Enantioselective Michael Addition of Aromatic Ketones to Nitroolefins Catalyzed by Bifunctional Thioureas and Mechanistic Insight

A highly enantioselective Michael reaction of aromatic ketones with nitroolefins was accomplished in the presence of a chiral bifunctional primary amine-thiourea catalyst and 4-nitrobenzoic acid as the co-catalyst; the corresponding adducts were obtained in excellent enantioselectivities (up to 99%ee) and yields (up to 98%). The catalytic mechanism of the Michael reaction was confirmed through the ESI-MS detection of proposed reaction inter-mediates and the H-1 NMR detection of hydrogen bonding between thiourea and the nitroolefins. DFT calculations showed that chiral moieties of the thiourea impacted the yields and enantioselectivities of the adducts remarkably, which corresponds to the observed experimental results.