrrolo[1,2-b]isoquinolines

Abstract

A convergent route to pyrrolo[1,2-b]isoquinolines with a quaternary center at C-10 has been developed, that implies a sequential Pd(0)-catalyzed carbopalladation followed by cross-coupling reaction with boronic acids. The adequate catalytic system and experimental conditions, with and without the use of phosphane ligands, have been selected to control the chemoselectivity of the process, allowing a 6-exo-carbopalladation to generate a quaternary center, and avoiding a direct Suzuki coupling. A variety of electron rich and electron deficient arylboronic acids can be used providing an efficient route to substituted pyrrolo[1,2-b]isoquinolines in moderate to good yields (up to 94%, 22 examples).