Chemoenzymatic Asymmetric Synthesis of Complex Heterocycles: Dihydrobenzoxazinones and Dihydroquinoxalinones

Abstract

(2-hydroxyphenyl)-l-aspartic acids with excellent enantiomeric excess (ee up to >99%). This biocatalytic hydroamination step was combined with an acid-catalyzed esterification-cyclization sequence to convert the enzymatically generated noncanonical amino acids into the desired dihydrobenzoxazinones in good overall yield (up to 63%) and high optical purity (ee up to >99%). By means of a similar one-pot, two-step chemoenzymatic approach, enantioenriched dihydroquinoxalinones (ee up to >99%) were prepared in good overall yield (up to 78%) using water as solvent for both steps. These chemoenzymatic methodologies offer attractive alternative routes to challenging dihydrobenzoxazinones and dihydroquinoxalinones, starting from simple and commercially available achiral building blocks.