Azaaldol condensation of a lithium enolate solvated by N,N,N',N'-tetramethylethylenediamine: dimer-based 1,2-addition to imines.

The lithium enolate of tert-amylacetate solvated by N,N,N',N'-tetramethylethylenediamine (TMEDA) is shown to be a doubly chelated dimer. Adding the dimeric enolate to 4-fluorobenzaldehyde-N-phenylimine affords an N-lithiated β-amino ester shown to be monomeric using (6)Li and (15)N NMR spectroscopies. Rate studies using (19)F NMR spectroscopy reveal reaction orders consistent with a transition structure of stoichiometry [(ROLi)2(TMEDA)2(imine)](‡). Density functional theory computations explore several possible dimer-based transition structures with monodentate and bidentate coordination of TMEDA. Supporting rate studies using trans-N,N,N',N'-1,2-tetramethylcyclohexanediamine showing analogous rates and rate law suggest that TMEDA is fully chelated.