Enzymatic kinetic resolution is a very efficient method for the multigram synthesis of enantioenriched cis-2-(hetera)cyclo)alkylsubstituted chroman-4-ols. The substituent(s) at the C-2 position had a crucial impact on the enzymatic reaction rate (that decreased with increasing the substituent size) and defined the choice of the most appropriate protocol. In particular, for n-alkylsubstituted derivatives, enzymatic acetylation catalyzed by Amano PS lipase was very efficient, and the target (2R,4S) and (2S,4R) enantiomers were obtained with over 96% ee. For the with -branched substituents isopropyl or (hetera)cycloalkyl) as well as 2,2-disubstituted counterparts, PLEcatalyzed enzymatic hydrolysis of pre-synthesized acetates should be used. In this way, (2R,4R) / (R) and (2S,4S) / (S) enantiomers were synthesized with 77-99% ee. Notably, both protocols were amenable to the multigram preparation of the target enantioenriched chromanols (up to 120 g in a single run). The synthetic utility of the synthesized intermediates was demonstrated by the Mitsunobu configuration inversion, this enabling access to all possible stereoisomers of 2-(hetera)cyclo)alkylsubstituted chroman-4-ols. In addition to that, their transformation into enantioenriched primary aminesvaluable sp 3enriched O-heterocyclic building blocks for drug discoverywas performed.