Synthesis of Optically Active syn- and anti-Chlorohydrins through a Bienzymatic Reductive Cascade

A bienzymatic cascade has been designed and optimized to obtain enantiopure chlorohydrins starting from the corresponding 1-aryl-2-chlorobut-2-en-1-ones. For the synthesis of these alpha-chloroenones, a two-step sequence was developed consisting of the allylation of the corresponding aldehyde with 3-dichloroprop-1-ene, followed by oxidation and further isomer-ization. The selective cooperative catalytic system involving ene-reductases (EREDs) and alcohol dehydrogenases (ADHs) afforded the desired optically active chlorohydrins under mild reaction conditions in excellent conversions (up to >99%) and selectivities (up to >99:1 diastereomeric ratio (dr), >99% enantiomeric excess (ee)).

Automated summary

In this study, a bienzymatic cascade was developed and optimized to efficiently synthesize enantiopure chlorohydrins. The reaction showed high conversion and selectivity under mild conditions.