Improved Asymmetric SNAr Reaction of β-Dicarbonyl Compounds Catalyzed by Quaternary Ammonium Salts Derived from Cinchona Alkaloids

The scope and limitation of the asymmetric nucleophilic aromatic substitution reaction of α-substituted 1,3-dicarbonyl compounds and activated aromatic systems catalyzed by N-benzyl-O-benzoylcinchoninium or cinchonidinium salts are presented. Several novel O-benzoylcinchona alkaloid derived salts have been prepared and evaluated as catalysts in this reaction, which can proceed with enantioselectivites up to 96% ee. Various 1,3-dicarbonyl compounds and activated aromatic systems are evaluated for the aromatic nucleophilic substitution reaction, and it has been found that the yield and enantioselectivity are very dependent on the substrate and reagent. The scope of the functionalization of the products to, e.g., spiro-oxoindole, a ring-opening reaction of 1,3 α,α-disubstituted dicarbonyl compounds with several nucleophiles, and the diastereoselective reduction of the keto functionality in the optically active SNAr product are reported.