Enantioselective catalytic synthesis of ethyl mandelate derivatives using Rh(I)–NHC catalysts and organoboron reagents

Herein we describe for the first time the enantioselective catalytic arylation of ethyl glyoxalate using phenylboron reagents and chiral rhodium(I)–NHC catalysts. KOtBu was the base of choice, along with tert-amyl alcohol as the solvent. A novel chiral bis-imidazolium salt was synthesized and evaluated for the first time in this catalytic transformation. Although moderate enantioselectivities (up to 34% ee) were obtained for the phenylation reaction, despite the excellent yields, very low enantioselectivities were obtained using other arylboronic acids with a variety of chiral rhodium(I)–NHC catalysts.

Figure optionsDownload as PowerPoint slide

3,3′-(((2R,3R,5R,6R)-5,6-Dimethoxy-5,6-dimethyl-1,4-dioxane-2,3-diyl)bis(methylene))bis(1-benzyl-1H-imidazol-3-ium) chlorideC30H38Cl2N4O4[α]D23=-94.8 (c 0.62, CHCl3)Source of chirality: chiral poolAbsolute configuration: (2R,3R,5R,6R)