Efficient and recyclable catalysts based on simple chiral N1-alkyl, N2-arylmethyl diamines in the Cu-catalyzed asymmetric Henry reactions

Abstract

A class of (1R,2R)-N1-alkyl, N2-(4-chlorobenzyl)cyclohexane-1,2-diamines (4) were designed and synthesized. They were used to form the corresponding copper(II) complexes, 4-Cu(OAc)2, as chiral catalysts in the asymmetric Henry reaction of benzaldehyde and nitromethane, in which the desired product was obtained with a good yield (up to 99%) and up to 96% ee. The optimized catalyst, 4g-Cu(OAc)2, was also found efficient in the asymmetric Henry reaction between different aldehydes (aromatic aldehydes or aliphatic aldehydes) and nitromethane. Upon scaling up to gram quantities, the β-nitroalcohol was obtained in good yield (91%) with excellent selectivities (93% ee). The recycled catalyst, 4g-Cu(OAc)2, worked well up to three catalytic runs with marginal loss in yield and the enantioselectivity of the product was retained. It is believed that this procedure provides an opportunity to facilely synthesize large amounts of enantiomerically enriched β-nitroalcohol. A possible catalytic transition state for the asymmetric Henry reactions with our catalyst was suggested.