Nickel-catalyzed Cross-coupling Reactions Research Articles

Metal-Catalyzed Remote Functionalization of ω-Ene Unsaturated Ethers: Towards Functionalized Vinyl Species.

The combined ruthenium-catalyzed chain walking with the nickel-catalyzed cross-coupling reaction of ω-alkenyl ethers provide a unique entry to functionalized vinyl species. This transformation illustrates the power and flexibility of remote functionalization by demonstrating the compatibility of two independent reactions involving unrelated sites.

Nickel-Catalyzed Reductive Cross-Coupling of Aryl Halides with Monofluoroalkyl Halides for Late-Stage Monofluoroalkylation.

A combinatorial nickel-catalyzed monofluoroalkylation of aryl halides with unactivated fluoroalkyl halides by reductive cross-coupling has been developed. This method demonstrated high efficiency, mild conditions, and excellent functional-group tolerance, thus enabling the late-stage monofluoroalkylation of diverse drugs. The key to success was the combination of diverse readily available bidentate and monodentate pyridine-type nitrogen ligands with nickel, which in situ generated a variety of readily tunable catalysts to promote fluoroalkylation with broad scope with respect to both coupling partners. This combinatorial catalysis strategy offers a solution for nickel-catalyzed reductive cross-coupling reactions and provides an efficient way to synthesize fluoroalkylated druglike molecules for drug discovery.

Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules.

The utilization of carboxylic acid esters as electrophiles in metal-catalyzed cross-coupling reactions is increasingly popular, as environmentally friendly and readily available ester derivatives can be powerful alternatives to the commonly used organohalides. However, key challenges associated with the use of these chemicals remain to be addressed, including the stability of ester substrates and the high energy barrier associated with their oxidative addition to low-valent metal species. Due to recent developments in nickel catalysis that make it easier to perform oxidative additions, chemists have become interested in applying less reactive electrophiles as coupling counterparts in nickel-catalyzed transformations. Hence, our group and others have independently investigated various ester group substitutions and functionalizations enabled by nickel catalysis. Such methods are of great interest as they enable the exchange of ester groups, which can be used as directing groups in metal-catalyzed C-H functionalizations prior to their replacement. Here, we summarize our recent efforts toward the development of nickel-catalyzed decarbonylative cross-coupling reactions of carboxylic esters. Achievements accomplished by other groups in this area are also included. To this day, a number of new transformations have been successfully developed, including decarbonylative arylations, alkylations, cyanations, silylations, borylations, aminations, thioetherifications, stannylations, and hydrogenolysis reactions. These transformations proceed via a nickel-catalyzed decarbonylative pathway and have shown a high degree of reactivity and chemoselectivity, as well as several other unique advantages in terms of substrate availability, due to the use of esters as coupling partners. Although the mechanisms of these reactions have not yet been fully understood, chemists have already provided some important insights. For example, Yamamoto explored the stoichiometric nickel-mediated decarbonylation process of esters and proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO extrusion. Key nickel intermediates were isolated and characterized by Shi and co-workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted C(acyl)-O bond activation and functionalization. Our combined experimental and computational study of a ligand-controlled chemoselective nickel-catalyzed cross-coupling of aromatic esters with alkylboron reagents provided further insight into the reaction mechanism. We demonstrated that nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step, resulting in decarbonylative alkylations, while nickel complexes with monodentate phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the production of ketone products. Although more detailed mechanistic investigations need to be undertaken, the successful development of decarbonylative cross-coupling reactions can serve as a solid foundation for future studies. We believe that this type of decarbonylative cross-coupling reactions will be of significant value, in particularly in combination with the retrosynthetic analysis and synthesis of natural products and biologically active molecules. Thus, the presented ester substitution methods will pave the way for successful applications in the construction of complex frameworks by late-stage modification and functionalization of carboxylic acid derivatives.

Multifunctional luminescent molecules of o-carborane-pyrene dyad/triad: flexible synthesis and study of the photophysical properties

The development of organic single-molecule multiple photoluminescence compounds hold a great promise for advanced opt-electronic devices, optical probes and temperature sensors. The pyrenyl-substituted o-carborane, CSP and CDP, were obtained via a modified nickel-catalyzed cross-coupling reaction in satisfactory yields. Based on variety of spectroscopic measurements, it was found that the CSP and CDP exhibit multifunctional luminescent properties, such as dual emissions as well as thermochromic luminescence between orange and blue for CSP, ternary species emissions for CDP, and aggregation induced emission (AIE) and AIE enhancements (AIEE) properties for both. The origination of the multiple photoluminescence attributes was investigated deeply. We demonstrated that the multiple photoluminescence in the pyrenyl-substituted o-carborane rose from the electronic interaction between pyrenyl and o-carboranyl leading to the formation of ICT state, and the mono-molecular excimer emission attributed to the interaction between the conformational of two “face−to−face” pyrene chromophores. In addition, clear thermochromic luminescence properties were caused by ICT at room temperature and excimer formation at 77 K in the solid state. The results are useful as a guideline for designing luminescent solid materials with multiple photoluminescence and thermochromic luminescence properties.

Copper- and Nickel-Catalyzed Cross-Coupling Reaction of Monofluoroalkenes with Tertiary, Secondary, and Primary Alkyl and Aryl Grignard Reagents

A highly efficient cross-coupling reaction of monofluoroalkenes with tertiary, secondary, and primary alkyl and aryl Grignard reagents in the presence of a catalytic amount of copper or nickel catalyst, respectively, has been developed. The reactions proceeded smoothly at room temperature, providing (E)-alkene isomers in moderate to high yields. Plausible mechanisms of the Ni-catalyzed coupling reaction of monofluoroalkene with Grignard reagents are suggested.

Keeping Track of the Electrons.

Mechanistic investigation and new reaction development are intertwined. This interdependence presents challenges and opportunities in development of all transformations, particularly for those that employ base metal catalysts. In comparison to precious metal counterparts, these catalysts yield less easily to mechanistic analysis. However, base metal catalysts can provide new modes of reactivity and opportunities for discovery. In this Commentary, we highlight a developing field: nickel-catalyzed stereoselective alkyl cross-coupling reactions. While key features of the relevant catalytic cycles remain ambiguous, chemical intuition and key mechanistic experiments have provided the stepping stones for discovery of stereoselective transformations.

Dual Photoredox/Nickel-Catalyzed Regioselective Cross-Coupling of 2-Arylaziridines and Potassium Benzyltrifluoroborates: Synthesis of β-Substitued Amines.

A dual visible light photoredox and nickel-catalyzed cross-coupling reaction of 2-arylaziridines and potassium benzyltrifluoroborates is described for the first time. This strategy features high functional group tolerance, exclusive regioselectivity for reaction at the more hindered C-N bond, easily accessible substrates, and mild redox-neutral reaction conditions. A variety of diversely substituted β-substituted amines are obtained in generally good yields.

Asymmetric synthesis via stereospecific C-N and C-O bond activation of alkyl amine and alcohol derivatives.

This perspective showcases our development of benzylic and allylic amine and alcohol derivatives as electrophiles for stereospecific, nickel-catalyzed cross-coupling reactions, as well as the prior art that inspired our efforts. The success of our effort has relied on the use of benzyl ammonium triflates as electrophiles for cross-couplings via C-N bond activation and benzylic and allylic carboxylates for cross-couplings via C-O bond activation. Our work, along with others' exciting discoveries, has demonstrated the potential of stereospecific, nickel-catalyzed cross-couplings of alkyl electrophiles in asymmetric synthesis, and enables efficient generation of both tertiary and quaternary stereocenters.

Nickel-catalyzed cross-coupling of aldehydes with aryl halides via hydrazone intermediates.

Traditional cross-couplings require stoichiometric organometallic reagents. A novel nickel-catalyzed cross-coupling reaction between aldehydes and aryl halides via hydrazone intermediates has been developed, merging the Wolff-Kishner reduction and the classical cross-coupling reactions. Aromatic aldehydes, aryl iodides and aryl bromides are especially effective in this new cross-coupling chemistry.

Mechanically triggered reversible stepwise tricolor switching and thermochromism of anthracene-o-carborane dyad.

A novel single organic molecule-carborane conjugate, CAN, was synthesized in a high yield via a modified nickel-catalyzed cross-coupling reaction incorporating an anthracene unit and an o-carborane moiety. CAN exhibits multiple functions of tricolored mechanochromism and mechanically triggered thermochromism. The fluorescence could be switched from blue to bright yellow then to pink by grinding. The robust and reversible thermochromic process was triggered by the mechanical force. The locally excited (LE) state emission, intermolecular excimer formation and twisted intermolecular charge transfer (TICT) are the primary origins of this tricolor switching property. High temperature sensitivity of the heavily ground CAN powders contribute to the mechanical force induced TICT emission enhancement and color switching.

Direct Aldehyde Csp2 -H Functionalization through Visible-Light-Mediated Photoredox Catalysis.

The development of methods for carbon-carbon bond formation under benign conditions is an ongoing challenge for synthetic chemists. In recent years there has been considerable interest in using selective C-H activation as a direct route for generating reactive intermediates. Herein, the use of visible-light-mediated dual photoredox organocatalysis as a mild and effective method for Csp2 -H activation of aldehydes is reported, resulting in the generation of acyl radicals. These nucleophilic acyl radical species can undergo either addition to electrophilic alkenes or nickel-catalyzed cross-coupling reactions to provide a quick access to broad range of unsymmetrical ketones, which are abundantly found in many organic building blocks.

Nickel-Catalyzed Cross-Coupling Reaction of Aryl Sulfoxides with Arylzinc Reagents: When the Leaving Group is an Oxidant

Nickel-catalyzed Negishi-type cross-coupling of aryl methyl sulfoxides with arylzinc reagents has been developed. By consuming the catalyst-oxidizing methanesulfenate anion through oxidative homocoupling of the arylzinc reagent, smooth catalyst turnover could be executed. Arylzinc reagents prepared from arylmagnesium bromide, zinc bromide, and lithium bromide were optimal to afford the products in good to high yields, while arylzinc reagents prepared through other procedures showed lower reactivities. The reactivity of aryl methyl sulfoxide was compared with that of typical aryl (pseudo)halides.

Color-tuning aggregation-induced emission of o-Carborane-bis(1,3,5-triaryl-2-pyrazoline) triads: Preparation and investigation of the photophysics

Four D−A−D triads with an o-Carborane moiety as the electron acceptor and 1,3,5-triaryl-2-pyrazoline as the electron donor were designed and synthesized via a novel nickel-catalyzed cross-coupling reaction. The four triads exhibited aggregation-induced emission (AIE) attributes. The photophysical properties and crystal packing structures of these compounds were systematically investigated by UV-Vis absorption and fluorescence spectroscopy, time-resolved fluorescence, X-ray crystallography, CV and DFT theoretical calculations. The photoluminescence spectra showed bathochromic shift (λmax = 596–638 nm) with the increase of electron-donating ability of the substituents and accompanied systematic color-tuning from yellow to bright red with high fluorescence quantum yield (35.7%) in the solid state. The AIE mechanism could be attributed to the restriction of molecular motions and Cc–Cc bond vibration in o-Carborane which enhanced the intramolecular charge transfer (ICT) of the o-Carborane-bis(1,3,5-triaryl-2-pyrazoline) derivatives. DFT calculation further demonstrated that substituent variation is a possible way for precise color-control of AIE.

Combinatorial Nickel-Catalyzed Monofluoroalkylation of Aryl Boronic Acids with Unactivated Fluoroalkyl Iodides.

A combinatorial nickel-catalyzed cross-coupling between arylboronic acids and unactived 1-fluoro-1-iodoalkanes has been developed, which demonstrated high efficiency, mild conditions, and excellent functional-group compatibility. Readily available nitrogen and phosphine ligands were combined with a nitrogen source, which in situ generated a variety of easily tunable catalysts to promote the fluoroalkylation for broad scopes of both coupling partners. This new strategy on combinatorial catalysis offers new solutions for nickel-catalyzed cross-coupling reactions.

Modeling reduces nickel needed in catalytic reactions

Nickel catalysts are much less expensive than precious metal catalysts, but the large amounts of nickel catalyst used in many catalytic cross-coupling reactions still discourage industrial adoption. Over roughly the past two years, the vast majority of newly reported nickel-catalyzed cross-coupling reactions required 5 to 20 mole % of nickel catalyst. Neil K. Garg of the University of California, Los Angeles, grad student Nicholas A. Weires, and colleague Daniel D. Caspi of AbbVie have now collaborated to develop a technique that reduces loading (mole percent of catalyst required) in nickel-catalyzed amide esterifications (ACS Catal. 2017, DOI: 10.1021/acscatal.7b01444). They used a kinetic-modeling program, DynoChem, to assess the effect of several variables—ligand-to-metal ratio, reactant stoichiometry, product and by-product generation rate, catalyst temperature-equilibration time, catalyst loading, and reaction concentration—on the rate of benzamide-menthol esterification. They then used the data to d...

Amide to Alkyne Interconversion via a Nickel/Copper-Catalyzed Deamidative Cross-Coupling of Aryl and Alkenyl Amides.

A nickel-catalyzed deamidative cross-coupling reaction of amides with terminal alkynes as coupling partners was disclosed. This newly developed methodology allows the direct interconversion of amides to alkynes and enables a facile route for C(sp2)-C(sp) bond formation in a straightforward and mild fashion.

Nickel-catalyzed Ring-opening Cross-coupling of Cyclic Alkenyl Ethers with Arylboronic Esters via Carbon–Oxygen Bond Cleavage

We have developed a nickel-catalyzed cross-coupling reaction of cyclic alkenyl ethers with arylboronic esters that leads to the formation of unsaturated alcohols via ring-opening by the cleavage of a C(sp2)–O bond. The use of 1,3-dicyclohexylimidazol-2-ylidene as the ligand is essential to promote this cross-coupling process.

Isolated Organometallic Nickel(III) and Nickel(IV) Complexes Relevant to Carbon-Carbon Bond Formation Reactions.

Nickel-catalyzed cross-coupling reactions are experiencing a dramatic resurgence in recent years given their ability to employ a wider range of electrophiles as well as promote stereospecific or stereoselective transformations. In contrast to the extensively studied Pd catalysts that generally employ diamagnetic intermediates, Ni systems can more easily access various oxidation states including odd-electron configurations. For example, organometallic NiIII intermediates with aryl and/or alkyl ligands are commonly proposed as the active intermediates in cross-coupling reactions. Herein, we report the first isolated NiIII-dialkyl complex and show that this species is involved in stoichiometric and catalytic C-C bond formation reactions. Interestingly, the rate of C-C bond formation from a NiIII center is enhanced in the presence of an oxidant, suggesting the involvement of transient NiIV species. Indeed, such a NiIV species was observed and characterized spectroscopically for a nickelacycle system. Overall, these studies suggest that both NiIII and NiIV species could play an important role in a range of Ni-catalyzed cross-coupling reactions, especially those involving alkyl substrates.

Ni-Catalyzed C-C Couplings Using Alkyl Electrophiles.

Much effort has been devoted to developing new methods using Ni catalysts for the cross-coupling reaction of alkyl electrophiles with organometallic reagents, and significant achievements in this area have emerged during the past two decades. Nickel catalysts have enabled the coupling reaction of not only primary alkyl electrophiles, but also sterically hindered secondary and tertiary alkyl electrophiles possessing β-hydrogens with various organometallic reagents to construct carbon skeletons. In addition, Ni catalysts opened a new era of asymmetric cross-coupling reaction using alkyl halides. Recent progress in nickel-catalyzed cross-coupling reaction of alkyl electrophiles with sp(3)-, sp(2)-, and sp-hybridized organometallic reagents including asymmetric variants as well as mechanistic insights of nickel catalysis are reviewed in this chapter.

Nickel-Catalyzed Cross-Coupling Reactions from Amides

Nickel-Catalyzed Cross-Coupling Reactions from Amides