Skip to main content
NCBI home page
ACS AuthorChoice logoLink to ACS AuthorChoice
. 2026 Jul 27;28(31):10022–10027. doi: 10.1021/acs.orglett.6c02736

Photocatalytic Decyanative Borylation of Dicyanoarenes Enabled by Radical–Radical Coupling

Naoki Yasukawa †,*, Ryota Nomura †, Waka Okada †, Kazutake Takada †, Tsunayoshi Takehara ‡, Takeyuki Suzuki ‡, Daniele Leonori §,*, Shuichi Nakamura †,*
PMCID: PMC13459413  PMID: 42506581

Abstract

Cyanoarenes are important scaffolds in pharmaceutical and materials science and serve as versatile building blocks in synthetic chemistry. Herein, we report an orthogonal strategy for the decyanative borylation of dicyanoarenes via radical–radical coupling between amine-ligated boryl radicals and dicyanoarene-derived radical anions, enabled by an oxidative quenching photoredox cycle. Importantly, the resulting amine–borane adducts readily engage in Suzuki–Miyaura cross-couplings with aryl halides, including late-stage functionalization of bioactive compounds.

graphic file with name ol6c02736_0005.jpg

graphic file with name ol6c02736_0004.jpg

Nitriles are integral building blocks in organic chemistry, owing to their ability to coordinate to metals and their role as a versatile synthetic handle that can be readily transformed into a wide range of other functional groups. In particular, aromatic nitriles are commonly found in the core structures of high-value molecules such as pharmaceuticals, agrochemicals, and optoelectronic materials (Scheme A). Moreover, because of the synthetic versatility of the CN group, aromatic nitriles are often employed as key intermediates to prepare bioactive molecules, including losartan, valsartan, and febuxostat. Notably, cyanobiaryls also serve as key intermediates for the synthesis of numerous sartan-type antihypertensive drugs.

1. Introduction.

1

Open in a new tab

Boron-containing molecules rank among the most versatile and broadly applicable building blocks in organic chemistry. Their value as synthetic handles is exemplified by their use as coupling partners in Nobel Prize-winning Suzuki–Miyaura cross-coupling and Chan–Lam coupling, thereby providing a versatile platform for the formation of new C–C and C–heteroatom bonds. Indeed, Suzuki–Miyaura cross-coupling accounts for >20% of all processes in the pharmaceutical sector, making it the fifth most frequently used reaction overall. Despite their broad utility, the synthesis of aryl organoboron compounds typically relies on the electrophilic borylation of organolithium or Grignard reagents, Miyaura borylation of aryl halides, and direct C–H activation. Consequently, the range of viable starting materials remains somewhat limited. Expanding the repertoire of feedstocks for aryl boron synthesis, particularly by utilizing unconventional yet abundant functional groups, would significantly enhance synthetic flexibility. In this context, the importance of the cyano group as a building block was underscored by a 2022 analysis of commercially available chemical building blocks, which found that approximately 20 000 of them contain CN groups. However, their direct conversion from aromatic nitriles into organoboron compounds remains largely unexplored, with only limited examples relying on Rh catalysis.

Recent advances in photocatalysis have enabled the generation of radical intermediates under mild conditions via single-electron pathways. This chemistry has predominantly focused on carbon-centered radicals. Through extensive efforts, electron-deficient aromatic compounds, such as aromatic nitriles, have been shown to act as radical acceptors or radical coupling partners, enabling the arylation of carbon-centered radicals. In contrast, heteroatom-centered radicals, e.g., boryl radicals, remain relatively unexplored in photocatalytic radical arylation reactions. Among the most widely used classes of boryl radicals are N-heterocyclic carbene (NHC)-ligated boryl radicals, which are characterized as planar π-radicals because of the stabilizing effect of the NHC system. Although these boryl radicals have been applied to the radical borylation of electron-deficient aromatic compounds, the resulting NHC–BH2–arenes do not directly participate in Suzuki–Miyaura cross-couplings (Scheme B). Furthermore, cyanoarenes readily participate in decyanative radical functionalization reactions with carbon-centered radicals under photoredox conditions. , By contrast, NHC-ligated boryl radicals, which form under photocatalytic conditions, have been reacted with 1,4-dicyanobenzenes predominantly to afford dearomatized 1,4-hydroborated products, while decyanative borylation products have also been obtained as minor products. A notable exception is 2-phenyl- or 2-N-methylamino-1,4-dicyanobenzene, which afforded the corresponding decyanative borylation products as the major products in up to 35% yield.

Our group recently investigated the synthetic potential of amine-ligated boryl radicals, which exhibit a σ-type electronic structure and strong nucleophilic character. These species are readily generated from inexpensive amine–borane complexes via a hydrogen atom transfer (HAT) process and have been utilized in radical additions to π-systems as well as in halogen atom transfer and HAT reactions. Very recently, the photoelectrocatalytic C­(sp2)–H borylation of electron-deficient (hetero)­arenes was developed. In this system, amine-ligated boryl radicals formed via a HAT process undergo radical addition to 1,4-dicyanobenzene at the ortho position of one of the CN groups, resulting in a Minisci-type C­(sp2)–H borylation (Scheme C).

We recently introduced a carboxylic acid-functionalized amine–borane complex as an effective boryl radical precursor. Upon single-electron oxidation under photoredox conditions, this species undergoes decarboxylation to furnish a nucleophilic amine-ligated boryl radical. Herein, we demonstrate that this platform enables the photocatalytic decyanative borylation of dicyanoarenes via radical–radical coupling between amine-ligated boryl radicals and cyanoarene-derived radical anions (Scheme D). This strategy overcomes the limitations of previously reported boryl radical systems and provides direct access to bench-stable cyanoaryl amine–borane adducts. Furthermore, the resulting cyanoaryl amine–borane adducts can be directly employed in Suzuki–Miyaura cross-coupling reactions, providing streamlined access to structurally diverse cyanoarenes.

Drawing inspiration from previous studies, , we hypothesized that an oxidative quenching photoredox cycle could enable the decyanative borylation of cyanoarenes via a radical–radical coupling mechanism (Scheme A). Specifically, the single-electron reduction of 1,4-dicyanobenzene (2a) by a visible-light-excited photocatalyst (*PC) would form the stabilized aryl radical anion (B). The subsequent single-electron oxidation of the deprotonated borane precursor (1 – ) by the oxidized photocatalyst (PC •+ ) would trigger decarboxylation, furnishing the nucleophilic amine-ligated boryl radical (A). Then, A could engage in a radical–radical coupling with B to form the Meisenheimer-type anion (C). This process may be facilitated by the persistent radical effect. Finally, eliminating the cyano group would restore aromaticity and deliver the desired cyanoaryl amine–borane product (3a).

2. Photocatalytic Decyanative Borylation.

2

Open in a new tab

Pleasingly, this proposed reaction was readily realized using 2a and Ir­(ppy)3 (PC1) as the photocatalyst and 1,8-diazabicycloundec-7-ene (DBU) as the organic base in a DMF/H2O solvent system under blue LED irradiation at room temperature (Scheme B). Under these conditions, the desired adduct (3a) was obtained in 41% isolated yield as a bench-stable solid (entry 1) (see Scheme C for its X-ray crystal structure). As expected, no corresponding 1,4-hydroboration product was detected by HRMS analysis (see Scheme S1), suggesting that hydroboration is not a competing pathway in the present reaction. Switching from PC1 to another Ir-based photocatalyst (PC2) or organic photocatalyst (PC3), each of which exhibits lower excited-state reduction potentials, markedly decreased efficiency (entry 2 or 3, respectively). Although the full optimization is detailed in the Supporting Information, this moderate yield may be partially attributed to the competitive hydrolysis of the CN group of 2a, as detected by electrospray ionization (ESI)-mass spectroscopic analysis (see Scheme S1). Notably, no significant byproducts other than 3a were identified upon completion of the reaction. The results of control experiments revealed some mechanistic insights. First, no reaction was observed in the absence of the photocatalyst, visible light, or base (entries 4–6). A light on/off experiment further revealed that continuous light irradiation is required for productive conversion (see Figure S3). In the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), the reaction was largely suppressed, and a TEMPO-trapped intermediate derived from B was detected by high-resolution mass spectrometry (HRMS) (see Scheme S2).

We next investigated the reaction mechanism through a series of experimental studies, including luminescence quenching and cyclic voltammetry analyses. As depicted in Scheme A, a Stern–Volmer analysis indicated that 2a efficiently quenched the excited photocatalyst (*PC1), implying that the photocatalytic cycle was initiated by the single-electron reduction of 2a by *PC1 (Scheme A). Furthermore, the reduction potential of 2a (E 1/2 red = −1.61 V vs SCE in CH3CN) , is more positive than the excited-state reduction potential of Ir­(ppy)3 (E 1/2 red(Ir­(IV)/Ir*­(III)) = −1.73 V vs the saturated calomel electrode (SCE) in CH3CN), , thus indicating the thermodynamic feasibility of the single-electron reduction of 2a by *PC1. Additionally, cyclic voltammetry revealed that the oxidative potential of the DBU salt of 1 (1-DBU) is relatively low (E ox = +0.66 V vs SCE in CH3CN). Consequently, the electron-deficient Ir­(IV) species (E 1/2 ox(Ir­(IV)/Ir­(III)) = +0.77 V vs SCE in CH3CN) should readily accept an electron from 1-DBU via single-electron transfer (SET), triggering decarboxylation to furnish the corresponding amine-ligated boryl radical (A). In contrast, given the excited-state oxidation potential of Ir­(ppy)3, (E 1/2 ox(*Ir­(III)/Ir­(II)) = +0.31 V vs SCE in CH3CN), the direct single-electron oxidation of 1-DBU by the excited photocatalyst (*PC1) is unlikely to operate competitively under the reaction conditions.

Conversely, density functional theory (DFT) calculations at the SMD­(DMF)/(U)­M06-2X/6-31+G­(3d,2p) level support the feasibility of the radical–radical coupling pathway. Although a transition state for the radical–radical coupling step between A and B was not identified, the computed activation barrier for the decyanative aromatization of C to 3a is consistent with that of a fast process (ΔG ⧧ = +12.4 kcal mol–1). Both radical–radical coupling and decyanative aromatization are highly exergonic (ΔG° = −25.9 and −32.9 kcal mol–1, respectively). These data are consistent with a mechanism involving a radical–radical coupling/elimination sequence.

With the optimized conditions in hand, we next examined the scope of substrates for the decyanative borylation reaction (Scheme C). Both 1,4-dicyanobenzene (2a) and 1,2-dicyanobenzene (2b) ) were borylated to afford products (3a and 3b) in 41% and 36% yields, respectively, whereas 1,3-dicyanobenzene (2c) proved to be an ineffective substrate. The lower reactivity of 2c may be attributed to its significantly more negative reduction potential (E 1/2 red = −1.87 V vs SCE in CH3CN) compared with that of both 2a and 2b (E 1/2 red ≈ −1.66 V vs SCE in CH3CN), rendering SET reduction by the excited photocatalyst less favorable. The reactions with 2a and 2b were successfully scaled up without a significant loss of yield. Substituted 1,4-dicyanobenzene derivatives were also evaluated and yielded the corresponding products as a mixture of regioisomers. The reaction tolerated alkyl substituents such as methyl (3d), ethyl (3e), and dimethyl (3g) groups, despite the presence of benzylic positions that are typically susceptible to HAT, and no side reactions were observed. We then turned to biaryl systems featuring a cyanoaryl ring. Phenyl substituents (3f) could also be used in this protocol, albeit affording lower yields. Similarly, 1,2-dicyanobenzene derivatives could also be used with alkyl-substituted (3h, 3i, 3m, and 3n), alkoxy-substituted (3k and 3l), and aryl-substituted (3j) substrates. DFT calculations suggest that the thermodynamic stability of the radical–radical coupling intermediates (C) may be one of the factors governing the observed regioselectivity (see Tables S6 and S7). Unfortunately, this strategy did not apply to several substrates, including methyl 4-cyanobenzoate (3o), 4-cyanopyridine (3p), dicyanonaphthalenes, and highly cyano-substituted arenes such as 1,3,5-tricyanobenzene and 1,2,4,5-tetracyanobenzene (3q) (see Table S3 for the limitation of the substrate scope). The lack of reactivity of pyridine derivatives is likely attributable to the weaker persistence of the corresponding radical anions, which disfavor the desired radical–radical coupling.

To harness the synthetic potential of these cyanoaryl amine–borane adducts (3), we examined their ability to serve as coupling partners. Aromatic organoboron compounds are most prominently employed in Pd-catalyzed Suzuki–Miyaura cross-coupling with aryl halides (Scheme ). Thus, we surveyed the reaction conditions for Suzuki–Miyaura cross-coupling between 3a and p-fluorobromobenzene (4a). Consequently, the Pd2dba3/XPhos system with Et3N in toluene/H2O efficiently catalyzed the coupling reaction at 80 °C, affording the corresponding biaryl (5aa) in 81% yield. The coupling was also successful with aryl chlorides and aryl triflates under the same conditions. A variety of aryl bromides were well tolerated without being significantly influenced by the electronic and steric properties of the aromatic ring, affording the corresponding products (5aa–5ak) in good yields. The method was further extended to 1- and 2-bromonaphthalenes (5al and 5am, respectively), 1-bromopyrene (5an), and heteroaryl bromides (5ao–5as), demonstrating broad substrate compatibility. Additionally, both 3b and 3n participated effectively. Finally, we used this chemistry for the late-stage functionalization of the pharmaceutical fenofibrate (4t), affording the corresponding product (5at) in 45% yield.

3. Suzuki–Miyaura Cross-Coupling.

3

Open in a new tab

a With 5 mol % Pd2dba3 and 20 mol % XPhos.

In conclusion, we developed a photoredox strategy for the decyanative borylation of dicyanoarenes using amine-ligated boryl radicals. The success of this approach likely arises from employing the oxidative quenching photoredox cycle, which enables efficient radical–radical coupling between amine-ligated boryl radicals and cyanoaryl radical anions. The resulting cyanoaryl amine–borane adducts are bench-stable, are readily purified by simple column chromatography, and can directly engage in Suzuki–Miyaura cross-coupling reactions. Overall, this work provides a platform for the modular functionalization of cyanoarenes and may offer new opportunities for the late-stage diversification of functional molecules in pharmaceuticals, agrochemicals, and optoelectronic materials.

Supplementary Material

ol6c02736_si_001.pdf (9.5MB, pdf)

Acknowledgments

This study was partially supported by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) (Grants JP24K17678 and JP26K17848, to N.Y.), the Research Foundation for the Electrotechnology of Chubu (N.Y.), the Tokuyama Science Foundation (N.Y.), and the Amano Institute of Technology (N.Y.). The computations were performed at the Research Center for Computational Science, Okazaki, Japan (26-IMS-C074).

The data underlying this study are available in the published article and its Supporting Information.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.6c02736.

  • Experimental procedures, optimization tables, characterization data (1H, 11B, 13C, and 19F NMR spectra, HRMS data, and X-ray data) for synthesized compounds, mechanistic studies, DFT calculations, and additional references (PDF)

The authors declare no competing financial interest.

References

  1. For selected reviews on the functionalization of nitriles, see:; a Wang, S. Y. ; Chu, X.-Q. ; Fang, Y. ; Ji, S.-J. . Acetonitrile as Reagents in Organic Synthesis: Reactions and Applications. In Solvents as Reagents in Organic Synthesis: Reactions and Applications; Wu, X. F. , Ed.; Wiley-VCH Verlag: Weinheim, Germany, 2017; Chapter 8, pp 355–375. [Google Scholar]; b López R., Palomo C.. Cyanoalkylation: Alkylnitriles in Catalytic C-C Bond-Forming Reactions. Angew. Chem., Int. Ed. 2015;54:13170–13184. doi: 10.1002/anie.201502493. [DOI] [PubMed] [Google Scholar]; c Chu X.-Q., Ge D., Shen Z.-L., Loh T.-P.. Recent Advances in Radical-Initiated C­(sp3)–H Bond Oxidative Functionalization of Alkyl Nitriles. ACS Catal. 2018;8:258–271. doi: 10.1021/acscatal.7b03334. [DOI] [Google Scholar]; d Zhong P., Zhang L., Luo N., Liu J.. Advances in the Application of Acetonitrile in Organic Synthesis since 2018. Catalysts. 2023;13:761. doi: 10.3390/catal13040761. [DOI] [Google Scholar]; e Kaur J., Chauhan P., Chimni S. S.. α,α-Dicyanoolefins: versatile substrates in organocatalytic asymmetric transformations. Org. Biomol. Chem. 2016;14:7832–7847. doi: 10.1039/C6OB01229A. [DOI] [PubMed] [Google Scholar]; f Sun K., Lv Q.-Y., Lin Y.-W., Yu B., He W.-M.. Nitriles as radical acceptors in radical cascade reactions. Org. Chem. Front. 2021;8:445–465. doi: 10.1039/D0QO01058H. [DOI] [Google Scholar]; g Fleming F. F., Wang Q.. Unsaturated Nitriles: Conjugate Additions of Carbon Nucleophiles to a Recalcitrant Class of Acceptors. Chem. Rev. 2003;103:2035–2078. doi: 10.1021/cr020045d. [DOI] [PubMed] [Google Scholar]; h Bonatto V., Lameiro R. F., Rocho F. R., Lameira J., Leitão A., Montanari C. A.. Nitriles: an attractive approach to the development of covalent inhibitors. RSC Med. Chem. 2023;14:201–217. doi: 10.1039/D2MD00204C. [DOI] [PMC free article] [PubMed] [Google Scholar]; i Fleming F. F., Yao L., Ravikumar P. C., Funk L., Shook B. C.. Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore. J. Med. Chem. 2010;53:7902–7917. doi: 10.1021/jm100762r. [DOI] [PMC free article] [PubMed] [Google Scholar]; j Uoyama H., Goushi K., Shizu K., Nomura H., Adachi C.. Highly efficient organic light-emitting diodes from delayed fluorescence. Nature. 2012;492:234–238. doi: 10.1038/nature11687. [DOI] [PubMed] [Google Scholar]; k Fleming F. F.. Nitrile-containing natural products. Nat. Prod. Rep. 1999;16:597–606. doi: 10.1039/a804370a. [DOI] [Google Scholar]
  2. a Madasu S. B., Vekariya N. A., Koteswaramma C., Islam A., Sanasi P. D., Korupolu R. B.. An Efficient, Commercially Viable, and Safe Process for Preparation of Losartan Potassium, an Angiotensin II Receptor Antagonist. Org. Process Res. Dev. 2012;16:2025–2030. doi: 10.1021/op300179u. [DOI] [Google Scholar]; b Komiyama M., Tsuchiya H., Teramoto M., Yajima N., Kurokawa N., Minamizono K., Tsuchiya N., Kato Y., Sato Y., Dohi M.. Process Development of Febuxostat Using Palladium- and Copper Catalyzed C–H Arylation. Org. Process Res. Dev. 2018;22:1306–1311. doi: 10.1021/acs.oprd.8b00164. [DOI] [Google Scholar]; c Wang G.-X., Sun B.-P., Peng C.-H.. An Improved Synthesis of Valsartan. Org. Process Res. Dev. 2011;15:986–988. doi: 10.1021/op200032b. [DOI] [Google Scholar]
  3. Hall, D. G. Structure, Properties, and Preparation of Boronic Acid Derivatives. In Overview of Their Reactions and Applications. Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine; Hall, D. G. , Ed.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2005; pp 1–99. [Google Scholar]
  4. a Blakemore, D. Chapter 1 Suzuki–Miyaura Coupling. In Synthetic Methods in Drug Discovery; Blakemore, D. C. , Doyle, P. M. , Fobian, Y. M. , Eds.; The Royal Society of Chemistry: Cambridge, U.K., 2016; Vol. 1, Chapter 1, pp 1–69. [Google Scholar]; b Suzuki A.. Cross-Coupling Reactions of Organoboranes: An Easy Way To Construct C–C Bonds. Angew. Chem., Int. Ed. 2011;50:6722–6737. doi: 10.1002/anie.201101379. [DOI] [PubMed] [Google Scholar]; c Qiao, J. X. ; Lam, P. Y. S. . Recent Advances in Chan–Lam Coupling Reaction: Copper-Promoted C–Heteroatom Bond Cross Coupling Reactions with Boronic Acids and Derivatives. Boronic Acids; Hall, D. G. , Ed.; John Wiley & Sons: Chichester, U.K., 2011; Chapter 6, pp 315–361. [Google Scholar]; d West M. J., Fyfe J. W. B., Vantourout J. C., Watson A. J. B.. Mechanistic Development and Recent Applications of the Chan–Lam Amination. Chem. Rev. 2019;119:12491–12523. doi: 10.1021/acs.chemrev.9b00491. [DOI] [PubMed] [Google Scholar]
  5. Brown D. G., Boström J.. Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone. J. Med. Chem. 2016;59:4443–4458. doi: 10.1021/acs.jmedchem.5b01409. [DOI] [PubMed] [Google Scholar]
  6. a Bonet A., Sole C., Gulyas H., Fernandez E.. Boron Conjugate Additions on Electron Deficient Olefins Towards Selective 1,3- Difunctionalization. Curr. Org. Chem. 2010;14:2531–2548. doi: 10.2174/138527210793358295. [DOI] [Google Scholar]; b 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. doi: 10.1021/jo00128a024. [DOI] [Google Scholar]; c Guerrand H. D. S., Marciasini L. D., Jousseaume M., Vaultier M., Pucheault M.. Borylation of Unactivated Aryl Chlorides under Mild Conditions by Using Diisopropylaminoborane as a Borylating Reagent. Chem. - Eur. J. 2014;20:5573–5579. doi: 10.1002/chem.201304861. [DOI] [PubMed] [Google Scholar]; d Mkhalid I. A. I., Barnard J. H., Marder T. B., Murphy J. M., Hartwig J. F.. C–H Activation for the Construction of C–B Bonds. Chem. Rev. 2010;110:890–931. doi: 10.1021/cr900206p. [DOI] [PubMed] [Google Scholar]
  7. Zabolotna Y., Volochnyuk D. M., Ryabukhin S. V., Horvath D., Gavrilenko K. S., Marcou G., Moroz Y. S., Oksiuta O., Varnek A.. A Close-up Look at the Chemical Space of Commercially Available Building Blocks for Medicinal Chemistry. J. Chem. Inf. Model. 2022;62:2171–2185. doi: 10.1021/acs.jcim.1c00811. [DOI] [PubMed] [Google Scholar]
  8. a Tobisu M., Kinuta H., Kita Y., Rémond E., Chatani N.. Rhodium­(I)-Catalyzed Borylation of Nitriles through the Cleavage of Carbon–Cyano Bonds. J. Am. Chem. Soc. 2012;134:115–118. doi: 10.1021/ja2095975. [DOI] [PubMed] [Google Scholar]; b Esteruelas M. A., Oliván M., Vélez A.. Conclusive Evidence on the Mechanism of the Rhodium-Mediated Decyanative Borylation. J. Am. Chem. Soc. 2015;137:12321–12329. doi: 10.1021/jacs.5b07357. [DOI] [PubMed] [Google Scholar]
  9. a Chao F., Yang H.-B., Fang Y.. Photoredox-catalyzed Decyanative Radical Cross-coupling Reactions of Aromatic Nitriles. ChemCatChem. 2024;16:e202301281. doi: 10.1002/cctc.202301281. [DOI] [Google Scholar]; b Proctor R. S. J., Phipps R. J.. Recent Advances in Minisci-Type Reactions. Angew. Chem., Int. Ed. 2019;58:13666–13699. doi: 10.1002/anie.201900977. [DOI] [PubMed] [Google Scholar]; c Pillitteri S., Van der Eycken E. V., Sharma U. K.. Recent developments in the photoredox catalyzed Minisci-type reactions under continuous flow. Chem. Commun. 2025;61:13–22. doi: 10.1039/D4CC04801F. [DOI] [PubMed] [Google Scholar]; d Zhou L.. Recent Advances in C-F Bond Cleavage Enabled by Visible Light Photoredox Catalysis. Molecules. 2021;26:7051. doi: 10.3390/molecules26227051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. a Friese W. F., Studer S.. New avenues for C–B bond formation via radical intermediates. Chem. Sci. 2019;10:8503–8518. doi: 10.1039/C9SC03765A. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Wang M., Shi Z.. Methodologies and Strategies for Selective Borylation of C–Het and C–C Bonds. Chem. Rev. 2020;120:7348–7398. doi: 10.1021/acs.chemrev.9b00384. [DOI] [PubMed] [Google Scholar]; c Tian Y.-M., Guo X.-N., Braunschweig H., Radius U., Marder T. B.. Photoinduced Borylation for the Synthesis of Organoboron Compounds. Chem. Rev. 2021;121:3561–3597. doi: 10.1021/acs.chemrev.0c01236. [DOI] [PubMed] [Google Scholar]; d Capaldo L., Noël T., Ravelli D.. Photocatalytic generation of ligated boryl radicals from tertiary amine-borane complexes: An emerging tool in organic synthesis. Chem. Catal. 2022;2:957–966. doi: 10.1016/j.checat.2022.03.005. [DOI] [Google Scholar]; e 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. doi: 10.1021/acs.accounts.2c00752. [DOI] [PubMed] [Google Scholar]; f Liang R.-B., Miao T.-T., Li X.-R., Huang J.-B., Ni S.-F., Li S., Tong Q.-X., Zhong J.-J.. Modular assembly of amines and diborons with photocatalysis enabled halogen atom transfer of organohalides for C­(sp3)–C­(sp3) bond formation. Chem. Sci. 2025;16:3580–3587. doi: 10.1039/D5SC00190K. [DOI] [PMC free article] [PubMed] [Google Scholar]; g Miao T.-T., Liang R.-B., Wang Y.-J., Li X.-R., Xiao Y., Tong Q.-X., Zhong J.-J.. A General Photoredox Platform for Divergent Couplings of Alkenes with Aliphatic Carbonyls via Ligated Boryl Radicals. ACS Catal. 2026;16:576–586. doi: 10.1021/acscatal.5c06961. [DOI] [Google Scholar]
  11. a Walton J. C., Brahmi M. M., Fensterbank L., Lacôte E., Malacria M., Chu Q., Ueng S.-H., Solovyev A., Curran D. P.. EPR Studies of the Generation, Structure, and Reactivity of N-Heterocyclic Carbene Borane Radicals. J. Am. Chem. Soc. 2010;132:2350–2358. doi: 10.1021/ja909502q. [DOI] [PubMed] [Google Scholar]; b Taniguchi T.. Advances in chemistry of N-heterocyclic carbene boryl radicals. Chem. Soc. Rev. 2021;50:8995–9021. doi: 10.1039/D1CS00385B. [DOI] [PubMed] [Google Scholar]
  12. Nerkar S., Curran D. P.. Synthesis and Suzuki Reactions of N-Heterocyclic Carbene Difluoro­(aryl)-boranes. Org. Lett. 2015;17:3394–3397. doi: 10.1021/acs.orglett.5b01101. [DOI] [PubMed] [Google Scholar]
  13. For selected and representative reports on photocatalytic reactions of cyanoarenes, see:; a Pirnot M. T., Rankic D. A., Martin D. B. C., MacMillan D. W. C.. Photoredox Activation for the Direct β-Arylation of Ketones and Aldehydes. Science. 2013;339:1593–1596. doi: 10.1126/science.1232993. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Zuo Z., MacMillan D. W. C.. Decarboxylative Arylation of α-Amino Acids via Photoredox Catalysis: A One-Step Conversion of Biomass to Drug Pharmacophore. J. Am. Chem. Soc. 2014;136:5257–5260. doi: 10.1021/ja501621q. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. a Dai W., Geib S. J., Curran D. P.. 1,4-Hydroboration Reactions of Electron-Poor Aromatic Rings by N-Heterocyclic Carbene Boranes. J. Am. Chem. Soc. 2020;142:6261–6267. doi: 10.1021/jacs.0c00490. [DOI] [PubMed] [Google Scholar]; b 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. doi: 10.1002/anie.201915619. [DOI] [PubMed] [Google Scholar]
  15. a Baban J. A., Marti V. P. J., Roberts B. P.. Ligated boryl radicals. Part 2. Electron spin resonance studies of trialkylamin–boryl radicals. J. Chem. Soc., Perkin Trans. 1985;2:1723–1733. doi: 10.1039/P29850001723. [DOI] [Google Scholar]; b Sheeller B., Ingold K. U.. Absolute rate constants for some reactions of the triethylamine-boryl radical and the boraneradical anion. J. Chem. Soc., Perkin Trans. 2001;2:480–486. doi: 10.1039/b009494n. [DOI] [Google Scholar]; c Wu C., Hou X., Zheng Y., Li P., Lu D.. Electrophilicity and Nucleophilicity of Boryl Radicals. J. Org. Chem. 2017;82:2898–2905. doi: 10.1021/acs.joc.6b02849. [DOI] [PubMed] [Google Scholar]; d Garwood J. J. A., Chen A. D., Nagib D. A.. Radical Polarity. J. Am. Chem. Soc. 2024;146:28034–28059. doi: 10.1021/jacs.4c06774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. a Song L., Zhuang J.-L., Xiong P., Xu H.-C.. Photoelectrocatalytic heteroarene C­(sp2)–H borylation. Green Chem. 2025;27:10556–10561. doi: 10.1039/D5GC03231H. [DOI] [Google Scholar]; b 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. doi: 10.1038/s41586-021-03637-6. [DOI] [PubMed] [Google Scholar]
  17. a Buettner C. S., Stavagna C., Tilby M. J., Górski B., Douglas J. J., Yasukawa N., Leonori D.. Synthesis and Suzuki–Miyaura Cross-Coupling of Alkyl Amine-Boranes. A Boryl Radical-Enabled Strategy. J. Am. Chem. Soc. 2024;146:24042–24052. doi: 10.1021/jacs.4c07767. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Yasukawa N., Okada W., Fimm M., Kawamura R., Nomura R., Takehara T., Suzuki T., Leonori D., Nakamura S.. Amine-Ligated Boryl Radicals Enables Direct C–F Borylation and Cross-Couplings of Polyfluoroarenes. Angew. Chem., Int. Ed. 2025;64:e202514741. doi: 10.1002/anie.202514741. [DOI] [PubMed] [Google Scholar]; c Yasukawa N., Naito S., Obata K., Nakamura S.. Amine-Ligated Boryl Radical Enabled Hydrofunctionalization of Styrenes via Halogen-Atom Transfer of Alkyl and Aryl Bromides. Synthesis. 2025;57:2609–2619. doi: 10.1055/a-2427-9313. [DOI] [Google Scholar]; d Yoshida Y., Okada W., Takada K., Nakamura S., Yasukawa N.. Photocatalytic Strategy for Decyanative Transformations Enabled by Amine-Ligated Boryl Radical. Org. Lett. 2025;27:2542–2547. doi: 10.1021/acs.orglett.4c04701. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Yoshida Y., Okada W., Takada K., Nakamura S., Yasukawa N.. Photocatalytic Decyanative Radical Addition Based on Cyano Group Transfer Mediated by Amine-Ligated Boryl Radicals. Org. Lett. 2025;27:7236–7241. doi: 10.1021/acs.orglett.5c02217. [DOI] [PubMed] [Google Scholar]
  18. a Leifert D., Studer A.. The Persistent Radical Effect in Organic Synthesis. Angew. Chem., Int. Ed. 2020;59:74–108. doi: 10.1002/anie.201903726. [DOI] [PubMed] [Google Scholar]; b Fischer H.. The Persistent Radical Effect: A Principle for Selective Radical Reactions and Living Radical Polymerizations. Chem. Rev. 2001;101:3581–3610. doi: 10.1021/cr990124y. [DOI] [PubMed] [Google Scholar]
  19. Mori Y., Sakaguchi Y., Hayashi H.. Magnetic Field Effects on Chemical Reactions of Biradical Radical Ion Pairs in Homogeneous Fluid Solvents. J. Phys. Chem. A. 2000;104:4896–4905. doi: 10.1021/jp0007437. [DOI] [Google Scholar]
  20. a Flamigni L., Barbieri A., Sabatini C., Ventura B., Barigelletti F.. Photochemistry and Photophysics of Coordination Compounds: Iridium. Top. Curr. Chem. 2007;281:143–203. doi: 10.1007/128_2007_131. [DOI] [Google Scholar]; b Dixon I. M., Collin J.-P., Sauvage J.-P., Flamigni L., Encinas S., Barigelletti F.. A family of luminescent coordination compounds: iridium­(iii) polyimine complexes. Chem. Soc. Rev. 2000;29:385–391. doi: 10.1039/b000704h. [DOI] [Google Scholar]; c Lemos A., Lemaire C., Luxen A.. Progress in Difluoroalkylation of Organic Substrates by Visible Light Photoredox Catalysis. Adv. Synth. Catal. 2019;361:1500–1537. doi: 10.1002/adsc.201801121. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Majek M., Jacobi von Wangelin A.. Mechanistic Perspectives on Organic Photoredox Catalysis for Aromatic Substitutions. Acc. Chem. Res. 2016;49:2316–2327. doi: 10.1021/acs.accounts.6b00293. [DOI] [PubMed] [Google Scholar]
  21. Sertel M., Yildiz A., Gambert R., Baumgärtel H.. The electroreduction mechanism of Di- and tricyanobenzenes. Electrochim. Acta. 1986;31:1287–1292. doi: 10.1016/0013-4686(86)80149-9. [DOI] [Google Scholar]
  22. Chan B., Easton C. J., Radom L.. Outcome-Changing Effect of Polarity Reversal in Hydrogen-Atom-Abstraction Reactions. J. Phys. Chem. A. 2015;119:3843–3847. doi: 10.1021/acs.jpca.5b01890. [DOI] [PubMed] [Google Scholar]
  23. Stevenson B. C., Gironda C., Talbott E., Prascsak A., Burnett N. L., Kompanijec V., Nakhamiyayev R., Fredin L. A., Swierk J. R.. Photoredox Product Selectivity Controlled by Persistent Radical Stability. J. Org. Chem. 2024;89:13818–13825. doi: 10.1021/acs.joc.3c00490. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ol6c02736_si_001.pdf (9.5MB, pdf)

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Articles from Organic Letters are provided here courtesy of American Chemical Society

RESOURCES