Organocatalysis with cationic chalcogen bond donors

• Applicant: Professor Dr. Stefan Huber
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 457341038

Even though chalcogen-bonding-based non-covalent organocatalysis is a comparably novel field of research, several studies have by now demonstrated proof-of-principle cases of this concept. The respective catalysts were structurally quite different and were based on neutral polyfluorinated compounds, chalkogen-containing heteroaromatics or (poly)cationic backbones. Next to SN1 substrates, imines as well as carbonyl and nitro derivatives could be successfully activated as well. However, all previously reported catalysts were achiral. In this project, chalcogen-bonding-based organocatalysis will be further developed. In the first subproject, known achiral catalysts will be employed to:a) conduct mechanistic studies of known catalyses via the analyses of reaction kinetics.b) determine the effect of various parameters on the Lewis acidity of catalysts via systematic ITC- or NMR-titrations.c) extend this catalysis concept continuously toward further substrate classes and reactions.d) study the regioselectivity in the activation of bifunctional substrates.In the second subproject, chiral chalogen bond donors will be developed for the first time and will be used in enantioselective transformations. All catalysts will be based on achiral dicationic backbones established by our group, but now chiral substituents will be introduced at the chalcogen centers. In this context, annelated ring systems will in particular be utilized to provide rigid chiral structures. Suitable bidentate catalysts will then be employed in potentially enantioselective reactions which have already been activated by achiral chalcogen bond donors. In the third subproject, novel mixed Lewis acids with a halogen- and chalcogen-bonding donor motif each will be synthesized. The primary focus will be on studies toward the cooperativity of both Lewis acidic centers, especially in comparison with the respective „pure“ bidentate variants. In the mid-term, both donor centers will be fixed in space via hindered rotation in a fashion which will generate atropisomers with intrinsic chirality. These unprecedented chiral Lewis acids will then also be used for asymmetric induction. By the further advancements in this projects, chalcogen-bonding-based non-covalent organocatalysts shall be established as „soft“ alternatives to hydrogen bond donors in the long term. First studies indicate already that the Lewis acidity of chalcogen-based catalysts is apparently superior to the one of comparable hydrogen- or halogen-bond-donors. In addition, the existence of a second substituent on the chalcogen center makes this interaction seem particularly predestined for chiral structures.

• DFG Programme: Research Grants