Chemoenzymatic synthesis of (S)-Pindolol using lipases

[Display omitted] •A straightforward chemoenzymatic synthesis of (S)-Pindolol has been developed.•The key step involved kinetic lipase-mediated resolution of a haloydrin acetate via hydrolytic process.•P. fluorescens was a robust biocatalyst and afforded the halohydrin acetate as chiral intermediate with 97% ee.•The use of THF as co-solvent was essential for a high enantioselectivity kinetic resolution process (E>200). A straightforward chemoenzymatic synthesis of (S)-Pindolol has been developed. The key step involved the enzymatic kinetic resolution of rac-2-acetoxy-1-(1H-indol-4-yloxy)-3-chloropropane with lipase from Pseudomonas fluorescens via hydrolytic process to obtain enantiomerically enriched halohydrin (2S)-1-(1H-indol-4-yloxy)-3-chloro-2-propanol (96% ee) and (2R)-2-acetoxy-1-(1H-indol-4-yloxy)-3-chloropropane (97% ee). The latter was subjected to a hydrolysis reaction catalyzed by Candida rugosa leading to (2R)-1-(1H-indol-4-yloxy)-3-chloro-2-propanol (97% ee), followed by a reaction with isopropylamine, producing (S)-Pindolol (97% ee) in quantitative yield.