Synthesis of Chiral 1,3-Diamines Derived from cis-2-Benzamidocyclohexanecarboxylic Acid and Their Application in the Cu-Catalyzed Enantioselective Henry Reaction

In this study, 13 different chiral 1,3-diamines were synthesized from (-)-cis-2-benzamidocyclohexanecarboxylic acid. They were successfully applied as ligands in the Cu-catalyzed asymmetric Henry reaction between benzaldehyde and nitromethane. It was confirmed that the enantioselectivity of the product could be controlled by the substituents on the two amino groups. A time-course study revealed a decrease in product enantioselectivity caused by spontaneous retro-Henry reaction, which was suppressed by conducting the reaction at 0 degrees C. This versatile reaction afforded various beta-nitroalcohols in excellent yields and enantioselectivities (up to 98% yield, 91% enantiomeric excess) under the optimized reaction conditions. The chiral induction mechanism was explained on the basis of a previously proposed transition-state model.