Microscale Synthesis of Chiral Alcohols via Asymmetric Catalytic Transfer Hydrogenation

Abstract

Synthesis of pure enantiomers is a key issue in industry, especially in areas connected to life sciences. Catalytic asymmetric synthesis has emerged as a powerful and practical tool. Here we describe an experiment on racemic reduction and asymmetric reduction via a catalytic hydrogen transfer process. Acetophenone and substituted acetophenones are reduced by NaBH4 either in the presence or in the absence of β-cyclodextrin, and by isopropanol in the presence of a rhodium catalyst with cyclopentadienyl and 1-amino-2-indanol ligands. After analysis by chiral gas chromatography, enantiomeric excess, conversion, and turnover frequency can be calculated. This experiment is suitable for upper-level undergraduate students. The experiment can be completed in a four hour laboratory session. It can also be extended in many ways: the influence of parameters such as reaction time; catalyst or substrate concentration; or temperature or catalyst type can be analyzed.