Doubly stereocontrolled asymmetric Michael addition of acetylacetone to nitroolefins promoted by an isosteviol-derived bifunctional thiourea

A novel class of chiral bifunctional thioureas bearing a chiral lipophilic beyerane scaffold and a tertiary amino group was designed and prepared. The thioureas were proven to be effective for catalyzing the doubly stereocontrolled asymmetric Michael addition between acetylacetone and nitroolefins. The corresponding adducts were obtained in high yields (up to 95%) and with good to excellent enantioselectivities (up to 97%). In addition, the reaction of tert-butyl acetoacetate and trans-β-nitrostyrene also proceeded smoothly with good enantioselectivity.

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1-(Ethyl ent-beyeran-19-oate-16-yl)-3-((1S,2S)-2-(dimethyl amino)cyclohexyl) thioureaC31H53N3O2S[α]D20=-70.8 (c 2.0, CHCl3)Source of chirality: ethyl ent-16β-aminobeyeran-19-oate 1,2-diaminocyclohexaneAbsolute configuration: (4R,8R,10S,13S,16R), (1′S,2′S)

1-(Ethyl ent-beyeran-19-oate-16-yl)-3-((1R,2R)-2-(dimethyl amino)cyclohexyl) thioureaC31H53N3O2S[α]D20=-149.5 (c 2.0, CHCl3)Source of chirality: ethyl ent-16β-aminobeyeran-19-oate 1,2-diaminocyclohexaneAbsolute configuration: (4R,8R,10S,13S,16R), (1′R,2′R)

1-(Ethyl ent-beyeran-19-oate-16-yl)-3-((1S,2S)-2-(N-phthaloyl amino)cyclohexyl) thioureaC37H51N3O4S[α]D20=+12.1 (c 2.0, CHCl3)Source of chirality: ethyl ent-16β-aminobeyeran-19-oate 1,2-diaminocyclohexaneAbsolute configuration: (4R,8R,10S,13S,16R), (1′S, 2′S)