Chemoenzymatic Synthesis of Optically Active cis ‐ and trans ‐2‐(1 H ‐Imidazol‐1‐yl)cycloalkanamines

The preparation of enantiopure 2‐(1 H ‐imidazol‐1‐yl)cycloalkanamines has been studied by independent chemoenzymatic approaches. We first explored a route involving the enzymatic resolution of racemic cycloalkanol analogs for the preparation of the corresponding optically active amines by diverse substitution methodologies including (a) the formation of a mesylated intermediate that could be later substituted by an amine group and (b) the combination of Mitsunobu inversion of the hydroxy group followed by a deprotection step. In order to overcome low isolated yields of the desired optically active amines, racemic‐ trans ‐2‐(1 H ‐imidazol‐1‐yl)cycloalkanamines were prepared, and their lipase‐catalyzed enzymatic resolutions were studied. These efforts revealed that lipase from Candida antarctica type B was an efficient biocatalyst. A combination of both chemoenzymatic methodologies has allowed us to obtain the four different enantiopure cis ‐ and trans ‐(1 H ‐imidazol‐1‐yl)cycloalkanamine isomers.