Enantioselective cyanosilylation of aldehydes catalysed by a diastereomeric mixture of atropisomeric thioureas

New bifunctional atropisomeric thioureas 1 were synthesised and tested as both a mixture of diastereomers (aR/aS)-(R,R)-1 and as single diastereomers (aR)-(R,R)-1 and (aR)-(S,S)-1, in the organocatalysed, enantioselective, cyanosilylation of a range of aldehydes (aromatic and aliphatic). Moderate enantiomeric excesses (up to 69% ee) and quantitative yields were obtained. The best results were achieved using a mixture of thiourea diastereomers (aR/aS)-(R,R)-1 instead of the single diastereomers alone.

Figure optionsDownload as PowerPoint slide

(aR)-1-((1R,2R)-Dimethylamino-cyclohexyl)-3-[2-(4-methyl-2-thioxo-thiazol-3-yl)-phenyl]-thioureaC19H26N4S3[α]D22=-485.0 (c 1.0, CHCl3)Source of chirality: (aR)-3-(2-isothiocyanato-phenyl)-4-methyl-thiazoline-2-thione and (1R,2R)-1-amino-2-(dimethylamino)cyclohexaneAbsolute configuration: (aR,1R,2R)

(aR)-1-((1S,2S)-Dimethylamino-cyclohexyl)-3-[2-(4-methyl-2-thioxo-thiazol-3-yl)-phenyl]-thioureaC19H26N4S3[α]D22=-358.0 (c 1.0, CHCl3)Source of chirality: (aR)-3-(2-isothiocyanato-phenyl)-4-methyl-thiazoline-2-thione and (1S,2S)-1-amino-2-(dimethylamino)cyclohexaneAbsolute configuration: (aR,1S,2S)

(aR/aS)-1-((1R,2R)-Dimethylamino-cyclohexyl)-3-[2-(4-methyl-2-thioxo-thiazol-3-yl)-phenyl]-thioureaC19H26N4S3[α]D22=-18.5 (c 1.0, CHCl3)Source of chirality: (aR/aS)-3-(2-isothiocyanato-phenyl)-4-methyl-thiazoline-2-thione and (1R,2R)-1-amino-2-(dimethylamino)cyclohexaneAbsolute configuration: (aR/aS,1R,2R)

(aR)-3-(2-Isothiocyanato-phenyl)-4-methyl-thiazoline-2-thioneC11H8N2S3[α]D23=-20.1 (c 0.5, CHCl3)Source of chirality: (aR)-3-(2-aminophenyl)-4-methyl-thiazoline-2-thioneAbsolute configuration: (aR)

(aR)-3-(2-Aminophenyl)-4-methyl-thiazoline-2-thioneC10H10N2S2[α]D25=-397.0 (c 0.5, CHCl3)Source of chirality: separation by semi-preparative chiral HPLCAbsolute configuration: (aR)