Lithiation selectivity in monoalkylamine/dialkylamine mixtures: A synthetic and ab initio molecular orbital study

Reaction of (BuLi)-Bu-n with a 1:1 mixture of diisopropylamine or tetramethylpiperidine and a simple alkylamine (RNH2)-N-1 (R-1 = Bu-n, Bu-s, Bu-t, (n)Pe, 1-Me-Bu-n, 1,2-Me-Pr-n, or 1,3-Me-Bu-n), under thermodynamic conditions, results in the exclusive isolation of lithium primary amides: no solid lithium secondary amides are isolated. Preformation of the lithium secondary amides followed by addition of the primary amine leads to complete transamination, to give a lithium primary amide. Ab initio molecular orbital calculations at the HF/6-31G* level show that the order of gas-phase Bronsted acidity increases in the sequence NH3 < RNH2 ( R2NH (R = Me, Pr-i, or tBu), but the relative stability of the lithium amides, as measured by anion exchange reactions, is in the order R2NLi < RN(H)Li. This reverse is due, in part, to a decrease in steric crowding surrounding the nitrogen and an increase in electrostatic stabilization, resulting in shorter Li-N bond distances. Solvation of the monomeric lithium primary or secondary amides with the corresponding primary or secondary amine, R2NLi.H2NR or RN(H)Li.HNR2, leads to anion exchange being essentially thermoneutral. Consideration of increasing aggregation (dimer, trimer, tetrameric ring, cubane, prismatic hexamer, and prismatic octamer) of the lithium primary amide MeN(H)Li results in a relative increase in stability. The possibility of forming aggregates or polymers with each lithium bridging three anionic centers is the main driving force for primary amine lithiation in the systems studied. The bulk of the secondary amides used limits their aggregation to being either rings or primary amine solvated dimers. By considering the effects of solvation, sterics, aggregation, and electronics in combination, a rationalization for selectivity preference can be achieved.