RESUMEN
A convenient trans-selective one-pot synthesis of tetrafunctionalized 2-imidazolines is described. Our approach to these valuable heterocyclic scaffolds involves a formal 1,3-dipolar cycloaddition between nitrile ylides or nitrilium triflates and imines. A detailed experimental study in combination with a high-level computational exploration of reaction routes reveals a plausible reaction pathway that accounts for the observed diastereoselectivity.
Asunto(s)
Compuestos Heterocíclicos/química , Imidazoles/síntesis química , Imidazolinas/síntesis química , Nitrilos/química , Catálisis , Cristalografía por Rayos X , Reacción de Cicloadición , Imidazoles/química , Imidazolinas/química , Estructura Molecular , EstereoisomerismoRESUMEN
We combine multicomponent reactions, catalytic performance studies and predictive modelling to find transfer hydrogenation catalysts. An initial set of 18 ruthenium-carbene complexes were synthesized and screened in the transfer hydrogenation of furfural to furfurol with isopropyl alcohol complexes gave varied yields, from 62% up to >99.9%, with no obvious structure/activity correlations. Control experiments proved that the carbene ligand remains coordinated to the ruthenium centre throughout the reaction. Deuterium-labelling studies showed a secondary isotope effect (k(H):k(D)=1.5). Further mechanistic studies showed that this transfer hydrogenation follows the so-called monohydride pathway. Using these data, we built a predictive model for 13 of the catalysts, based on 2D and 3D molecular descriptors. We tested and validated the model using the remaining five catalysts (cross-validation, R(2)=0.913). Then, with this model, the conversion and selectivity were predicted for four completely new ruthenium-carbene complexes. These four catalysts were then synthesized and tested. The results were within 3% of the model's predictions, demonstrating the validity and value of predictive modelling in catalyst optimization.