Synthesis of Enantiomerically Pure 5,6‐Dihydropyran‐2‐ones via Chemoenzymatic Sequential DKR‐RCM Reaction

Abstract

The enantiomerically pure 5,6‐dihydropyran‐2‐ones play a crucial role as the building blocks in the synthesis of various bioactive compounds. A new straightforward protocol toward enantiomerically pure 5,6‐dihydropyran‐2‐ones based on enzymatic dynamic kinetic resolution (DKR) resulted in non‐racemic homoallylic crotonates, sequentially combined with ring‐closing metathesis (RCM) was designed. The influence of the reaction conditions on the catalytic behavior of selected hydrolases in the synthesis of non‐racemic homoallylic crotonates was investigated. Under optimized conditions for enzymatic DKR desired homoallylic esters were obtained with high yields and enantiomeric excesses exceeding 99 %. Finally, established enzymatic DKR was successfully combined as a two‐steps sequential procedure with RCM affording target 5,6‐dihydropyran‐2‐ones with high yields up to 75 % and enantiomeric excesses exceeding 99 %.