Diastereo- and enantioselective synthesis of densely functionalized cyclohexanones via double Michael addition of curcumins with nitroalkenes

The asymmetric double Michael additions of curcumins to nitroalkenes to afford highly functionalized cyclohexanones have been carried out for the first time. A combination of a dihydrocinchonine-thiourea organocatalyst and K2CO3 was found to be the most effective in obtaining the desired cyclohexanones in good yield, diastereoselectivity and enantioselectivity.

Figure optionsDownload as PowerPoint slide

3,5-Bis(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanoneC30H29NO7[α]D18=-41.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

3-(3,4-Dimethoxyphenyl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanoneC31H31NO8[α]D19=-49.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(4-Methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-(3,4,5-trimethoxyphenyl)cyclohexanoneC32H33NO9[α]D19=-47.6 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

3-(Benzo[d][1,3]dioxol-5-yl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanoneC30H27NO8[α]D18=-91.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(4-Methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-(p-tolyl)cyclohexanoneC30H29NO6[α]D21=-50.7 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(4-Methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryoloyl)-4-nitro-3-phenylcyclohexanoneC29H27NO6[α]D21=-55.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

3-(4-Chlorophenyl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanoneC29H26NO6Cl[α]D21=-104.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

3-(4-Bromophenyl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanoneC29H26NO6Br[α]D21=-112.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

3-(3-Bromophenyl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanoneC29H26NO6Br[α]D19=-79.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(4-Methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-(2-nitrophenyl)cyclohexanoneC29H26N2O8[α]D19=+5.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(4-Methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-(3-nitrophenyl)cyclohexanoneC29H26N2O8[α]D19=-18.6 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

3-(Furan-2-yl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanoneC27H25NO7[α]D19=-71.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(4-Methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-(thiophen-2-yl)cyclohexanoneC27H25NO6S[α]D18=-77.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-2-((E)-3-(3,4-dimethoxyphenyl)acryloyl)-4-nitrocyclohexanoneC32H33NO9[α]D25=-44.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

3-(4-Methoxyphenyl)-4-nitro-5-phenyl-2-((E)-3-phenylacryloyl)cyclohexanoneC28H25NO5[α]D25=-40.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd

5-(Furan-2-yl)-2-((E)-3-(furan-2-yl)-acryloyl)-3-(4-methoxyphenyl)-4-nitrocyclohexanoneC24H21NO7[α]D25=-26.6 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: nd