Continuous-flow chemoenzymatic enantioselective synthesis of chiral β-nitroalcohols

The synthesis of enantiopure β-nitroalcohols is of great meaningful, but remains highly challenging especially for commercial applications. Herein, we developed a continuous-flow chemoenzymatic system for the enantioselective synthesis of chiral β-nitroalcohols by combing metal-catalyzed non-enantioselective Henry reaction and enzymatic enantioselective kinetic resolution (KR) reaction. A Lewis acidic metal catalyst (Co(II)@DON) for Henry reaction was prepared by immobilizing cobalt ions on dendrimeric organosilica nanoparticle (DON), which exhibited high activity and reusability for production of racemic β-nitroalcohols. A biocatalyst (BCL@DON) for KR reaction with high activity and high enantioselectivity was prepared by immobilizing the lipase from Burkholderia cepacia (BCL) on DON. The integration of these two catalysts in continuous-flow systems produced enantiopure chiral β-nitroalcohols in 37-49% yields and 99% ee, and achieved a 26-fold improvement in space-time yield (STY) compared to the batch system.