Enantioselective Organocatalytic Direct Michael Addition of Nitroalkanes to Nitroalkenes Promoted by a Unique Bifunctional DMAP-Thiourea

A new catalyst is designed, synthesized, and evaluated for the asymmetric Michael addition of nitroalkanes to nitroalkenes. The obdurate nature of this reaction has made this a formidable challenge to subdue by asymmetric catalysis. The catalyst design includes a thiourea function to activate the nitroalkene by a double H-bond and a 4-dimethylaminopyridine unit to deprotonate the nitroalkane and to bind the resulting nitronate anion also by a double H-bond. The chiral scaffold for the catalyst is 2,2′-diamino-1,1′-binaphthalene (BINAM), and a bis-conjugate is prepared by the attachment of the thiourea unit and the dimethylaminopyridine moiety (DMAP) via the two amino groups. The resulting catalyst will effect the reaction of nitroalkanes to a variety of nitrostyrenes and gives excellent asymmetric inductions (91−95% ee) over a range of 10 substrates. Remarkably, the asymmetric induction increases with decreasing catalyst loading with the optimal compromise between rate and induction at a loading of 2 mol %.