Photoredox Nickel-Catalyzed C–S Cross-Coupling: Mechanism, Kinetics, and Generalization

Han D., Li S., Xia S., Su M., Jin J.

An efficient and operationally simple Ni-catalyzed amination protocol has been developed. This methodology features a simple NiII salt, an organic base and catalytic amounts of both a pyridinium additive and Zn metal. A diverse number of (hetero)aryl halides were coupled successfully with primary and secondary alkyl amines, and anilines in good to excellent yields. Similarly, benzophenone imine gave the corresponding N-arylation product in an excellent yield.

Till N.A., Tian L., Dong Z., Scholes G.D., MacMillan D.W.

The combined use of reaction kinetic analysis, ultrafast spectroscopy, and stoichiometric organometallic studies has enabled the elucidation of the mechanistic underpinnings to a photocatalytic C-N cross-coupling reaction. Steady-state and ultrafast spectroscopic techniques were used to track the excited-state evolution of the employed iridium photocatalyst, determine the resting states of both iridium and nickel catalysts, and uncover the photochemical mechanism for reductive activation of the nickel co- catalyst. Stoichiometric organometallic studies along with a comprehensive kinetic study of the reaction, including rate-driving force analysis, unveiled the crucial role of photocatalysis in both initiating and sustaining a Ni(I)/Ni(III) cross-coupling mechanism. The insights gleaned from this study further enabled the discovery of a new photocatalyst providing a >30-fold rate increase.

Qin Y., Martindale B.C., Sun R., Rieth A.J., Nocera D.G.

Nickel-catalysed aryl amination and etherification are driven with sunlight using a surface-modified carbon nitride to extend the absorption of the photocatalyst such that they may be driven with solar light.

Sun R., Qin Y., Nocera D.G.

We establish self-sustained Ni(I/III) cycles as a potentially general paradigm in photoredox Ni-catalyzed carbon-heteroatom cross-coupling reactions by presenting a strategy that allows us to recapitulate photoredox-like reactivity in the absence of light across a wide range of substrates in the amination, etherification, and esterification of aryl bromides, the latter of which has remained, hitherto, elusive under thermal Ni catalysis. Moreover, the accessibility of esterification in the absence of light is especially notable since previous mechanistic studies on this transformation under photoredox conditions have unanimously invoked energy transfer-mediated pathways.

Ting S.I., Garakyaraghi S., Taliaferro C.M., Shields B.J., Scholes G.D., Castellano F.N., Doyle A.G.

Synthetic organic chemistry has seen major advances due to the merger of nickel and photoredox catalysis. A growing number of Ni-photoredox reactions are proposed to involve generation of excited nickel species, sometimes even in the absence of a photoredox catalyst. To gain insights about these excited states, two of our groups previously studied the photophysics of Ni(t-Bubpy)(o-Tol)Cl, which is representative of proposed intermediates in many Ni-photoredox reactions. This complex was found to have a long-lived excited state (τ = 4 ns), which was computationally assigned as a metal-to-ligand charge transfer (MLCT) state with an energy of 1.6 eV (38 kcal/mol). This work evaluates the computational assignment experimentally using a series of related complexes. Ultrafast UV-Vis and mid-IR transient absorption data suggest that a MLCT state is generated initially upon excitation but decays to a long-lived state that is 3d-d rather than 3MLCT in character. Dynamic cis,trans-isomerization of the square planar complexes was observed in the dark using 1H NMR techniques, supporting that this 3d-d state is tetrahedral and accessible at ambient temperature. Through a combination of transient absorption and NMR studies, the 3d-d state was determined to lie ∼0.5 eV (12 kcal/mol) above the ground state. Because the 3d-d state features a weak Ni-aryl bond, the excited Ni(II) complexes can undergo Ni homolysis to generate aryl radicals and Ni(I), both of which are supported experimentally. Thus, photoinduced Ni-aryl homolysis offers a novel mechanism of initiating catalysis by Ni(I).

Park B.Y., Pirnot M.T., Buchwald S.L.

We report a visible light-mediated flow process for C-N cross-coupling of (hetero)aryl halides with a variety of amine coupling partners through the use of a photoredox/nickel dual catalyst system. Compared to the method in batch, this flow process enables a broader substrate scope, including less-activated (hetero)aryl bromides and electron-deficient (hetero)aryl chlorides, and significantly reduced reaction times (10 to 100 min). Furthermore, scale up of the reaction, demonstrated through the synthesis of tetracaine, is easily achieved, delivering the C-N cross-coupled products in consistently high yield of 84% on up to a 10 mmol scale.

Diccianni J.B., Diao T.

Advances in nickel-catalyzed cross-coupling reactions have expanded the chemical space of accessible structures and enabled new synthetic disconnections. The unique properties of Ni catalysts facilitate the activation of traditionally inert substrates, tolerate alkyl coupling partners that undergo decomposition via β-hydride (β-H) elimination with Pd, and enable stereoconvergent cross-couplings. The radical pathways accessed by Ni catalysts have been merged with photoredox and electrochemical catalysis to achieve new reactivity. The growing utility of Ni catalysis is, in no small part, due to advances in our fundamental understanding of the properties of Ni catalysts and the mechanisms by which the reactions occur. This review highlights recent important contributions to the field with an emphasis on studies that have afforded mechanistic insight.

Qiu G., Knowles R.R.

While the mechanistic understanding of proton-coupled electron transfer (PCET) has advanced significantly, few reports have sought to elucidate the factors that control chemoselectivity in these reactions. Here we present a kinetic study that provides a quantitative basis for understanding the chemoselectivity in competitive PCET activations of amides and thiols relevant to catalytic olefin hydroamidation reactions. These results demonstrate how the interplay between PCET rate constants, hydrogen-bonding equilibria, and rate-driving force relationships jointly determine PCET chemoselectivity under a given set of conditions. In turn, these findings predict reactivity trends in a model hydroamidation reaction, rationalize the selective activation of amide N-H bonds in the presence of much weaker thiol S-H bonds, and deliver strategies to improve the efficiencies of PCET reactions employing thiol co-catalysts.

Yin H., Fu G.C.

In recent years, a wide array of methods for achieving nickel-catalyzed substitution reactions of alkyl electrophiles by organometallic nucleophiles, including enantioconvergent processes, have been described; however, experiment-focused mechanistic studies of such couplings have been comparatively scarce. The most detailed mechanistic investigations to date have examined catalysts that bear tridentate ligands and, with one exception, processes that are not enantioselective; studies of catalysts based on bidentate ligands could be anticipated to be more challenging, due to difficulty in isolating proposed intermediates as a result of instability arising from coordinative unsaturation. In this investigation, we explore the mechanism of enantioconvergent Kumada reactions of racemic α-bromoketones catalyzed by a nickel complex that bears a bidentate chiral bis(oxazoline) ligand. Utilizing an array of mechanistic tools (including isolation and reactivity studies of three of the four proposed nickel-containing intermediates, as well as interrogation via EPR spectroscopy, UV-vis spectroscopy, radical probes, and DFT calculations), we provide support for a pathway in which carbon-carbon bond formation proceeds via a radical-chain process wherein a nickel(I) complex serves as the chain-carrying radical and an organonickel(II) complex is the predominant resting state of the catalyst. Computations indicate that the coupling of this organonickel(II) complex with an organic radical is the stereochemistry-determining step of the reaction.

Hossain A., Bhattacharyya A., Reiser O.

Spotlight on copper Photoredox catalysis relies on visible-light excitation to accelerate a burgeoning number of chemical reactions. Initially, the technique relied primarily on complexes of precious metals, such as ruthenium or iridium, to absorb the light. Hossain et al. review recent progress in the use of copper complexes as an alternative. In addition to its Earth abundance, copper opens up a variety of distinct mechanisms involving electron transfer within the coordination sphere. Science , this issue p. eaav9713

McAtee R.C., McClain E.J., Stephenson C.R.

Over the past decade, photoredox catalysis has risen to the forefront of synthetic organic chemistry as an indispensable tool for selective small-molecule activation and chemical-bond formation. This cutting-edge platform allows photosensitizers to convert visible light into chemical energy prompting generation of reactive radical intermediates. In this Review, we highlight some of the recent key contributions in the field, including: the impact of the chosen light arrays; promoting fundamental cross-coupling steps; selectively functionalizing aliphatic amines; engaging complementary mechanistic paradigms; and applications in industry. With such a wide breadth of reactivity already realized, the presence of photoredox catalysis in all sectors of organic chemistry is expected for years to come.

Ren H., Li G., Zhu B., Lv X., Yao L., Wang X., Su Z., Guan W.

Photoredox-mediated iridium/nickel dual catalysis has successfully triggered a series of traditionally challenging carbon–heteroatom cross-coupling reactions. However, detailed mechanisms, such as ...

Sikari R., Sinha S., Das S., Saha A., Chakraborty G., Mondal R., Paul N.D.

A simple and efficient approach of C-S cross-coupling of a wide variety of (hetero)aryl thiols and (hetero)aryl halides under mild conditions, mostly at room temperature, catalyzed by well-defined singlet diradical Ni(II) catalysts bearing redox noninnocent ligands is reported. Taking advantage of ligand centered redox events, the high-energetic Ni(0)/Ni(II) or Ni(I)/Ni(III) redox steps were avoided in the catalytic cycle. The cooperative participation of both nickel and the coordinated ligands during oxidative addition/reductive elimination steps allowed us to perform the catalytic reactions under mild conditions.

Hockin B.M., Li C., Robertson N., Zysman-Colman E.

Visible light photoredox catalysis has exploded into the consciousness of the synthetic chemist. We critically review Earth-abundant metal complexes photocatalysts including Cu(i), Zn(ii), Ni(0), V(v), Zr(iv), W(0), W(vi), Mo(0), Cr(iii), Co(iii) and Fe(ii).

Sun R., Qin Y., Ruccolo S., Schnedermann C., Costentin C., Nocera D.G.

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.

Sinha S., Singh P.P., Kanaujia S., Singh P.K., Srivastava V.

Kan C., Ge C., Liu S., Shi S., He H., Su W.

Sun X., Wang D., Chang S., Yin L., Zhang H., Ji S., Fei H., Jin Y.

Zwick C.R., Eckhoff M., Henle J.J., Bay A.V., Swiatowiec R., Shekhar S., Yang C., Zhou Y., Wall A.L., Henry R.F., Hoskins J.N., Sigman M.S.

Gao A., Liu H., Zhou Y., Fu M.

We present a catalyst- and thiol-free protocol for arene C–H thioetherification under visible light irradiation.

Das D., Dinh L.P., Smith R.E., Kalyani D., Sevov C.S.

The structural diversification of pharmaceutically relevant compounds presents unique challenges to catalytic methodologies that have been developed and optimized on simpler substrates that lack drug-like complexity. Here we report a general strategy for carbon–heteroatom (C–X) bond formation through reactions between a wide range of nucleophiles and nickel-based oxidative addition complexes of drug-like aryl and heteroaryl electrophiles. These organonickel complexes are easily synthesized by oxidative addition of the corresponding electrophiles under electroreductive conditions using an inexpensive nickel precursor. Redox-induced oxidative coupling from these persistent complexes proved challenging, but mechanistic studies guided the development of a simple aerobic oxidation procedure to rapidly form C–X coupled products. Exposure of the organonickel complexes to ambient air forms a high-valent (peroxo)NiIIIAr complex intermediate that can undergo substitution with a variety of nitrogen-, oxygen-, sulfur-, carbon-, phosphorus- or halide-based nucleophiles, which are incorporated into the product. The breadth of this methodology was demonstrated by reactions with unreactive electrophiles, such as aryl chlorides, drug-like (hetero)aryl electrophiles and small peptides. Finally, the aerobic chemistry was miniaturized to allow for high-throughput exploration of substrate diversity with an equally complex set of nucleophilic partners. Aerobic oxidation of isolable organonickel complexes enables reliable cross-coupling of aryl electrophiles with oxygen-, nitrogen-, sulfur- and phosphorus-based nucleophiles. Organonickel complexes are electroreductively prepared from simple aryl electrophiles and inexpensive metal complexes, and the chemistry can be applied in high-throughput coupling reactions of medicinally relevant substrates.

Nikitin M., Ötvös S.B., Ghosh I., Philipp M., Gschwind R., Kappe C.O., König B.

Rodriguez-Lugo R.E., Sander J., Dietzmann S., Rittner T., Rueckel J., Landaeta V.R., Park J., Nuernberger P., Baik M., Wolf R.

We present a photocatalytic protocol for the O-arylation of carboxylic acids using nickel complexes bearing C8-pyridyl xanthines. Our mechanistic studies suggest that the underlying mechanism operates independently of external photosensitizers....

Wang C., Liu L., Sun W., Wang J., Li Q., Feng K., Liao B., Fang W., Chen X.

AbstractThe design of iridium(III) complex‐based photofunctional materials is challenged by commercial viability issues in organic light‐emitting diodes (OLEDs) and the limitation of polypyridyl structures for Ir(III) catalysts in photocatalysis. The burgeoning advancement of data‐driven science provides new solutions to this challenge. Herein, a three‐step data‐driven design approach is reported to target multifunctional red phosphorescent Ir(III) complexes. The approach uses machine learning and quantum chemistry calculations coupled with key excited‐state physical and chemical descriptors to identify the promising natural uracil‐based Ir(III) complexes from the self‐established “OLED Materials and Photocatalyst Database.” The newly designed red complexes demonstrate higher quantum yields and longer radiative lifetimes compared to their commercial counterparts. As photosensitizers, they display electron and energy transfer rates with substrates at the nanosecond level and are validated for lab‐scale photocatalysis. As the guests for OLEDs, their devices produce excellent red emission with low turn‐on voltages, minimal efficiency roll‐off, and decent electroluminescence efficiency. This research stands for an innovative endeavor in the data‐driven design of Ir(III) complexes, diverging from the traditional structure‐mimicking model, and can be generalized to the design of more photofunctional molecular materials.

Teixeira R.I., Waldron Clarke T.H., Love A., Sun X., Kayal S., George M.W.

Ishitani O.

Liang K.J., Taylor O.R., López A.L., Woo R.J., Bahamonde A.

AbstractThis study presents a Ni‐photoredox method for indole N‐arylation, broadening the range of substrates to include indoles with unprotected C3‐positions and base‐sensitive groups. Through detailed mechanistic inquiries, a Ni(I/III) mechanism was uncovered, distinct from those commonly proposed for Ni‐catalyzed amine, thiol, and alcohol arylation, as well as from the Ni(0/II/III) cycle identified for amide arylation under almost identical conditions. The key finding is the formation of a Ni(I) intermediate bearing the indole nucleophile as a ligand prior to oxidative addition, which is rare for Ni‐photoredox carbon‐heteroatom coupling and has a profound impact on the reaction kinetics and scope. The pre‐coordination of indole renders a more electron‐rich Ni(I) intermediate, which broadens the scope by enabling fast reactivity even with challenging electron‐rich aryl bromide substrates. Thus, this work highlights the often‐overlooked influence of X‐type ligands on Ni oxidative addition rates and illustrates yet another mechanistic divergence in Ni‐photoredox C‐heteroatom couplings.

Limburg B.

Wang X., He J., Wang Y., Zhao Z., Jiang K., Yang W., Zhang T., Jia S., Zhong K., Niu L., Lan Y.

Liu D., Hazra A., Liu X., Maity R., Tan T., Luo L.

AbstractHere, we report CdS quantum dot (QD) gels, a three‐dimensional network of interconnected CdS QDs, as a new type of direct hydrogen atom transfer (d‐HAT) photocatalyst for C−H activation. We discovered that the photoexcited CdS QD gel could generate various neutral radicals, including α‐amido, heterocyclic, acyl, and benzylic radicals, from their corresponding stable molecular substrates, including amides, thio/ethers, aldehydes, and benzylic compounds. Its C−H activation ability imparts a broad substrate and reaction scope. The mechanistic study reveals that this reactivity is intrinsic to CdS materials, and the neutral radical generation did not proceed via the conventional sequential electron transfer and proton transfer pathway. Instead, the C−H bonds are activated by the photoexcited CdS QD gel via a d‐HAT mechanism. This d‐HAT mechanism is supported by the linear correlation between the logarithm of the C−H bond activation rate constant and the C−H bond dissociation energy (BDE) with a Brønsted slope α=0.5. Our findings expand the currently limited direct hydrogen atom transfer photocatalysis toolbox and provide new possibilities for photocatalytic C−H activation.