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

J Am Chem Soc. 2013 Mar 13;135(10):4103-9. doi: 10.1021/ja400345c. Epub 2013 Mar 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aldehydes / chemical synthesis*
  • Aldehydes / chemistry
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Dimerization
  • Ethylenediamines / chemistry*
  • Imines / chemistry*
  • Lithium / chemistry*
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Solubility

Substances

  • Aldehydes
  • Aza Compounds
  • Ethylenediamines
  • Imines
  • Organometallic Compounds
  • N,N,N',N'-tetramethylethylenediamine
  • Lithium