AlCHiMIE

In recent year, aliphatic, three-dimensional molecules have been attracting a growing interest, in particular in medicinal chemistry. Indeed, such chiral scaffolds appear as appealing drug candidates as their unique stereogenic configuration allows improved therapeutic properties. Asymmetric synthesis of such molecules still presents, however, an extremely challenging task. AlCHiMIE aims at providing modern and ecocompatible routes towards these structural motifs. Targeting sustainability, AlCHiMIE will entirely focus on approaches implying the use of simple, non-prefunctionalized substrates, by means of C-H functionalization reactions. In order to access a large panel of structurally diversified chiral aliphatics two complementary strategies are envisioned. Less sterically congested alkanes will be accessed via asymmetric earth-abundant metal-catalyzed C-H activation. To achieve this yet largely unmet goal, design of conceptually new catalysts is proposed; that is multitasking bifunctional chiral ligands with unique modes of actions for Co- and Ni-catalyzed C(sp3)-H activation. In parallel, to build-up more encumbered alkanes, metal-free transformations will be aimed. The synthetic tool that will uncover this unique reactivity consists in the utilization of hypervalent bromines. Indeed bromanes, despite their extreme reactivity, have remained almost totally unexplored compounds due to their arduous synthesis. Accordingly, a challenge of AlCHiMIE is to reveal this unknown family of highly reactive molecules with great potential to be used in original, metal-free C-H functionalization reactions. Moreover, the stereoselective couplings will be achieved by using chiral hypervalent bromines as recyclable mediators. Finally, the high reactivity of newly accessed smart 3d-metal catalysts and hypervalent bromine coupling partners will be combined to reach unprecedented and mild asymmetric C(sp3)-H couplings.