Shaping Chirality via Stereoselective, Organocatalytic [4+2] Cycloadditions involving Heterocyclic ortho-Quinodimethanes.

Polycyclic compounds bearing a complex heterocyclic core such as an aromatic heterocycle "fused" with one or more functionalized rings, are widespread leading molecules in the domain of synthetic organic chemistry and pharmaceuticals. Although many synthetic methodologies have been devised to access achiral, fused heteroaromatic scaffolds, or related chiral variants adorned with out-of-cycle stereogenic elements, equally efficient strategies to afford chiral heterocycles featuring in-cycle stereocenters, exist to a lesser extent and presently represent a growing field of investigation. The mild, organocatalytic generation of elusive ortho-quinodimethane intermediates (oQDMs), derived from suitable heteroaromatic carbonyl- or carbonyl-like pronucleophiles has recently proved successful in the synthesis of such peculiar chiral architectures via stereoselective [4+2] cycloadditions. This review provides an overview of the most important advances attained in this field over the last decade.

Turning the Imidazole Core into Three-Dimensional Ring Systems: Mild Organocatalytic Entry to Enantiopure 6,7-Dihydrobenzimidazoles.

Organocatalytic asymmetric transformation of common aromatic heterocycles via in situ formation of highly reactive dearomatized ortho-quinodimethane diene species and subsequent [4+2] cycloaddition with suitable dienophiles has become a powerful tool to enter cyclohexane-fused heterocycles. Most of these reactions were previously applied to benzo-fused heterocycles or poorly aromatic rings. Herein, we disclose how previously intractable aromatic imidazole rings, equipped with removable methylidene malononitrile activating handle, could be involved as competent cycloaddends with ß-aryl enals in efficient eliminative [4+2] cycloadditions under mild organocatalytic conditions. This method allowed the efficient and direct preparation of scantly represented 6,7-dihydrobenzo[d]imidazoles with optimal enantio- and regioselectivities. Post-cycloaddition chemical editing provided imidazole-based ring systems with diverse oxidation state and functional groups.

Photochemical organocatalytic enantioselective radical γ-functionalization of α-branched enals.

Reported herein is a rare example of asymmetric catalytic functionalisation of enals at the remote γ-position, proceeding via a radical path. The process requires visible light and exploits the synergistic actions of two distinct organocatalysts. A nucleophilic organic catalyst generates radicals upon SN2-based activation of commercially available alkyl halides and blue light irradiation. Concomitantly, a chiral secondary amine catalyst triggers the formation of a dienamine from α-branched enals. This chiral dienamine intercepts the photogenerated radicals with excellent γ-selectivity and good stereocontrol.