Elucidation of a Redox-Mediated Reaction Cycle for Nickel-Catalyzed Cross Coupling

Abstract

A reaction cycle for redox-mediated, Ni-catalyzed aryl etherification is proposed under both photoredox and electrochemically mediated conditions. We demonstrate that a self-sustained Ni(I/III) cycle is operative in both cases by chemically synthesizing and characterizing a common paramagnetic Ni intermediate and establishing its catalytic activity. Furthermore, deleterious pathways leading to off-cycle Ni(II) species have been identified, allowing us to discover optimized conditions for achieving self-sustained reactivity at a ∼15-fold increase in the quantum yield and a ∼3-fold increase in the faradaic yield. These results highlight the importance of leveraging insight of complete reaction cycles for increasing the efficiency of redox-mediated reactions.

General Paradigm in Photoredox Nickel‐Catalyzed Cross‐Coupling Allows for Light‐Free Access to Reactivity

“…Control experiments wherein 1,5‐cyclooctadiene (COD) was added to the reactions under the “A” conditions of Figure showed that the difference in reactivity between the “A” and “B” conditions of Figure is not entirely attributable to the presence of COD (see the Supporting Information). This is consistent with a Ni I/III mechanism being the dominant productive pathway as suggested by our previous mechanistic study and literature precedent proposing the necessity of Ni III for reductive elimination . The background reactivity observed in these control experiments with Ni 0 sources may be attributed to the generation of Ni I equivalents during oxidative addition of aryl bromide to Ni 0 as previously proposed .…”

“…As shown in Entry 1 of Table , we obtained the expected cross‐coupled product in the reaction between methanol and 4′‐bromoacetophenone by using only 0.01 equivalents of Zn 0 and 1 mol % (dtbbpy)NiCl 2 (dtbbpy=4,4′‐di‐ tert ‐butyl‐2,2′‐dipyridyl) prepared in situ from (dme)NiCl 2 and dtbbpy. This result further lends credence to the productive Ni I/III cycle invoked in our previous mechanistic study …”

“…We were able to establish further parallels between the reactivity reported herein and that under the previously studied photochemical conditions. For example, we observed the formation of a previously characterized Ni I –Ni II dimer upon treatment of a solution containing Ni II precatalyst with Zn 0 (see Figure S1 in the Supporting Information), suggesting that Zn 0 serves a role analogous to the Ir photocatalyst in the related photoredox reaction by providing access to Ni I equivalents necessary for catalysis. Furthermore, similar to the photoredox reaction, there is evidence to suggest the existence of deleterious bimetallic pathways leading to the formation of off‐cycle intermediates because we observed a decrease in reaction yield with increasing nickel loading under certain conditions (see Figure S2 in the Supporting Information for details).…”

Site‐Selective, Remote sp3 C−H Carboxylation Enabled by the Merger of Photoredox and Nickel Catalysis

“…Although unraveling the underpinnings of our Ni/photoredox chain‐walking carboxylation at sp 3 C−H sites should await further investigations, we decided to shed light into the mechanism through combined experimental and theoretical studies (Scheme ) . Synergistic spectroelectrochemical measurements and in situ UV/Vis spectroscopy on ( L1 )NiBr 2 and ( L7 )NiBr 2 revealed that low‐valent Ni I and Ni 0 species are formed during light irradiation in the presence of 4‐CzIPN and Hantzsch ester . The assumption that the benzylic carboxylation featured a rather facile β‐H elimination from cationic Ni II species was experimentally corroborated by detecting styrenes in small amounts, the concentration of which decays to zero after consumption of the alkyl bromide .…”

“…[14] Synergistic spectroelectrochemical measurementsa nd in situ UV/Vis spectroscopy on (L1)NiBr 2 and (L7)NiBr 2 revealed that low-valent Ni I and Ni 0 speciesa re formed during light irradiation in the presenceo f4 -CzIPN and Hantzsch ester. [14,23] The assumption thatt he benzylic carboxylation featured ar ather facile b-H elimination from cationic Ni II species was experimentally corroborated by detecting styrenes in small amounts, the concentration of which decayst oz ero after consumption of the alkyl bromide. [14] In addition, olefins were not detected in the absence of Ni/L1 or Ni/L7,a rguing against base-promoted E2-elimination/olefin carboxylation event.…”