Synthesis and elaboration of molecular scaffolds through directed C(sp3)-H bond activation for application as peptidomimetics

Molecular complexity and structural diversity are fundamental aspects in Diversity-Oriented Synthesis (DOS) for obtaining organic compounds of interest for bio-medical purposes.1 The possibility of simply obtaining complex C(sp3)-rich structures, as well as of increasing their molecular complexity through functionalization, would represent a significant goal for synthetic chemists. Directed Pdcatalyzed C(sp2/sp3)-H activation reactions are an interesting tool for chemists, due to their capability of making a non-acidic C-H bond stereoselectively reacting, to create new sites for functionalization, otherwise unexploitable.2 C(sp3)-H bonds are the most challenging, as well as the most interesting, due to their abundancy in organic compounds and their relationship with molecular complexity. Accordingly, we synthesized hetero- and carbocycles, and we took advantage of amino and carboxylic acid Functional Groups (FGs) on the compounds for applying a directed Pd-catalyzed C(sp3)-H bond activation strategy to functionalize such scaffolds. Specifically, we achieved variously arylated carboxamides with good chemo- and stereoselectivity, possessing the rare trans 2,4-diaryl configuration,3 and cyclic α- and β-(hetero)aryl-β-amino acids with good to excellent yields, all amenable to peptidomimetic chemistry.