Catalytic, Asymmetric Inverse Electron Demand Hetero Diels-Alder Reactions of o-Benzoquinone Derivatives and Ketene Enolates

Abstract

We present an array of [4+2] cycloaddition reactions between ketene enolates, catalytically derived from acid chlorides and cinchona alkaloid nucleophilic catalysts in the presence of stoichiometric base, and o-benzoquinone derivatives. These cycloaddition reactions proceed with excellent stereochemical control (up to >99% ee). In fact, for both the o-benzoquinone imide and the o-benzoquinone diimide manifolds, these Diels-Alder reactions occurred with uniformly >99% ee. The wide scope of this methodology provides access to a diverse range of biologically and synthetically useful chiral products, including ?-hydroxyesters, non-natural ?-amino acids, quinoxalinones, and many others, all with remarkable, catalytic control of regio- and stereochemistry.

Keywords

• Asymmetric catalysis
• Bifunctional catalysis
• [4 2] cycloaddition
• Hetero diels-alder
• Ketene enolates