Iodine–Iodine Cooperation Enables Metal-Free C–N Bond-Forming Electrocatalysis via Isolable Iodanyl Radicals

Abstract

Small molecule redox mediators convey interfacial electron transfer events into bulk solution and can enable diverse substrate activation mechanisms in synthetic electrocatalysis. Here, we report that 1,2-diiodo-4,5-dimethoxybenzene is an efficient electrocatalyst for C−H/E−H coupling that operates at as low as 0.5 mol % catalyst loading. Spectroscopic, crystallographic, and computational results indicate a critical role for a three-electron I−I bonding interaction in stabilizing an iodanyl radical intermediate (i.e., formally I(II) species). As a result, the optimized catalyst operates at more than 100 mV lower potential than the related monoiodide catalyst 4iodoanisole, which results in improved product yield, higher Faradaic efficiency, and expanded substrate scope. The isolated iodanyl radical is chemically competent in C−N bond formation. These results represent the first examples of substrate functionalization at a well-defined I(II) derivative and bona f ide iodanyl radical catalysis and demonstrate one-electron pathways as a mechanistic alternative to canonical two-electron hypervalent iodine mechanisms. The observation establishes I−I redox cooperation as a new design concept for the development of metal-free redox mediators.

Toward a General Protocol for Catalytic Oxidative Transformations Using Electrochemically Generated Hypervalent Iodine Species

“…In view of the results of these control experiments and the previously published studies on the mechanisms of hypervalent iodine-mediated N -allylamide cyclization and α-tosyloxylation of ketones and catalytic transformations with electrochemically generated hypervalent iodine reagents, a proposed reaction mechanism is presented for the cyclization (Scheme ). ,− ,, Initially, iodobenzene is anodically oxidized in the presence of HFIP to the corresponding hypervalent iodine species I that undergoes ligand exchange with tosylic acid to form the more stable Koser’s reagent ( II ). This activates the double bond of substrate 1a forming species III that undergoes intramolecular cyclization to form the dihydrooxazole core in species IV .…”

“…Despite the impressive developments in the chemistry of electrochemically generated hypervalent iodine reagents, − the vast majority of the reported methods use stoichiometric amounts of iodine compounds − and the development of catalytic protocols − using iodine reagents as redox-active mediators is far behind. The reported catalytic methods using iodine compounds under electrolysis conditions are scarce and suffer from several limitations such as the necessity of large amounts of added electrolytes and narrow applicability.…”

Electrocatalytic Synthesis of Substituted Pyrazoles via Hypervalent Iodine Mediated Intramolecular C−N Coupling

“…Application of 4‐iodoanisole C or 1‐iodo‐4‐nitrobenzene D as the mediator led to a significant decrease in 2 a yield (Table 1, Entries 16 and 17, 38–44%). In the reaction with a low loading (5 mol%) of 1,2‐diiodoveratrole E , recently implemented [18b] in the electrochemical generation of stabilized iodanyl radical intermediate, product 2 a was obtained in a 26% yield (Table 1, Entry 18). The increase in the loading of iodobenzene to 30 mol% with respect to 1 a (Table 1, Entry 19) promoted electrochemical C−N coupling in a 87% yield (85% isolated yield, 20% of iodobenzene recovered).…”

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

“…In contrast to the standard mechanism, in which iodine(III) is an active intermediate species, in the case of 1,2-diiodo-4,5dimethoxybenzene, the iodine-iodine bonding interaction stabilizes the iodanyl radical intermediate (I(II) species, Scheme 36). This allows reactions to be carried out at lower potentials with lower catalyst loadings extending the applicability of the method to more labile substrates, such as those containing an anisole moiety [151] (Scheme 36).…”