Development and applications of palladium(0)-catalyzed-C(sp3)-H activation

Abstract

Over the last decade, the transition metal-catalyzed intramolecular activation of unactivated CH bonds has emerged as a powerful method to transform otherwise inert entities allowing access to molecular complexity in an atom- and step-economical fashion. Research in our group is centered on the activation and functionalization of C(sp3)-H bonds that lead to the development of new methodologies and applications including asymmetric catalysis, mechanistic studies and total synthesis of complex molecules. Recently, our group developed a straightforward access to hexahydroindoles scaffolds by intramolecular C(sp3)-H alkenylation. As a follow-up, we first investigated the application of this new methodology in combination with a directed C(sp3)-H arylation to achieve a collective synthesis of aeruginosins. In a second part, we extended this methodology to the development of a modular C(sp3)-H alkenylation for the synthesis of a wide variety of g -lactams, which are prevalent scaffolds found in numerous bioactive natural molecules. Finally, we developed a highly efficient synthesis of b-lactams, which are valuable compounds widely used in pharmaceutical chemistry, by palladium(0)-catalyzed-C(sp3)-H carbamoylation. Keywords : C-H functionalization, C-H activation, organometallic catalysis, palladium, total synthesis, aeruginosins, g-lactams, b-lactams