An expeditious preparation of E-2-amino-5-hydroxyadamantane and its Z-isomer

Reductive amination of 5-hydroxy-2-adamantanone with S-α-methylbenzylamine using 5% Rh–C as the catalyst in the presence of Al(iOPr)3 gave a 3:1 mixture of the E- and Z-5-hydroxy-adamantane-1-phenethylamines. Choice of catalyst, concentration, solvent and the presence of the hydroxyl group on the adamantane influenced the stereoselectivity of the amination reaction. The desired E-isomer could be isolated by fractional crystallization from diisopropyl ether. Debenzylation gave the elusive E-2-amino-5-hydroxyadamantane in a 45% overall yield.