Synthesis of cyclic amino acids via C-H functionalization for the development of peptidomimetics

The possibility to make a precise nonacidic C-H bond reacting allows to generate a site of functionalization otherwise unexploitable, and this is obviously of great interest for organic chemists. Unsurprisingly, selective transition metal-assisted C(sp2/sp3)-H activation reactions have been set up on a wide range of substrates [1-2], including amino acids and derivatives [3-5]. To achieve selectivity, a Directing Group (DG) is often used, due to its ability to chelate metal ions, which can be exploited for bringing the catalytic metal centre closer to the C(sp2/sp3)-H bond of interest and making the distance as the distinctive parameter [6]. In this view, we aimed at functionalizing heterocyclic amino acid precursors coming from multicomponent processes (MCRs), such as the Castagnoli-Cushman reaction, taking advantage of the COOH handle coming out from the reaction to install suitable DG for the functionalization of the heterocycle. We developed a range of compounds containing aryl substituents that may be further processed to achieve novel constrained amino acids for application in peptidomimetic chemistry.