Stereoselective synthesis of optically active cyclic α- and β-amino esters through lipase-catalyzed transesterification or interesterification processes

A series of cyclic α- and β-amino esters belonging to a family of indolines and quinolines have been efficiently synthesized to study their behavior in lipase-mediated kinetic resolution reactions. The influence of the fused ring structure to the benzene ring and the position of the ester functionality relative to the amino group have been demonstrated, finding excellent values of enantiodiscrimination in the transesterification reaction of methyl indoline-3-carboxylate with n-butanol catalyzed by Candida antarctica lipase B being observed. On the other hand, low to moderate selectivities have been found when using a wide panel of lipases toward methyl indoline-2-carboxylate or 1,2,3,4-tetrahydroquinoline derivatives in alkoxycarbonylation, transesterification or interesterification reactions.

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(R)-(−)-Methyl indoline-2-carboxylateC10H11NO2Ee >99% (HPLC, Chiralcel OD)[α]D20=-47.3 (c 0.28, CH2Cl2)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (R)

(R)-(−)-Methyl indoline-3-carboxylateC10H11NO2Ee >99% (HPLC, Chiralcel OJ-H)[α]D20=-94.7 (c 0.88, CH2Cl2)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (R)

(S)-(+)-Butyl indoline-3-carboxylateC13H17NO2Ee >99% (HPLC, Chiralcel OJ-H)[α]D20=+78.3 (c 0.60, CH2Cl2)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (S)