Activating Pronucleophiles with High pKa Values: Chiral Organo-Superbases

Abstract

Direct deprotonation represents an extremely simple, straightforward, and atom-economic strategy to activate pronucleophiles bearing an acidic proton. However, the difficulty often arises in activating pronucleophiles with high pK_a values by using conventional chiral tertiary amines. To overcome this challenge, a handful of novel chiral Brønsted superbases, including amidines, guanidines, cyclopropenimines, and iminophosphoranes, have been discovered in recent years. This minireview focuses on the application of these organo-superbases in the catalytic asymmetric reactions of weakly acidic pronucleophiles, and highlights their comparison to the conventional tertiary amines, demonstrating the highly efficient deprotonation processes and stereoselectivity controlled conversions of the superbases. The advantage of these new superbases brings a great opportunity for developing more asymmetric transformations of weakly acidic pronucleophiles.

Keywords: Brønsted bases; acidity; organocatalysis; superbases; synthetic methods.