Recent Advances in Methodologies for Radical-Mechanistic Borylation

Chang Lian, ${}^{a, b}$ Jianning Zhang, ${}^{a, b}$ Di Qiu, ${}^{*, c}$ and Fanyang Mo*, ${}^{b}$

${}^{a}$ College of Engineering, Peking University, Beijing 100871, China

${}^{b}$ School of Materials Science and Engineering, Peking University, Beijing 100871, China

${}^{c}$ Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, China

We reviewed works on radical borylation reactions since 2020 from two aspects. 1. Borylation from alkyl or aryl radicals: This approach involves the generation of alkyl or aryl radicals from various precursors such as halides and carboxylic acids, followed by their reaction with diboron reagents to form boron esters. 2. Borylation from boron-centered radicals: This approach involves generating boron-centered radicals, which then react with substrates to achieve borylation.

Introduction 105
Borylation Involving Carbon Radicals 106

2.1. Transition-metal induced borylation 106

2.2. Transition-metal free borylation 108

Borylation Involving Boron-Centered Radical 111
Conclusions and Perspectives 112
Introduction

Organoboron compounds are extensively utilized in both academic research and industry, ${}^{\left\lbrack 1\right\rbrack }$ highlighting the importance of developing new synthetic methods. Traditional methods for synthesizing organoboron compounds often rely on organometallic reagents. Examples include the electrophilic borylation of organolithium reagents, ${}^{\left\lbrack 2\right\rbrack }$ the hydroboration of alkenes, ${}^{\left\lbrack 3\right\rbrack }$ and the transition metal-catalyzed borylation of $\mathrm{C} - \mathrm{H}$ bonds. ${}^{\left\lbrack 4\right\rbrack }$ However, these methods are not always ideal for practical applications because of the harsh reaction conditions, expensive metal catalysts and limited functional group compatibility. In the past decades, radical-mechanistic borylation has stood out due to its mild conditions, excellent functional group tolerance, and environmental friendliness. Numerous radical borylation methods have been proposed, diversifying synthetic approaches for organoboron compounds. ${}^{\left\lbrack 5 - {10}\right\rbrack }$

Boryl radicals can typically be generated by the cleavage of B-B or B-H bonds. ${}^{\left\lbrack {11}\right\rbrack }$ Due to the high B-B bond dissociation energy (BDE, for example, the calculated B-B BDE for ${\mathrm{B}}_{2}{\left( \mathrm{{pin}}\right) }_{2}$ is 101.6 kcal $\cdot {\mathrm{{mol}}}^{-1}$ ), diborane reagents often require activation. This can be achieved by coordinating a strong base, like $N$ -heterocyclic carbenes (NHCs) or ‘BuOK, to the boron center, which reduces the B-B BDE, facilitates homolysis, and stabilizes the resulting boryl radical. ${}^{\left\lbrack {12}\right\rbrack }$

Alternatively, B-H bond homolysis can occur via hydrogen atom abstraction (HAT) in the presence of a radical initiator, ${}^{\left\lbrack {13} - {14}\right\rbrack }$ or through single-electron transfer (SET), ${}^{\left\lbrack {15}\right\rbrack }$ which forms a radical cation intermediate that can be deprotonated to produce the boryl radical. The computational studies indicate that the B-H bond BDE is approximately 105.2 kcal.mol ${}^{-1}$ . ${}^{\left\lbrack {16}\right\rbrack }$ To overcome the challenge posed by the high B-H BDE, NHC-boron complexes have been developed. These complexes reduce the B-H BDE to around ${70} - {90}\mathrm{{kcal}} \cdot {\mathrm{{mol}}}^{-1},{}^{\left\lbrack {17}\right\rbrack }$ facilitating B $- \mathrm{H}$ bond cleavage and enabling the formation of stable boron-centered radicals.

Previously, radical borylation methods were successfully used to achieve the borylation of C-N, ${}^{\left\lbrack {18} - {23}\right\rbrack }$ C-O, ${}^{\left\lbrack {24} - {25}\right\rbrack }$ and C-X ${}^{\left\lbrack {26} - {27}\right\rbrack }$ bonds, yielding aryl or alkyl borates. In recent years, this synthetic method has rapidly advanced to include the borylation of $\mathrm{C} - {\mathrm{C}}^{\left\lbrack {28} - {29}\right\rbrack }$ and $\mathrm{C} - {\mathrm{H}}^{\left\lbrack {30}\right\rbrack }$ bonds, offering a clean and environmentally friendly method for synthesizing boron compounds. Based on the types of radicals involved, works in this area can be categorized into two groups: (1) Borylation methodologies involving alkyl or aryl radicals. This research can be traced back to Wang’s pioneering work on the borylation of aromatic diazonium salts in 2010, ${}^{\left\lbrack {18}\right\rbrack }$ utilizing benzoyl peroxide (BPO) as a catalyst to achieve the first Sandmeyer-type borylation reaction involving aromatic amines, tert-butyl nitrite, and pinacolborane esters. In this reaction, aromatic diazonium salts are generated in situ from inexpensive and readily available aromatic amines, and the transformation from aromatic C-N bonds to C-B bonds is achieved via a radical pathway. Since then, research on carbon radical borylation reaction has received increasing attention. (2) Borylation methodologies driven by Lewis base boron-centered radical. This field has greatly benefited from the groundbreaking work by Curran in 2008. ${}^{\left\lbrack {31}\right\rbrack }$ They first synthesized complexes of borane and $N$ -heterocyclic carbenes, which act as a new class of radical hydrogen atom donors and facilitate borylation. In this article, we review the recent advances in radical-mechanistic borylation reactions since 2020 and discuss potential future trends in this field (Scheme 1).

2. Borylation Involving Carbon Radicals

2.1. Transition-metal induced borylation

Transition-metal-induced borylation is not a new topic. Palladium-catalyzed classical Miyaura borylation ${}^{\left\lbrack {32}\right\rbrack }$ and many other transition-metal-catalyzed borylation reactions have been well applied in drug synthesis. ${}^{\left\lbrack {33} - {34}\right\rbrack }$ Transition-metal catalysts are also efficient reagents that can activate substrates to generate alkyl or aryl radicals. For example, Ni catalysts can induce single-electron reduction of halides to generate alkyl or aryl radicals, ${}^{\left\lbrack {35}\right\rbrack }$ and Ir and Ru photocatalysts can also act as efficient activators under light irradiation. ${}^{\left\lbrack {36}\right\rbrack }$ Consequently, transition-metal-induced radical borylation has also been developed.

2.1.1. Borylation of C-X bond. Aryl halides can undergo single-electron reduction reactions with transition-metal catalysts to generate aryl radicals. Previous work has shown that aryl bromides and iodides readily form aryl radicals through the elimination of bromide and iodide anions. Once trapped by a diboron reagent, these radicals generate aryl boronates. ${}^{\left\lbrack {37}\right\rbrack }$ However, the activation of aryl chlorides and fluorides has been challenging due to the high bond energies of the C-Cl and C-F bonds. Marder

Scheme 1 Radical borylation reactions

Traditional borylation methods

and Radius discovered that [Ni(IMes) ${}_{2}$ ] (IMes = 1,3-dimesitylimid-azoline-2-ylidene) can facilitate an oxidative addition with aryl halides. ${}^{\left\lbrack {38} - {39}\right\rbrack }$ The resulting intermediate can then react with boron reagents to generate aryl boronates. This mechanism has proven to be highly efficient and applicable to $\mathrm{C} - \mathrm{F}$ bond formation. ${}^{\left\lbrack {40}\right\rbrack }$ In 2020, Radius and Marder also demonstrated a photoinduced borylation reaction of aryl chlorides catalyzed by $\left\lbrack {\mathrm{{Ni}}{\left( \mathrm{{IMes}}\right) }_{2}}\right\rbrack .{}^{\left\lbrack {41}\right\rbrack }$ Under 400 nm light irradiation, 4-chloroanisole reacted with ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ in the presence of KOMe, using 10 mol% [Ni(IMes) ${}_{2}$ ] as the catalyst at 25 °C, yielding 86% of 1-Bpin-4-methoxybenzene after 6 h (Scheme 2). Radical trapping experiments suggested the formation of aryl radicals during the transformation. The proposed mechanism involves [Ni(IMes) ${}_{2}$ ] undergoing rapid chlorine atom abstraction from aryl chlorides to form [Nil(IMes) ${}_{2}$ Cl] and aryl radicals. Further irradiation leads to $\left\lbrack {\mathrm{{Nil}}{\left( \mathrm{{IMes}}\right) }_{2}\mathrm{{Cl}}}\right\rbrack$ reacting with additional aryl chlorides to form [Nill(IMes) ${}_{2}{\mathrm{{Cl}}}_{2}$ ] and more aryl radicals. These aryl radicals then react with the nucleophilic $\left\lbrack {{\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}\left( \mathrm{{OMe}}\right) }\right\rbrack$ - to yield the final borylated product.

In addition to aryl halides, alkyl halides can also serve as radical precursors, generating alkyl radicals upon activation. Transition-metal-catalyzed radical borylation of alkyl halides has been widely utilized for the synthesis of alkyl boronates. In 2011, Marder and Liu reported a copper(I)-catalyzed borylation reaction of primary and secondary alkyl halides and pseudohalides (Scheme 3a). ${}^{\left\lbrack {42}\right\rbrack }$ Inspired by this work, various transition-metal-catalyzed methods for synthesizing alkyl boronates have been developed, using metals such as Copper(II) (Scheme 3b), ${}^{\left\lbrack {43}\right\rbrack }$ manganese, ${}^{\left\lbrack {44}\right\rbrack }$ iron (Scheme 3c), ${}^{\left\lbrack {45}\right\rbrack }$ and cobalt. ${}^{\left\lbrack {46}\right\rbrack }$ In 2021, Mankad developed a copper-catalyzed carbonylation boronization of alkyl

Scheme 2 Ni catalyzed radical borylation reaction of aryl chloride

halides (Scheme 3d). This method involved the in situ formation of tetracoordinated acylboron intermediates in the presence of CO. By treating these intermediates with aqueous ${\mathrm{{KHF}}}_{2}$ , aliphatic potassium acyltrifluoroborates were synthesized. The reaction proceeded efficiently under mild conditions, with the key mechanism step being the formation of acyl halide intermediates. ${}^{\left\lbrack {47}\right\rbrack }$

Scheme 3 Transition-metal catalyzed radical borylation of alkyl halides

Recently, novel catalysts have been proposed to promote the borylation of alkyl radicals. For example, Xie synthesized a dinu-clear gold catalyst that can catalyze the photoinduced synthesis of gem-diboronates (Scheme 4). ${}^{\left\lbrack {48}\right\rbrack }$ Mechanistic investigations suggested that the interaction between the diboron reagent and the catalyst forms an intermediate capable of absorbing light, thereby facilitating the radical borylation process.

Scheme 4 Dinuclear gold catalyzed borylation of alkyl radicals

2.1.2. Borylation of C-H bond. In comparison to C-X bonds, C-H bonds are more common in organic compounds, but their borylation is not straightforward. The abundance of $\mathrm{C} - \mathrm{H}$ bonds in a molecule makes the selective activation of a specific $\mathrm{C} - \mathrm{H}$ bond particularly challenging. Aggarwal and Noble reported a light-induced, copper-mediated C-H bond borylation (Scheme 5a), achieving high yields for inactivated alkanes like cyclohexane. However, for long-chain alkanes, the regioselectivity was limited. ${}^{\left\lbrack {49}\right\rbrack }$ Similarly, Xia reported a photocatalyzed borylation of alkanes, but the regioselectivity remained limited (Scheme 5b). ${}^{\left\lbrack {50}\right\rbrack }$ In 2024, Hu reported a highly regioselective radical borylation of long-chain alkanes (Scheme 5c). Despite the high regioselectivity, the yields of most examples were not good. ${}^{\left\lbrack {51}\right\rbrack }$ Achieving both high efficiency and high selectivity in the borylation of C-H bonds remains an area of ongoing research.

2.1.3. Borylation of C-C bond. The C-C bond is a widely existing covalent linkage in organic molecules. To achieve the borylation of C-C bonds, redox-active esters (RAEs), synthesized from carboxylic acids, are well-known reactants. RAEs of alkyl are more prone to producing alkyl radicals, making it suitable for the borylation of alkyl radicals. These alkyl RAEs easily form alkyl radicals, which promote the borylation and enable the decarboxyla-tive borylation reaction. For example, Li discovered a light-induced decarboxylative borylation reaction of aliphatic acids, where the acids were pre-transformed into $N$ -acyloxyphthali-mides (Scheme 6a). ${}^{\left\lbrack {28}\right\rbrack }$ This reaction was facilitated by an iridium photocatalyst. Recently, research has expanded this strategy for the synthesis of more valuable boronates. Wang reported a photo-induced borylation reaction useful for synthesizing $\alpha - {\mathrm{{CF}}}_{3}$ boronates, which are highly valuable building blocks in medicinal chemistry (Scheme 6b). ${}^{\left\lbrack {52}\right\rbrack }$ Xu and Song described a 1,2-boron shift reaction of $\beta$ -boron NHPI esters, demonstrating a new approach to enhance the value of borylation reactions involving RAEs (Scheme 6c). ${}^{\left\lbrack {53}\right\rbrack }$

Compared to alkyl RAEs, aryl RAEs are less likely to produce aryl radicals. The main challenge in this process is the high energy barrier for aryl RAEs to produce aryl radicals. A notable advancement in the borylation of aryl RAEs is the transition-metal-free method developed by Glorius in 2017. ${}^{\left\lbrack {54}\right\rbrack }$

Scheme 5 Transition-metal catalyzed radical borylation of alkanes

However, in recent years, there have been significant advancements achieving borylation of aryl acids. Aryl carboxylic acids themselves are inherently radical precursors, making direct borylation of carboxylic acids a significant area of scientific research. MacMillan reported a photo-induced, copper-catalyzed decarboxylative borylation of aryl acids (Scheme 7a). ${}^{\left\lbrack {55}\right\rbrack }$ Mechanistic investigations showed that the copper catalyst formed a complex with the aryl acid, which, upon excitation by light, underwent a ligand-to-metal charge transfer (LMCT) process to form an acetoxyl radical. This radical then decarboxylates to produce an aryl radical, which was subsequently captured by a diboron reagent. Liu also reported a direct borylation reaction of carboxylic acids (Scheme 7b). ${}^{\left\lbrack {56}\right\rbrack }$ This reaction combined guanidine catalysis and iridium catalysis, utilizing cobalt to enhance the reaction.

Besides RAEs and carboxylic acids, other radical precursors have been applied in the radical borylation of C-C bonds. For example, Mo proposed a photocatalyzed decarbonylative borylation of aliphatic aldehydes in 2024, where the aldehydes were pre-transformed into 1,4-dihydropyridines. ${}^{\left\lbrack {57}\right\rbrack }$ We believe that with the advancement of radical chemistry, more radical-based methodologies will be developed and applied in this area, like alkyl carboxylic acid.

2.2. Transition-metal free borylation

Transition-metal-free reactions provide cleaner conditions by avoiding the use of metal catalysts. These reactions are particularly valuable in medicinal synthesis, as they eliminate the risk of metal contamination. Through methods such as electrochemistry, light, or organic small molecule catalysis, substrates can be efficiently activated without the need for transition-metal catalysts, providing a more environmentally friendly approach to borylation. Metal-free radical borylation has become an important and well-explored research topic. In this chapter, we will introduce significant works since 2020 on transition-metal-free borylation.

2.2.1. Electrochemical borylation. The electrochemical method is an efficient procedure in organic synthesis, where substrates can be activated by applying the necessary redox potential, thus avoiding the use of additional reagents. Electrochemical boryla-tion has been applied for the synthesis of boronates from aryl chlorides, bromides, ${}^{\left\lbrack {58}\right\rbrack }$ and iodides. ${}^{\left\lbrack {59}\right\rbrack }$ Recently, this method has been expanded to different substrates.

Lu and Qi reported an electrochemical borylation of alkyl halides (Scheme 8a). ${}^{\left\lbrack {60}\right\rbrack }$ By using magnesium as a sacrificial anode, they successfully avoided the need for excess reducing agents. In 2023, this group further advanced the electrooxidation of a solvent-ligated ${\mathrm{B}}_{2}{\mathrm{{cat}}}_{2}$ complex, successfully synthesizing gem-dibor-ylalkanes (Scheme 8b). ${}^{\left\lbrack {61}\right\rbrack }$ The process involved the formation of the boryl radical through the homolytic cleavage of B-B bond in a DMF-ligated ${\mathrm{B}}_{2}{\mathrm{{cat}}}_{2}$ radical cation. Concurrently, the $\alpha$ -bromo radical was generated via the reduction of gem-bromide at the cathode. The computational studies show that the diboration occurred through C-B radical-radical cross-coupling in solution.

In another instance, Baran and Blackmond proposed using aliphatic NHPI esters to achieve electrochemical decarboxylative borylation (Scheme 8c). ${}^{\left\lbrack {62}\right\rbrack }$ Additionally, other studies have explored the use of various substrates such as arylazo sulfones ${}^{\left\lbrack {63}\right\rbrack }$ and nitroarenes ${}^{\left\lbrack {64}\right\rbrack }$ in electrochemical borylation reactions.

2.2.2. Light-induced borylation. In addition to electrochemical methods, small organic molecule catalysis is also a strategy for eliminating the need for transition-metal activation. This approach encompasses the use of various organic reagents. For instance, König reported a thiolate-catalyzed activation strategy for multiple aryl $\mathrm{C}$ -hetero bonds to form aryl radicals, facilitating the synthesis of aryl boronates (Scheme 9). ${}^{\left\lbrack {65}\right\rbrack }$ The authors proposed that the aryl reagent coordinated with thiolate and the diboron reagent to form an electron donor-acceptor (EDA) complex. This EDA complex absorbed light, leading to an inner-sphere electron transfer process. This process generated an aryl radical anion, which subsequently underwent C-LG bond cleavage to produce an aryl radical and a leaving anion. The aryl radical was then captured by the diboron reagent to form an aryl boronate in a process similar to previously discussed methods.

Scheme 7 Transition-metal catalyzed direct borylation of aryl carboxylic

This strategy, which combines light catalysis and organic molecular catalysis, is not unusual. For example, Aggarwal used CI-Bcat as a catalyst to achieve a photoinduced C-H bond borylation reaction (Scheme 10). ${}^{\left\lbrack {30}\right\rbrack }$ In this system, the additive $N$ -alkoxyphthalimide was excited by light to release an oxygen radical. This oxygen radical underwent a radical reaction with the CI-Bcat catalyst, releasing a CI radical. The CI radical then initiated a HAT reaction with alkanes to generate alkyl radicals. These alkyl radicals were subsequently transformed into the desired boron esters.

In fact, several other systems use this strategy to achieve radical borylation. One representative system is Jiao’s pyridine/base method. They used pyridine (typically 4-phenylpyridine) as a

Scheme 8 Electrochemical borylation an alkyl radical, which then led to the formation of alkyl boro-nates. Larionov also reported a photo-induced borylation reaction of aryl phosphates, phenols, and other substrates (Scheme 11b). ${}^{\left\lbrack {69}\right\rbrack }$ They used phenothiazine as a photocatalyst, whose anion can absorb light and promote the SET process. Its strong reductive power allows it to reduce substrates that are not easily reduced, facilitating the formation of the desired borylated products. Yoshima also reported an organic photoredox-catalyzed decar-boxylative radical borylation of benzoic acids. ${}^{\left\lbrack {70}\right\rbrack }$ Recently, Chu reported a three-component defluorinative borylation of alkenes with trifluoromethyls and ${\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}$ via dual photoredox/copper catalysis (Scheme 11c). The key step in the mechanism involved a SET event between the in situ generated ${\mathrm{{PhCF}}}_{3}/{\left\lbrack {\mathrm{{HO}}}_{ - }{\mathrm{B}}_{2}{\mathrm{{pin}}}_{2}\right\rbrack }^{ - }$ anionic intermediate and the excited photocatalyst. This process was accompanied by the elimination of fluoride ions, leading to the formation of difluoroalkyl radical.

Scheme 9 Light-induced radical borylation catalyzed by thiolate

photocatalyst to successfully achieve the borylation of aryl or alkyl halides. ${}^{\left\lbrack {66} - {68}\right\rbrack }$ Here, we list one of the typical reaction conditions (Scheme 11a). In-depth studies on the mechanism of this

Scheme 10 Light-induced C-H bond borylation catalyzed by CI-Bcat

Scheme 11 Light-induced radical borylation catalyzed by organic molecules

system revealed that pyridine forms a complex with the diboron reagent in the presence of a base. Upon light irradiation, this intermediate underwent a SET process with alkyl bromides, forming

Furthermore, by designing suitable substrate structures, the substrates themselves can exhibit optical activity, which can be exploited to achieve borylation under simple conditions. RAEs are typical substrates that can release an alkyl radical under light irradiation. In 2017, Aggarwal reported a decarboxylative borylation reaction using NHPI esters as substrates (Scheme 12a). ${}^{\left\lbrack {29}\right\rbrack }$ These esters formed an intermediate with ${\mathrm{B}}_{2}{\mathrm{{cat}}}_{2}$ and solvent that could be directly excited by blue light. Upon elimination of a ${\mathrm{{CO}}}_{2}$ molecule, an alkyl radical was generated. This strategy can also be expanded to fragmentation borylation when cyclic alcohols or hemiacetals are used as substrates, as reported by Aggarwal in 2021 (Scheme 12b). ${}^{\left\lbrack {71}\right\rbrack }$ Some other substrates, such as iodides and chlorides, can also be directly excited under light irradiation, enabling borylation under very mild conditions. ${}^{\left\lbrack {72} - {74}\right\rbrack }$

Scheme 12 Direct borylation reaction of NHPI ester

Recently, a novel strategy has attracted the attention of researchers. This method involves activating the substrate to generate an $N$ -centered radical or a radical at another site, which then undergoes an intramolecular HAT process, leading to the formation of another carbon-centered radical in the substrate. This process has been successfully employed in borylation reactions. For instance, Gevorgyan reported a selective $\alpha$ -C-H bond boryla-tion of aliphatic amines (Scheme 13a). ${}^{\left\lbrack {75}\right\rbrack }$ They used 2-iodoben-zoyl-tethered amines as substrates, which firstly generated aryl radicals on the amine. The subsequent HAT process facilitated the formation of alkyl radicals and $\alpha$ -borylated amines. The driving force behind this process was the bond energy difference between aryl and alkyl C-H bonds. Similarly, Mo applied a related strategy using hydroxamic acid derivatives as substrates (Scheme 13b). ${}^{\left\lbrack {76}\right\rbrack }$ In the presence of the photocatalyst eosin Y, an $N$ -centered radical was generated, which then underwent an intramolecular HAT process to form an alkyl radical. This design enabled Mo to achieve selective borylation at the $\gamma$ -position of carbonyl compounds.

Scheme 13 Borylation using remote HAT strategy

2.2.3. Borylation reaction under thermal conditions. Besides light-induced conditions, additives or catalysts can also directly promote the activation of substrates under non-light irradiation conditions, leading to borylation. For example, Marder and Radius reported a direct borylation reaction of alkyl sulfones mediated by a base (Scheme 14a). ${}^{\left\lbrack {77}\right\rbrack }$ The preliminary mechanism study revealed a rational pathway of the formation of adduct involving Lewis base, ${B}_{2}{\text{ neop }}_{2}$ and alkyl sulfones. In addition, Mo reported a radical borylation of alkyl halides using silane as an additive (Scheme 14b). ${}^{\left\lbrack {78}\right\rbrack }$ The proposed mechanism was a classical radical-involved substitution process.

3. Borylation Involving Boron-Centered Radical

Borane Lewis base compounds can produce a boron-centered radical through a HAT reaction. This boron-centered radical exhibits strong reactivity and can interact with various substrates. Notably, in 2008, Curran made significant advancements by synthesizing a special borane where the NHC was linked with boranes. ${}^{\left\lbrack {31}\right\rbrack }$ This NHC-borane was found to be applicable in a range of synthetic transformations. This reagent was utilized to facilitate various organic reactions such as radical dehalogenation, ${}^{\left\lbrack {79}\right\rbrack }$ decyana-tion, ${}^{\left\lbrack {80}\right\rbrack }$ and others. ${}^{\left\lbrack {81}\right\rbrack }$ However, this reagent initially did not attract widespread interest among researchers, mainly because the synthesized alkyl borane had limited utility in subsequent transformations, making it less valuable as an intermediate in medicinal chemistry.

Scheme 14 Borylation under thermal conditions

Recently, this reagent has garnered renewed attention due to the work of researchers. There have been several publications exploring the applications of borane derivatives. For example, So and co-workers reported a boron ester synthesis reaction catalyzed by NHC-diborene. ${}^{\left\lbrack {82}\right\rbrack }$ Curran also reported the synthesis of NHC-boralactones reagents, ${}^{\left\lbrack {83}\right\rbrack }$ indicating the potential for expanding the application of borane derivatives in organic synthesis.

Wang has published extensively on reactions involving ${\mathrm{{NHC}}}_{ - }{\mathrm{{BH}}}_{3}$ and has recently reviewed borylation ${}^{\left\lbrack {84}\right\rbrack }$ and hydrobora-tion ${}^{\left\lbrack {11}\right\rbrack }$ reactions involving borane Lewis base compound. Therefore, instead of detailing all the works on this reagent, we will highlight a few representative studies to illustrate some typical reaction types and recent advancements in this area.

Borylation using boranes involves the boron-centered radical attacking the substrate. In this process, the reactivity is influenced by the properties of both the boron reagent and the substrate, making it easier to achieve selectivity. This control over reactivity enhances the potential for selective and stereoselective transformations.

One promising strategy involves light-induced reactions. For example, Lewis base boranes can undergo a Minisci-type reaction with pyridine and its derivatives. By using different boron reagents, borylation reactions at different sites on pyridines can be achieved. Leonori reported a C2-selective Minisci borylation reaction using ${\mathrm{{BH}}}_{3} - {\mathrm{{NMe}}}_{3}$ as the borylation reagent and 4-CzIPN as the photocatalyst, achieving C2 borylation of azines (Scheme 15a). ${}^{\left\lbrack {85}\right\rbrack }$ Hong used ${\mathrm{{BH}}}_{3}$ -phosphate as the borylation reagent to achieve C4-selective borylation of pyridinium derivatives (Scheme 15b). ${}^{\left\lbrack {86}\right\rbrack }$ Additionally, Cao reported a C5-selective Minisci reaction using NHC- ${\mathrm{{BH}}}_{3}$ . ${}^{\left\lbrack {87}\right\rbrack }$

The generation of boron-centered radicals requires a reagent to abstract a hydrogen atom from borane base compounds. Traditional methods involve the use of radical initiators, which can introduce pollutants and necessitate high temperatures, leading to safety concerns. Therefore, exploring alternative methods for generating boron-centered radicals has become an important research direction.

Wu reported a visible light-induced selective defluoroboryla-tion reaction of fluoroarenes. They used an iridium catalyst or the organic photocatalyst 4-CzIPN along with a thiol compound as the HAT catalyst (Scheme 16a). ${}^{\left\lbrack {27}\right\rbrack }$ Mechanistic experiments revealed that under light irradiation, the excited photocatalyst helped the thiol compound generate a sulfur radical. Due to the low bond energy of the B-H bond, this sulfur radical can abstract a hydrogen atom from the $\mathrm{{NHC}} - {\mathrm{{BH}}}_{3}$ , forming a boron-centered radical. This radical then reacted with fluoroarenes to produce the desired boronate.

Wang reported another activation method for ${\mathrm{{NHC}}}_{ - }{\mathrm{{BH}}}_{3}$ that does not require the addition of a thiol compound (Scheme 16b). ${}^{\left\lbrack {88}\right\rbrack }$ Instead, this method utilizes the SET process between ${\mathrm{{NHC}}}_{ - }{\mathrm{{BH}}}_{3}$ and an iridium catalyst to generate boron-centered radical. Using this approach, they successfully carried out several different transformations including diastereoselective transformation.

Hydroboration is another important reaction type achieved with ${\mathrm{{NHC}}}_{ - }{\mathrm{{BH}}}_{3}$ . For instance, Curran and Dai reported a selective hydroboration reaction at the same year. ${}^{\left\lbrack {89}\right\rbrack }$ They also reported a hydroboration reaction of various substrates using NHC-BH ${}_{3}$ with CdS nanosheets as a photocatalyst. ${}^{\left\lbrack {90}\right\rbrack }$ Additionally, the borylation of unsaturated bonds is another significant reaction facilitated by NHC-BH3. ${}^{\left\lbrack {91} - {92}\right\rbrack }$

In the previously mentioned borylation of carbon radicals, many reactions lacked selectivity. Typically, the mechanism involves generating alkyl or aryl radicals within the reaction system, which are then captured by a diboron reagent. This radical process often lacks efficient means to achieve selective transformations, particularly stereoselectivity.

4. Conclusions and Perspectives

Outstanding achievements have been made in borylation reactions based on radical mechanisms. Various aryl or alkyl radical precursors, such as halides, carboxylic acids, and other substrates, have been successfully utilized for the synthesis of boron esters. However, several challenges remain. Exploring borylation from new radical precursors is necessary. For instance, most previous C-C bond borylations have used aryl acids or aliphatic acid derivatives as substrates. More exploration is needed for borylating other types of C-C bonds, like aliphatic acid. Additionally, achieving high steroselective radical borylation is a significant challenge because radical reactions usually lack steroselectivity. Another research direction is developing new boron reagents beyond diboron esters for the synthesis of boronates. Although some new borylation reagents have been discovered, their applications are still limited. ${}^{\left\lbrack {93} - {95}\right\rbrack }$

Borylation based on boron-centered radicals offers another strategy for achieving radical borylation. This approach shows significant advantages in selective borylation, but efficient subsequent transformations of borane derivatives remain underex-plored. With continued scientific research and exploration, effective post-conversion methods may be developed in the future, enabling the widespread application of borane-type boron compounds in synthetic chemistry (Scheme 17).

Scheme 17 Unresolved issues and challenges of radical borylation

Acknowledgement

The author thanks the National Natural Science Foundation of China (Grant Nos. 22071004, 21933001 and 22150013) for financial support.

References

[1] Hall, D. G. Boronic Acids: Preparation, Applications in Organic Synthesis and Medicine, John Wiley & Sons, 2006.

[2] Brown, H. C.; Cole, T. E. Organoboranes. 31. A Simple Preparation of Boronic Esters from Organolithium Reagents and Selected Trialkoxy-boranes. Organometallics 1983, 2, 1316-1319.

[3] Brown, H. C.; Rao, B. S. Hydroboration. II. A Remarkably Fast Addition of Diborane to Olefins-Scope and Stoichiometry of the Reaction. J. Am. Chem. Soc. 1959, 81, 6428-6434.

[4] Chen, H.; Hartwig, J. F. Catalytic, Regiospecific End-Functionalization of Alkanes: Rhenium-Catalyzed Borylation under Photochemical Conditions. Angew. Chem. Int. Ed. 1999, 38, 3391-3393.

[5] Friese, F. W.; Studer, A. New Avenues for C-B Bond Formation via Radical Intermediates. Chem. Sci. 2019, 10, 8503-8518.

[6] Taniguchi, T. Advances in Chemistry of N-Heterocyclic Carbene Boryl Radicals. Chem. Soc. Rev. 2021, 50, 8995-9021.

[7] Tian, Y.-M.; Guo, X.-N.; Braunschweig, H.; Radius, U.; Marder, T. B. Photoinduced Borylation for the Synthesis of Organoboron Compounds: Focus Review. Chem. Rev. 2021, 121, 3561-3597.

[8] Yan, G.; Huang, D.; Wu, X. Recent Advances in C-B Bond Formation through a Free Radical Pathway. Adv. Synth. Catal. 2018, 360, 1040- 1053.

[9] Xu, L. Decarboxylative Borylation: New Avenues for the Preparation of Organoboron Compounds. Eur. J. Org. Chem. 2018, 2018, 3884- 3890.

[10] Wang, M.; Shi, Z. Methodologies and Strategies for Selective Borylation of C-Het and C-C Bonds. Chem. Rev. 2020, 120, 7348- 7398.

[11] Phang, Y. L.; Jin, J.-K.; Zhang, F.-L.; Wang, Y.-F. Radical Hydroboration for the Synthesis of Organoboron Compounds. Chem. Commun. 2024, 60, 4275-4289.

[12] Wang, G.; Zhang, H.; Zhao, J.; Li, W.; Cao, J.; Zhu, C.; Li, S. Homolytic Cleavage of a B-B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification. Angew. Chem. Int. Ed. 2016, 55, 5985-5989.

[13] Shimoi, M.; Watanabe, T.; Maeda, K.; Curran, D. P.; Taniguchi, T. Radical Trans-Hydroboration of Alkynes with N-Heterocyclic Carbene Boranes. Angew. Chem. Int. Ed. 2018, 57, 9485-9490.

[14] Ren, S.-C.; Zhang, F.-L.; Xu, A.-Q.; Yang, Y.; Zheng, M.; Zhou, X.; Fu, Y.; Wang, Y.-F. Regioselective Radical $\alpha$ -Borylation of $\alpha ,\beta$ -Unsaturated Carbonyl Compounds for Direct Synthesis of $\alpha$ -Borylcarbonyl Molecules. Nat. Commun. 2019, 10, 1934.

[15] Jian, Y.; Wen, F.; Shang, J.; Li, X.; Liu, Z.; An, Y.; Wang, Y. Photoredox Dearomative β-Hydroborylation of Indoles for the Synthesis of Borylated Indolines. Org. Chem. Front. 2024, 11, 149-155.

[16] Rablen, P. R.; Hartwig, J. F. Accurate Borane Sequential Bond Dissociation Energies by High-Level Ab Initio Computational Methods. J. Am. Chem. Soc. 1996, 118, 4648-4653.

[17] Lalevée, J.; Blanchard, N.; Tehfe, M.-A.; Chany, A.-C.; Fouassier, J.-P. New Boryl Radicals Derived from N-Heteroaryl Boranes: Generation and Reactivity. Chem. - Eur. J. 2010, 16, 12920-12927.

[18] Mo, F.; Jiang, Y.; Qiu, D.; Zhang, Y.; Wang, J. Direct Conversion of Arylamines to Pinacol Boronates: A Metal-Free Borylation Process. Angew. Chem. Int. Ed. 2010, 49, 1846-1849.

[19] Qiu, D.; Jin, L.; Zheng, Z.; Meng, H.; Mo, F.; Wang, X.; Zhang, Y.; Wang, J. Synthesis of Pinacol Arylboronates from Aromatic Amines: A Metal-Free Transformation. J. Org. Chem. 2013, 78, 1923-1933.

[20] Yu, J.; Zhang, L.; Yan, G. Metal-Free, Visible Light-Induced Borylation of Aryldiazonium Salts: A Simple and Green Synthetic Route to Arylboronates. Adv. Synth. Catal. 2012, 354, 2625-2628.

[21] Ahammed, S.; Nandi, S.; Kundu, D.; Ranu, B. C. One-Pot Suzuki Coupling of Aromatic Amines Via Visible Light Photocatalyzed Metal Free Borylation Using T-Buono at Room Temperature. Tetrahedron Lett. 2016, 57, 1551-1554.

[22] Xu, Y.; Yang, X.; Fang, H. Additive-and Photocatalyst-Free Borylation of Arylazo Sulfones under Visible Light. J. Org. Chem. 2018, 83, 12831-12837.

[23] Mfuh, A. M.; Doyle, J. D.; Chhetri, B.; Arman, H. D.; Larionov, O. V. Scalable, Metal- and Additive-Free, Photoinduced Borylation of Haloarenes and Quaternary Arylammonium Salts. J. Am. Chem. Soc. 2016, 138, 2985-2988.

[24] Liu, W.; Yang, X.; Gao, Y.; Li, C.-J. Simple and Efficient Generation of Aryl Radicals from Aryl Triflates: Synthesis of Aryl Boronates and Aryl Iodides at Room Temperature. J. Am. Chem. Soc. 2017, 139, 8621- 8627.

[25] Friese, F. W.; Studer, A. Deoxygenative Borylation of Secondary and Tertiary Alcohols. Angew. Chem. Int. Ed. 2019, 58, 9561-9564.

[26] Liu, Q.; Hong, J.; Sun, B.; Bai, G.; Li, F.; Liu, G.; Yang, Y.; Mo, F. Transition-Metal-Free Borylation of Alkyl lodides via a Radical Mechanism. Org. Lett. 2019, 21, 6597-6602.

[27] Xu, W.; Jiang, H.; Leng, J.; Ong, H. W.; Wu, J. Visible-Light-Induced Selective Defluoroborylation of Polyfluoroarenes, Gem-Difluoroal-kenes, and Trifluoromethylalkenes. Angew. Chem. Int. Ed. 2020, 59, 4009-4016.

[28] Hu, D.; Wang, L.; Li, P. Decarboxylative Borylation of Aliphatic Esters under Visible-Light Photoredox Conditions. Org. Lett. 2017, 19, 2770-2773.

[29] Fawcett, A.; Pradeilles, J.; Wang, Y.; Mutsuga, T.; Myers, E. L.; Aggarwal, V. K. Photoinduced Decarboxylative Borylation of Carboxylic Acids. Science 2017, 357, 283-286.

[30] Shu, C.; Noble, A.; Aggarwal, V. K. Metal-Free Photoinduced C(sp ${}^{3}$ )-H Borylation of Alkanes. Nature 2020, 586, 714-719.

[31] Ueng, S.-H.; Brahmi, M. M.; Derat, É.; Fensterbank, L.; Lacôte, E.; Malacria, M.; Curran, D. P. Complexes of Borane and $N$ -Heterocyclic Carbenes: A New Class of Radical Hydrogen Atom Donor. J. Am. Chem. Soc. 2008, 130, 10082-10083.

[32] Ishiyama, T.; Murata, M.; Miyaura, N. Palladium(0)-Catalyzed Cross-Coupling Reaction of Alkoxydiboron with Haloarenes: A Direct Procedure for Arylboronic Esters. J. Org. Chem. 1995, 60, 7508- 7510.

[33] Ishiyama, T.; Miyaura, N. Transition Metal-Catalyzed Borylation of Alkanes and Arenes Via C-H Activation. J. Organomet. Chem. 2003, 680, 3-11.

[34] Hassan, M. M. M.; Guria, S.; Dey, S.; Das, J.; Chattopadhyay, B. Transition Metal-Catalyzed Remote C-H Borylation: An Emerging Synthetic Tool. Sci. Adv. 2023, 9, eadg3311.

[35] Tendera, L.; Fantuzzi, F.; Marder, T. B.; Radius, U. Nickel Boryl Complexes and Nickel-Catalyzed Alkyne Borylation. Chem. Sci. 2023, 14, 2215-2228.

[36] Crespi, S.; Fagnoni, M. Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy. Chem. Rev. 2020, 120, 9790-9833.

[37] Jiang, M.; Yang, H.; Fu, H. Visible-Light Photoredox Borylation of Aryl Halides and Subsequent Aerobic Oxidative Hydroxylation. Org. Lett. 2016, 18, 5248-5251.

[38] Schaub, T.; Radius, U. Efficient C-F and C-C Activation by a Novel N-Heterocyclic Carbene-Nickel(0) Complex. Chem. - Eur. J. 2005, 11, 5024-5030.

[39] Zhou, J.; Kuntze-Fechner, M. W.; Bertermann, R.; Paul, U. S. D.; Bert-hel, J. H. J.; Friedrich, A.; Du, Z.; Marder, T. B.; Radius, U. Preparing (Multi)Fluoroarenes as Building Blocks for Synthesis: Nickel-Catalyzed Borylation of Polyfluoroarenes via C-F Bond Cleavage. J. Am. Chem. Soc. 2016, 138, 5250-5253.

[40] Tian, Y.-M.; Guo, X.-N.; Kuntze-Fechner, M. W.; Krummenacher, I.; Braunschweig, H.; Radius, U.; Steffen, A.; Marder, T. B. Selective Photocatalytic C-F Borylation of Polyfluoroarenes by Rh/Ni Dual Catalysis Providing Valuable Fluorinated Arylboronate Esters. J. Am. Chem. Soc. 2018, 140, 17612-17623.

[41] Tian, Y.-M.; Guo, X.-N.; Krummenacher, I.; Wu, Z.; Nitsch, J.; Braunschweig, H.; Radius, U.; Marder, T. B. Visible-Light-Induced Ni-Catalyzed Radical Borylation of Chloroarenes. J. Am. Chem. Soc. 2020, 142, 18231-18242.

[42] Yang, C.-T.; Zhang, Z.-Q.; Tajuddin, H.; Wu, C.-C.; Liang, J.; Liu, J.-H.; Fu, Y.; Czyzewska, M.; Steel, P. G.; Marder, T. B.; Liu, L. Alkylboronic Esters from Copper-Catalyzed Borylation of Primary and Secondary Alkyl Halides and Pseudohalides. Angew. Chem. Int. Ed. 2012, 51, 528-532.

[43] Bose, S. K.; Brand, S.; Omoregie, H. O.; Haehnel, M.; Maier, J.; Bringmann, G.; Marder, T. B. Highly Efficient Synthesis of Alkyl-boronate Esters via Cu(II)-Catalyzed Borylation of Unactivated Alkyl Bromides and Chlorides in Air. ACS Catal. 2016, 6, 8332-8335.

[44] Atack, T. C.; Cook, S. P. Manganese-Catalyzed Borylation of Unactivated Alkyl Chlorides. J. Am. Chem. Soc. 2016, 138, 6139-6142.

[45] Wang, S.; Sun, M.; Zhang, H.; Zhang, J.; He, Y.; Feng, Z. Iron-Catalyzed Borylation and Silylation of Unactivated Tertiary, Secondary, and Primary Alkyl Chlorides. CCS Chem. 2020, 3, 2164-2173.

[46] Verma, P. K.; Prasad, K. S.; Varghese, D.; Geetharani, K. Cobalt(I)- Catalyzed Borylation of Unactivated Alkyl Bromides and Chlorides. Org. Lett. 2020, 22, 1431-1436.

[47] Cheng, L.-J.; Zhao, S.; Mankad, N. P. One-Step Synthesis of Acylboron Compounds Via Copper-Catalyzed Carbonylative Borylation of Alkyl Halides. Angew. Chem. Int. Ed. 2021, 60, 2094-2098.

[48] Ji, C.-L.; Chen, H.; Gao, Q.; Han, J.; Li, W.; Xie, J. Dinuclear Gold-Catalyzed Divergent Dechlorinative Radical Borylation of gem-Dichloroalkanes. Nat. Commun. 2024, 15, 3721.

[49] Sang, R.; Han, W.; Zhang, H.; Saunders, C. M.; Noble, A.; Aggarwal, V. K. Copper-Mediated Dehydrogenative $\mathrm{C}\left( {\mathrm{{sp}}}^{3}\right) - \mathrm{H}$ Borylation of Alkanes. J. Am. Chem. Soc. 2023, 145, 15207-15217.

[50] Tu, J.-L.; Hu, A.-M.; Guo, L.; Xia, W. Iron-Catalyzed C(sp ${}^{3}$ )-H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer. J. Am. Chem. Soc. 2023, 145, 7600- 7611.

[51] Wang, M.; Huang, Y.; Hu, P. Terminal C(sp ${}^{3}$ )-H Borylation through Intermolecular Radical Sampling. Science 2024, 383, 537-544.

[52] Zhang, Q.; Li, X.; Zhang, W.; Ni, S.; Wang, Y.; Pan, Y. Decarboxylative Borylation of Stabilized and Activated Carbon Radicals. Angew. Chem. Int. Ed. 2020, 59, 21875-21879.

[53] Guo, Y.; Wang, X.; Li, C. et al. Decarboxylation of β-Boryl Nhpi Esters Enables Radical 1,2-Boron Shift for the Assembly of Versatile Organoborons. Nat. Commun. 2023, 14, 5693.

[54] Candish, L.; Teders, M.; Glorius, F. Transition-Metal-Free, Visible-Light-Enabled Decarboxylative Borylation of Aryl N-Hydroxyphthali-mide Esters. J. Am. Chem. Soc. 2017, 139, 7440-7443.

[55] Dow, N. W.; Pedersen, P. S.; Chen, T. Q.; Blakemore, D. C.; Dechert-Schmitt, A.; Knauber, T.; MacMillan, D. W. C. Decarboxy-lative Borylation and Cross-Coupling of (Hetero)Aryl Acids Enabled by Copper Charge Transfer Catalysis. J. Am. Chem. Soc. 2022, 144, 6163-6172.

[56] Wei, Q.; Lee, Y.; Liang, W.; Chen, X.; Mu, B.-S.; Cui, X.-Y.; Wu, W.; Bai, S.; Liu, Z. Photocatalytic Direct Borylation of Carboxylic Acids. Nat. Commun. 2022, 13, 7112.

[57] Lian, C.; Zhang, J.; Mo, F. Photoinduced Decarbonylative Borylation of Alkyl Aldehydes through 4-Alkyl-1,4-Dihydropyridines. Org. Chem. Front. 2024, 11, 1140-1149.

[58] Kim, H.; Kim, H.; Lambert, T. H.; Lin, S. Reductive Electrophoto-catalysis: Merging Electricity and Light to Achieve Extreme Reduction Potentials. J. Am. Chem. Soc. 2020, 142, 2087-2092.

[59] Hong, J.; Liu, Q.; Li, F.; Bai, G.; Liu, G.; Li, M.; Nayal, O. S.; Fu, X.; Mo, F. Electrochemical Radical Borylation of Aryl lodides. Chin. J. Chem. 2019, 37, 347-351.

[60] Wang, B.; Peng, P.; Ma, W.; Liu, Z.; Huang, C.; Cao, Y.; Hu, P.; Qi, X.; Lu, Q. Electrochemical Borylation of Alkyl Halides: Fast, Scalable Access to Alkyl Boronic Esters. J. Am. Chem. Soc. 2021, 143, 12985- 12991.

[61] Wang, B.; Zhang, X.; Cao, Y.; Zou, L.; Qi, X.; Lu, Q. Electrooxidative Activation of B-B Bond in B2cat2: Access to Gem-Diborylalkanes via Paired Electrolysis. Angew. Chem. Int. Ed. 2023, 62, e202218179.

[62] Barton, L. M.; Chen, L.; Blackmond, D. G.; Baran, P. S. Electrochemical Borylation of Carboxylic Acids. Proc. Natl. Acad. Sci. U. S. A. 2021, 118, e2109408118.

[63] Wang, R.; Chen, F.; Jiang, L.; Yi, W. Electrochemical Thiolation and Borylation of Arylazo Sulfones with Thiols and B2pin2. Adv. Synth. Catal. 2021, 363, 1904-1911.

[64] Du, L.; Zhang, B.; Ji, S.; Cai, H.; Zhang, H. Electrochemical Borylation of Nitroarenes. Sci. China Chem. 2023, 66, 534-539.

[65] Wang, S.; Wang, H.; König, B. Photo-Induced Thiolate Catalytic Activation of Inert Caryl-Hetero Bonds for Radical Borylation. Chem 2021, 7, 1653-1665.

[66] Zhang, L.; Jiao, L. Pyridine-Catalyzed Radical Borylation of Aryl Halides. J. Am. Chem. Soc. 2017, 139, 607-610.

[67] Zhang, L.; Jiao, L. Super Electron Donors Derived from Diboron. Chem. Sci. 2018, 9, 2711-2722.

[68] Zhang, L.; Wu, Z. Q.; Jiao, L. Photoinduced Radical Borylation of Alkyl Bromides Catalyzed by 4-Phenylpyridine. Angew. Chem. Int. Ed. 2020, 59, 2095-2099.

[69] Jin, S.; Dang, H. T.; Haug, G. C.; He, R.; Nguyen, V. D.; Nguyen, V. T.; Arman, H. D.; Schanze, K. S.; Larionov, O. V. Visible Light-Induced Borylation of C-O, C-N, and C-X Bonds. J. Am. Chem. Soc. 2020, 142, 1603-1613.

[70] Kubosaki, S.; Takeuchi, H.; Iwata, Y.; Tanaka, Y.; Osaka, K.; Yamawaki, M.; Morita, T.; Yoshimi, Y. Visible- and Uv-Light-Induced Decarboxylative Radical Reactions of Benzoic Acids Using Organic Photoredox Catalysts. J. Org. Chem. 2020, 85, 5362-5369.

[71] Shu, C.; Madhavachary, R.; Noble, A.; Aggarwal, V. K. Photoinduced Fragmentation Borylation of Cyclic Alcohols and Hemiacetals. Org. Lett. 2020, 22, 7213-7218.

[72] Pan, L.; Deckert, M. M.; Cooke, M. V.; Bleeke, A. R.; Laulhé, S. Solvent Anions Enable Photoinduced Borylation and Phosphonation of Aryl Halides Via Eda Complexes. Org. Lett. 2022, 24, 6466-6471.

[73] Bai, L.; Jiao, L. Photoinduced Radical Borylation of Alkyl Chlorides. Eur. J. Org. Chem. 2024, 27, e202400043.

[74] Wang, C.; Zhou, L.; Yang, K.; Zhang, F.; Song, Q. Photoinduced Nai-Promoted Radical Borylation of Alkyl Halides and Pseudohalides. Chin. J. Chem. 2021, 39, 1825-1830.

[75] Sarkar, S.; Wagulde, S.; Jia, X.; Gevorgyan, V. General and Selective Metal-Free Radical α-C-H Borylation of Aliphatic Amines. Chem 2022, 8, 3096-3108.

[76] Sun, B.; Li, W.; Liu, Q.; Zhang, G.; Mo, F. Transition Metal-Free Visible Light Photoredox-Catalyzed Remote C(sp ${}^{3}$ )-H Borylation Enabled by 1,5-Hydrogen Atom Transfer. Commun. Chem. 2023, 6, 156.

[77] Huang, M.; Hu, J.; Krummenacher, I.; Friedrich, A.; Braunschweig, H.; Westcott, S. A.; Radius, U.; Marder, T. B. Base-Mediated Radical Borylation of Alkyl Sulfones. Chem. - Eur. J. 2022, 28, e202103866.

[78] Sun, B.; Zheng, S.; Mo, F. Transition Metal- and Light-Free Radical Borylation of Alkyl Bromides and Iodides Using Silane. Chem. Commun. 2021, 57, 5674-5677.

[79] Pan, X.; Lacote, E.; Lalevee, J.; Curran, D. P. Polarity Reversal Catalysis in Radical Reductions of Halides by N-Heterocyclic Carbene Boranes. J. Am. Chem. Soc. 2012, 134, 5669-5674.

[80] Kawamoto, T.; Geib, S. J.; Curran, D. P. Radical Reactions of N-Heterocyclic Carbene Boranes with Organic Nitriles: Cyanation of NHC-Boranes and Reductive Decyanation of Malononitriles. J. Am. Chem. Soc. 2015, 137, 8617-8622.

[81] Pan, X.; Vallet, A.-L.; Schweizer, S.; Dahbi, K.; Delpech, B.; Blanchard, N.; Graff, B.; Geib, S. J.; Curran, D. P.; Lalevée, J.; Lacôte, E. Mechanistic and Preparative Studies of Radical Chain Homolytic Substitution Reactions of N-Heterocyclic Carbene Boranes and Disulfides. J. Am. Chem. Soc. 2013, 135, 10484-10491.

[82] Fan, J.; Mah, J.-Q.; Yang, M.-C.; Su, M.-D.; So, C.-W. A N-Phosphino-amidinato NHC-Diborene Catalyst for Hydroboration. J. Am. Chem. Soc. 2021, 143, 4993-5002.

[83] Dai, W.; Geib, S. J.; Curran, D. P. Ring-Opening Reactions of NHC-Boriranes with in Situ Generated HCI: Synthesis of a New Class of NHC-Boralactones. J. Am. Chem. Soc. 2019, 141, 3623-3629.

[84] Peng, T.-Y.; Zhang, F.-L.; Wang, Y.-F. Lewis Base-Boryl Radicals Enabled Borylation Reactions and Selective Activation of Carbon-Heteroatom Bonds. Acc. Chem. Res. 2023, 56, 169-186.

[85] Kim, J. H.; Constantin, T.; Simonetti, M.; Llaveria, J.; Sheikh, N. S.; Leonori, D. A Radical Approach for the Selective C-H Borylation of Azines. Nature 2021, 595, 677-683.

[86] Choi, W.; Kim, M.; Lee, K.; Park, S.; Hong, S. C4-Selective C-H Borylation of Pyridinium Derivatives Driven by Electron Donor-Acceptor Complexes. Org. Lett. 2022, 24, 9452-9457.

[87] Zheng, H.; Lu, H.; Su, C., Yang, R.; Zhao, L.; Liu, X.; Cao, H. Visible Light-Induced C-5 Selective C-H Radical Borylation of Imidazo[1,2-a]- Pyridines with NHC-Boranes. Chin. J. Chem. 2023, 41, 193-198.

[88] Qi, J.; Zhang, F.-L.; Jin, J.-K.; Zhao, Q.; Li, B.; Liu, L.-X.; Wang, Y.-F. New Radical Borylation Pathways for Organoboron Synthesis Enabled by Photoredox Catalysis. Angew. Chem. Int. Ed. 2020, 59, 12876-12884.

[89] Li, G.; Huang, G.; Sun, R.; Curran, D. P.; Dai, W. Regioselective Radical Borylation of $\alpha ,\beta$ -Unsaturated Esters and Related Compounds by Visible Light Irradiation with an Organic Photocatalyst. Org. Lett. 2021, 23, 4353-4357.

[90] Xie, F.; Mao, Z.; Curran, D. P.; Liang, H.; Dai, W. Facile Borylation of Alkenes, Alkynes, Imines, Arenes and Heteroarenes with N-Heterocyclic Carbene - Boranes and a Heterogeneous Semiconductor Photocatalyst. Angew. Chem. Int. Ed. 2023, 62, e202306846.

[91] Zhu, C.; Gao, S.; Li, W.; Zhu, C. Photoredox Radical Borylation of Electron-Deficient Alkenes with NHC-Boranes. Chem. Commun. 2020, 56, 15647-15650.

[92] Zhang, Y.; Liao, Y.; Liu, P.; Ran, Y.; Liu, X. Radical Borylation of Vinyl Azides with NHC-Boranes: Divergent Synthesis of α-Boryl Ketones and Borylated Triazoles. Org. Biomol. Chem. 2022, 20, 3550-3557.

[93] Zhang, Q.; Li, X.; Zhang, W.; Wang, Y.; Pan, Y. Photocatalyzed Radical Relayed Regio- and Stereoselective Trifluoromethylthiolation-Bora-tion. Org. Lett. 2021, 23, 5410-5414.

[94] Suzuki, K.; Nishimoto, Y.; Yasuda, M. (O-Phenylenediamino)Boryl-stannanes: Efficient Reagents for Borylation of Various Alkyl Radical Precursors. Chem. - Eur. J. 2021, 27, 3968-3973.

[95] Suzuki, K.; Sugihara, N.; Nishimoto, Y.; Yasuda, M. Anti-Selective Borylstannylation of Alkynes with (O-Phenylenediaminato) Boryl-stannanes by a Radical Mechanism. Angew. Chem. Int. Ed. 2022, 61, e202201883.

Chang Lian (Top left) received her M.S. in Tianjin Normal University in 2020, then she studied for a Ph.D. at Peking University under the supervision of Prof. Fanyang Mo.

Jianning Zhang (Top right) received his B.S. degree in Peking University in 2019 and he studied for a Ph.D. at Peking University under the supervision of Prof. Fanyang Mo.

Di Qiu (Bottom left) was born in Tianjin, China, in 1987. He received his B.S. degree from Peking University in 2010. He continued his graduate study in Prof. Jianbo Wang’s laboratory and obtained his Ph.D. in 2015. In the same year, he joined in Tianjin Normal University as an Assistant Professor.

Fanyang Mo (Bottom right) received his B.Sc. and M.S. degree in Chemistry from Beijing Institute of Technology in 2004 and 2006, respectively. He carried out graduate research under the guidance of Prof. Jianbo Wang at Peking University. He then performed postdoctoral research with Prof. Qinghai Zhang at the Scripps Research Institute from 2010 to 2011, and with Prof. Guangbin Dong at The University of Texas at Austin from 2011 to 2015. He joined Peking University in April 2015.

Manuscript received: June 29, 2024

Manuscript revised: August 16, 2024

Manuscript accepted: September 4, 2024

Version of record online: October 17, 2024