Photo-Initiated Nickel Catalysis (PiNiC): Unmasking Dimethylnickel with Light

Abstract

Nickel catalysis has garnered interest in mainstream organic synthesis for constructing chemical bonds and has been merged with photoredox catalysis and electrocatalysis. Despite its success and increasing adoption by academia and industry, the mechanism by which Ni catalyzes C−C cross-coupling reactions and how the precatalyst is activated remains unclear. An exploration of stabilized dimethylNi II complexes, [(dtbbpy)Ni-(Me) 2 ] (dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine, 1) and [(bpy)-Ni(Me) 2 ] (bpy = 2,2′-bipyridine, 2), as Ni-precatalysts for promoting C sp 2 −C sp 3 cross-coupling revealed that they readily undergo photo-induced Ni−C bond homolysis upon exposure to visible light and are a source of Ni 0 species. Photo-initiation of dimethylNi II complexes 1 and 2 produced active Ni 0 and reactive methyl radicals, which were harnessed to promote methylative and other C sp 2 −C sp 3 cross-coupling reactions.The mechanistic studies conducted to illuminate aspects of the process include a competition reaction, Ni II ArBr-complex synthesis, light-on and lightoff studies, density functional theory (DFT) calculations of the bond dissociation free energies (BDFE), as well as control experiments with a Ni 0 -precursor. We further demonstrated the robustness and utility of dimethylNi II as a Ni 0 -precursor in the latestage installation of methyl, CD 3 , alkyl, and benzyl groups on aryl bromides that have potential value in drug design and optimization. This work sheds light on the activation mechanism of Ni-catalyzed cross-coupling of aryl halides with organozinc reagents when a Ni II -precatalyst is employed and the critical role that visible light plays in the process.

Photochemical Synthesis of Anilines via Ni-Catalyzed Coupling of Aryl Halides with Ammonium Salts

“…Heating may be required to facilitate the oxidative addition of Ni­(I) with the aryl halide . In addition, the light-on and off experiments showed that continuous illumination is required throughout to sustain the catalytic turnover, presumably to generate the active Ni­(I) catalyst from off-cycle Ni­(II) species (Table S9 in the Supporting Information, and below). It is noted that the presence of oxygen dramatically decreased the reaction efficiency (entry 13).…”

Metallaphotoredox Decarboxylative Arylation of Natural Amino Acids via an Elusive Mechanistic Pathway

“…Electron-rich aryl iodides have been used to circumvent this limitation; however, this remedy is still plagued by either low yield or no reactivity. Since ligated Ni 0 complexes have been shown to undergo facile oxidative addition to both electron-poor and electron-rich aryl halides (I, Br, Cl, and F), we considered that the underlying explanation resides beyond the oxidative addition event. Nevertheless, probing this aspect of reactivity might unravel an alternative pathway by which Ni promotes the cross-coupling process.…”

“…With the complexes in hand, control experiments to test the viability of Ni II adducts of 4-bromobenzotrifluoride (complex 73 ), bromobenzene (complex 74 ), and 3-bromotoluene (complex 75 ), which are electronically differentiated, were then carried out (Scheme A–C). , In contrast to previous studies, , bromobenzene and 3-bromotoluene were chosen instead of 2-bromotoluene to avoid the potential for either steric bias or influence of the latter. When complex 73 was used as a catalyst (6 mol %) to promote the coupling of 1 and 4-bromobenzotrifluoride, the decarboxylative arylated product 50a was obtained in 80% yield.…”

“…Examination of the transition structure 1 D-TS reveals a stabilizing interaction between the carboxamide CO group and the Ni II center (Ni–O = 2.11 Å) to form a five-coordinated species that resembles a distorted square pyramid. , Regeneration of 1 A by the coordination of aryl halide 2a to the ensuing Ni 0 intermediate closes the cycle with an exergonic balance of −67.2 kcal/mol. It is noteworthy that the reactivity of the triplet state of the Ni II ArBr complex, which can be accessed by an energy-transfer process, was explored by DFT calculations and found to have no influence on the Ni-cycle. , …”

A Paradigm Shift in Catalysis: Electro- and Photomediated Nickel-Catalyzed Cross-Coupling Reactions

“…This experiment led to the quantitative formation of the methylated product (Figure 3A). 23 We surmised that Ni(0) formation occurred before the oxidative addition of the aryl halide. Similar to previous metallaphotoredox reports, we proposed that the generated methyl radical can recombine with the Ni(II)ArX complex to generate Ni(III)ArMeX that undergoes reductive elimination to form the methylated product.…”