Azaaldol Condensation of a Lithium Enolate Solvated by N,N,N′,N′-Tetramethylethylenediamine: Dimer-Based 1,2-Addition to Imines

• Published in: Journal of the American Chemical Society Vol. 135; no. 10; pp. 4103 - 4109
• Main Authors: De Vries, Timothy S, Bruneau, Angela M, Liou, Lara R, Subramanian, Hariharaputhiran, Collum, David B
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.03.2013; Amer Chemical Soc
• Subjects: Aldehydes - chemical synthesis; Aldehydes - chemistry; Aza Compounds - chemical synthesis; Aza Compounds - chemistry; Chemistry; Chemistry, Multidisciplinary; Dimerization; Ethylenediamines - chemistry; Imines - chemistry; Lithium - chemistry; Molecular Structure; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Physical Sciences; Science & Technology; Solubility; CLAISEN ACYLATION REACTIONS; ASYMMETRIC-SYNTHESIS; METHYL 3,3-DIMETHYLBUTANOATE; ANIONIC-POLYMERIZATION; DEGENERATE TRANSESTERIFICATION; AB-INITIO; CRYSTAL-STRUCTURES; N-BUTYLLITHIUM; ALKYLATION KINETICS; SOLID-STATE
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja400345c

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 6Li and 15N NMR spectroscopies. Rate studies using 19F 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.