First stereocontrolled acetylation of a hydroxypropargylpiperidone by lipase CALB

Abstract

Hydroxypropargylpiperidones rac- 1– 3 were efficiently obtained by a one-pot three-component coupling reaction; enantioenriched propargylpiperidones were then obtained by a kinetic resolution process using the lipase from Candida antarctica. Lipase CALB has been shown to efficiently catalyse the stereocontrolled acetylation of hydroxypropargylpiperidones rac- 3 by promoting stereodiscrimination at the carbinolic centre. The enzymatic catalytic processes allow the separation of the ( S, R)- and ( S, S)- 3 diastereoisomers into the corresponding acetates produced as a ( R, S)- and ( R, R)- 6 diastereoisomeric pair. The CALB was able to discriminate the stereogenic centre of the secondary ( R) -enantiomer of rac- 3 according to the Kaslauzkas rule. The remote stereogenic centre was not discriminated by the lipase. The functionalised enantioenriched diastereoisomers obtained are important building blocks in organic synthesis.