Tetramisole-Based Organocatalyst for the Kinetic Resolution of Alcohols

Significance

Several benzylic and allylic secondary alcohols (rac-3) could be resolved with selectivity factors up to 355 (s = 200 corresponds to 98% ee at 40% conversion) to the corresponding enantiomerically pure alcohols 3 and esters 4, employing commercially available tetramisole 1 or its derivative 2 (BTM - Benzotetramisole) with a catalyst loading between 4 mol% and 10 mol% at 0 °C in a reasonable timescale (1-48 h). Due to moisture sensitivity of the reaction mixture it was neces­sary to add Na₂SO₄ to give higher levels of conversion. The tetramisole derivative 2 could be easily synthesized from 2-chloro-benzothiazole and (S)-2-amino-2-phenylethanol in two steps (81% overall yield). This catalyst is somehow more active than 1 but gives the same high selectivity. This has been explained by the fewer steric hindrance (no hydrogen on the thiazole ring) and π-stacking of the benzene moiety.