Enantioselective acylation of rac-2-phenylcycloalkanamines catalyzed by lipases

The kinetic resolution of some 2-phenylcycloalkanamines was performed by means of aminolysis reactions catalyzed by lipases, with Kazlauskas’ rule being obeyed in all cases. The size of the ring and the stereochemistry of the stereogenic centers of the amines had a strong influence on both the enantiomeric ratio and the reaction rate of these aminolysis processes. Lipase B from Candida antarctica (CAL-B) showed excellent enantioselectivities toward trans-2-phenylcyclohexanamine in a variety of reaction conditions (E >150), whereas lipase A from C. antarctica (CAL-A) was the best catalyst for the acylation of cis-2-phenylcyclohexanamine (E = 34) and trans-2-phenylcyclopropanamine (E = 9).

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(1R,2S)-N-(2-Phenylcyclohexyl)methoxyacetamideC15H21NO2Ee = 96% (HPLC, Chiralcel-OD)[α]D20 = +27.4 (c 0.87, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 1R,2S

(1R,2R)-N-(2-Phenylcyclohexyl)methoxyacetamideC15H21NO2Ee = 55% (HPLC, Chiralcel-OD)[α]D20 = −22.9 (c 0.60, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 1R,2R

(1R,2S)-N-(2-Phenylcyclopropyl)acetamideC11H13NOEe = 69% (HPLC, Chiralcel-OD)[α]D20 = −76.2 (c 0.66, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 1R,2S