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. 2004 Aug 11;126(31):9724-34.
doi: 10.1021/ja047794s.

Elucidating the significance of beta-hydride elimination and the dynamic role of acid/base chemistry in a palladium-catalyzed aerobic oxidation of alcohols

Jaime A Mueller  1 , Christopher P Goller, Matthew S Sigman
Affiliations

Elucidating the significance of beta-hydride elimination and the dynamic role of acid/base chemistry in a palladium-catalyzed aerobic oxidation of alcohols

Jaime A Mueller et al. J Am Chem Soc. .

Abstract

The mechanistic details of aerobic alcohol oxidation with catalytic Pd(IiPr)(OAc)(2)(H(2)O) (IiPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) are disclosed. Under optimal conditions, beta-hydride elimination is rate-limiting supported by kinetic studies including a high primary kinetic isotope effect (KIE) value of 5.5 +/- 0.1 and a Hammett rho value of -0.48 +/- 0.04. On the basis of these studies, a late transition state is proposed for beta-hydride elimination, which is further corroborated by theoretical calculations using density functional theory. Additive acetic acid modulates the rates of both the alcohol oxidation sequence and regeneration of the Pd catalyst. With no additive [HOAc], turnover-limiting reprotonation of intermediate palladium peroxo is kinetically competitive with beta-hydride elimination, allowing for reversible oxygenation and decomposition of Pd(0). With additive [HOAc] (>2 mol %), reprotonation of the palladium peroxo is fast and beta-hydride elimination is the single rate-controlling step. This proposal is supported by an apparent decomposition pathway modulated by [HOAc], a change in alcohol concentration dependence, a lack of [O(2)] dependence at high [HOAc], and significant changes in the KIE values at different HOAc concentrations.

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Figures

Figure 1
Figure 1
Optimized alcohol oxidation conditions using catalyst 1.
Figure 2
Figure 2
Ortep representation of 1.
Figure 3
Figure 3
Overlaid 1H NMR spectra from −60 to 0 °C of 1 in CDCl3.
Figure 4
Figure 4
log kobs vs σ for the oxidation of benzylic alcohols at 50 °C. Conditions: 0.5 mol % 1, 0.45 M alcohol, 2 mol % AcOH in benzene, with 3 Å molecular sieves and a balloon charged with O2.
Figure 5
Figure 5
Transition-state model for β-hydride elimination using catalyst 1.
Figure 6
Figure 6
Limiting pathways for β-hydride elimination with 4-coordinate Pd.
Figure 7
Figure 7
Optimized ground-state and transition-state structures for the oxidation of sec-phenylethyl alcohol with catalyst 1 using the B3LYP and the LANL2DZ basis sets.
Figure 8
Figure 8
Translation of the acetate counterion from the ground state to the transition state. Dihedral angles (C1–Pd–O2–C3) of 2C and 2C‡ are 181.1° and 145.1°, respectively.
Figure 9
Figure 9
Eyring plots of benzyl alcohol, sec-phenethyl alcohol, and 2-decanol oxidation using catalyst 1. Conditions: 0.5 mol % 1, 0.45 M alcohol, 2 mol % AcOH in benzene, with 3 Å molecular sieves and a balloon charged with O2, temperature range from 40 to 55 °C.
Figure 10
Figure 10
Rate dependence of sec-phenethyl alcohol oxidation using various HOAc concentrations at 50 °C. Conditions: 0.5 mol % 1, 0.45 M alcohol in benzene, with 3 Å molecular sieves and a balloon charged with O2. The range of [AcOH] is 0–67.5 mM (0–15 mol %).
Figure 11
Figure 11
Inverse first-order rate dependence on [HOAc] for the oxidation of sec-phenethyl alcohol using 1. The plotted range of [AcOH] is from 6.75 to 67.5 mM (from 1.5 to 15 mol %).
Figure 12
Figure 12
Natural logarithm of sec-phenethyl alcohol concentration vs time at various HOAc concentrations at 50 °C (every 10 time points displayed). Conditions: 0.5 mol % 1, 0.45 M alcohol in benzene, with 3 Å molecular sieves and a balloon charged with O2.
Figure 13
Figure 13
log–log plot of the rate of sec-phenethyl alcohol oxidation vs sec-phenethyl alcohol concentration. Conditions: 2.25 mM 1, 0% AcOH in benzene, with 3 Å molecular sieves and a balloon charged with O 2. The range of sec-phenethyl alcohol concentration is from 0.03 to 0.45 M.
Figure 14
Figure 14
Initial rates of the sec-phenethyl alcohol oxidation at 50 °C using various AcOH concentrations and oxygen/nitrogen mixtures. Conditions: 0.5 mol % 1, 0.45 M sec-phenethyl alcohol, with 3 Å molecular sieves and a balloon charged with O2.
Figure 15
Figure 15
Brønsted-type plot of alcohol oxidation with a 2 mol % concentration of the corresponding acid at 50 °C. Conditions: 0.5 mol % Pd catalyst, 0.25 M sec-phenethyl alcohol in benzene, with 3 Å molecular sieves and a balloon charged with O2.
Figure 16
Figure 16
Brønsted-type plot of alcohol oxidation with 0 mol % additive acid at 50 °C. Conditions: 0.5 mol % Pd catalyst, 0.25 M sec-phenethyl alcohol in benzene, with 3 Å molecular sieves and a balloon charged with O2.
Scheme 1
Scheme 1
Design of a New Pd(II) Catalyst for Aerobic Oxidation of Alcohols
Scheme 2
Scheme 2
A Proposed Mechanism for the Pd(II)-Catalyzed Oxidation of Alcohols Using 1
Scheme 3
Scheme 3
An Unlikely Alternative Scenario That May Lead to a Large KIE
Scheme 4
Scheme 4
Revised Proposed Mechanism: Possible Rate-Influencing Steps of Pd-Catalyzed Aerobic Oxidation
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