Abstract

Venerable aldol, Michael, and Mannich reactions have undergone a renaissance in the past fifteen years, as a consequence of the development of direct organocatalytic versions, mediated by chiral amines. Chiral enamines are key intermediates in these reactions. This review focuses on the formation of enamines from secondary amines and their relative thermodynamic stability, as well as on the reverse reactions (hydrolysis). Experimental results and predictions based on MO calculations are reviewed to show which enamine forms may predominate in the reaction medium and to compare several secondary amines as organocatalysts. 1 Introduction 2 Relative Stability of Enamines as Determined Experimentally 3 Pyrrolidine Enamines 4 Enamines of the Jorgensen-Hayashi Catalyst 5 Proline Enamines 6 Free Enthalpies and Polar Solvent Effects 7 Comparison of Organocatalysts 8 Summary and Outlook 9 Appendix