Diastereoisomeric Salt Formation and Enzyme-Catalyzed Kinetic Resolution as Complementary Methods for the Chiral Separation of cis-/trans-Enantiomers of 3-Aminocyclohexanol

This contribution demonstrates the preparative-scale synthesis of (1 S,3 S )-3-aminocyclohexanol by either enzymatic kinetic resolution of Cbz-protected 3-aminocyclohexanols or direct diastereoisomeric salt formation with ( R )-mandelic acid. The salt formation demonstrates how a single enantiomer, (1 S,3 S )-3-aminocyclohexanol ( R )-mandelate, can be effectively isolated from the cis / trans racemic mixture and subsequently converted to the free amine, (1 S,3 S )-3-aminocyclohexanol, by ion-exchange chromatography. We have also demonstrated how the other three enantiomers of 3-aminocyclohexanol can be prepared by either diastereoisomeric salt formation or enzymatic kinetic resolution.