Computer-Aided Insight into the Relative Stability of EnaminesThe 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).
Received: 10 July 2017
Accepted after revision: 23 August 2017
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.
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