Group 13 ion coordination to pyridyl breaks the reduction potential vs. hydricity scaling relationship for dihydropyridinates

Abstract

The relationship E_pvs. ΔG_H- correlates the applied potential (E_p) needed to drive organohydride formation with the strength of the hydride donor that is formed: in the absence of kinetic effects E_pvs. ΔG_H- should be linear but it would be more energy efficient if E_p could be shifted anodically using kinetic effects. Biological hydride transfers (HT) performed by cofactors including NADH and lactate racemase do occur at low potentials and functional modeling of those processes could lead to low energy HT reactions in electrosynthesis and to accurate models for cofactor chemistry. Herein we probe the influence of N-alkylation or N-metallation on ΔG_H- for dihydropyridinates (DHP^-) and on E_p of the DHP^- precursors. We synthesized a series of DHP^- complexes of the form (pz₂^HP^-)E via hydride transfer from their respective [(pz₂P)E]⁺ forms where E = AlCl₂⁺, GaCl₂⁺ or Me⁺. Relative ΔG_H- for the (pz₂^HP^-)E series all fall within 1 kcal mol^-1, and ΔG_H- for (pz₂^HP)CH₃ was approximated as 47.5 ± 2.5 kcal mol^-1 in MeCN solution. Plots of E_pvs. ΔG_H- including [(pz₂P)E]⁺ suggest kinetic effects shift E_p anodically by ∼215 mV.

Scheme 1. (Left) Outline of electron and proton steps to generic cationic hydride precursor, D⁺, leading to hydride formation of a general hydride donor D–H and subsequent HT to substrate. (Right) Line drawing of NAD⁺, NADH and dihydropyridinate, DHP. A = Adenine dinucleotide.

Scheme 2. Interconversion of (pz₂P)E⁺ with (pz₂HP⁻)E via HT, where E = AlCl₂⁺, GaCl₂⁺, and CH₃⁺.

Scheme 3. Syntheses of 1H, 2H and 3H.

Fig. 1. Solid state structures of 1H (top left) and 3H (top right) and pz₂P atom naming convention used throughout (bottom). Blue, light blue, green, gray ellipsoids, and white circles represent N, Ga, Cl, C, and H atoms, respectively. H atoms except C_p–H omitted for clarity. The thermal ellipsoids are shown at 30% probability.

Chart 1. 1,4-DHPs and benzimidazoles discussed in the text and their reported hydricities in MeCN.

Scheme 4. HT equilibria between 1-GaCl₄ and 2H, and 4-AlCl₄ and 2H. Counter ions omitted for clarity.

Fig. 2. Plot of E_pvs. ΔG_H– for benzimidazoles (circles), 1,4-DHPs (triangles) 2⁺ and those previously published and complexe 1⁺. Black outlines around markers represent experimentally determined ΔG_H– values, green markers indicate computational ΔG_H– values and red markers corresponds to compounds reported herein. The figure key displays R² values for linear fits to: 1,4-DHPs with experimentally determined ΔG_H– values (dashed grey line). 1,4-DHPs with computationally determined ΔG_H– values (dashed green line), 1,4-DHPs and benzimidazoles with computationally determined ΔG_H– values (solid green line), and benzimidazoles with computationally determined ΔG_H– values (dotted green line).4⁺ is not included on the plot since it is not stable in MeCN.