Lithium amide-mediated metalations of ketones and the corresponding N-alkylimines were studied through semiempirical (MNDO) calculations. We explored the influence of lithium amide, solvent, and substrate substituents on the absolute and relative stabilities of the monomer and open dimer transition structures. In general, relief of the high steric demands inherent to the disolvated cyclic dimer reactant structures upon proceeding to the transition structures is the dominant determinant of the activation enthalpies. The results shed light on a number of issues central to lithium amide-mediated metalations including the syn effect observed in imine metalations, E/Z ketone enolization selectivities, the dramatically reduced kinetic acidities of imines relative to ketones, and the role of the chelate effect in Ligand-assisted imine metalations. Acyclic transition structures involving monomer, open dimer, and triple ion amide fragments implicate substantially different properties; however, their relatively high energy precluded detailed discussion.