Project ELDORADO was subdivided into three work packages focusing on 1,n-difunctionalizations (n ≥ 2) and asymmetric transformations of alkenes, including the design of chiral π-acidic catalysts, oxidative vinylations and allenylations of heteroatomic nucleophiles, and semipinacol reactions including the application in the synthesis of biologically active molecules. Key idea was to demonstrate that non-aromatic carbon–carbon π-bonds can be exploited as highly versatile building blocks in catalytic, photo-aerobic functionalization reactions. We intended to showcase the high expedience of this methodological concept through the selective formation of frequent and representative bonding motifs such as carbon–carbon, carbon–nitrogen, carbon–oxygen, and carbon–sulfur bonds. Prognostic outcomes of WPI revolve around the design of a new family of chiral selenium catalysts being employed, for instance, in asymmetric, photo-aerobic allylic functionalizations (ACS Catal. 2023, 13, 16240-16248; ACS Catal. 2024, 14, 9586-9593). Enantioselective photoredox catalytic reactions are still posing immense challenges to modern method-oriented research. Concretely, when looking at asymmetric photoredox catalysis in its current state, most protocols are predicated on the covalent or noncovalent binding of the photocatalysts or a co-catalysts to heteroatomic binding sites (e.g. possessing O- or N-atoms) within the substrates. In most cases, these coordinating groups are of no other use than directing the action of the catalysts, which can entail laborious operations for the removal of these directing groups. In addition, simple alkenes that are void of such heteroatomic binding sites were not sufficiently investigated in the context of such enantioselective reactions. During the ERC project, we were able to show that non-directed alkenes are indeed suitable substrates for asymmetric photo-aerobic functionalizations, as is exemplified, e.g. in enantioselective migratory Tsuji-Wacker oxidations and some total syntheses of biologically active compounds.
On the basis of mechanistic investigations, we were also able to develop oxidative allenylations (Eur. J. Org. Chem. 2021, 1720-1725), vinylations (ACS Catal. 2024, 14, 9586-9593), and photo-aerobic aminocyclizations (ACS Catal. 2023, 13, 16240-16248; ChemSusChem 2024, e202301518). The latter study included the first example of highly sought-after catalytic 5-endo-trig cyclizations to access 3-pyrroline derivatives, which are structurally related to important, pharmaceutically active agents. We could further elucidate the decisive role of H-bond interactions of selenium acceptors in photoredox catalytic semipinacol reactions (Angew. Chem. Int. Ed. 2022, e202208611, WPIII). The prevailing notion of such interactions prior to our study was that they are too feeble in nature to be of any significance in chemical reactions. This perception could be refuted by showing that they can be directive, e.g. in modulating the nucleofugality of selenium(III) species.
