On the mechanism of the palladium-catalyzed tert-butylhydroperoxide-mediated Wacker-type oxidation of alkenes using quinoline-2-oxazoline ligands

Abstract

The mechanism of the tert-butylhydroperoxide-mediated, Pd(Quinox)-catalyzed Wacker-type oxidation was investigated to evaluate the hypothesis that a selective catalyst-controlled oxidation could be achieved by rendering the palladium coordinatively saturated using a bidentate amine ligand. The unique role of the Quinox ligand framework was probed via systematic ligand modifications. The modified ligands were evaluated through quantitative Hammett analysis, which supports a "push-pull" relationship between the electronically asymmetric quinoline and oxazoline ligand modules.

Figure 1

a) Proximal Lewis-basic groups proposed to chelate to palladium resulting in mixtures of products. b) Oxypalladation may occur through a hydrogen bonding network of three water molecules. c) Hypothesized coordinatively saturated palladium complex with anionic tert-butylperoxide ligand.

Figure 2

a) Previously reported oxidation of styrenes using TBHP as the terminal oxidant. b) Reaction performed with anhydrous TBHP and ¹⁸OH₂ shows the rate of ¹⁸O incorporation in the product under reaction conditions is the same as the rate of washing ¹⁸O into the product via hydrate formation. Use of α-deuterostyrene shows that the hydrogen atoms in the substrate are maintained in the product.

Figure 3

a) Evaluation of bidentate amine ligands for the TBHP-mediated Wacker-type oxidation. b) Summary of substrate scope.

Figure 4

Initial rates to determine dependencies a) Conditions: [Pd(Quinox)Cl₂] = 0 to 5 × 10^-3 M; [AgSbF₆] = 2.5 × [Pd(Quinox)Cl₂]; aqueous [TBHP] = 1.2 M; [alkene] = 0.05 M; CH₂Cl₂; rt. b) Conditions: [Pd(Quinox)Cl₂] = 2 × 10^-3 M; [AgSbF₆] = 5 × 10^-3 M; aqueous [TBHP] = 3.0 M; [alkene] = 0 to 0.2 M; CH₂Cl₂; rt. c) Conditions: [Pd(Quinox)Cl₂] = 2 × 10^-3 M; [AgSbF₆] = 5 × 10^-3 M; anhydrous [TBHP] = 0 to 1.80 M; [H₂O] = 2.5 M; [alkene] = 0.045 M; CH₂Cl₂; rt. d) Conditions: [Pd(Quinox)Cl₂] = 2 × 10^-3 M; [AgSbF₆] = 5 × 10^-3 M; anhydrous [TBHP] = 1.2 M; [H₂O] = 0.3 – 4.0 M; [alkene] = 0.05 M; CH₂Cl₂; rt.

Figure 5

a) Plot of the log of the rate as a function of counterion conjugate acid pKa. b) Evaluation of inhibitor concentration on initial rate of reaction.

Figure 6

a) Proposed coordination model of the penultimate intermediate prior to oxypalladation. b) Alternative possible coordination model of the penultimate intermediate prior to oxypalladation.

Figure 7

Hammett analysis of electronically disparate styrenes. For 4-methoxystyrene the σ_ρ⁺ value provides a good linear fit, which is a nearly identical fit to a plot with that substrate omitted. The σ_ρ value for 4-methoxystryrene is also plotted to highlight its deviation from linearity.

Figure 8

a) Linear free energy relationship observed for plotting the log(rate) for a series of 4-substituted quinox ligands 8a-d as a function of Hammett σ_p values. b) Linear free energy relationship observed for plotting the log(rate) for a series of ligands 16a-d as a function of Hammett σ_p values

Scheme 1

Mechanism proposed by Mimoun.

Scheme 2

Possible mechanisms.

Scheme 3

Synthesis of Quinoline-2-oxazole 2 and Quinoline-2-(5,5-dimethyloxazoline) 3.

Scheme 4

Synthesis of 4-substituted quinox ligands.

Scheme 5

Stille cross-coupling preparation of 4-quinoline-2-(4-pyridyl) ligands.