Imidazolidinethiones: underexplored organocatalysts that show promise in catalyzing prebiotic and modern organic reactions
As elements in metal-based catalysis are becoming increasingly high risk, organocatalysts represent versatile, green, and robust catalysts as effective alternatives. Imidazolidine-4-thiones are 5-membered thioamide heterocycles with a secondary amine at ring position 1, which have structural similarity to imidazolidinones, successfully used as chiral organocatalysts. However, unlike imidazolidinones and proline-based catalysts, imidazolidinethiones are underexplored and underutilized as catalysts in organic reactions, their catalytic cycle is not proven, and the relative intermediates involved in the cycle have not been isolated to date. Earlier in 2020, imidazolidinethiones have been demonstrated by the Trapp group as suitable catalysts in the alkylation of aldehydes in prebiotic media, and they show promise as organocatalysts in modern organic reactions. In this project, I will investigate the reactivity of relevant intermediates in the organocatalytic cycle, that is, the enamines and iminium ions derived from the imidazolidinethiones and enolizable and non-enolizable aldehydes, respectively. The reactivity of imidazolidine-4-thione derived enamines and iminium ions will be quantified by kinetic measurements and results will embedded in the comprehensive Mayr reactivity scales. Experimental kinetic data will be acquired by applying photometric methods, which cover different timescales from conventional UV-vis spectroscopy to follow slow reactions via stopped-flow techniques to laser flash photolysis for reactions close to diffusion control, which proceed within nanoseconds. This fellowship will shed light on the unproven catalytic cycle and provide a quantitative basis for the future exploitation of this underutilized class of catalysts. Furthermore, I will develop skills in physical organic chemistry using quantitative structure-reactivity relationships and time resolved spectroscopy, while also refining soft skills such as leadership and teaching.