Organocerium Additions to Hydrazones: Effects of Reagent Stoichiometry on Efficiency and Selectivity

The effects of reagent stoichiometry on the efficiency and selectivity of organocerium additions to chiral and achiral hydrazones have been investigated. The reagent formed in-situ from 1 equiv of CH₃Li and 0.33 equiv of CeCl₃ adds efficiently (>65% yield) to N,N-dimethylhydrazone 1, but this same reagent reacts only sluggishly with chiral SAMEMP hydrazone 2 (<30% yield). The optimal stoichiometry of the organocerium reagent is 1:1 CH₃Li/CeCl₃, despite the fact that not all of the CeCl₃ is consumed in the transmetalation. At least 2 equiv of methyl nucleophile is required to obtain acceptable yields in additions to 2, suggesting that the auxiliary side chain inhibits the reactivity of the first equivalent of organometallic reagent and that binding of the reagent to one of the hydrazone nitrogen atoms facilitates addition. This hypothesis is supported by the observation that competitive ligands such as amines or alkoxides effectively inhibit the addition of organocerium reagents to 1. The active reagent formed at all mixing stoichiometries is proposed to be a trimethyllanthanide species on the basis of reactivity and the presence of unreacted MCl₃ at less than 3:1 CH₃Li/MCl₃ mixing ratios.