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

The deprotonation of N,N-diphenyl amides with LDA and subsequent reaction with [(cp)(2)ZrCl2] (cp = eta(5)-C5H5) allowed the enolate complexes [{Ph(2)NC(CH2)O}Zr(cp)(2)(Cl)] (5) and [{Ph(2)NC(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 [Ph(2)NC{CH2Cr(CO)(5)}{OZr(Cl)(cp)(2)}] (7), an 0- 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 [Ph(2)NC(=O)CH(CH3)C(Me)(Ph)OZr(cp)(2)(Cl)(OSO2CF3)] (11) as a diastereoisomeric mixture in the ratio anti:syn = 65:35. The crystal structure of sym-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: Delta H-double dagger = 38.3 +/- 0.9 kJ mol(-1); Delta S-double dagger greater than or equal to -181 +/- 3 J mol(-1) K-1; Delta G(298)(double dagger) = 92.2 +/- 1.2 kJ mol(-1). A similar study with 4-fluoroacetophenone gave Delta H-double dagger = 43.5 +/- 1.3 kJ mol(-1), Delta S-double dagger greater than or equal to -167 +/- 4 J mol(-1) K-1, and Delta G(298)(double dagger) = 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 rho = 0.41. This value is implicit of a carbon-carbon bond-forming, rate-limiting step.