From Oxygen to Tellurium: The Impact of the Chalcogen on Nucleophilicities and Basicities of Isochalcogenourea Catalysts.

Abstract

Isochalcogenoureas (IChU) embedded in bi- or tricyclic ring systems have proven to be versatile Lewis base/nucleophilic catalysts that activate a wide range of electrophilic substrates for organocatalytic transformations. Ring size, variation of substituents, and the choice of the chalcogen atom affect the efficiency of IChU catalysis in a complex way. To gain a systematic insight into the key parameters that influence reactivity, 14 IChUs covering the fundamental motifs of these structural variations were selected and analyzed by a combination of kinetic, thermodynamic, and quantum-chemical methods. Two previously unknown tricyclic isotellurourea catalysts were synthesized to facilitate a comparison of all naturally abundant chalcogens (O, S, Se, and Te) in the IChU structure. Furthermore, their reactivity on the Mayr nucleophilicity scale as well as their Brønsted and Lewis basicities were determined in polar organic solvents under standardized conditions. Catalyst performance was assessed in two alcohol acylation reactions and in allenoate activation. The low electronegativity of tellurium gave rise to superior nucleophilicity and Lewis basicity of the isotelluroureas when compared to O-, S-, or Se-containing IChUs. Embedding tellurium in IChU structures thus provides a novel handle to influence and fine-tune the effectiveness of IChU organocatalysis.