Distinguishing the early and late transition states and exploring the validity of σ→σ^∗#, σ#→σ^∗, and σ→π^∗_C=O concepts in diastereoselection from NBO analysis

Abstract

Natural bond orbital (NBO) analysis of several early TSs does not support the σ→σ^∗# hypothesis. The σ→π^∗_C=O interaction controls the carbonyl pyramidalization that, in turn, controls the π-selectivity of a nucleophilic addition. In contrast, late TSs are devoid of σ→π^∗_C=O interactions, and they benefit from σ→σ^∗# interactions that control π-selectivity. The evidence in favor of Anh-Felkin's σ#→σ^∗ hypothesis is weak. The electron-withdrawing σ^C-F in the 2-fluoropropanal-LiCN TS did not align anti to the incipient bond even though there was complete conformational freedom. The initial guess for the TS in which σ^C-F was held anti to σ# optimized to what had lost the said geometrical relationship. Furthermore, in the TS for axial addition of LiCN to 2-ax-F-cyclohexanone, the net σ→σ^∗# interaction was considerably larger than the net σ#→σ^∗ interaction. The relative TS energies require that the equatorial addition of LiCN to 2-ax-F-cyclohexanone be favored over the axial addition in good compliance with the available experimental results.