Zirconium-assisted aldol condensation reactions of amido enolates: Structural and kinetic analysis of the reaction of N,N-diphenylacetamide and N,N-diphenylpropionamide enolates with benzaldehyde and p-substituted acetophenones

Article abstract of DOI:10.1021/om00009a012

The deprotonation of N,N-diphenyl amides with LDA and subsequent reaction with [(Cp)₂ZrCl₂] (cp = η⁵-C₅H₅) allowed the enolate complexes [{Ph₂NC(CH₂)O}Zr(cp)₂(Cl)] (5) and [{Ph₂NC(CHCH₃)O}Zr(cp)₂(Cl)] (6) to be isolated. The crystal structure of 6 is reported. Reaction of 5 with [Cr(CO)₅]·THF gave [Ph₂NC{CH₂Cr(CO)₅}{OZr(Cl)(cp)₂}] (7), an O- and C-bonded dimetallic amido enolate. Reaction of 5 and 6 with benzaldehyde gave the corresponding aldol products 8 and 9; according to previous reports, the conversion of 6 into 9 is syn selective. Reaction of 6 with acetophenone followed by addition of silver triflate gave the complex [Ph₂NC(=O)CH(CH₃)C(Me)(Ph)OZr(cp)₂(Cl)(OSO ₂CF₃)] (11) as a diastereoisomeric mixture in the ratio anti:syn = 65:35. The crystal structure of syn-11 is reported. This cyclic complex mimics the postulated cyclic transition state of the aldol reaction mediated by zirconium amide enolates. A kinetic investigation of the reaction of 6 with acetophenone was performed and gave the following activation parameters: ΔH? = 38.3 ± 0.9 kJ mol^-1; ΔS? ≥ -181 ± 3 J mol^-1 K^-1; ΔG?₂₉₈ = 92.2 ± 1.2 kJ mol^-1. A similar study with 4-fluoroacetophenone gave ΔH? = 43.5 ± 1.3 kJ mol^-1, ΔS? ≥ -167 ± 4 J mol^-1 K^-1, and ΔG?₂₉₈ = 93.3 ± 1.8 kJ mol^-1. The reaction rate at 320 K determined with 4-chloro-, 4-methyl-, and 4-nitroacetophenone allowed the determination of a Hammett plot with ρ = 0.41. This value is implicit of a carbon-carbon bond-forming, rate-limiting step.