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

The relationship Epvs. ΔGH– correlates the applied potential (Ep) needed to drive organohydride formation with the strength of the hydride donor that is formed: in the absence of kinetic effects Epvs. ΔGH– should be linear but it would be more energy efficient if Ep 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 ΔGH– for dihydropyridinates (DHP−) and on Ep of the DHP− precursors. We synthesized a series of DHP− complexes of the form (pz2HP−)E via hydride transfer from their respective [(pz2P)E]+ forms where E = AlCl2+, GaCl2+ or Me+. Relative ΔGH– for the (pz2HP−)E series all fall within 1 kcal mol−1, and ΔGH– for (pz2HP)CH3 was approximated as 47.5 ± 2.5 kcal mol−1 in MeCN solution. Plots of Epvs. ΔGH– including [(pz2P)E]+ suggest kinetic effects shift Ep anodically by ∼215 mV.


Calculations
Calculation S1: General determination of species concentration during equilibrium reactions monitored by 1 H NMR. Calculation S2: Determination of equilibrium constants for equilibrium reactions between 1-GaCl4 with 2H and 4-AlCl 4 with 2H.Calculation S3: Hydricity difference between species in equilibrium.

Figures
Figure S1: 1 H NMR and 13 C NMR of 3H. Figure S2: 1 H NMR and 13 C NMR of 1H. Figure S3: 1 H NMR and 13 C NMR of 2H.

References
Experimental Section Preparation of Compounds.All manipulations were carried out using standard Schlenk or glovebox techniques under a dinitrogen atmosphere.Unless otherwise noted, solvents were deoxygenated and dried by thorough sparging with Ar gas followed by passage through an activated alumina column.Deuterated solvents were purchased from Cambridge Isotopes Laboratories, Inc. and were degassed and stored over activated 3 Å molecular sieves prior to use.2,6-bis(5-isobutyl-1isopropyl-1H-pyrazol-3-yl)pyridine (pz 2 P), 1 4-AlCl 4 , 1 and 1,3-dimethyl-1H-benzimidazolium iodide, 2 were synthesized according to literature methods.All other reagents were purchased from commercial vendors and used without further purification.
Reaction of 2H with 1-GaCl 4 .Reaction solution was prepared by weighing 5 mg (0.012 mmol, 1 eq.) of 2H in a 20 mL vial and dissolving in 400 μL C 6 D 6 and transferring to a NMR tube.To a separate vial was weighed first 8.9 mg (0.012 mmol, 1 eq.) 1-GaCl 4 , then 7.3 mg (0.040 mmol, 3.3 eq.) trimethoxy benzene was added to vial.The solid 1-GaCl 4 and trimethoxy benzene were brought up in 400 μL C 6 D 6 and transferred to NMR tube with 2H.The vial containing residual 1-GaCl 4 and trimethoxy benzene was then washed with an additional 100 μL C 6 D 6 and transferred to the NMR tube.
Reaction of 2H with 4-AlCl 4 .Reaction solution was prepared by weighing 5 mg (0.01 mmol, 1 eq.) of 2H in a 20 mL vial and dissolving in 400 μL C 6 D 6 and transferring to a NMR tube.To a separate vial was weighed first 7.9 mg (0.01 mmol, 1 eq.) 4-AlCl 4 , then 2.0 mg (0.01 mmol, 1 eq.) trimethoxy benzene was added to vial.The solid 4-AlCl 4 and trimethoxy benzene were brought up in 300 μL C 6 D 6 and transferred to the NMR tube with 2H.
X-ray Structure Determinations.X-ray diffraction studies were carried out on a Bruker SMART APEX Duo diffractometer equipped with a CCD detector. 3Measurements were carried out at −175 °C using Mo Kα (0.71073 Å) and Cu Kα (1.54178 Å) radiation.Crystals were mounted on a Kaptan loop with paratone-N oil.The initial lattice parameters were obtained from least-squares analysis of more than 100 centered reflections; these parameters were later refined against all data.Data were integrated and corrected for Lorentz polarization effects using SAINT 4 and were corrected for absorption effects using SADABS2.3. 5 Space-group assignments were based on systematic absences, E statistics, and the successful refinement of the structures.Structures were solved by direct methods with the aid of successive difference Fourier maps and were refined against all data using the SHELXTL 2014/7 software package. 6Thermal parameters for all non-H atoms were refined anisotropically.H atoms, where added, were assigned to ideal positions, and refined using a riding model with an isotropic thermal parameter 1.2 times that of the attached C atom (1.5 times for methyl H atoms).
Other Physical Measurements. 1 H and 13 C NMR spectra were recorded at ambient temperature using a Varian 600 MHz spectrometer.Chemical shifts were referenced to a residual solvent.Elemental analyses were performed by the Microanalytical Laboratory at The University of California, Berkeley.For HRMS analysis, samples were analyzed by flow-injection analysis into a Thermo Fisher Scientific LTQ Orbitrap XL (San Jose, CA) operated in the centroided mode.Samples were injected into a mixture of 50% MeOH and 0.1% Formic Acid/H20 at a flow of 200 ul/min.Source parameters were 5kV spray voltage, capillary temperature of 275C and sheath gas setting of 20.Spectral data were acquired at a resolution setting of 100,000 FWHM with the lockmass feature which typically results in a mass accuracy < 2 ppm.

Calculations and Equations
Calculation S1.Determination of species concentration during equilibrium reactions monitored by 1 H NMR.
Diagnostic signals for all peaks were integrated over a constant ppm range for each 1 H NMR spectrum recorded.Integration of the O-CH 3 signal from the trimethoxy benzene standard was set to 100.00 for each spectrum and concentrations of diagnostic signals were calculated from the peak integration relative to internal standard.Using equation S1 (equation S1) where [X] is the concentration of the species of interest, I X is the raw integration of the species of interest, H X is the number of protons corresponding to the signal of interest and [Std.] is the concentration of internal standard.

Calculation S2.
Equilibrium constants were calculated based off the concentration of each species at equilibrium determined by 1 H NMR (Figure 2).
(equation S2) Equilibrium concentrations were taken from empirical data at 94 hours for the reaction of 1-GaCl 4 and 2H (K 1 ) and at 94 hours for reaction of 4-AlCl 4 and 2H (K 2 ).

Figure S6 :
Time dependent 1 H NMR spectra of 2 + -OTf and concentration vs time plot.

Figure S7 :
Time dependent 1 H NMR spectra of 2H and concentration vs time plot.

Table S2 .
Selected bond length and angles for 1H and 3H.