Electrochemical Synthesis of Biaryls via Oxidative Intramolecular Coupling of Tetra(hetero)arylborates

Abstract

We report herein versatile, transition metal-free and additive-free (hetero)­aryl–aryl coupling reactions promoted by the oxidative electrocoupling of unsymmetrical tetra­(hetero)­arylborates (TABs) prepared from ligand-exchange reactions on potassium trifluoroarylborates. Exploiting the power of electrochemical oxidations, this method complements the existing organoboron toolbox. We demonstrate the broad scope, scalability, and robustness of this unconventional catalyst-free transformation, leading to functionalized biaryls and ultimately furnishing drug-like small molecules, as well as late stage derivatization of natural compounds. In addition, the observed selectivity of the oxidative coupling reaction is related to the electronic structure of the TABs through quantum-chemical calculations and experimental investigations.

Transition‐Metal‐Free Oxidative Cross‐Coupling of Tetraarylborates to Biaryls Using Organic Oxidants

“…[14,16] During the preparation of this manuscript, Didier and co-workers reported an electrochemical oxidative coupling of unsymmetric tetraarylborates to give the corresponding mixed biaryls. [17] We envisioned that a nitroxide-derived oxoammonium salt, such as the commercial Bobbitt salt 1, [18] could be used as a mild and cheap oxidant for the transition-metal-free coupling of tetraarylborates. Herein we disclose the realization of that idea and show that this approach can be used not only for the preparation of symmetric biaryls, but also for the selective cross-coupling of in situ generated unsymmetric tetraarylborates.…”

Photocatalyzed Transition-Metal-Free Oxidative Cross-Coupling Reactions of Tetraorganoborates

“…While classical cross-coupling methods usually give complex mixtures of products through uncontrolled oxidative additions, [24] we have previously demonstrated that an electrochemical process can be employed to gain control over the formation of desired functionalized compounds. [13] Remarkably, iodinated and brominated substrates were tolerated under our photocatalyzed conditions, furnishing halogenated biaryls 2w-2z in up to 69% yield. Nitrile-substituted trifluoroborate substrates were also used in this two-step sequence, leading to structures 2aa-ab in moderate yields (47 to 63%).…”

“…We previously demonstrated that the first oxidation of a TOB salt preferentially occurs on the most electron rich unsaturated moiety. [13,14] As a logical consequence, structures 1 were designed to possess one electron-richer aryl group (Ar 1 ), surrounded by electron-poorer groups (Ar 2 ). With optimized conditions and setup in hands, we started evaluating the scope of the aryl-aryl photocoupling (Scheme 2).…”

“…Blue light irradiation (470 nm) allows for the acridinium to reach its active, excited state to abstract an electron from substrate 1a. The resulting oxidized species [1a . ] undergoes a pseudo 1,2-metallate rearrangement, [13,14] giving the cyclic intermediate 6, which further opens towards 7 through [TS] # .…”

Übergangsmetallfreie oxidative Kreuzkupplung von Tetraarylboraten zu Biarylen mit organischen Oxidationsmitteln

“…[14,16] Während der Fertigstellung dieses Manuskripts berichteten Didier und Mitarbeiter über die elektrochemische oxidative Kupplung von unsymmetrischen Tetraarylboraten zu den entsprechenden gemischten Biarylen. [17] Wir erwogen, dass ein Nitroxid-abgeleitetes Oxoammoniumsalz, wie das kommerziell erhältliche Bobbitt-Salz 1, [18] als mildes und kostengünstiges Oxidationsmittel für die übergangsmetallfreie Kupplung von Tetraarylboraten genutzt werden kann und berichten nun von der Umsetzung dieser Idee. Es wird gezeigt, dass dieser Ansatz nicht nur zur Darstellung symmetrischer Biaryle, sondern auch für selektive Kreuzkupplungen von in situ erzeugten unsymmetrischen Tetraarylboraten genutzt werden kann.…”