Analysis of the effect of the number of α-oxygen and α-fluorine atoms on the nucleophilicity of amines relative to a carbonyl substrate

The dependence of the nucleophilicity of methoxyamines and fluoroamines on the number of heteroatomic substituents is a function of the electron-withdrawing properties of the α-heteroatoms which are manifest in opposite effects: On one hand, the stabilization of the initially formed zwitterion increases due to coulombic attraction of the nonbonded amine nitrogen atom and carbonyl substrate oxygen atom, while, on the other hand, the zwitterion is destabilized due to weakening of the N-C bond between the nucleophile and the substrate. The destabilization of the N-C bond predominates in methoxyamines, leading to a steady decrease in nucleophilicity with increasing number of methoxy groups. Both factors are significant in fluoroamines and thus the nucleophilicity decreases in the following series: F₂NH > FHNH₂ > F₃N.