Kinetic resolution of (E)-4-(2′,5′-dimethylphenyl)-but-3-en-2-ol and (E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol through lipase-catalyzed transesterification

Abstract

A short and efficient chemoenzymatic pathway was developed to produce both enantiomeric forms of allyl alcohols possessing a bulky aromatic substituent at the stereogenic center, namely (E)-4-(2′,5′-dimethylphenyl)-but-3-en-2-ol and (E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol. Alcohols were subjected to the lipase-catalyzed transesterification and the lipase from Candida antarctica (CAL-B) proved to be the most effective biocatalyst in the screening experiments showing a high enantiopreference toward (R)-enantiomers. Replacing vinyl propionate with isopropenyl acetate decreased the conversion degree of all lipase-catalyzed transesterifications of (E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol, but in the case of CAL-B and two preparations of Amano Lipase PS, the enantioselectivity was significantly enhanced (E >100). In a preparative-scale reaction of (E)-4-(2′,5′-dimethylphenyl)-but-3-en-2-ol with vinyl propionate catalyzed by CAL-B, unreacted (−)-(S)-alcohol (ee=98%) and (+)-(R)-propionate (ee=98%) were obtained after 2h in yields of 43% and 45%, respectively. The kinetic resolution of (E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol using isopropenyl acetate and CAL-B after 1h gave (−)-(S)-alcohol (ee=99%) and (+)-(R)-acetate (ee=91%) in yields of 44% and 46%, respectively. (+)-(R)-Alcohols were obtained by the hydrolysis of the corresponding esters. Except for (+)-(R,E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol, all enantiomerically enriched compounds were not previously reported. The absolute configurations of their stereogenic centers were assigned by comparison with literature data or based on the Kazlauskas rule. The presented methodology provides straightforward access to valuable building blocks, which can be widely employed in organic synthesis for the production of non-racemic chiral molecules with different biological activities.