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 tetrameth ylpiperidine 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 condition s, results in the exclusive isolation of lithium primary amides: no solid l ithium secondary amides are isolated. Preformation of the lithium secondary amides followed by addition of the primary amine leads to complete transam ination, to give a lithium primary amide. Ab initio molecular orbital calcu lations at the HF/6-31G* level show that the order of gas-phase Bronsted ac idity increases in the sequence NH3 < RNH2 ( R2NH (R = Me, Pr-i, or tBu), b ut the relative stability of the lithium amides, as measured by anion excha nge reactions, is in the order R2NLi < RN(H)Li. This reverse is due, in par t, to a decrease in steric crowding surrounding the nitrogen and an increas e in electrostatic stabilization, resulting in shorter Li-N bond distances. Solvation of the monomeric lithium primary or secondary amides with the co rresponding primary or secondary amine, R2NLi.H2NR or RN(H)Li.HNR2, leads t o anion exchange being essentially thermoneutral. Consideration of increasi ng aggregation (dimer, trimer, tetrameric ring, cubane, prismatic hexamer, and prismatic octamer) of the lithium primary amide MeN(H)Li results in a r elative increase in stability. The possibility of forming aggregates or pol ymers 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 pri mary amine solvated dimers. By considering the effects of solvation, steric s, aggregation, and electronics in combination, a rationalization for selec tivity preference can be achieved.