Enantioselective synthesis of 3,5,6-substituted dihydropyranones and dihydropyridinones using isothiourea-mediated catalysis

Abstract

The scope of dihydropyranone and dihydropyridinone products accessible by isothiourea-catalysed processes has been expanded and explored through the use of 2-N-tosyliminoacrylates and 2-aroylacrylates in a Michael addition-lactonisation/lactamisation cascade. Notably, in order to ensure reproducibility it is essential to use homoanhydrides as ammonium enolate precursors with 2-aroyl acrylates, while carboxylic acids can be used with 2-N-tosyliminoacrylates, delivering a range of 3,5,6-substituted dihydropyranones and dihydropyridinones with high enantioselectivity (typically >90% ee). The derivatisation of the heterocyclic core of a model 3,5,6-substituted dihydropyranone through hydrogenation is also reported.