Mechanistic Studies of the Lithium Enolate of 4-Fluoroacetophenone: Rapid-Injection NMR Study of Enolate Formation, Dynamics, and Aldol Reactivity

Lithium enolates are widely used nucleophiles with a complicated and only partially understood solution chemistry. Deprotonation of 4-fluoroacetophenone in THF with lithium diisopropylamide occurs through direct reaction of the amide dimer to yield a mixed enolate-amide dimer (3), then an enolate homodimer (1-Li)2, and finally an enolate tetramer (1-Li)4, the equilibrium structure. Aldol reactions of both the metastable dimer and the stable tetramer of the enolate were investigated. Each reacted directly with the aldehyde to give a mixed enolate-aldolate aggregate, with the dimer only about 20 times as reactive as the tetramer at −120 °C.