Bond Energies of Enamines

Energetics of reactive intermediates underlies their reactivity. The availability of these data provides a rational basis for understanding and predicting a chemical reaction. We reported here a comprehensive computational study on the energetics of enamine intermediates that are fundamental in carbonyl chemistry. Accurate density functional theory (DFT) calculations were performed to determine the bond energies of enamines and their derived radical intermediates. These efforts led to the compilation of a database of enamine energetics including a thermodynamic index such as free-energy stability, bond dissociation energy (BDE), and acid dissociation constant (pK _a) as well as a kinetic index such as nucleophilicity and electrophilicity. These data were validated by relating to experimentally determined parameters and their relevance and utility were discussed in the context of modern enamine catalysis. It was found that pK _a values of enamine radical cations correlated well with redox potentials of their parent enamines, the former could be used to rationalize the proton-transfer behavior of enamine radical cations. An analysis of the BDE of enamine radical cations indicated that these species underwent facile β-C-H hydrogen transfer, in line with the known oxidative enamine catalysis. The enamine energetics offers the possibility of a systematic evaluation of the reactivities of enamines and related radicals, which would provide useful guidance in exploring new enamine transformations.