Thermodynamics Evaluation of Selective Hydride Reduction for α,β-Unsaturated Carbonyl Compounds

Abstract

The selective reduction of α,β-unsaturated carbonyl compounds is one of the core reactions and also a difficult task for organic synthesis. We have been attempting to study the thermodynamic data of these compounds to create a theoretical basis for organic synthesis and computational chemistry. By electrochemical measurement method and titration calorimetry, in acetonitrile at 298 K, the hydride affinity of two types of unsaturated bonds in α,β-unsaturated carbonyl compounds, their single-electron reduction potential, and the single-electron reduction potential of the corresponding radical intermediate are determined. Their hydrogen atom affinity, along with the hydrogen atom affinity and proton affinity of the corresponding radical anion, is also derived separately based on thermodynamic cycles. The above data are used to establish the corresponding "Molecule ID Card" (Molecule identity card) and analyze the reduction mechanism of unsaturated carbonyl compounds. Primarily, the mixture of any carbonyl hydride ions and Ac-tempo⁺ will stimulate hydride transfer process and create corresponding α,β-unsaturated carbonyl compounds and Ac-tempoH from a thermodynamic point of view.

Keywords: hydride affinity; reduction potential; selective reduction; α; β-unsaturated carbonyl compounds.

Scheme 1

The compounds synthesized in this work.

Scheme 2

The hydride transfer reactions in this work.

Figure 1

Thermodynamic cycles between compounds and hydrogen.

Figure 2

Cyclic voltammetry (CV) and Osteryoung square wave voltammetry (OSWV) of unsaturated ketone A(R = OCH₃) (a) and an anion accepting a hydride anion at position 4 A(R = OCH₃) (b) in deaerated acetonitrile containing 0.1 M n-Bu₄NPF₆ as supporting electrolyte. Solid line: CV graph (sweep rate = 0.1 V/s); dashed line: OSWV graph. The CV values are cathodic peak potentials if the CV figure does not have peaks and troughs. CV and OSWV graphs all have two troughs s or peaks, and one part s is visible.

Figure 3

ITC (Isothermal titration calorimetry) for determining the heat of the reaction between Ac-tempo⁺ClO₄⁻ and BH₄ (R = CH₃) in acetonitrile at 298 K. Titration was conducted by adding 10 μL of Ac-tempo⁺ClO₄⁻(1.1 mM) every 400 s into the acetonitrile containing the BH₄(R=CH₃) (10 mM).

Figure 4

Hydricity of some typical hydride donors to release a hydride anion in acetonitrile.

Scheme 3

Synthesis of saturated ketones.

Figure 5

Cyclic voltammetry (CV) of A, B, and BH₂ (R=CH₃) in deaerated acetonitrile containing 0.1 M n-Bu₄NPF₆ as supporting electrolyte.

Scheme 4

The free radical of an unsaturated carbonyl compound and its conjugate form.

Figure 6

“Molecule ID Card” of ketones and Ac-tempo⁺ and thermodynamic Characteristic Graph (TCG) of the hydride transfer reaction.