Highly efficient route for enantioselective preparation of chlorohydrins via dynamic kinetic resolution

ORGN 714

Annika Träff, annika@organ.su.se, Krisztián Bogár, Madeleine Warner, and Jan E. Bäckvall, jeb@organ.su.se. Department of Organic Chemistry, Stockholm University, Arrheniuslaboratory, SE-106 91 Stockholm, Sweden

Enantiomerically pure chlorohydrins can be prepared via dynamic kinetic resolution (DKR) by employing ruthenium catalyst 1 for in situ racemization and Pseudomonas cepacia lipase for kinetic resolution. Optically active chlorohydrins are versatile intermediates and can be used as direct precursors in the synthesis of epoxides, β-aminoalcohols, pyrrolidines and functionalized cyclopropanes. Therefore this is an efficient route for the preparation of a variety of enantiomerically enriched compounds.

The DKR developed for this system is applicable on a variety of different β-chloro-aryl-alcohols with both electron-withdrawing and electron-donating groups. Conversions of up to 99% and ee up to >99 % were obtained. A few of the enantiomerically enriched chlorohydrins were transformed to the corresponding epoxides with high isolated yield. The ee was retained during the ring closure.

Scheme 1. Preparation of enantiomerically pure chloroacetates via dynamic kinetic resolution and further ring closure to the corresponding epoxides.