Novel chiral bis(oxazolines): synthesis and application as ligands in the copper-catalyzed enantioselective conjugate addition of diethylzinc to enones

Novel chiral C2-symmetric bis(oxazolines) were prepared from tartaric acid. They were applied as ligands in the copper-catalyzed conjugate addition of diethylzinc to chalcone and 2-cyclohexenone. Maximum enantiomeric excesses of 50% and 53% were obtained, respectively. The sense of induction was found to depend on the configuration of the stereogenic centre in the oxazoline ring, and not on the stereogenic centres of the 1,4-dioxane backbone.

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(2R,3R,5R,6R)-2,3-Bis[N-(1′S)-(1′-phenyl-2′-hydroxyethyl)-amido]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC26H32N2O8Ee = 100%[α]D23=-12.0 (c 0.70, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,1′S

(2R,3R,5R,6R)-2,3-Bis[N-(1′R)-(1′-phenyl-2′-hydroxyethyl)-amido]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC26H32N2O8Ee = 100%[α]D18=-90.0 (c 0.98, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,1′R

(2R,3R,5R,6R)-2,3-Bis[N-(1′S)-(1′-isopropyl-2′-hydroxyethyl)-amido]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC20H38N2O8Ee = 100%[α]D20=-86.0 (c 0.70, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,1′S

(2R,3R,5R,6R)-2,3-Bis[N-(1′S)-(1′-tert-butyl-2′-hydroxyethyl)-amido]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC22H42N2O8Ee = 100%[α]D22=-70.7 (c 1.03, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,1′S

(2R,3R,5R,6R)-2,3-Bis[(4′S)-phenyloxazolin-2′-yl]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC26H28N2O6Ee = 100%[α]D21=-151.4 (c 1.56, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,4′S

(2R,3R,5R,6R)-2,3-Bis[N-(4′R)-(1′-phenyl-2′-hydroxyethyl)-amido]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC26H28N2O6Ee = 100%[α]D20=-32.6 (c 0.78, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,4′R

(2R,3R,5R,6R)-2,3-Bis[(4′S)-isopropyloxazolin-2′-yl]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC20H34N2O6Ee = 100%[α]D18=-130.4 (c 0.43, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,4′S

(2R,3R,5R,6R)-2,3-Bis[(4′S)-tert-butyloxazolin-2′-yl]-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC22H38N2O6Ee = 100%[α]D28=-161.5 (c 2.08, CHCl3)Source of chirality: tartaric acid, amino acidAbsolute configuration: 2R,3R,5R,6R,4′S