Proline–calixarene thiourea host–guest complex catalyzed enantioselective aldol reactions: from nonpolar solvents to the presence of water

A proline–calix[4]arene thiourea host–guest complex catalyzed intermolecular aldol reaction of aromatic aldehydes with cyclohexanone has been developed. The anti-configured products were obtained in good yields and with high enantioselectivities. The reaction is proposed to work via a modified Houk–List model, where the carboxylate part of the proline constitutes as a supramolecular system with the thiourea. The outcome of the study indicates the influence of the calix[4]arene thiourea on both the reactivity and selectivity in a non-polar reaction medium, even in the presence of water at moderate temperatures.

Figure optionsDownload as PowerPoint slide

(S)-2-[(R)-Hydroxy(4-nitrophenyl)methyl]cyclohexanoneC13H15NO4[α]Drt=+11.5 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)

(S)-2-((R)-(4-Bromophenyl)(hydroxy)methyl)cyclohexanoneC13H15BrO2[α]Drt=+11.5 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)

4-((R)-Hydroxy((S)-2-oxocyclohexyl)methyl)benzonitrileC14H15NO2[α]Drt=+19.2 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,4R)

(S)-2-((R)-Hydroxy(4-(trifluoromethyl)phenyl)methyl)cyclohexanoneC14H15F3O2[α]Drt=+2.3 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)

(S)-2-((R)-Hydroxy(3-(trifluoromethyl)phenyl)methyl)cyclohexanoneC14H15F3O2[α]Drt=+10.2 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)

(S)-2-((R)-Hydroxy(3-(nitrophenyl)methyl)cyclohexanoneC13H15NO4[α]Drt=+38.4 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)

(S)-2-((R)-(2-Bromophenyl)(hydroxy)methyl)cyclohexanoneC13H15BrO2[α]Drt=+20.2 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)

(S)-2-((R)-(2-Fluorophenyl)(hydroxy)methyl)cyclohexanoneC13H15FO2[α]Drt=+20.8 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)

(S)-2-((R)-Hydroxy(4-methoxyphenyl)methyl)cyclohexan-1-oneC14H18O3[α]Drt=+26.3 (c 1.0, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)