Nickel‐Catalyzed Amination of Aryl Chlorides with Ammonia or Ammonium Salts

The nickel‐catalyzed amination of aryl chlorides to form primary arylamines occurs with ammonia or ammonium sulfate and a well‐defined single‐component nickel(0) precatalyst containing a Josiphos ligand and an η²‐bound benzonitrile ligand. This system also catalyzes the coupling of aryl chlorides with gaseous amines in the form of their hydrochloride salts.     

Electrochemically Enabled,Nickel‐Catalyzed Amination

Along with amide bond formation, Suzuki cross‐coupling, and reductive amination, the Buchwald–Hartwig–Ullmann‐type amination of aryl halides stands as one of the most employed reactions in modern medicinal chemistry. The work herein demonstrates the potential of utilizing electrochemistry to provide a complementary avenue to access such critical bonds using an inexpensive nickel catalyst under mild reaction conditions. Of note is the scalability, functional‐group tolerance, rapid rate, and the ability to employ a variety of aryl donors (Ar−Cl, Ar−Br, Ar−I, Ar−OTf), amine types (primary and secondary), and even alternative X−H donors (alcohols and amides).     

Nickel‐Catalyzed Difluoromethylation of Arylboronic Acids with Bromodifluoromethane

Although bromodifluoromethane (BrCF₂H) is a simple and readily available fluorine source, direct formation of difluoromethylated arenes with BrCF₂H has not been reported. Herein, we describe an efficient method to access difluoromethylated arenes through a nickel‐catalyzed difluoromethylation of arylboronic acids with BrCF₂H. The reaction exhibits high efficiency, good functional group tolerance and broad substrate scope, thus providing an efficient route for applications in drug discovery and development. Preliminary mechanistic studies reveal that a difluoromethyl radical is involved in the reaction.     

Ni‐Catalyzed Amination Reactions: An Overview

Nitrogen‐containing organic compounds are valuable in many fields of science and industry. The most reliable method for the construction of C(sp²)–N bonds is undoubtedly palladium‐catalyzed amination. In spite of the great achievements made in this area, the use of expensive Pd‐based catalysts constitutes an important limitation for large‐scale applications. Since nickel is the least expensive and most abundant among the group 10 metals, the interest in Ni‐based catalysts for processes typically catalyzed by palladium has grown considerably over the last few years. Herein, we revise the development of Ni‐catalyzed amination reactions, emphasizing the most relevant and recent advances in the field.     

Selective Monoarylation of Primary Amines Using the Pd‐PEPPSI‐IPentCl Precatalyst

A single set of reaction conditions for the palladium‐catalyzed amination of a wide variety of (hetero)aryl halides using primary alkyl amines has been developed. By combining the exceptionally high reactivity of the Pd‐PEPPSI‐IPent^Cl catalyst (PEPPSI=pyridine enhanced precatalyst preparation, stabilization, and initiation) with the soluble and nonaggressive sodium salt of BHT (BHT=2,6‐di‐tert‐butyl‐hydroxytoluene), both six‐ and five‐membered (hetero)aryl halides undergo efficient and selective amination.     

Nickel‐Catalyzed Dehydrogenative Cross‐Coupling: Direct Transformation of Aldehydes into Esters and Amides

By exploring a new mode of nickel‐catalyzed cross‐coupling, a method to directly transform both aromatic and aliphatic aldehydes into either esters or amides has been developed. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α‐trifluoroacetophenone or excess aldehyde. Mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C? H bond is also presented.     

Dialkyl Ether Formation by Nickel‐Catalyzed Cross‐Coupling of Acetals and Aryl Iodides

A new substrate class for nickel‐catalyzed C(sp³) cross‐coupling reactions is reported. α‐Oxy radicals generated from benzylic acetals, TMSCl, and a mild reductant can participate in chemoselective cross‐coupling with aryl iodides using a 2,6‐bis(N‐pyrazolyl)pyridine (bpp)/Ni catalyst. The mild, base‐free conditions are tolerant of a variety of functional groups on both partners, thus representing an attractive C? C bond‐forming approach to dialkyl ether synthesis. Characterization of a [(bpp)NiCl] complex relevant to the proposed catalytic cycle is also described.     

Nickel‐Catalyzed Amination of Silyloxyarenes through C–O Bond Activation

Silyloxyarenes were utilized as electrophilic coupling partners with amines in the synthesis of aniline derivatives. A diverse range of amine substrates were used, including cyclic or acyclic secondary amines, secondary anilines, and sterically hindered primary anilines. Additionally, a range of sterically hindered and unhindered primary aliphatic amines were employed, which have previously been challenging with other classes of aryl ether electrophiles. Orthogonal couplings of silyloxyarenes with aryl methyl ethers are illustrated, where selectivity between the two C?O electrophiles is determined by ligand control, thereby allowing complementary and selective late‐stage diversification of either electrophile. Finally, a sequential coupling displays the utility of this amination method along with the reversal in intrinsic reactivity between aryl methyl ethers and silyloxyarenes.     

Nickel‐Catalyzed Cross‐Coupling Reactions of o‐Carboranyl with Aryl Iodides: Facile Synthesis of 1‐Aryl‐o‐Carboranes and 1,2‐Diaryl‐o‐Carboranes

A nickel‐catalyzed arylation at the carbon center of o‐carborane cages has been developed, thus leading to the preparation of a series of 1‐aryl‐o‐carboranes and 1,2‐diaryl‐o‐carboranes in high yields upon isolation. This method represents the first example of transition metal catalyzed C,C′‐diarylation by cross‐coupling reactions of o‐carboranyl with aryl iodides.     

Microwave‐Assisted Heterogeneous Cross‐Coupling Reactions Catalyzed by Nickel‐in‐Charcoal (Ni/C)

A study involving the relatively rare combination of heterogeneous catalysis conducted under microwave conditions is presented. Carbon–carbon bond formation, including Negishi and Suzuki couplings, can be quickly effected with aryl chloride partners by using a base metal (nickel) adsorbed in the pores of activated charcoal. Aminations were also studied, along with cross‐couplings of vinyl alanes with benzylic chlorides as a means to stereodefined allylated aromatics. Reaction times for all these processes are typically reduced from several hours to minutes in a microwave reactor.     

Nickel‐Catalyzed Direct Coupling of Allylic Alcohols with Organoboron Reagents

The direct coupling of allylic alcohols with arylboronic acids or their derivatives catalyzed by Ni(cod)₂ in the presence of a catalytic amount of base has been developed. A wide variety of allylic substrates or arylboronic acids turned out to be applicable to this catalytic system. The present method does not require the use of ligands for stabilizing the nickel catalyst in most cases or additional activators for activation of allylic alcohols.     

Facile Access to Fluoromethylated Arenes by Nickel‐Catalyzed Cross‐Coupling between Arylboronic Acids and Fluoromethyl Bromide

The nickel‐catalyzed fluoromethylation of arylboronic acids was achieved with the industrial raw material fluoromethyl bromide (CH₂FBr) as the coupling partner. The reaction proceeded under mild reaction conditions with high efficiency; it features the use of a low‐cost nickel catalyst, synthetic simplicity, and excellent functional‐group compatibility, and provides facile access to fluoromethylated biologically relevant molecules. Preliminary mechanistic studies showed that a single‐electron‐transfer (SET) pathway is involved in the catalytic cycle.     

Nickel‐Catalyzed Csp2Csp3 Bond Formation by CarbonFluorine Activation

We report herein a general catalytic method for Csp²?Csp³ bond formation through C?F activation. The process uses an inexpensive nickel complex with either diorganozinc or alkylzinc halide reagents, including those with β‐hydrogen atoms. A variety of fluorine substitution patterns and functional groups can be readily incorporated. Sequential reactions involving different precatalysts and coupling partners permit the synthesis of densely functionalized fluorinated building blocks.