Sodium Borohydride Goes With The Flow

Sodium borohydride has been a go-to reagent for carrying out selective reductions of aldehydes and ketones to alcohols for 60 years. But in a new development involving the old standard, a research team led by Kerry Gilmore and Peter H. Seeberger of the Max Planck Institute of Colloids & Interfaces have used solid NaBH₄ mixed with LiCl and the filtration medium Celite (diatomaceous earth) to carry out reductions in a flow reactor system (Org. Process Res. Dev. 2014, DOI: 10.1021/op500310s). The development offers a continuous, gram-scale process that matches the reaction efficiency of batch methods. The work stems from an earlier effort by Seeberger’s group to find an inexpensive way to reduce artemisinin during the synthesis of the antimalarial drugs artesunate, artemether, and artemotil. Seeberger cofounded the company ArtemiFlow to commercialize a flow-through reaction system to produce the drugs. After using NaBH₄ in one step of the artemisinin flow synthesis, the researchers realized it might be useful for other continuous reductions. In the new report, they describe using a NaBH₄ column for reductions of a variety of aldehydes and ketones to alcohols as well as reductions of in situ-generated imines to form amines.