An effective approach to the enantiomers of alicyclic β-aminonitriles by using lipase catalysis

Lipase-catalyzed N-acylations of racemic cis- and trans-2-aminocyclopentane- (and cyclohexane-) carbonitriles with 2,2,2-trifluoethyl butanoate in tert-butyl methyl ether (TBME) and in room-temperature ionic liquids (RTILs) were studied. The racemates were effectively resolved (E >200) on a preparative scale by lipase PS-C II (lipase from Burkholderia cepacia) in TBME, resulting in two enantiomers in their enantiopure forms at 50% conversion. The reactions in RTILs with Novozym 435 (Candida antarctica lipase B) were slow and proceeded with low enantioselectivity.

Graphical abstractRacemic alicyclic β-aminonitriles were resolved through lipase-catalyzed asymmetric N-acylation at the 2R stereocenter.Figure optionsDownload full-size imageDownload as PowerPoint slide

(1S,2R)-cis-N-Butanoyl-2-amino-cyclopentanecarbonitrileC10H16N2OEe = 98% (by GC on CP-Chirasil-Dex CB column)[α]D25=127.5 (c 0.53, MeOH)Source of chirality: lipase PS-C II-catalyzed N-acylationAbsolute configuration: 1S,2R

(1S,2R)-cis-N-Butanoyl-2-amino-cyclohexanecarbonitrileC11H18N2OEe = 96% (by GC on CP-Chirasil-Dex CB column)[α]D25=+98.7 (c 0.5, MeOH)Source of chirality: lipase PS-C II-catalyzed N-acylationAbsolute configuration: 1S,2R

(1R,2R)-cis-N-Butanoyl-2-amino-cyclopentanecarbonitrileC10H16N2OEe >99% (by GC on CP-Chirasil-Dex CB column)[α]D25=-44.2 (c 0.5, MeOH)Source of chirality: lipase PS-C II-catalyzed N-acylationAbsolute configuration: 1R,2R

(1R,2R)-cis-N-Butanoyl-2-amino-cyclohexanecarbonitrileC11H18N2OEe >99% (by GC on CP-Chirasil-Dex CB column)[α]D25=-6.7 (c 0.5, MeOH)Source of chirality: lipase PS-C II-catalyzed N-acylationAbsolute configuration: 1R,2R