Candida antarctica lipase‐B‐catalyzed kinetic resolution of 1,3‐dialkyl‐3‐hydroxymethyl oxindoles

Abstract

Candida antarctica (CAL-B) lipase-catalyzed resolution of 1,3-dialkyl-3hydroxymethyl oxindoles has been performed to obtain (R)-1,3-dialkyl-3acetoxymethyl oxindoles with up to 99% ee and (S)-1,3-dialkyl-3-hydroxymethyl oxindoles with up to 78% ee using vinyl acetate as acylating agent and acetonitrile as solvent transforming (S)-3-allyl-3-hydroxymethyl oxindole to (3S)-1 0-benzyl-5-(iodomethyl)-4,5-dihydro-2H-spiro[furan-3,3 0-indolin]-2 0-one. The optically active 3-substituted-3-hydroxymethyl oxindoles and spirooxindoles are among the key synthons in the synthesis of potentially biologically active molecules.

Synthesis of the spiroimine fragment of portimines A and B

“…Work by Chimni and co-workers demonstrated that enzymatic enantioselective acetylation of oxindole intermediates can be effected using an immobilised lipase from Candida antarctica (CALB). 56 Given some structural similarities between 11 and their substrates, we chose the same lipase to effect the resolution. Pleasingly, after screening a series of reaction conditions (see ESI † for details), 57,58 the racemic sample was successfully resolved, affording (−)-11 in 95% ee (determined by chiral HPLC) and 45% isolated yield together with acetate (+)-25.…”