Asymmetric Synthesis of 1,2-Diamino-4,5-dimethylcyclohexanes by Zirconium-Catalyzed and -Promoted Reductive Cyclization Reactions

The asymmetric synthesis of 1,2-diamino-4,5-dimethylcyclohexanes was achieved by the zirconium-catalyzed and -promoted reductive cyclization of N,N‘-di[(S)-1-phenylethyl]-4(R),5(R)-diamino-1,7-octadiene. The reaction of the diene with 5 equiv of butylmagnesium chloride and 0.1 mol % of bis(cyclopentadienyl)zirconium dichloride in diethyl ether at 0−20 °C gave mainly the 1(R),2(R)-diamino-4(S),5(S)-dimethylcyclohexane derivative having C₂ symmetry, but the reaction with 4 equiv of dibutylzirconocene in tetrahydrofuran at −78 to −50 °C gave prevalently the diastereomer with the 4(R),5(S) configuration. By reductive cleavage of the auxiliary, followed by sulfonylation reaction, 1(R),2(R)-di(4-toluenesulfonyl)amino)-4(S),5(S)-dimethylcyclohexane was prepared.