Isothiourea-catalysed acylative kinetic resolution of aryl-alkenyl (sp² vs. sp²) substituted secondary alcohols

摘要

The non-enzymatic acylative kinetic resolution of challenging aryl–alkenyl (sp vs. sp) substituted secondary alcohols is described, with effective enantiodiscrimination achieved using the isothiourea organocatalyst HyperBTM (1 mol %) and isobutyric anhydride. The kinetic resolution of a wide range of aryl–alkenyl substituted alcohols has been evaluated, with either electron-rich or naphthyl aryl substituents in combination with an unsubstituted vinyl substituent providing the highest selectivity (=2–1980). The use of this protocol for the gram-scale (2.5 g) kinetic resolution of a model aryl–vinyl (sp vs. sp) substituted secondary alcohol is demonstrated, giving access to >1 g of each of the product enantiomers both in 99:1 .