Asymmetric Synthesis of β-Hydroxyphosphonates via a Chemoenzymatic Cascade.

Abstract

Chiral β-hydroxyphosphonates are essential building blocks for organophosphorus compounds. However, the asymmetric synthesis of these units remains a significant challenge. Herein, we describe a one-pot chemoenzymatic cascade process to access chiral β-hydroxyphosphonates, which combines photo-oxidative chemical reactions and bioreductions. The incorporation of photooxidation in the chemical reaction resulted in up to 92% yield and >99% enantiomeric excess (ee) of β-hydroxyphosphonates in the cascade. In addition, the scale-up of diethyl (S)-(2-hydroxy-2-phenylethyl)phosphonate demonstrates the potential application of this strategy.