First chemoenzymatic synthesis of (R)- and (S)-1-(9H-fluoren-9-yl)ethanol

A simple chemoenzymatic synthesis of 1-(9H-fluoren-9-yl)ethanol stereoisomers is described. The enantiomers were resolved by a kinetically controlled transesterification with vinyl acetate in the presence of commercially available lipases. High-throughput screening and subsequent exhaustive investigation of the utility of the lipases in a stereoselective process of introducing chirality have been carried out. Lipase A from Candida antarctica as a cross-linked aggregate (CAL-A-CLEA) was the most efficient enzyme for the resolution of the title compound providing (S)-1-(9H-fluoren-9-yl)ethanol and its (R)-acetate in enantiopure form (>99% ee). Under mild reaction conditions, excellent enantioselectivity (E = 407), and good isolated yields of the products were obtained.

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(S)-(−)-1-(9H-Fluoren-9-yl)ethanolC15H14O>99% ee[α]D25=-43.2 (c 1.6, CHCl3)Chiral HPLC: >99% eeSource of chirality: Enzymatic kinetic resolutionAbsolute configuration: (S)

(R)-(+)-1-(9H-Fluoren-9-yl)ethyl acetateC17H16O2>99% ee[α]D25=+54.7 (c 2.34, CHCl3)Chiral HPLC: >99% eeSource of chirality: Enzymatic kinetic resolutionAbsolute configuration: (R)