DFT Study of Brønsted Acid Catalyzed Nitroso Aldol Reaction Between Achiral Enamines and Nitrosobenzene: The Reason for Regio‐ and Enantioselectivity

The regio‐ and enantioselectivity of the nitroso aldol reaction between achiral enamines and nitrosobenzene catalyzed by chiral Brønsted acid catalysts (TADDOL or 1‐naphthylglycolic acid) were investigated in experimental and theoretical studies. The use of a model involving a simple organic acid (MeOH or AcOH) revealed that the reaction was catalyzed by two or more molecules of the organic acid and that the transition‐state structure encompassed several hydrogen bonds. The role of hydrogen bonding in the regioselectivity was also examined carefully. The enantioselectivity in the reaction catalyzed by chiral organic acids ( S , S )‐TADDOL and ( S )‐1‐naphthylglycolic acid was also confirmed through computational study.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)