Lipase-catalyzed kinetic and dynamic kinetic resolution of 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid

A dynamic kinetic resolution method for the preparation of enantiopure 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (R)-2 was developed involving the CAL-B-catalyzed enantioselective hydrolysis of the corresponding ethyl ester (±)-1 in toluene/acetonitrile (4:1) containing 1 equiv of added water and 0.25 equiv of dipropylamine. This method allowed the preparation of (R)-2 (ee = 96%) with 80% isolated yield. The kinetic resolution of (±)-1 in diisopropyl ether at 3 °C afforded both enantiomers with ee ⩾92%.

Kinetic (KR) and dynamic kinetic resolution (DKR) of (±)-1 has been performed through hydrolysis in organic solvents in the presence of Candida antarctica lipase B.Figure optionsDownload as PowerPoint slide

(R)-1,2,3,4-Tetrahydroisoquinoline-1-carboxylic acidC10H11NO2Ee = 96%[α]D25=-63.1 (c 1, 1 mol dm−3 HCl)[α]D25=+18.8 (c 2, 1 mol dm−3 NaOH)Source of chirality: enzyme-catalyzed resolution with lipase B from Candida antarcticaAbsolute configuration: (R)

(S)-1-(Ethoxycarbonyl)-1,2,3,4-tetrahydroisoquinolinium 2,4,6-trinitrophenolateC18H18N4O9Ee = 92%[α]D25=-28.2 (c 0.5, CHCl3)[α]D25=-30.2 (c 0.5, toluene)Source of chirality: enzyme-catalyzed resolution with lipase B from Candida antarcticaAbsolute configuration: (S)