Reduction of CO₂ to Methanol Catalyzed by a Biomimetic Organo-Hydride Produced from Pyridine

We use quantum chemical calculations to elucidate a viable mechanism for pyridine-catalyzed reduction of CO₂ to methanol involving homogeneous catalytic steps. The first phase of the catalytic cycle involves generation of the key catalytic agent, 1,2-dihydropyridine (<b>PyH</b>_<b>2</b>). First, pyridine (Py) undergoes a H⁺ transfer (PT) to form pyridinium (PyH⁺), followed by an e^– transfer (ET) to produce pyridinium radical (PyH⁰). Examples of systems to effect this ET to populate PyH⁺’s LUMO (<i>E</i>⁰_calc ∼ −1.3 V vs SCE) to form the solution phase PyH⁰ via highly reducing electrons include the photoelectrochemical p-GaP system (<i>E</i>_CBM ∼ −1.5 V vs SCE at pH 5) and the photochemical [Ru­(phen)₃]²⁺/ascorbate system. We predict that PyH⁰ undergoes further PT–ET steps to form the key closed-shell, dearomatized (<b>PyH</b>_<b>2</b>) species (with the PT capable of being assisted by a negatively biased cathode). Our proposed sequential PT–ET–PT–ET mechanism for transforming Py into <b>PyH</b>_<b>2</b> is analogous to that described in the formation of related dihydropyridines. Because it is driven by its proclivity to regain aromaticity, <b>PyH</b>_<b>2</b> is a potent recyclable organo-hydride donor that mimics important aspects of the role of NADPH in the formation of C–H bonds in the photosynthetic CO₂ reduction process. In particular, in the second phase of the catalytic cycle, which involves three separate reduction steps, we predict that the <b>PyH</b>_<b>2</b>/Py redox couple is kinetically and thermodynamically competent in catalytically effecting hydride and proton transfers (the latter often mediated by a proton relay chain) to CO₂ and its two succeeding intermediates, namely, formic acid and formaldehyde, to ultimately form CH₃OH. The hydride and proton transfers for the first of these reduction steps, the homogeneous reduction of CO₂, are sequential in nature (in which the formate to formic acid protonation can be assisted by a negatively biased cathode). In contrast, these transfers are coupled in each of the two subsequent homogeneous hydride and proton transfer steps to reduce formic acid and formaldehyde