Nickel-catalyzed (hetero)aryl borylations: an update

Aromatic organoboron compounds serve as important intermediates in synthetic organic chemistry. While the traditional electrophilic borylations using aromatic lithium or magnesium reagents had several limitations, transition metal catalyzed borylations emerged as a promising method. In recent years, borylation reactions catalyzed by Ni have gained great attention due to its enormous importance as a cheaper and less toxic alternative to Pd catalysts. The present review focuses on the recent developments in the arena of Ni catalyzed (hetero)aryl borylations after 2013.

pattern and cost-efficiency. 15 The first nickel complex bearing a boryl moiety that could act as a recyclable reagent for the borylation of bromobenzene was reported by Mindiola and co-workers in 2007. 28,29 Later, numerous Ni based catalytic systems were developed for aryl borylation reactions. The boron sources, used in general, for the reactions were pinacolborane(HBpin), Bis(neopentylglycolato)diboron(B2nep2) and bis(pinacolato)diboron(B2pin2). The first catalytic system for neopentylglycolborylation, NiCl2(dppp)/dppp [dppp = 1,3bis(diphenylphosphanyl)propane] was effective for aryl iodide and bromide substrates. 30,31 The borylation of even more challenging substrates such as aryl chlorides 32 , and the less reactive aryl sulfonates 5 was attained by the use of mixed-ligand systems, in particular NiCl2(dppp)/dppf [dppf = bis(diphenylphosphanyl)ferrocene]. 12 Interestingly, though some aryl mesylates and tosylates were successfully neopentylglycolborylated in high yields with NiCl2(dppp)/dppf, without any additives, the inclusion of zerovalent Zn metal as additive was found to further enhance the rate of thereaction, presumably by activating the Ni catalyst. The role of Zn was assumed to be as a reducing agent, which arguably compensated for the slower reduction of the precatalyst or oxidative addition adduct in such systems. Such reactions exhibited broad substrate compatibility and higher reaction rates and the neopentylglycolborylation of iodides, bromides, and chlorides proceeded faster achieving complete conversions and high yields. 33 Using bis(pinacolato)diboron as the borylating agent, borylation of aryl chlorides was catalyzed by NiCl2(PMe3)2. 34 In addition to the general borylating agents mentioned earlier, 4,4,6-trimethyl-1,3,2-dioxaborinane was presented as an alternative, cheaper boron source for the borylation of aryl halides catalyzed by NiCl2(dppp). 35 Though a detailed discussion on the Ni-catalyzed borylation of aryl halides and sulfonates up to late 2012 is included in the review paper by Kwong et al 6 of 2013, attempts to summarize (hetero)aryl and benzyl borylation reactions catalyzed by Ni specifically are rather scarce. Considering the ever-increasing demand for Ni catalysts owing to their low cost compared to Pd catalysts, wide applicability, and the potential of aryl substrates with boron functionality for synthetic transformations, we have consolidated the works on Nicatalyzed aryl and (hetero)aryl borylation reactions reported from 2013 to late 2021. In this review, for the sake of convenience, we have categorized the (hetero)aryl borylation reactions into different sections based on the substrates used.

Borylation of Simple (Hetero)Arenes
The following section illustrates the use of Ni catalysts for the borylation of simple arenes and heteroarenes like benzene, naphthalene, indole, pyridine and their derivatives. Such reactions, in general, proceed via C-H activation, and Ni(COD)2 based catalytic systems are used in all cases, except for the directed C3-H borylation of indoles, where a [Ni(IMes)2] based system is employed.
In 2015, Tobisu et al. carried out the first nickel-catalyzed borylation of C-H bonds in arenes and indoles. 36 Their study focused on the development of an appropriate Ni based catalytic system for the direct introduction of useful boron functionality at the C-H bond of an arene without the aid of a directing group. A cyclohexyl-substituted N-heterocyclic carbene, ICy (1,3-dicyclohexylimidazolin-2-ylidene) was proven to be the most efficient ligand with Ni(COD)2 for the reaction (Scheme 1). On the borylation of benzene and its derivatives with HBpin as boron source and 3 mol% of Ni(COD)2/ICy system in the presence of 6 mol% of NaO t Bu at 80 C, good to excellent yields was obtained. In the case of mono and disubstituted alkyl benzenes, the proportion of ortho, meta, para and benzylic products varied greatly depending on the steric factors of the substrate, however, meta and para products predominated and the mono substituted compounds were more reactive than the disubstituted ones. Surprisingly with anisole, ortho-borylated isomer was the major product and the C(aryl)-OMe bond in anisole was also cleaved to give the corresponding borylated product.
On analyzing heteroarenes as potential substrates, pyrrole was found to be exceptionally reactive while other heteroarenes like furan, thiophene, pyridine and their benzo-fused derivatives were unreactive. Regioselective borylation at position-2 was observed for indole derivatives in relatively high yields (Scheme 2). The practical utility of the nickel-catalyzed system was established by the gram scale synthesis of 2-borylindole using Ni(OAc)2 as the precatalyst. Further investigation into the mechanistic aspects suggested the involvement of heterogeneous Ni species, though the authors emphasized the need for further studies to provide a detailed explanation. Scheme 1. Borylation of benzene and its derivatives using Ni(COD)2/ICy catalytic system. At the same time, Itami and coworkers documented the C-H borylation of aromatic compounds using a Ni based catalyst. 37 The aromatic C-H borylation of benzene and its derivatives was achieved using [Ni(COD)2]/PCyp3 catalytic system, with B2pin2 as boron source and CsF as additive at 140 C and rendered the products in reasonable yields (Scheme 3). The carbene ligand, IPr was found to be more efficient than PCyp3 for electron-deficient benzene derivatives. Though [Ni(COD)2]/PCyp3/CsF catalysis was not compatible with electron-deficient heteroarenes, electron-rich indole derivatives proceeded with C-H borylation exclusively at C-2 position. The work demanded further studies to expand the substrate scope of the reaction under study.  More recently, Mandal et al. came up with a novel strategy for C(sp 2 )−H borylation of arenes mediated by an abnormal NHC based nickel catalyst to compensate for the limited substrate scope encountered in the former works. 38 The abnormal N-heterocyclic carbene 1,3-bis(2,6-diisopropylphenyl)-2,4-diphenylimidazol-5ylidene in association with the Ni precursor Ni(COD)2 was found to be more catalytically active and nucleophilic than its normal NHC counterpart (Scheme 4). 39 The reaction proceeded under the conditions of 5 mol% of catalyst, HBPin as boron source and arene at 80 C for 16 h to give C(sp 2 )−H borylated compounds. In addition to the direct C(sp 2 )−H borylation of simple arenes like benzene, different alkyl and alkoxy arenes like n-hexylbenzene, n-butylbenzene, n-propylbenzene, phenylcyclohexane, naphthalene, biphenyl, 1,3diisopropylbenzene, and 1,3-dimethoxybenzene were borylated at C(sp 2 )−H position for the first time using this catalytic system.
Mechanistic studies revealed the existence of a heterogeneous pathway. They identified the black particles formed during the reaction on the walls of the reaction vessel as nickel nanoparticles through several control experiments and characterization techniques, which along with a boron(III) compound constituted the catalytically active species.  40 Regioselective C−H diborylations of peri-xanthenoxanthene derivatives were accomplished by their reaction with B2pin2 in the presence of Ni(COD)2 and 1,2bis(dicyclohexylphosphino)ethane (dcype) as the catalyst in the presence of an additive, trifluoroethanol in xylene at 150 ᵒC in 18 h (Scheme 5). Monoborylation of fused aromatic compounds including perixanthenoxanthene(PXX), perylene, fluoranthene, and anthracene at their sterically congested α-positions was achieved under the similar reaction conditions, but the amounts of B2pin2 and trifluoroethanol were reduced to 1 equivalent and 1.2 equivalent respectively, and a lower temperature of 80 ˚C was employed for the completion of the reaction in 36 h. On the contrary, the reaction did not work with naphthalene, Nmethylindole and anisole.
The mechanism put forward by the group was different from that of the previous reports, where a σbond metathesis mechanism has been proposed and the first step is considered to be the formation of a nickel(0)-anthracene η 2 -complex by the η 2 -coordination of the C4−C5 double bond of PXX to the Ni species (Scheme 6).  A highly selective, traceless, directed C3−H borylation of indoles using a Ni catalyst was documented by Radius et al. in 2020. 41 The catalyst, [Ni(IMes)2] (10 mol%) borylated indole derivatives selectively at C3-H position using B2pin2 as the boron source in hexane at 60 ˚C within 4 h (Scheme 7). Irrespective of the nature of the substituent present, C3-borylated indoles were obtained in good to excellent yields which revealed the functional group tolerance of the protocol. Of note, the reactions proceeded under mild conditions in the absence of a base.
The direct synthesis of a C3-arylated indole by a one-pot C3−H borylation/Suzuki-Miyaura crosscoupling sequence was accomplished by the group to prove the synthetic utility of the proposed reaction.

Borylation of Aryl and Aroyl Halides or Pseudo Halides
Earlier, the reports on Ni-catalyzed borylations of aryl halides were less frequent than that of Pd catalyzed aryl halide borylations. 42 More works on the borylation of aryl halides were published in the subsequent years. The present section discusses the borylation of aryl fluorides, chlorides and bromides catalyzed by Ni. Two reports on Ni-catalyzed borylations of aroyl fluorides are also included.

Scheme 9.
Ni-catalyzed borylation of monofluoroarenes by Ni(COD)2/PCy3 system. The first Ni-catalyzed borylation of monofluoroarenes was demonstrated by Martin et al. employing Ni(COD)2/PCy3 in 1:4 ratio with B2(nep)2 as boron source, THF as solvent and NaOPh as an additive that rendered borylated aryl fluorides in good to high yields (Scheme 9). 43 The reaction was found to be highly chemoselective and unaffected by the presence of other functional groups.
Mechanistic studies revealed the existence of an oxidative addition complex via C(sp 2 )-F activation which is then subjected to a boryl transfer from the boron source assisted by NaOPh (Scheme 10). The final borylated arene is released by C-B bond-reductive elimination and the active species Ni(PCy3)2 is regenerated. This unconventional strategy for C-C-B bond-formation via catalytic C-F cleavage of unactivated fluoroarenes marked the synthetic utility of such compounds for the development of novel molecules of interest.  45 They assessed the C-F bond cleavage and subsequent borylation in several polyfluoroarenes using the catalyst [Ni(IMes)2] (10 mol%), B2pin2 (0.2 mmol) as the source of boron, NMe4F or CsF (0.5 equiv.) as fluoride source and methylcyclopentane (1 mL) as solvent at 80 C affording moderate to good yields of the product (Scheme 11). Interestingly, the catalytic system [Ni(IMes)2] was found to be less effective for pentafluorobenzene, whereas [Ni(IPr)2] improved the reaction yield considerably. They also proposed a mechanism for the reaction (Scheme 12). The work is significant due to the high utility of borylated fluoroaromatics as precursors in organic synthesis. Nishihara et al. disclosed an efficient method for the decarbonylative borylation of aroyl fluorides aided by Ni/PPh3 catalytic system. 46 The reaction of aroyl fluorides with bis(pinacolato)diboron in the presence of 10 mol% of Ni(COD)2, 30 mol% of PPh3, 2.5 equiv. of KF, and 2.0 equiv. of NaCl at 140 °C for 24 h in a mixed solvent system of toluene and octane(v/v = 2/1) proceeded to give the corresponding arylboronates in good to high yields (Scheme 13). The scope for large scale synthesis was also established.
A general and selective base-free decarbonylative borylation of carboxylic acid fluorides catalyzed by Ni was described by Sanford and coworkers in 2019. 47 The study aimed at solving the riddle of competing transmetalation reactions of the Ar−Ni−F intermediate with the organoboron product and the diboron reagent which resulted in the formation of undesired biaryl products by undesirable cross-coupling reactions instead of selective borylation.
The group investigated the scope of decarbonylative borylation in the absence of a base because it had already been established from the previous works that Ar−Ni−F intermediate, formed by the oxidative addition and carbonyl deinsertion of aroyl fluorides to the nickel catalyst was able to take part in direct, basefree transmetalation with the boron source (Scheme 14). They isolated the Aryl−Ni−F intermediate and investigated its transmetalation reactivity with aryl boronate esters and alkoxy diboron reagents separately in toluene at room temperature under base free conditions. The results revealed that the relative rates of transmetalation of the intermediate with diboron reagents were significantly faster than that of their aryl boronate ester congeners so that the conditions can be tailored to favour the selective formation of Ar-B(OR)2 products over unwanted biaryls. Interestingly, in both cases, the transmetalation activities were found to be directly proportional to the Lewis acidity at the boron center.
Furthermore, they investigated the potential of the transmetalation active intermediate, (PCy3)2Ni-(Ph)(F) (10 mol%) to act as an air-stable Ni precatalyst for the conversion of aroyl flourides to aryl boronates and the catalyst was found to be effective for the reaction (Scheme 15). Using the precatalyst, they also carried out the direct conversion of aryl carboxylic acids to aryl boronic acid esters via in situ generation of acid fluorides by activation followed by nickel-catalyzed decarbonylative borylation.  48 The uniqueness of the catalytic system was marked by its ability to work efficiently even in the absence of other coligands or additives except for the mild base NaOAc as additive. Chloroarenes with electron-donating or electron-withdrawing groups on reaction with B2pin2 as boron source using 2.5 mol% of [Ni2(ICy)4(μ-(η 2 :η 2 )-COD)] as the catalyst, 1.5 equiv. of NaOAc as an additive in methylcyclohexane at 100 ˚C gave the expected borylated products in good to excellent yields. The boron source, Bis(neopentylglycolato)diboron (B2nep2) was also found to be effective with the catalyst. The formation of C-Cl oxidative addition products of the type trans-[Ni(ICy)2(Cl)(Ar)] was also investigated by the stoichiometric reactions of the proposed catalyst with different aryl chlorides.  The research groups of Darcel and Ghosh synthesized a series of nickel complexes of the chelating anionic amido functionalized N-heterocyclic carbene ligands and investigated their role as potential catalysts for the borylation reactions of different aryl bromides. 50 The reaction between 1.5 equiv. of bis(pinacolato)diboron reagent (B2pin2) and 1 equiv. of arylbromide substrates, in the presence of 3 equiv. of The methodology was compatible with a wide range of substrates including electron-rich, neutral, electron-deficient and heteroaryl bromides. In addition to bromides, a diverse set of compounds such as aryl and heteroaryl chlorides, mesylates, tosylates, triflates and sulfamates underwent the reaction under the same conditions. Surprisingly, while good to excellent yields were obtained for a range of heteroarenes, heteroaryls like pyrimidine, isoxazole, and thiazole failed to give the reaction. Aryl mesylates, which did not give the desired product in Pd-catalyzed borylarions, proceeded under the given reaction conditions to yield potassium trifluoroborate salts in good yields.
Later in 2019, He et al. employed the aforementioned reaction as the first catalytic cycle in a sequential nickel-and rhodium-catalyzed relay reaction incorporating Miyaura borylation and Hayashi−Miyaura conjugate addition in one pot (Scheme 22). 52 The aryl halides or triflates were converted into the corresponding boronic acids by the Ni catalyst and enantioselective conjugate addition to the electrondeficient olefins was mediated by the chiral-diene rhodium catalyst Scheme 22. General representation of the sequential nickel-and rhodium-catalyzed relay reaction.
The work of Molander also served as a reference for the development of a screening platform for nickel-catalyzed borylations of aryl(pseudo)halides with B2(OH)4 by the research group of Wisniewski in 2019. 53 Initially, the screening study was focused on the development of an arylboronic acid of their interest for the generation of an active pharmaceutical ingredient (API), BMS-986142 (Scheme 23). Their first attempt was to analyse the effect of class variables like ligand, solvent and base on this particular borylation reaction, but later they extended the scope of their work to develop a general screening platform that can be applied for the borylation of any aryl halide. A general set of 24 reaction conditions that can be applied to any aryl (pseudo)halide was designed to serve as an effective guide for the borylation of aryl chlorides, bromides, and iodides and pseudohalides (Scheme 24).  Later, in 2020, Frantz et al. conducted a comparative study on the catalytic borylation of aryl (pseudo)halides with B2(OH)4 by Pd-and Ni-based systems. 54 Compared to Pd based catalysts, Ni catalysts were inexpensive, and unligated Ni(II) salts were utilized in the borylation procedure. Their attempt to make a comparison between Pd and Ni-catalyzed borylations with BBA was based on three catalytic systems developed by the Frantz team, 55 (AtaPhos)2PdCl2 (Pd-1), XPhos-Pd-G3 (Pd-2) and NiCl2·6H2O/CyJohnPhos (Ni-1). The catalysts selected for the study were efficient to progress under milder reaction conditions in terms of temperature and catalyst loadings.
Initially, borylation reactions of simple aryl electrophiles using the three catalyst systems were assessed and the resultant boronic acids or diethanolamine adducts were isolated. While all the three catalyst systems were found to be efficient, differential reactivity between Pd-1 for aryl bromides and iodides, Pd-2 for aryl chlorides and Ni-1 catalysts for a range of aryl halides and (pseudo)halides was observed for some entries. They extended the scope of their work by conducting late-stage borylations coupled with sequential Suzuki−Miyaura cross-coupling reactions. A tandem one-pot borylation/cross-coupling reaction sequence with Pd-1 and Pd-2 catalyst systems was carried out, but a similar strategy could not be adopted for Ni-1 catalyst system and therefore, a Ni/Pd tandem sequence was designed. The work holds the potential to serve as a "user's guide" to design feasible metal-catalyzed direct borylations with BBA to drive the synthesis of complex organic molecules.
In 2017, Hu et al. performed Ni(COD)2/PCy3-catalyzed borylation of aryl arene sulfonates with bis(pinacolato)diboron at room temperature. 56 With respect to the previous reports on the same reaction at higher temperatures of 80 °C, the present work at room temperature achieved better results (Scheme 25). The base, K3PO4 and the solvent, degassed THF were found to have a profound influence on the reaction rates. To account for the extreme air sensitivity of Ni(COD)2 in Ni(COD)2/PCy3, air stable 4-MeOC6H4Ni II (PCy3)2OTs, the oxidative addition adduct of 4-MeOC6H4OTs with Ni(COD)2/PCy3 was developed and employed in Miyaura borylation reaction. Good to high yields were obtained which proved the efficiency of 4-MeOC6H4Ni II (PCy3)2OTs as catalyst.

Borylation of Aryl (Silyl)Ethers
This section includes reports on the Ni-catalyzed borylations of aryl ethers and silyl ethers. The reactions proceed via the activation of relatively inert C-O bonds.
The first ipso-borylation of aryl methyl ethers to achieve a carbon−heteroatom bond via an unconventional Ni-catalyzed C-OMe bond cleavage was reported by Martin and coworkers in 2015. 57 Naphthyl methyl ethers were productively ipso-borylated by Ni(COD)2/PCy3 catalytic system via C(sp 2 )-OMe bond cleavage using B2(nep)2 in the presence of HCO2Na at 95 °C (Scheme 26). Ipso borylation was also achieved by the same catalytic system via C(sp 3 )−OMe cleavage when B2(pin)2 was used in the presence of CsF at 120 ˚C. Thus, orthogonal site-selective C−B bond formation was achieved using specific boron reagents. When C(sp 3 )−OMe cleavage was observed with B2(pin)2, B2(nep)2 resulted in C(sp 2 )−OMe bond cleavage of naphthyl methyl ethers. On the other hand, C(sp 2 )−OMe bond cleavage with B2(pin)2 was achieved in regular arenes. This novel approach was extended towards the ipso-halogenation of aryl methyl ethers in good yields employing a one-pot borylation/iodination sequence.  58 The borylation of C(aryl)-O bond in diverse aryl 2-pyridyl ethers activated by the presence of a 2-pyridyl moiety, was performed in good to high yields using NiCl2(DME) catalytic system with PCy3·HBF4 as ligand and K3PO4 as the base in DME at 100 ˚C for 15 h (Scheme 27). The reaction was found to be chemoselective and functional group tolerant, which worked well with amines, ethers, fluorides, esters, acetals and even heteroaromatic systems. The same catalytic system was applied to arylmethyl 2-pyridyl ethers and the reaction proceeded under similar reaction conditions to give borylated products in notable yields. However, there was a need for a stronger ligand, ICy to achieve the C(benzyl)-O borylation of benzyl ethers, which were found to be less reactive than naphthyl ethers. Further, the study was extended to secondary benzylic substrates to determine the stereospecificity of the reaction. Retention of configuration was observed following the initial C(benzyl)-O bond cleavage, contrary to the previously reported overall inversion of the benzylic stereocenter in common substrates. The transformation of a useful directing group like OPy to a boryl group enhances the scope of its synthetic utility.

Scheme 28.
Ipso-borylation of silyloxyarenes by Ni(acac)2/IPr Me ·HCl catalytic system. Montgomery et al. proposed a novel strategy for the ipso-borylation of silyloxyarenes aided by a Ni catalyst (Scheme 28). 59 The method succeeded in the activation of relatively inert C-O bond in the absence of any directing group in isolated aromatic systems, and thus stands out from the previous works where the focus was on polyaromatic systems bearing ortho-directing groups. A range of siyloxyarenes were ipsoborylated in good to excellent yields by Ni(acac)2/IPr Me ·HCl catalytic system with B2pin2 as the boron source, and LiO t Bu as the base in cyclopentyl methyl ether solvent. Aryl fluorides and isolated aromatic species bearing ester and amide groups failed to give the reaction. However, the direct borylation of silyl ethers by the functionalization of relatively less reactive C(sp 2 )-O and C(sp 3 )-O bonds was achieved, and the synthetic utility of the method was also demonstrated.

Borylation of Esters and Aldehydes
This part describes the Ni-catalyzed decarbonylative borylation of phenolic esters and aldehydes, which proceed via C(acyl)−O and C(acyl)−H activation respectively.
Shi et al. carried out a nickel-catalyzed direct borylation of phenolic esters by acyl C-O bond activation in 2016. 60 The conversion of a ester functionality into a readily convertible C-B bond in phenolic esters was achieved in moderate to excellent yields by their reaction with B2(nep)2, in the presence of 5 mol% of Ni(COD)2 as the catalyst, ICy·HCl (10 mol%) as ligand, 2.0 equiv. Na2CO3 and NaCl (1:1) as the additive and NaO t Bu (10 mol%) as the base in dioxane at 160 °C (Scheme 29). The novel strategy was successfully applied in the latestage decarbonylative borylation of a second-generation topical retinoid, adapalene, and the targeted arylboronate was obtained in 61% yield (Scheme 30). A novel strategy for the Nickel-catalyzed ipso-borylation of aldehydes was reported by the research group of Rueping in 2020. 61 The decarbonylative borylation of aldehydes was carried out using Ni(COD)2 (5 mol%)/P(Oct)3 (10 mol%) catalytic system, 2,2,2-trifluoro-1-(4-fluorophenyl)-ethanone (1.5 equiv.) as Hacceptor in toluene at 160 C for 36 h resulting in good to high yields (Scheme 31). The role of the H-acceptor was found to be crucial in the reaction as it prevented the conversion of the acyl nickel hydride species formed in the first step into the corresponding arenes via CO migration and subsequent reductive elimination by a key hydride transfer step to the pi-coordinated H-acceptor. The base-free decarbonylative ipso borylation of aldehydes was successfully applied to a wide variety of substrates including the derivatives of complex natural products. The reaction exhibited functional group tolerance and a chemoselective bond cleavage in the case of esters, leaving the ester groups intact. Furthermore, the scalability of the proposed reaction was also established.

Borylation of Aryl Sulfoxides
The transformation of aryl sulfoxides into the corresponding aryl boronic esters by a nickel/NHC catalytic system was performed by Marder et al. in 2021. 62 The Ni-NHC catalyzed borylation of aryl sulfoxides with B2(nep)2 in the presence of 5 mol% of [Ni(COD)2], 10 mol% of ICy·HBF4, and 2.5 equivalents of NaO t Bu in 1,4 dioxane at 110 ˚C afforded arylboronates in good yields (Scheme 32). The reaction exhibited a wide substrate scope wherein both electron-rich and electron-poor diaryl sulfoxides underwent borylation to give the desired products in good yields. On the contrary, cyano-, amino-, ester-and indole based substrates failed to give the reaction. The group also reported regioselective borylation with sterically biased unsymmetrical diaryl sulfoxides. In addition, the effect of the electronic properties of aryl sulfoxides was studied through competition reactions. Intramolecular and intermolecular competitive borylations of unsymmetrical diaryl sulfoxides revealed the selective preference for electron-deficient moieties.

Borylation of Aryl amines, Amides and Carbamates
The Ni-catalyzed borylations of amines, amides and carbamates that proceed via C-N bond cleavage are included in this section.
A promising method for aromatic and benzylic C-N borylation catalyzed by nickel-phosphine complexes was proposed by Itami and his group in 2015. 63 The borylation of aryl ammonium salts (0.2 mmol) was carried out by employing bis(pinacolato)diboron (B2pin2, 0.4 mmol) as the boron source in the presence of [Ni(COD)2] (10 mol%; cod = 1,5-cyclooctadiene), trin-butylphosphine (PnBu3, 20 mol%), and NaOtBu (2 equiv.) in 1,4-dioxane at 70 °C for 24 h resulting in good yields (Scheme 33). Under standard conditions, substrates with electron-donating substituents achieved higher yields compared to those bearing electron-withdrawing groups. Interestingly, on studying the C-N borylation of benzylic amine derivatives, the precatalyst Ni(NO3)2·6H2O was found to be more efficient than the previously used Ni(COD)2 catalyst for C-N borylation of phenyl amines (Scheme 34). Another notable difference between aromatic and benzylic C-N borylation was in the choice of the solvent, where 1,4-doxane was found to be the best solvent for aromatic C-N borylation, higher yields were observed when DME was used as the solvent in the latter case.
An investigation into the mechanism based on the experimental observations suggested three main steps, namely oxidative addition, -bond metathesis and reductive elimination. The first step involves the oxidative addition of aryl or benzylic ammonium salt to the Ni 0 -PnBu3 species with the elimination of NMe3. In the next step, (boryl)organonickel(II) species is obtained by the σ-bond metathesis of the organonickel(II) triflate formed in the first step with B2pin2. This σ-bond metathesis is considered to be promoted by the tertbutoxide base. In the final step, the borylated product is released by the reductive elimination of the C-B bond and the active Ni 0 species is regenerated.
The group explored the synthetic utility of the reaction by coupling C-N borylation with a class of Me2N-directed aromatic functionalization reactions and C-B transformations which made possible the synthesis of a wide variety of aromatics in good to high yields. The work highlighted the scope of using Me2N group as a potential transformable directing group to drive diverse organic transformations.
Scheme 33. C-N borylation of phenyl amines with Ni(COD)2/ PnBu3 catalytic system. Shi et al. proposed a highly chemo-and regioselective C-N bond borylation method for aryl and benzyl trimethylammonium salts catalyzed by nickel under mild conditions. 64 The reaction of various arylammonium triflates with bis(pinacolato)diboron aided by Ni(COD)2(5 mol%)/ICy·HCl(10 mol%) catalytic system in 1:1 Toluene/EE (2-ethoxyethanol) solvent mixture in the presence of t BuOK as the base at 50  C, provided the corresponding aryl boronic esters in moderate to good yields (Scheme 35). Benzylamines were also found to be borylated by this protocol. Selective C-N borylation was observed even in the presence of functional groups except for halide substituents (other than aryl fluorides) where borylation proceeded at both C-N and C-X sites. Importantly, the group also reported the tertiary C-N bond activation of benzylamines for the first time. The potential of the method for gram-scale synthesis and late-stage borylative C-N bond cleavage of complex molecules was also demonstrated. Ring-opening via borylative cleavage of C-N bonds in aza heterocyclic compounds was also accomplished in moderate to good yields using this strategy.
The mechanistic studies suggested three important steps, namely oxidative addition, transmetallation and reductive elimination (Scheme 36). An SN2 mechanism is likely to get involved in the oxidative addition of the nickel catalyst into the benzylic C−N bond, resulting in an inversion of configuration at the benzylic stereo center. The co-solvent EE generates an anionic adduct of the borylating agent in the presence of KO t Bu, which facilitates the transmetallation. The significance of the work is highlighted by the incorporation of this functional group tolerant, highly efficient and chemoselective strategy into various synthetic routes for the preparation of versatile biologically active compounds and other relevant transformations.  65 While the previous reports on C-N bond cleavage catalyzed by ruthenium were restricted only to aniline derivatives bearing an ortho group, Tobisu's group derived an efficient route towards the catalytic conversion of C-N bonds in aryl amides and carbamates having no ortho substituents into C-H and C-B bonds for the first time. The borylation reaction catalyzed by the Ni(COD)2/IMes system using the diborane reagent B2(nep)2, worked well with both cyclic and acyclic amides. Polyaromatic compounds like naphthalenes, quinolines, anthracenes and phenanthrenes exhibited high reactivity, but the steric environment of the substrate had a profound effect on the reaction yield. Similarly, they also conducted the reductive C-N cleavage reaction using the hydroborane reagent HB(pin). The present work demonstrated a valuable approach towards a new bond disconnection strategy that can be utilized in synthetic applications.
Rueping et al. developed a useful procedure for the Ni-catalyzed decarbonylative borylation of amides via the cleavage of C-N bond. 66 Aryl amides, on reaction with bispinacolato diboron in the presence of Ni(COD)2 (10 mol%) /P n Bu3 (40 mol%) catalyst and Li2CO3 (1.5 equiv.) base in dioxane at 160 °C for 36 h produced the corresponding arylboronates in acceptable yields (Scheme 38). The group also studied nickelcatalyzed decarbonylative silylations and aminations of amides under similar reaction conditions.

Conclusions
In this review, we have attempted to summarize the available works on (hetero)aryl borylations catalyzed by nickel, reported since 2013. While nickel was initially introduced as a cost-effective substitute for other transition metal catalysts, the later works demonstrated its ability to display a unique reactivity profile, and even substrates that were previously inaccessible to other transition metals were successfully borylated. A wide spectrum of substrates including, but not limited to, aryl halides, N-aryl amides, carbamates, aryl methyl ethers, amides, phenolic esters, arenes, indoles, aryl sulfoxides, and aldehydes were successfully borylated by Ni catalysts.
Most of the Ni-based catalysts, with a few exceptions, demanded the presence of suitable coligand for their activity, whereas the reason behind the preferential choice of specific coligands in a reaction could not be mechanistically explained in all instances. A detailed investigation into this aspect may contribute towards the development of more efficient reactions in near future. Recently, there has been a tendency to incorporate innovative routes encompassing the realms of photochemistry and sonochemistry into the genre of transition metal catalysis to enhance catalytic efficiency. Though the advent of such methodologies into Nicatalyzed hetero(aryl) and benzylic borylation reactions are still in their infancy, attempts to move out of the conventional catalytic systems and to embrace newer pathways can be regarded as a positive change capable of bringing in promising results. The progress made in the field of (hetero)aryl borylation by Ni catalysts within the discussed short period is indicative of the multitude of reactions to be born in the brains of researchers in the following years