DOI: 10.1055/s-0036-1590909
short review
© Georg Thieme Verlag Stuttgart · New York

Computer-Aided Insight into the Relative Stability of Enamines

Alejandro Castro-Alvarez, Héctor Carneros, Anna M Costa, Jaume Vilarrasa*
  • Organic Chemistry Section, Facultat de Química, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Catalonia, Spain   Email:
The authors acknowledge the Spanish Government for financial support (CTQ2015-71506R, FEDER). A.C.A. is grateful to Fundació Privada Cellex de Barcelona for a fellowship. H.C. has a studentship of the Spanish Government (CTQ2012-39230, FEDER).
Further Information

Publication History

Received: 10 July 2017

Accepted after revision: 23 August 2017

Publication Date:
04 October 2017 (eFirst)

Dedicated to Pere Mir, in memoriam


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 Jørgensen–Hayashi Catalyst

5 Proline Enamines

6 Free Enthalpies and Polar Solvent Effects

7 Comparison of Organocatalysts

8 Summary and Outlook

9 Appendix