Synthesis And Asymmetric Catalysis Of (1r, 2s)-2-amino-1, 2-diphenylethanol Derivatives

(1R,2S)-2-amino-1,2-diphenylethanol reacted with twelve kinds of prochiral ketones respectively to give the imine intermediates. The novel twelve kinds of chiral aminoalkylphenols were synthesized by stereoselective reducing the imine intermediates with NaBH4. All chiral aminoalkylphenols were obtained in good chemical yields and high d.e. values under mild reaction conditions.Single crystals of (R,S,R)-5b, (R,S,R)-5d, (R,S,R)-5e and (R,S,R)-5f crystallized from n-hexane/ethyl acetate solvate, and their structures were determined by X-ray diffraction. The absolute configuration of their new stereogenic center was determined to be R configuration, from which absolute configurations of chiral ligand (R,S,R)-4a~l were inferred. By calculating the total energy of the transition state with RM1 semi-empirical method, the absolute configuration of the new stereogenic center can also be inferred.The catalytic activity of the aminoalkylphenols was examined for the addition of diethyl malonate to cyclohexenone, resulting in moderate to good enantioselectivities (15.3~65.9%e.e.) and high yields (61.7~87.5%). The effective factors such as reaction time, the amounts of chiral catalyst and reaction temperature were studied in this paper. It was also found that the enantioselectivity of the reaction was effected mainly by chiral catalyst and the aryl substituents on the substrate.Structures of all the products prepared in this paper were confirmed by IR, 1HNMR and element analysis.