Highly Enantioselective Michael Addition Of Ketones To Nitroolefins Promoted By Chiral Glycosyl Thiourea

Organocatalysis has become an important protocol in the field of asymmetric catalysis. Among these organocatlysts, chiral thiourea is a outstanding bifunctional catalyst for many reactions.Michael addition is one of most important carbon-carbon bond-forming reactions in organic synthesis. Over the past decades highly enantioselective Michael addition attracts lots of attention. In the context, asymmetric addition of ketone to trans-nitroolefin is involved in synthesis of many natural products. Chiral thiourea bearing primary amine group is ideal catalyst which can dually activate both ketone and olefin.A series of chiral primary amine-thiourea were synthesized from commercially, non-toxic carbohydrates through three-easy handle-step. These catalysts were screened in addition of ketone to trans-nitroolefin. Different parameters were tested to disclose the appropriate catalyst loading, solvent, temperature, additive et al. Thiourea based on 1, 2-cyclohexanediamine promoted the aryl ketones addition to trans -nitroolefin with up to 99% yield and 98% ee. Thiourea prepared from 1, 2-diphenylethane -1, 2-diamine gave excellent results in catalyzing cyclic ketones Michael addition nitroolefins.Under the optimized condition, 35 adducts were separated and all new products were characterized by NMR, IR, MS and HRMS. The thiourea 4a was applied to X-ray analysis. The presumed transition state was rationalized by the crystalline structure of the thiourea.