Enantioselective Michael addition of aldehydes to maleimides organocatalysed by chiral 1,2-diamines: an experimental and theoretical study

Simple and commercially available chiral 1,2-diamines were used as organocatalysts for the enantioselective conjugate addition of aldehydes, including α,α-disubstituted, to maleimides. The reaction was carried out in the presence of hexanedioic acid as an additive in aqueous solvents at room temperature. By employing (1S,2S)- and (1R,2R)-cyclohexane-1,2-diamine as organocatalysts, the corresponding Michael adducts bearing new stereocenters were obtained in high or quantitative yields with enantioselectivities of up to 92%, whereas the use of (1S,2S)-1,2-diphenylethane-1,2-diamine gave a much lower ee. Theoretical calculations were used to justify the observed sense of the stereoinduction.

We thank the financial support from the Spanish Ministerio de Economía y Competitividad (projects CTQ2010-20387, CTQ2010-21263-C02 and Consolider Ingenio 2010, CSD2007-00006), FEDER, the COST Action CM0905 ‘Organocatalysis’, the Generalitat Valenciana (Prometeo/2009/039), the Basque Government (GV Grant IT-291-07) and the Universities of Alicante and the Basque Country.