Regioselective Allylic Alkene Amination by Photo-Aerobic Selenium-π-Acid Multicatalysis

The aim of this thesis was the development of regioselective protocols for the inter- and intramolecular oxidative allylic amination of simple alkenes with exogenous N-nucleophiles, not derived from the oxidant. The transformation was proposed to be accomplished by a dual catalytic system consisting of a photoredox catalyst and a selenium-π-acid, which previously proved to be highly applicable in the allylic functionalisation with O-nucleophiles by the group of Breder. The first project involved the intramolecular allylic amination of sulfonamides and the successful expansion of the scope from five-membered heterocycles to six-membered heterocycles. The role of disulfide was elucidated by mechanistic investigations involving upon others quenching experiments and electrochemical investigations. It was found that the disulfide exhibits a dual function during the reaction, for once serving as an electron hole shuttle, promoting the formation of the (PhSe)₂ radical cation, which itself engages in the interaction with the double bond. Secondly, (4-ClPhS)₂ is proposed to form an interchalcogen species with the selenoaminated intermediate, which enables a faster elimination step. Both functions are suggested to enhance the reaction rate and increase the product yield. In a further study, the method could be expanded to an enantioselective variant using newly developed chiral selenium spiro catalysts. The second project involved the intermolecular allylic amination of simple alkenes with sulfonamides. A lot of effort was put into the optimisation of the reaction, which led to the development of a stable protocol for the transformation. First reported method with the usage of exogenous nucleophiles with Se-π-acid catalysis. Lastly, a highly regioselective intermolecular process for the allylic amination of alkenes with azoles was developed. The broad substrate scope proved high functional group tolerance. The application of alkenes with different connectivity such as 1,2- 1,1,2- and terminal olefins all lead to a highly selective outcome of the favoured allylic amines versus the vinylic regioisomer. Compared to classical thermal Pd-catalysed protocols, the developed method was able to transform internal alkenes in high regioselectivity. Unsummetrically substituted olefins lead to the formation of the respective Markovnikov products, which complements previous allylic amination protocols via photocatalysis, which afforded the anti-Markovnikov products. The applicability of the developed protocol was demonstrated by successful late-stage functionalisation of drug analogs and natural products derivatisation. Efforts towards the further development of an enantioselective variant were conducted. Simple amines were successfully transformed with spiro selenium catalysts developed by the Breder group, with a high enantiomeric excess of up to 84% and an isolated yield of up to 30%.