Enzymatic acetylation of 1a with isopropenyl acetate in the presence of Amano PS lipase in t-BuOMe at 30 C reached nearly 50% conversion after 15 h (monitored by 1 H NMR spectroscopy) (Table , Entry 1). After the chromatographic separation and alkaline hydrolysis of acetate (2S,4R)-3a, both enantiomers (2R,4S)-1a and (2S,4R)-1a were obtained in 84% and 71% yield, respectively, with over 99% ee following recrystallization. Notably, the target products could be obtained on up to 79 g scale in a single run. Being inspired by these results, we have attempted extending the above protocol to other 2-substituted chromanols 1b-q. Compounds 1b-q were obtained by the Kabbe condensation of 2-hydroxyacetophenone (4) and corresponding carbonyl compounds 5a-q (41-99% yield) followed by reduction of chromanones 6a-q with NaBH4 (45-99% yield) (Scheme 3). Products 1b-q were obtained as single cis diastereomers, with 1b-d purified by recrystallization, while the others required no additional purification. Enzymatic acetylation of 1b and 1c at the conditions described above for 1a proceeded slowly, so that 50% conversion was achieved in 144 and 168 h, respectively (Table , Entries 2 and 3). Corresponding enantiopure alcohols were obtained with >99% ee following recrystallization. Apparently, the relative size of the substituent at the C-2 position was crucial for the method efficiency. Indeed, with -branched isopropyl derivative 1d, 62% conversion was achieved in 36 h; furthermore, the enantiomeric excess of product (2S,4S)-1d was only 27% (Table , Entry 4). Replacing Amano PS with Novozym 435 lipase as the catalyst only slightly improved the outcome (36% ee). Obviously, the kinetic resolution method based on the enzymatic acetylation was not suitable for chromanol 1d and (likely) all remaining substrates 1e-q.