Kinetic Analysis of Electrochemical Lactonization of Ketones Using Water as the Oxygen Atom Source

Abstract

Lactones serve as key synthetic intermediates for the large-scale production of several important chemicals, such as polymers, pharmaceuticals, and scents. Current thermochemical methods for the formation of some lactones rely on molecular oxidants, which yield stoichiometric side products that result in a poor atom economy and impose safety hazards when in contact with organic substrates and solvents. Electrochemical synthesis can alleviate these concerns by exploiting an applied potential to enable the possibility of a clean and safe route for lactonization. In this study, we investigated the mechanism of electrochemical lactone formation from cyclic ketones. When using a platinum anode and cathode in acetonitrile with 10 M H 2 O and 400 mM cyclohexanone, we found that non-Baeyer−Villiger products, δhexanolactone and γ-caprolactone, are formed with a total Faradaic efficiency of ∼20%. Isotope labeling experiments support that water is the oxygen atom source for this reaction. In addition, electrochemical kinetic data suggest a first-order dependence on water at low water concentrations (<2 M H 2 O) and a zeroth order dependence on the substrate, cyclohexanone. A Tafel slope of 139 mV/decade was measured at 400 mM cyclohexanone and 10 M H 2 O, implying an initial electron transfer as the ratedetermining step. Literature-proposed mechanisms for similar transformations suggest an outer-sphere pathway. However, on the basis of the collected electrochemical kinetic data, we propose the possibility that Pt reacts with water in an initial electron transfer that forms Pt−OH, which can subsequently react with the ketone substrate. A subsequent electron transfer forms a ring-opened carboxylic acid cation that can reclose to form either of the observed fiveor six-membered ring lactone products.

Free Energies of Proton-Coupled Electron Transfer Reagents and Their Applications

“…These are important considerations for reporting catalyst metrics that are comparable across conditions. Other recent work has used acetonitrile with ≥5 M water (4:1 mole fraction MeCN/H 2 O) for the electrochemical oxidations of cyclohexene and cyclic ketones. , As shown by the elegant O’Hagan studies above, OCP measurements of E °(H + /H 2 ) in such mixed solvent systems enable the determination of thermochemical parameters and comparisons with potentials of hydrogenation since those are almost solvent-independent. We encourage researchers to use this approach, which offers simple access to accurate overpotentials and enables quantitative analysis of effects of solvent identity on catalyst performance.…”

Directing transition metal-based oxygen-functionalization catalysis

“…Manthiram et al then investigated the possibility of electrochemical lactone formation by following the same concept of their previous study. 163 In their proposed reaction mechanism (Fig. 10c), the water molecule is initially activated on a Pt electrode surface following an inner-sphere electron transfer to form Pt-OH.…”

“…The rate-determining step involves the activation of water molecules by Pt in an electron transfer to form Pt-OH. Reproduced with permission 163. Copyright 2020, American Chemical Society.…”

Carbon-Electrode-Mediated Electrochemical Synthesis of Hypervalent Iodine Reagents Using Water as the O-Atom Source

“…However, the kinetic bottleneck of water splitting is the anodic oxidation of water, a 4e – /4H + process and yields O 2 as a product of little economic value. We and others − hypothesize that water oxidation could be coupled to other chemical processes to yield value-added products. Attempts to do direct oxygenation of organic substrates anodically often lead to overoxidation or 1e – chemistry forming unwanted byproductsnecessitating the use of an electrocatalytic mediator. ,, An important recent example using an electrocatalytic mediator is the anodic epoxidation of ethylene to ethylene oxide mediated by Cl/ClO – .…”