Isothiourea-Catalysed Acylative Kinetic Resolution of Aryl-Alkenyl (sp(2) vs. sp(2)) Substituted Secondary Alcohols

摘要

The non-enzymatic acylative kinetic resolution of challenging aryl-alkenyl (sp(2) vs. sp(2)) 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 (S = 2-1980). The use of this protocol for the gram-scale (2.5 g) kinetic resolution of a model aryl-vinyl (sp(2) vs. sp(2)) substituted secondary alcohol is demonstrated, giving access to > 1 g of each of the product enantiomers both in 99:1 e.r.