ACS Publications. Most Trusted. Most Cited. Most Read
Photocatalytic Strategy for Decyanative Transformations Enabled by Amine-Ligated Boryl Radical
My Activity
  • Open Access
Letter

Photocatalytic Strategy for Decyanative Transformations Enabled by Amine-Ligated Boryl Radical
Click to copy article linkArticle link copied!

  • Yuto Yoshida
    Yuto Yoshida
    Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
    More by Yuto Yoshida
  • Waka Okada
    Waka Okada
    Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
    More by Waka Okada
  • Kazutake Takada
    Kazutake Takada
    Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
  • Shuichi Nakamura*
    Shuichi Nakamura
    Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
    *E-mail: [email protected]
  • Naoki Yasukawa*
    Naoki Yasukawa
    Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
    *E-mail: [email protected]
Open PDFSupporting Information (1)

Organic Letters

Cite this: Org. Lett. 2025, XXXX, XXX, XXX-XXX
Click to copy citationCitation copied!
https://doi.org/10.1021/acs.orglett.4c04701
Published January 10, 2025

© 2025 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY-NC-ND 4.0 .

Abstract

Click to copy section linkSection link copied!

Decyanation after α-functionalization by exploiting the inherent properties of cyano groups enables the strategic assembly of a carbon scaffold. Herein, we demonstrate an amine-ligated boryl radical-mediated cyano group transfer (CGT) strategy of malononitriles under photocatalytic conditions. This strategy allows for the cleavage of C(sp3)–CN and the formation of C(sp3)–D and C(sp3) to realize decyanative deuteration and cyclization via radical-polar crossover. Computational studies successfully demonstrated the reactivity of CGT promoters can be accurately assessed.

This publication is licensed under

CC-BY-NC-ND 4.0 .
  • cc licence
  • by licence
  • nc licence
  • nd licence
© 2025 The Authors. Published by American Chemical Society

The assembly of molecular complexities is a basic principle of organic chemistry. One goal of this study is to introduce, utilize, and remove functional group (FG) handles on demand. For example, streamlined access to molecular complexity can be achieved by combining FG-facilitated C–C bond construction with structural diversification involving FG-removal (Scheme 1-A). Among the various FGs, the cyano (CN) group is one of the most valuable and powerful activating groups for the functionalization of adjacent carbon atoms owing to its inherent electron-withdrawing properties and coordination ability. (1) Indeed, various protocols based on CN group-handles have been adopted for the total synthesis of (±)-isoretronecanol, (±)-xanthorrhizol, etc. (2) Nevertheless, the decyanation step is generally restricted the applicable substrates and diminishes the tolerance for other functional groups because the high C–CN bond dissociation energy (BDE) leads to the need for harsh conditions (transition metals and strong reductants). (3,4)

Scheme 1

Scheme 1. Introduction of Cyano Group Transfer (CGT) and Synthetic Scenario

Recently, photoredox catalysis has emerged as a powerful tool for the in situ formation of open-shell radical species under mild reaction conditions. (5) However, the use of organonitriles as radical precursors in (photo)redox chemistry is difficult due to their highly negative reduction potentials [e.g., Ered < −2 V vs saturated calomel electrode (SCE) for dimethylmalononitrile] (Scheme 1-B). To overcome the high negative reduction potential in the decyanation of organonitriles, stoichiometric samarium diiodide (SmI2) in hexamethylphosphoric triamide (HPMA) or organic superelectron donors is required. (6,7)

As an alternative strategy, an open-shell radical-mediated approach has proven to be highly reliable in accessing carbon-centered radicals from alkyl nitriles by homolytic C(sp3)–CN bond cleavage (Scheme 1-B). (8) Roberts discovered the phenomenon in which ammonia-ligated boryl radicals react with alkyl nitriles to form iminyl radicals, after which β-scission can proceed. (8a) However, synthetic applicability of this decyanative process was lacking.

Activated alkyl nitriles, which possess electron-withdrawing group at α-position, are ideal molecules for radical decyanation due to the dramatic improvement of their inherent nature such as BDEs of C–CN (acetonitrile vs malononitrile = 121.1 kcal mol−1 vs 78.9 kcal mol−1). (3) Curran pioneered the CGT process starting from malononitriles, involving a radical chain mechanism based on hydrogen atom transfer (HAT), which was first achieved with toxic tin hydride as a radical mediator. (8b) Thereafter, Curran, Kawamoto, and co-workers developed more environmentally friendly methods using N-heterocyclic borane (NHC-BH3), (8c,d) or tris(trimethylsilyl)silane, (8e) involving the formation of the corresponding radical species in the presence of radical initiators such as azonitriles and peroxides at elevated temperatures. Recently, similar reactions of mononitrile compounds have been achieved using sodium borohydride or NHC-BH3. (9) Very recently, Turlik, Schuppe, and co-workers introduced photoredox/HAT dual catalysis based on a de(iso)cyanation approach using NHC-ligated boryl radicals (Scheme 1-C). (10) Furthermore, from a structural point of view, a π-configuration with the unpaired electron in conjugation with the NHC ring feature in NHC-ligated boryl radicals, resulting in their low nucleophilicity. (11) Because the reactivity of CGT process stemmed from the reaction mechanism that nucleophilic addition of open-shell radicals to electrophilic CN group (Scheme 1-B), we reasoned that strongly nucleophilic boryl-radicals might benefit and exceed the reactivity of NHC-ligated boryl radicals. More importantly, all reported reactions rely on HAT events for preparation of the CGT promoters. Thus, the reaction mode is limited to hydrodecyanation because the in situ generated carbon-centered radicals abstract hydrogen atoms from the heteroatom-centered radical precursors.

We recently became interested in the synthetic potential of amine-ligated boryl radicals, which exhibit high nucleophilicity due to σ-conjugation on a tetrahedral B atom. (12−14) In our previous collaborative work with Leonori, the photocatalytic generation of these species from carboxylic acid-containing boron was exploited in the borylation of π-systems such as olefins and imines and halogen atom transfer (XAT) protocol, demonstrating the unique reactivity of amine-ligated boryl radicals. (14) The ability of amine-ligated boryl radicals to participate in decyanation has been overlooked by the synthetic community, although the possibility was suggested by Roberts. (8a) Thus, we questioned whether amine-ligated boryl radicals can be applied to decyanation and subsequent versatile functionalization based on the photocatalytic strategy, such as radical–polar crossover manifolds, for the assembly of molecular complexes. (15)

Herein, we demonstrate the cyano group transfer (CGT) concept of a mechanically distinct and decyanative transformation (Scheme 1-D). This method integrates an amine-ligated boryl radical-mediated decyanation process with photoredox catalysis and has enabled decyanative deuteration and cyclization by trapping carbanion intermediate.

Based on Roberts’s and Curran’s previous works, (8a,c) we hypothesized that the CGT step proceeds via in situ formation of the iminyl radical (B) by boryl radical addition to dimethylmalononitrile (2a) and subsequent β-fragmentation into the corresponding carbon-centered radical (C) and cyanoborane-amine complex (3). In fact, 3 was observed through 11B NMR monitoring of the reaction between 2a and the amine-ligated boryl radical (A), which was generated in situ in our previous study. (14) Therefore, computational studies were performed to evaluate CGT from 2a to A (Scheme 2-A). Density functional theory (DFT) calculations at the CPCM (DMF) UM06/6-311++G(3d,2p)//UM06/6-31+G(d,p) level of theory indicated that this CGT step is kinetically feasible (ΔG = +5.2 and +6.3 kcal mol−1 in each step). Notably, the boryl radical addition and β-fragmentation steps are both exothermic, with ΔG° values of −20.3 and −23.9 kcal mol–1, respectively.

Scheme 2

Scheme 2. Theoretical and Experimental Evaluations of CGT Process and Application to Decyanative Deuteration

The proposed approach for the decyanative transformation is based on a photoredox catalytic cycle using the boryl radical (A)-mediated CGT process (Scheme 2-B). Initially, oxidative SET from a visible-light-excited photocatalyst (*PC) with the carboxylate formed upon deprotonation of boracarboxylic acid (1) generates a carboxyl radical, which, after subsequent decarboxylation, furnishes the boryl radical (A). This species undergoes CGT with malononitrile derivatives (2), followed by SET between the resulting carbon-centered radical (C) and the reduced photoredox catalyst (PC•–) to provide carbanion (D) while reinitiating the catalytic cycle. Finally, D reacts with the electrophiles to afford the product.

To demonstrate the above-mentioned strategy, we proposed a scenario in which carbanion (D), formed in situ, is trapped by deuterium oxide (D2O) as an electrophile to access α-deuterated nitriles. Due to their low acidity, the synthesis of α-deuterated nitriles, especially α,α-dialkyl-substituted nitriles, is still challenging. (16) The decyanative deuteration of 2 was implemented using boracarboxylic acid (1) as the CGT promoter, 4CzIPN as the photoredox catalyst, potassium carbonate (K2CO3) as the base, and D2O as the electrophile in DMF under irradiation by blue LEDs at room temperature (Scheme 2-C-top). Under these mild conditions, α,α-diphenethyl-substituted malononitrile (2b) was converted into 4b-d in 89% yield with 92% deuterium content (Table S1 in the SI). Based on the literature, (14a,17) the excited state 4CzIPN* (*Ered = +1.35 V vs SCE) would oxidize deprotonated boracarboxylic acid (1; Eox of Cs-salt = +0.38 V vs SCE) in the initiation point of the photoredox catalytic cycle. Furthermore, the reduced 4CzIPN•– (*E1/2 = −1.21 V vs SCE) would be able to smoothly reduce the in situ formed alkyl radical (C) to carbanion (D) (E1/2 of α-cyano radical ≈ −0.7 V vs SCE). (17c) Detailed mechanistic studies, such as light on/off experiments and radical trapping using DMF-d7 as a deuterating agent, imply the radical-polar crossover mechanism to form carbanion (D) (Figure S2 and Scheme S2 in the SI). More importantly, the previously reported decyanation reaction, which proceeds through a radical chain mechanism, using NHC-ligated boryl radical and D2O did not incorporate D atom to the decyanative product (Table S12 in the SI). Overall, these results demonstrate the photocatalytic strategy using 1 is a mechanically distinct concept and the potential for diversification of decyanative transformation.

Next, we evaluated the CGT promoters and their precursors (Scheme 2-C-top; Tables S11 and S12 in the SI). Borane-trimethylamine complex (Me3NBH3) is the simplest radical precursor for A, however, all our attempts to decyanative deuteration using photocatalysis and radical initiators failed. This is most likely due to the inherent properties of Me3NBH3, such as high BDEs of B–H (100.5 kcal mol−1) and redox potential (E1/2ox = +2.60 V vs SCE). (12a,c) Although the NHC-ligated boryl radical and silyl radical-mediated decyanation, which proceed in the presence of a radical initiator at elevated temperature, have been also previously reported, (8c,e) importantly, the use of these radicals instead of Me3N-ligated boryl radical was not successful under the photoredox catalytic conditions (18,19) at room temperature. To further demonstrate the reactivities of the Me3N-ligated boryl, NHC-ligated boryl, and silyl radicals, DFT calculations were performed at the same level as in Scheme 2-A (Scheme 2-C-bottom). The free-energy barriers of the addition step and β-fragmentation step for the Me3N-ligated boryl radical were much less among the evaluated radicals (NHC-ligated boryl radical and trimethylsilyl radical). This difference is attributed to the higher nucleophilicity, higher polarity, and less steric hindrance of the Me3N-ligated boryl radicals.

Control experiments using nondeuterated product (4b) as a starting material revealed that the deuteration of C–H via deprotonation and the HAT event with A is not involved in the reaction mechanism (Scheme 2-D). Computational studies to provide more detailed insight into the chemical properties of 4b also indicated that deprotonation is unfavorable under the standard reaction conditions owing to the low acidity of 4b (pKa = 34). Although HAT of the amine-ligated boryl radicals with the α-proton of nitriles was previously reported, (8a,12b,c) the radical addition of A to 2a is favored compared to the HAT of A with isobutylnitrile (ΔG = +5.2 kcal/mol vs +11.4 kcal/mol).

With the optimized reaction conditions in hand, the generality of the transformation was evaluated (Scheme 3). The 10-fold scale-up reaction of 2b (1 mmol) could also be successfully performed without loss of yield and D-contents. α,α-Dibenzyl- or α-phenyl-substituted malononitriles and cyclic malononitriles with 5–7 members, cyanoacetic esters, and cyanoacetic amides efficiently underwent the decyanative deuteration to afford the corresponding products (4c-d4j-d) in good yields with high deuterium contents. Next, we tested the compatibility with useful functionalities using various α-aryl-substituted substrates and demonstrated that electron-rich methyl (4k-d) and methoxy (4l-d) groups, as well as electron-withdrawing fluoro (4m-d) and chloro (4n-d) atoms, at the para-position of each aromatic nucleus were applicable. Substrates with a methoxy group at the ortho or meta position were transformed into the desired deuterated products (4o-d and 4p-d). Furthermore, various types of α-(aryl-methyl)-substituted α-phenethylmalononitrile were screened, and these substrates provided the desired products containing halide (4q-d and 4r-d), trifluoromethyl (4s-d), and cyano (4t-d) functionalities, as well as heterocyclic (4u-d4x-d) and naphthyl (4y-d) units, in moderate to high yields with high deuterium contents. The effects of the steric hindrance and functional groups on the alkyl motifs were evaluated. As the functional group on the α-carbon of the malononitriles became more sterically bulky, a stepwise decrease in the reactivity was observed (4z-d4ac-d). Under the present reaction conditions, terminal olefin, alkyl chloride, ester, and cyano functionalities (4ad-d4ag-d) were tolerated. However, considering the reactivity of boryl radical (A), the CGT strategy of substrates with α-proton and bromine failed because HAT and XAT processes are favored. Furthermore, mononitriles are not applicable for this decyanative deuteration.

Scheme 3

Scheme 3. Substrate Scope

a1.2 equiv of 1 and 1.5 equiv of K2CO3 were used.

b1 mmol of 2 was used.

c100.0 equiv of D2O was used.

To demonstrate the utility of this CGT event, electrophiles were screened instead of D2O. Although trapping in situ generated carbanion (D) with a variety of electrophiles is feasible, in the case of intermolecular reactions, most efforts at intermolecular 1,2- or 1,4-addition did not succeed (up to 23% yield of acetylated adducts). We decided to adapt the CGT process to intramolecular transformations. Recently, a radical-polar crossover approach was applied to the synthesis of cyclopropanes via intramolecular alkylation. (15) These transformations are generally accomplished using two fragments via intermolecular radical addition and subsequent intramolecular alkylation. In contrast, the process developed herein represents a unimolecular fragment transformation, which is a potentially powerful strategy because the starting materials can be easily prepared by α-dialkylation of malononitriles. The reaction conditions were evaluated using α-(2-chloroethyl)-α-phenethyl-substituted malononitrile (2’a) as a starting material in the presence of boracarboxylic acid (1) and 4CzIPN under blue-light irradiation at room temperature (Scheme 4). Cesium fluoride (CsF) in DMA was chosen as the optimal reagent, affording the desired cyclopropane (5a) in 78% yield (Table S3 in the SI). No effect of the electron density on the aromatic ring (5a5d) or carbon linker (5e5f) was observed. Although a homolytic substitution between the radical intermediate and alkyl halide is also presumed, poor ability of chlorine as radical leaving group also supports the radical-polar crossover mechanism. (20)

Scheme 4

Scheme 4. CGT Strategy for Intramolecular Cyclization

Inspired by the pioneering work on decarboxylative olefination by Ritter and Wu, (21) we decided to adapt this CGT process to retro-hydrocyanation by merging it with cobalt catalysis. Although retro-hydrocyanation can be achieved via oxidative addition to the C–CN bond and subsequent β-hydride elimination with the aid of nickel and aluminum dual catalysis, a high reaction temperature is typically required owing to the slow-rate of oxidative addition and endothermic nature of the reaction. (22) After the CGT process, the cobaloxime catalyst can trap in situ generated carbon-centered radicals and trigger a dehydrogenation reaction. However, none of the reactions using 1 as the boryl radical precursor afforded the desired unsaturated compounds. Considering the incompatibility of the redox potentials in the reaction system, the incorporation of a HAT catalyst into the catalytic system was explored, based on recent related studies on the Heck-type olefinations of Me3NBH3 using photoredox, cobalt, and HAT hybrid catalysis. (12d) This catalytic protocol was feasible, allowing the retro-hydrocyanation of malononitriles under mild reaction conditions (Table S5 and S6 in the SI; Scheme S5 in the SI for the assumed reaction mechanism); however, all efforts did not succeed in further improving the yield of olefins (6) (Scheme 5).

Scheme 5

Scheme 5. CGT Strategy for Decyanative Olefination

In conclusion, a photocatalytic approach for the decyanative transformation of activated alkyl nitriles was developed in which photoredox catalysis was used to generate amine-ligated boryl radicals. This method reduces carbon-centered radical intermediates to carbanion intermediates, which trap the electrophiles (radical-polar crossover manifolds). Furthermore, DFT calculations accurately corroborated the experimentally proven unique reactivity of amine-ligated boryl radicals. Further studies of the CGT reactions are currently ongoing in our laboratory.

Data Availability

Click to copy section linkSection link copied!

The data underlying this study are available in a published article and online Supporting Information.

Supporting Information

Click to copy section linkSection link copied!

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.4c04701.

  • Experimental procedures, characterization data for all compounds, 1H, 11B, 13C, and 19F NMR spectra, and DFT calculations (PDF)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

Click to copy section linkSection link copied!

  • Corresponding Authors
  • Authors
    • Yuto Yoshida - Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
    • Waka Okada - Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
    • Kazutake Takada - Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
  • Notes
    The authors declare no competing financial interest.

Acknowledgments

Click to copy section linkSection link copied!

This study was partially supported by JSPS KAKENHI (JSPS, numbers JP24K17678 and JP23K19242 to N.Y.) and Takahashi Industrial and Economic Research Foundation to N.Y. Computations were performed at the Research Center for Computational Science, Okazaki, Japan (Project: 24-IMS-C078).

References

Click to copy section linkSection link copied!

This article references 22 other publications.

  1. 1

    Selected reviews on the functionalization of nitriles:

    (a) Wang, S. Y.; Chu, X.-Q.; Fang, Y.; Ji, S.-J. Chapter 8 Acetonitrile as Reagents in Organic Synthesis: Reactions and Applications. In Solvents as Reagents in Organic Synthesis: Reactions and Applications , 2017; pp 355375.
    (b) López, R.; Palomo, C. Cyanoalkylation: Alkylnitriles in Catalytic C–C Bond-Forming Reactions. Angew. Chem., Int. Ed. 2015, 54 (45), 1317013184,  DOI: 10.1002/anie.201502493
    (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 (1), 258271,  DOI: 10.1021/acscatal.7b03334
    (d) Zhong, P.; Zhang, L.; Luo, N.; Liu, J. Advances in the Application of Acetonitrile in Organic Synthesis since 2018. Catalysts 2023, 13 (4), 761,  DOI: 10.3390/catal13040761
  2. 2
    (a) Li, J.; Zhao, H.; Jiang, X.; Wang, X.; Hu, H.; Yu, L.; Zhang, Y. The Cyano Group as a Traceless Activation Group for the Intermolecular [3 + 2] Cycloaddition of Azomethine Ylides: A Five-Step Synthesis of (±)-Isoretronecanol. Angew. Chem., Int. Ed. 2015, 54 (21), 63066310,  DOI: 10.1002/anie.201500961
    (b) Lujan-Montelongo, J. A.; Covarrubias-Zuniga, A.; Romero-Ortega, M.; Avila-Zarraga, J. G. An Efficient Synthesis of (±)-Xanthorrhizol: One Pot Decyanation and Demethylation. Lett. Org. Chem. 2008, 5 (6), 470472,  DOI: 10.2174/157017808785740525
  3. 3
    (a) Zavitsas, A. A. The Relation between Bond Lengths and Dissociation Energies of Carbon-Carbon Bonds. J. Phys. Chem. A 2003, 107 (6), 897898,  DOI: 10.1021/jp0269367
    (b) Lee, J. C.; Koh, H. Y.; Lee, Y. S.; Kang, H.-Y. Geminal substituent Effects on Decyanation Reactions. Bull. Korean Chem. Soc. 1997, 18 (7), 783785
  4. 4
    (a) Mattalia, J.-M.; Marchi-Delapierre, C.; Hazimeh, H.; Chanon, M. The reductive decyanation reaction: chemical methods and synthetic applications. Arkivoc 2006, 2006, 90118,  DOI: 10.3998/ark.5550190.0007.408
    (b) Mattalia, J.-M. R. The reductive decyanation reaction: an overview and recent developments. Beilstein J. Org. Chem. 2017, 13, 267284,  DOI: 10.3762/bjoc.13.30
    (c) Paul, N.; Patra, T.; Maiti, D. Recent Developments in Hydrodecyanation and Decyanative Functionalization Reactions. Asian J. Org. Chem. 2022, 11 (1), e202100591  DOI: 10.1002/ajoc.202100591
    (d) Nakao, Y. Metal-mediated C–CN Bond Activation in Organic Synthesis. Chem. Rev. 2021, 121 (1), 327344,  DOI: 10.1021/acs.chemrev.0c00301
  5. 5

    Recent reviews on the photoredox catalysis:

    (a) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.; MacMillan, D. W. C. The merger of transition metal and photocatalysis. Nat. Rev. Chem. 2017, 1, 0052,  DOI: 10.1038/s41570-017-0052
    (b) Romero, N. A.; Nicewicz, D. A. Organic Photoredox Catalysis. Chem. Rev. 2016, 116 (17), 1007510166,  DOI: 10.1021/acs.chemrev.6b00057
    (c) Douglas, J. J.; Sevrin, M. J.; Stephenson, C. R. J. Visible Light Photocatalysis: Applications and New Disconnections in the Synthesis of Pharmaceutical Agents. Org. Process Res. Dev. 2016, 20 (7), 11341147,  DOI: 10.1021/acs.oprd.6b00125
    (d) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. Photoredox Catalysis in Organic Chemistry. J. Org. Chem. 2016, 81 (16), 68986926,  DOI: 10.1021/acs.joc.6b01449
    (e) Sakakibara, Y.; Murakami, K. Switchable Divergent Synthesis Using Photocatalysis. ACS Catal. 2022, 12 (3), 18571878,  DOI: 10.1021/acscatal.1c05318
    (f) Leitch, J. A.; Rossolini, T.; Rogova, T.; Maitland, J. A. P.; Dixon, D. J. α-Amino Radicals via Photocatalytic Single-Electron Reduction ofImine Derivatives. ACS Catal. 2020, 10 (3), 20092025,  DOI: 10.1021/acscatal.9b05011
  6. 6
    Kang, H.-Y.; Hong, W. S.; Cho, Y. S.; Koh, H. Y. Reductive decyanation of α-cyano and α-alkoxycarbonyl substituted nitriles promoted by samarium(II) iodide. Tetrahedron Lett. 1995, 36 (42), 76617664,  DOI: 10.1016/0040-4039(95)01606-I
  7. 7
    (a) Doni, E.; Murphy, J. A. Reductive decyanation of malononitriles and cyanoacetates using photoactivated neutral organic super-electron-donors. Org. Chem. Front. 2014, 1 (9), 10721076,  DOI: 10.1039/C4QO00202D
    (b) Hanson, S. S.; Doni, E.; Traboulsee, K. T.; Coulthard, G.; Murphy, J. A.; Dyker, C. A. Pushing the Limits of Neutral Organic Electron Donors: A Tetra(iminophosphorano)-Substituted Bispyridinylidene. Angew. Chem., Int. Ed. 2015, 54 (38), 1123611239,  DOI: 10.1002/anie.201505378
  8. 8
    (a) Paul, V.; Roberts, B. P. Homolytic reactions of ligated boranes. Part 8. Electron spin resonance studies of radicals derived from ligated alkylboranes. J. Chem. Soc., Perkin Trans. 1988, 2 (7), 11831193,  DOI: 10.1039/p29880001183
    (b) Curran, D. P.; Seong, C. M. The Tin Hydride Reductive Decyanation of Geminal Dinitriles. Synlett 1991, 1991 (2), 107108,  DOI: 10.1055/s-1991-20644
    (c) 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 (26), 86178622,  DOI: 10.1021/jacs.5b04677
    (d) Bolt, D. A.; Curran, D. P. 1-Butyl-3-methylimidazol-2-ylidene Borane: A Readily Available, Liquid N-Heterocyclic Carbene Borane Reagent. J. Org. Chem. 2017, 82 (24), 1374613750,  DOI: 10.1021/acs.joc.7b02730
    (e) Kawamoto, T.; Shimaya, Y.; Curran, D. P.; Kamimura, A. Tris(trimethylsilyl)silane-mediated Reductive Decyanation and Cyano Transfer Reactions of Malononitriles. Chem. Lett. 2018, 47 (4), 573575,  DOI: 10.1246/cl.171231
  9. 9
    (a) Kawamoto, T.; Oritani, K.; Curran, D. P.; Kamimura, A. Thiol-Catalyzed Radical Decyanation of Aliphatic Nitriles with Sodium Borohydride. Org. Lett. 2018, 20 (7), 20842087,  DOI: 10.1021/acs.orglett.8b00626
    (b) Kawamoto, T.; Oritani, K.; Kawabata, A.; Morioka, T.; Matsubara, H.; Kamimura, A. Hydrodecyanation of Secondary Alkyl Nitriles and Malononitriles to Alkanes using DiMeImd-BH3. J. Org. Chem. 2020, 85 (9), 61376142,  DOI: 10.1021/acs.joc.0c00105
  10. 10

    An example of deisocyanative deuteration using NHC-BD3. However, decyanative deuteration has not been reported.

    Jiao, Z.; Jaunich, K. T.; Tao, T.; Gottschall, O.; Hughes, M. M.; Turlik, A.; Schuppe, A. W. Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation. Angew. Chem., Int. Ed. 2024, 63 (25), e202405779  DOI: 10.1002/anie.202405779
  11. 11
    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 (7), 23502358,  DOI: 10.1021/ja909502q
  12. 12

    Representative recent reports on the reaction using amine-ligated boryl radicals:

    (a) 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, 677683,  DOI: 10.1038/s41586-021-03637-6
    (b) Lei, G.; Xu, M.; Chang, R.; Funes-Ardoiz, I.; Ye, J. Hydroalkylation of Unactivated Olefins via Visible-Light-Driven Dual Hydrogen Atom Transfer Catalysis. J. Am. Chem. Soc. 2021, 143 (29), 1125111261,  DOI: 10.1021/jacs.1c05852
    (c) Zhang, Z.-Q.; Sang, Y.-Q.; Wang, C.-Q.; Dai, P.; Xue, X.-S.; Piper, J. L.; Peng, Z.-H.; Ma, J.-A.; Zhang, F.-G.; Wu, J. Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer. J. Am. Chem. Soc. 2022, 144 (31), 1428814296,  DOI: 10.1021/jacs.2c05356
    (d) Jiang, H.-W.; Yu, W.-L.; Wang, D.; Xu, P.-F. Photocatalyzed H2-Acceptorless Dehydrogenative Borylation by Using Amine Borane. ACS Catal. 2024, 14 (11), 86668675,  DOI: 10.1021/acscatal.4c00401
    (e) Zhang, Z.; Tilby, M. J.; Leonori, D. Boryl radical-mediated halogen-atom transfer enables arylation of alkyl halides with electrophilic and nucleophilic coupling partners. Nat. Synth. 2024, 3, 12211230,  DOI: 10.1038/s44160-024-00587-5
    (f) Zhang, Z.; Poletti, L.; Leonori, D. A Radical Strategy for the Alkylation of Amides with Alkyl Halides by Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis. J. Am. Chem. Soc. 2024, 146 (32), 2242422430,  DOI: 10.1021/jacs.4c05487
    (g) Park, C.; Gi, S.; Yoon, S.; Kwon, S. J.; Lee, S. ChemRxiv 2024. DOI: 10.26434/chemrxiv-2024-4fj46 .
    (h) Jiang, H.-W.; Qin, H.-N.; Wang, A.-L.; Zhang, R.; Xu, P.-F. Photocatalytic Borylation of Imines and Alkenes via Decarboxylation of Trimethylamine Carboxyborane: A New Approach for Generating Boryl Radicals. Org. Lett. 2024, 26 (43), 92829287,  DOI: 10.1021/acs.orglett.4c03443
    (i) Corpas, J.; Alonso, M.; Leonori, D. Boryl Radical-Mediated Halogen-Atom Transfer (XAT) Enables the Sonogashira-Like Alkynylation of Alkyl Halides. Chem. Sci. 2024, 15 (45), 1911319118,  DOI: 10.1039/D4SC06516F
  13. 13
    (a) Garwood, J. J. A.; Chen, A. D.; Nagib, D. A. Radical Polarity. J. Am. Chem. Soc. 2024, 146 (41), 2803428059,  DOI: 10.1021/jacs.4c06774
    (b) Wu, C.; Hou, X.; Zheng, Y.; Li, P.; Lu, D. Electrophilicity and Nucleophilicity of Boryl Radicals. J. Org. Chem. 2017, 82 (6), 28982905,  DOI: 10.1021/acs.joc.6b02849
  14. 14
    (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 (34), 2404224052,  DOI: 10.1021/jacs.4c07767
    (b) 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 2024,  DOI: 10.1055/a-2427-9313
  15. 15

    Recent reviews on the radical–polar crossover approach:

    (a) Pitzer, L.; Schwarz, J. L.; Glorius, F. Reductive radical-polar crossover: traditional electrophiles in modern radical reactions. Chem. Sci. 2019, 10 (36), 82858291,  DOI: 10.1039/C9SC03359A
    (b) Sharma, S.; Singh, J.; Sharma, A. Visible Light Assisted Radical-Polar/Polar-Radical Crossover Reactions in Organic Synthesis. Adv. Synth. Catal. 2021, 363 (13), 31463169,  DOI: 10.1002/adsc.202100205
    (c) Liu, M.; Ouyang, X.; Xuan, C.; Shu, C. Advances in photoinduced radical–polar crossover cyclization (RPCC) of bifunctional alkenes. Org. Chem. Front. 2024, 11 (3), 895915,  DOI: 10.1039/D3QO01929B
  16. 16
    (a) Makosza, M.; Judka, M. New Reactions of γ-Halocarbanions: Simple Synthesis of Substituted Tetrahydrofurans. Chem. Eur. J. 2002, 8 (18), 42344240,  DOI: 10.1002/1521-3765(20020916)8:18<4234::AID-CHEM4234>3.0.CO;2-G
    (b) Krishnakumar, V.; Gunanathan, C. Ruthenium-catalyzed selective a-deuteration of aliphatic nitriles using D2O. Chem. Commun. 2018, 54 (63), 87058708,  DOI: 10.1039/C8CC03971B
    (c) Zhou, Q.-Q.; Zou, Y.-Q.; Kar, S.; Diskin-Posner, Y.; Ben-David, Y.; Milstein, D. Manganese Pincer Catalyzed Nitrile Hydration, α-Deuteration, and α-Deuterated Amide Formation via Metal Ligand Cooperation. ACS Catal. 2021, 11 (16), 1023910245,  DOI: 10.1021/acscatal.1c01748
    (d) Gao, Y.; Pink, M.; Carta, V.; Smith, J. M. Ene Reactivity of an Fe = NR Bond Enables the Catalytic α-Deuteration of Nitriles and Alkynes. J. Am. Chem. Soc. 2022, 144 (37), 1716517172,  DOI: 10.1021/jacs.2c07462
  17. 17
    (a) Luo, J.; Zhang, J. Donor–Acceptor Fluorophores for Visible-Light-Promoted Organic Synthesis: Photoredox/Ni DualCatalytic C(sp3)–C(sp2) Cross-Coupling. ACS Catal. 2016, 6 (2), 873877,  DOI: 10.1021/acscatal.5b02204
    (b) Speckmeier, E.; Fischer, T. G.; Zeitler, K. A Toolbox Approach To Construct Broadly Applicable Metal-Free Catalysts for Photoredox Chemistry: Deliberate Tuning of Redox Potentials and Importance of Halogens in Donor–Acceptor Cyanoarenes. J. Am. Chem. Soc. 2018, 140 (45), 1535315365,  DOI: 10.1021/jacs.8b08933
    (c) Bortolamei, N.; Isse, A. A.; Gennaro, A. Estimation of standard reduction potentials of alkyl radicals involved in atom transfer radical polymerization. Electrochim. Acta 2010, 55 (27), 83128318,  DOI: 10.1016/j.electacta.2010.02.099
  18. 18
    (a) Xia, P.-J.; Song, D.; Ye, Z.-P.; Hu, Y.-Z.; Xiao, J.-A.; Xiang, H.-Y.; Chen, X.-Q.; Yang, H. Photoinduced Single-Electron Transfer as an Enabling Principle in the Radical Borylation of Alkenes with NHC-Borane. Angew. Chem., Int. Ed. 2020, 59 (17), 67066710,  DOI: 10.1002/anie.201913398
    (b) Xia, P.-J.; Ye, Z.-P.; Hu, Y.-Z.; Xiao, J.-A.; Chen, K.; Xiang, H.-Y.; Chen, X.-Q.; Yang, H. Photocatalytic C–F Bond Borylation of Polyfluoroarenes with NHC-boranes. Org. Lett. 2020, 22 (5), 17421747,  DOI: 10.1021/acs.orglett.0c00020
  19. 19
    (a) Xu, N.-X.; Li, B.-X.; Wang, C.; Uchiyama, M. Sila- and Germacarboxylic Acids: Precursors for the Corresponding Silyl and Germyl Radicals. Angew. Chem., Int. Ed. 2020, 59 (26), 1063910644,  DOI: 10.1002/anie.202003070
    (b) Zhang, G.; Wang, K.; Zhang, D.; Zhang, C.; Tan, W.; Chen, Z.; Chen, F. Decarboxylative Allylation of Silanecarboxylic Acids Enabled by Organophotocatalysis. Org. Lett. 2023, 25 (40), 74067411,  DOI: 10.1021/acs.orglett.3c02907
  20. 20
    (a) Phelan, J. P.; Lang, S. B.; Compton, J. S.; Kelly, C. B.; Dykstra, R.; Gutierrez, O.; Molander, G. A. Redox-Neutral Photocatalytic Cyclopropanation via Radical/PolarCrossover. J. Am. Chem. Soc. 2018, 140 (25), 80378047,  DOI: 10.1021/jacs.8b05243
    (b) Wu, Y.-W.; Tseng, M.-C.; Li, C.-Y.; Chou, H.-H.; Tseng, Y.-F.; Hsieh, H.-J. The Leaving Group Effect in Free Radical SH2’ Reactions. J. Chin. Chem. Soc. 1999, 46 (6), 861863,  DOI: 10.1002/jccs.199900116
  21. 21
    (a) Sun, X.; Chen, J.; Ritter, T. Catalytic dehydrogenative decarboxyolefination of carboxylic acids. Nat. Chem. 2018, 10, 12291233,  DOI: 10.1038/s41557-018-0142-4
    (b) Cao, H.; Jiang, H.; Feng, H.; Kwan, J. M. C.; Liu, X.; Wu, J. Photo-induced Decarboxylative Heck-Type Coupling of Unactivated Aliphatic Acids and Terminal Alkenes in the Absence of Sacrificial Hydrogen Acceptors. J. Am. Chem. Soc. 2018, 140 (47), 1636016367,  DOI: 10.1021/jacs.8b11218
    (c) Dam, P.; Zuo, K.; Azofra, L. M.; El-Sepelgy, O. Biomimetic Photoexcited Cobaloxime Catalysis in Organic Synthesis. Angew. Chem., Int. Ed. 2024, 63 (33), e202405775  DOI: 10.1002/anie.202405775
  22. 22
    (a) Fang, X.; Yu, P.; Morandi, B. Catalytic reversible alkene-nitrile interconversion through controllable transfer hydrocyanation. Science 2016, 351 (6275), 832836,  DOI: 10.1126/science.aae0427
    (b) Yu, P.; Morandi, B. Nickel-Catalyzed Cyanation of Aryl Chlorides and Triflates Using Butyronitrile: Merging Retro-hydrocyanation with Cross-Coupling. Angew. Chem., Int. Ed. 2017, 56 (49), 1569315697,  DOI: 10.1002/anie.201707517
    (c) Bhawal, B. N.; Morandi, B. Catalytic Transfer Functionalization through Shuttle Catalysis. ACS Catal. 2016, 6 (11), 75287535,  DOI: 10.1021/acscatal.6b02333
    (d) Bhawal, B. N.; Morandi, B. Shuttle Catalysis─New Strategies in Organic Synthesis. Chem. Eur. J. 2017, 23 (50), 1200412013,  DOI: 10.1002/chem.201605325

Cited By

Click to copy section linkSection link copied!
Citation Statements
Explore this article's citation statements on scite.ai

This article is cited by 1 publications.

  1. Changhee Park, Seyun Gi, Seongkyeong Yoon, Seong Jung Kwon, Sunggi Lee. The Giese reaction of alkyl bromides using amine carboxyboranes. Organic Chemistry Frontiers 2025, 22 https://doi.org/10.1039/D4QO02325K

Organic Letters

Cite this: Org. Lett. 2025, XXXX, XXX, XXX-XXX
Click to copy citationCitation copied!
https://doi.org/10.1021/acs.orglett.4c04701
Published January 10, 2025

© 2025 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY-NC-ND 4.0 .

Article Views

2296

Altmetric

-

Citations

Learn about these metrics

Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.

  • Abstract

    Scheme 1

    Scheme 1. Introduction of Cyano Group Transfer (CGT) and Synthetic Scenario

    Scheme 2

    Scheme 2. Theoretical and Experimental Evaluations of CGT Process and Application to Decyanative Deuteration

    Scheme 3

    Scheme 3. Substrate Scope

    a1.2 equiv of 1 and 1.5 equiv of K2CO3 were used.

    b1 mmol of 2 was used.

    c100.0 equiv of D2O was used.

    Scheme 4

    Scheme 4. CGT Strategy for Intramolecular Cyclization

    Scheme 5

    Scheme 5. CGT Strategy for Decyanative Olefination
  • References


    This article references 22 other publications.

    1. 1

      Selected reviews on the functionalization of nitriles:

      (a) Wang, S. Y.; Chu, X.-Q.; Fang, Y.; Ji, S.-J. Chapter 8 Acetonitrile as Reagents in Organic Synthesis: Reactions and Applications. In Solvents as Reagents in Organic Synthesis: Reactions and Applications , 2017; pp 355375.
      (b) López, R.; Palomo, C. Cyanoalkylation: Alkylnitriles in Catalytic C–C Bond-Forming Reactions. Angew. Chem., Int. Ed. 2015, 54 (45), 1317013184,  DOI: 10.1002/anie.201502493
      (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 (1), 258271,  DOI: 10.1021/acscatal.7b03334
      (d) Zhong, P.; Zhang, L.; Luo, N.; Liu, J. Advances in the Application of Acetonitrile in Organic Synthesis since 2018. Catalysts 2023, 13 (4), 761,  DOI: 10.3390/catal13040761
    2. 2
      (a) Li, J.; Zhao, H.; Jiang, X.; Wang, X.; Hu, H.; Yu, L.; Zhang, Y. The Cyano Group as a Traceless Activation Group for the Intermolecular [3 + 2] Cycloaddition of Azomethine Ylides: A Five-Step Synthesis of (±)-Isoretronecanol. Angew. Chem., Int. Ed. 2015, 54 (21), 63066310,  DOI: 10.1002/anie.201500961
      (b) Lujan-Montelongo, J. A.; Covarrubias-Zuniga, A.; Romero-Ortega, M.; Avila-Zarraga, J. G. An Efficient Synthesis of (±)-Xanthorrhizol: One Pot Decyanation and Demethylation. Lett. Org. Chem. 2008, 5 (6), 470472,  DOI: 10.2174/157017808785740525
    3. 3
      (a) Zavitsas, A. A. The Relation between Bond Lengths and Dissociation Energies of Carbon-Carbon Bonds. J. Phys. Chem. A 2003, 107 (6), 897898,  DOI: 10.1021/jp0269367
      (b) Lee, J. C.; Koh, H. Y.; Lee, Y. S.; Kang, H.-Y. Geminal substituent Effects on Decyanation Reactions. Bull. Korean Chem. Soc. 1997, 18 (7), 783785
    4. 4
      (a) Mattalia, J.-M.; Marchi-Delapierre, C.; Hazimeh, H.; Chanon, M. The reductive decyanation reaction: chemical methods and synthetic applications. Arkivoc 2006, 2006, 90118,  DOI: 10.3998/ark.5550190.0007.408
      (b) Mattalia, J.-M. R. The reductive decyanation reaction: an overview and recent developments. Beilstein J. Org. Chem. 2017, 13, 267284,  DOI: 10.3762/bjoc.13.30
      (c) Paul, N.; Patra, T.; Maiti, D. Recent Developments in Hydrodecyanation and Decyanative Functionalization Reactions. Asian J. Org. Chem. 2022, 11 (1), e202100591  DOI: 10.1002/ajoc.202100591
      (d) Nakao, Y. Metal-mediated C–CN Bond Activation in Organic Synthesis. Chem. Rev. 2021, 121 (1), 327344,  DOI: 10.1021/acs.chemrev.0c00301
    5. 5

      Recent reviews on the photoredox catalysis:

      (a) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.; MacMillan, D. W. C. The merger of transition metal and photocatalysis. Nat. Rev. Chem. 2017, 1, 0052,  DOI: 10.1038/s41570-017-0052
      (b) Romero, N. A.; Nicewicz, D. A. Organic Photoredox Catalysis. Chem. Rev. 2016, 116 (17), 1007510166,  DOI: 10.1021/acs.chemrev.6b00057
      (c) Douglas, J. J.; Sevrin, M. J.; Stephenson, C. R. J. Visible Light Photocatalysis: Applications and New Disconnections in the Synthesis of Pharmaceutical Agents. Org. Process Res. Dev. 2016, 20 (7), 11341147,  DOI: 10.1021/acs.oprd.6b00125
      (d) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. Photoredox Catalysis in Organic Chemistry. J. Org. Chem. 2016, 81 (16), 68986926,  DOI: 10.1021/acs.joc.6b01449
      (e) Sakakibara, Y.; Murakami, K. Switchable Divergent Synthesis Using Photocatalysis. ACS Catal. 2022, 12 (3), 18571878,  DOI: 10.1021/acscatal.1c05318
      (f) Leitch, J. A.; Rossolini, T.; Rogova, T.; Maitland, J. A. P.; Dixon, D. J. α-Amino Radicals via Photocatalytic Single-Electron Reduction ofImine Derivatives. ACS Catal. 2020, 10 (3), 20092025,  DOI: 10.1021/acscatal.9b05011
    6. 6
      Kang, H.-Y.; Hong, W. S.; Cho, Y. S.; Koh, H. Y. Reductive decyanation of α-cyano and α-alkoxycarbonyl substituted nitriles promoted by samarium(II) iodide. Tetrahedron Lett. 1995, 36 (42), 76617664,  DOI: 10.1016/0040-4039(95)01606-I
    7. 7
      (a) Doni, E.; Murphy, J. A. Reductive decyanation of malononitriles and cyanoacetates using photoactivated neutral organic super-electron-donors. Org. Chem. Front. 2014, 1 (9), 10721076,  DOI: 10.1039/C4QO00202D
      (b) Hanson, S. S.; Doni, E.; Traboulsee, K. T.; Coulthard, G.; Murphy, J. A.; Dyker, C. A. Pushing the Limits of Neutral Organic Electron Donors: A Tetra(iminophosphorano)-Substituted Bispyridinylidene. Angew. Chem., Int. Ed. 2015, 54 (38), 1123611239,  DOI: 10.1002/anie.201505378
    8. 8
      (a) Paul, V.; Roberts, B. P. Homolytic reactions of ligated boranes. Part 8. Electron spin resonance studies of radicals derived from ligated alkylboranes. J. Chem. Soc., Perkin Trans. 1988, 2 (7), 11831193,  DOI: 10.1039/p29880001183
      (b) Curran, D. P.; Seong, C. M. The Tin Hydride Reductive Decyanation of Geminal Dinitriles. Synlett 1991, 1991 (2), 107108,  DOI: 10.1055/s-1991-20644
      (c) 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 (26), 86178622,  DOI: 10.1021/jacs.5b04677
      (d) Bolt, D. A.; Curran, D. P. 1-Butyl-3-methylimidazol-2-ylidene Borane: A Readily Available, Liquid N-Heterocyclic Carbene Borane Reagent. J. Org. Chem. 2017, 82 (24), 1374613750,  DOI: 10.1021/acs.joc.7b02730
      (e) Kawamoto, T.; Shimaya, Y.; Curran, D. P.; Kamimura, A. Tris(trimethylsilyl)silane-mediated Reductive Decyanation and Cyano Transfer Reactions of Malononitriles. Chem. Lett. 2018, 47 (4), 573575,  DOI: 10.1246/cl.171231
    9. 9
      (a) Kawamoto, T.; Oritani, K.; Curran, D. P.; Kamimura, A. Thiol-Catalyzed Radical Decyanation of Aliphatic Nitriles with Sodium Borohydride. Org. Lett. 2018, 20 (7), 20842087,  DOI: 10.1021/acs.orglett.8b00626
      (b) Kawamoto, T.; Oritani, K.; Kawabata, A.; Morioka, T.; Matsubara, H.; Kamimura, A. Hydrodecyanation of Secondary Alkyl Nitriles and Malononitriles to Alkanes using DiMeImd-BH3. J. Org. Chem. 2020, 85 (9), 61376142,  DOI: 10.1021/acs.joc.0c00105
    10. 10

      An example of deisocyanative deuteration using NHC-BD3. However, decyanative deuteration has not been reported.

      Jiao, Z.; Jaunich, K. T.; Tao, T.; Gottschall, O.; Hughes, M. M.; Turlik, A.; Schuppe, A. W. Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation. Angew. Chem., Int. Ed. 2024, 63 (25), e202405779  DOI: 10.1002/anie.202405779
    11. 11
      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 (7), 23502358,  DOI: 10.1021/ja909502q
    12. 12

      Representative recent reports on the reaction using amine-ligated boryl radicals:

      (a) 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, 677683,  DOI: 10.1038/s41586-021-03637-6
      (b) Lei, G.; Xu, M.; Chang, R.; Funes-Ardoiz, I.; Ye, J. Hydroalkylation of Unactivated Olefins via Visible-Light-Driven Dual Hydrogen Atom Transfer Catalysis. J. Am. Chem. Soc. 2021, 143 (29), 1125111261,  DOI: 10.1021/jacs.1c05852
      (c) Zhang, Z.-Q.; Sang, Y.-Q.; Wang, C.-Q.; Dai, P.; Xue, X.-S.; Piper, J. L.; Peng, Z.-H.; Ma, J.-A.; Zhang, F.-G.; Wu, J. Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer. J. Am. Chem. Soc. 2022, 144 (31), 1428814296,  DOI: 10.1021/jacs.2c05356
      (d) Jiang, H.-W.; Yu, W.-L.; Wang, D.; Xu, P.-F. Photocatalyzed H2-Acceptorless Dehydrogenative Borylation by Using Amine Borane. ACS Catal. 2024, 14 (11), 86668675,  DOI: 10.1021/acscatal.4c00401
      (e) Zhang, Z.; Tilby, M. J.; Leonori, D. Boryl radical-mediated halogen-atom transfer enables arylation of alkyl halides with electrophilic and nucleophilic coupling partners. Nat. Synth. 2024, 3, 12211230,  DOI: 10.1038/s44160-024-00587-5
      (f) Zhang, Z.; Poletti, L.; Leonori, D. A Radical Strategy for the Alkylation of Amides with Alkyl Halides by Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis. J. Am. Chem. Soc. 2024, 146 (32), 2242422430,  DOI: 10.1021/jacs.4c05487
      (g) Park, C.; Gi, S.; Yoon, S.; Kwon, S. J.; Lee, S. ChemRxiv 2024. DOI: 10.26434/chemrxiv-2024-4fj46 .
      (h) Jiang, H.-W.; Qin, H.-N.; Wang, A.-L.; Zhang, R.; Xu, P.-F. Photocatalytic Borylation of Imines and Alkenes via Decarboxylation of Trimethylamine Carboxyborane: A New Approach for Generating Boryl Radicals. Org. Lett. 2024, 26 (43), 92829287,  DOI: 10.1021/acs.orglett.4c03443
      (i) Corpas, J.; Alonso, M.; Leonori, D. Boryl Radical-Mediated Halogen-Atom Transfer (XAT) Enables the Sonogashira-Like Alkynylation of Alkyl Halides. Chem. Sci. 2024, 15 (45), 1911319118,  DOI: 10.1039/D4SC06516F
    13. 13
      (a) Garwood, J. J. A.; Chen, A. D.; Nagib, D. A. Radical Polarity. J. Am. Chem. Soc. 2024, 146 (41), 2803428059,  DOI: 10.1021/jacs.4c06774
      (b) Wu, C.; Hou, X.; Zheng, Y.; Li, P.; Lu, D. Electrophilicity and Nucleophilicity of Boryl Radicals. J. Org. Chem. 2017, 82 (6), 28982905,  DOI: 10.1021/acs.joc.6b02849
    14. 14
      (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 (34), 2404224052,  DOI: 10.1021/jacs.4c07767
      (b) 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 2024,  DOI: 10.1055/a-2427-9313
    15. 15

      Recent reviews on the radical–polar crossover approach:

      (a) Pitzer, L.; Schwarz, J. L.; Glorius, F. Reductive radical-polar crossover: traditional electrophiles in modern radical reactions. Chem. Sci. 2019, 10 (36), 82858291,  DOI: 10.1039/C9SC03359A
      (b) Sharma, S.; Singh, J.; Sharma, A. Visible Light Assisted Radical-Polar/Polar-Radical Crossover Reactions in Organic Synthesis. Adv. Synth. Catal. 2021, 363 (13), 31463169,  DOI: 10.1002/adsc.202100205
      (c) Liu, M.; Ouyang, X.; Xuan, C.; Shu, C. Advances in photoinduced radical–polar crossover cyclization (RPCC) of bifunctional alkenes. Org. Chem. Front. 2024, 11 (3), 895915,  DOI: 10.1039/D3QO01929B
    16. 16
      (a) Makosza, M.; Judka, M. New Reactions of γ-Halocarbanions: Simple Synthesis of Substituted Tetrahydrofurans. Chem. Eur. J. 2002, 8 (18), 42344240,  DOI: 10.1002/1521-3765(20020916)8:18<4234::AID-CHEM4234>3.0.CO;2-G
      (b) Krishnakumar, V.; Gunanathan, C. Ruthenium-catalyzed selective a-deuteration of aliphatic nitriles using D2O. Chem. Commun. 2018, 54 (63), 87058708,  DOI: 10.1039/C8CC03971B
      (c) Zhou, Q.-Q.; Zou, Y.-Q.; Kar, S.; Diskin-Posner, Y.; Ben-David, Y.; Milstein, D. Manganese Pincer Catalyzed Nitrile Hydration, α-Deuteration, and α-Deuterated Amide Formation via Metal Ligand Cooperation. ACS Catal. 2021, 11 (16), 1023910245,  DOI: 10.1021/acscatal.1c01748
      (d) Gao, Y.; Pink, M.; Carta, V.; Smith, J. M. Ene Reactivity of an Fe = NR Bond Enables the Catalytic α-Deuteration of Nitriles and Alkynes. J. Am. Chem. Soc. 2022, 144 (37), 1716517172,  DOI: 10.1021/jacs.2c07462
    17. 17
      (a) Luo, J.; Zhang, J. Donor–Acceptor Fluorophores for Visible-Light-Promoted Organic Synthesis: Photoredox/Ni DualCatalytic C(sp3)–C(sp2) Cross-Coupling. ACS Catal. 2016, 6 (2), 873877,  DOI: 10.1021/acscatal.5b02204
      (b) Speckmeier, E.; Fischer, T. G.; Zeitler, K. A Toolbox Approach To Construct Broadly Applicable Metal-Free Catalysts for Photoredox Chemistry: Deliberate Tuning of Redox Potentials and Importance of Halogens in Donor–Acceptor Cyanoarenes. J. Am. Chem. Soc. 2018, 140 (45), 1535315365,  DOI: 10.1021/jacs.8b08933
      (c) Bortolamei, N.; Isse, A. A.; Gennaro, A. Estimation of standard reduction potentials of alkyl radicals involved in atom transfer radical polymerization. Electrochim. Acta 2010, 55 (27), 83128318,  DOI: 10.1016/j.electacta.2010.02.099
    18. 18
      (a) Xia, P.-J.; Song, D.; Ye, Z.-P.; Hu, Y.-Z.; Xiao, J.-A.; Xiang, H.-Y.; Chen, X.-Q.; Yang, H. Photoinduced Single-Electron Transfer as an Enabling Principle in the Radical Borylation of Alkenes with NHC-Borane. Angew. Chem., Int. Ed. 2020, 59 (17), 67066710,  DOI: 10.1002/anie.201913398
      (b) Xia, P.-J.; Ye, Z.-P.; Hu, Y.-Z.; Xiao, J.-A.; Chen, K.; Xiang, H.-Y.; Chen, X.-Q.; Yang, H. Photocatalytic C–F Bond Borylation of Polyfluoroarenes with NHC-boranes. Org. Lett. 2020, 22 (5), 17421747,  DOI: 10.1021/acs.orglett.0c00020
    19. 19
      (a) Xu, N.-X.; Li, B.-X.; Wang, C.; Uchiyama, M. Sila- and Germacarboxylic Acids: Precursors for the Corresponding Silyl and Germyl Radicals. Angew. Chem., Int. Ed. 2020, 59 (26), 1063910644,  DOI: 10.1002/anie.202003070
      (b) Zhang, G.; Wang, K.; Zhang, D.; Zhang, C.; Tan, W.; Chen, Z.; Chen, F. Decarboxylative Allylation of Silanecarboxylic Acids Enabled by Organophotocatalysis. Org. Lett. 2023, 25 (40), 74067411,  DOI: 10.1021/acs.orglett.3c02907
    20. 20
      (a) Phelan, J. P.; Lang, S. B.; Compton, J. S.; Kelly, C. B.; Dykstra, R.; Gutierrez, O.; Molander, G. A. Redox-Neutral Photocatalytic Cyclopropanation via Radical/PolarCrossover. J. Am. Chem. Soc. 2018, 140 (25), 80378047,  DOI: 10.1021/jacs.8b05243
      (b) Wu, Y.-W.; Tseng, M.-C.; Li, C.-Y.; Chou, H.-H.; Tseng, Y.-F.; Hsieh, H.-J. The Leaving Group Effect in Free Radical SH2’ Reactions. J. Chin. Chem. Soc. 1999, 46 (6), 861863,  DOI: 10.1002/jccs.199900116
    21. 21
      (a) Sun, X.; Chen, J.; Ritter, T. Catalytic dehydrogenative decarboxyolefination of carboxylic acids. Nat. Chem. 2018, 10, 12291233,  DOI: 10.1038/s41557-018-0142-4
      (b) Cao, H.; Jiang, H.; Feng, H.; Kwan, J. M. C.; Liu, X.; Wu, J. Photo-induced Decarboxylative Heck-Type Coupling of Unactivated Aliphatic Acids and Terminal Alkenes in the Absence of Sacrificial Hydrogen Acceptors. J. Am. Chem. Soc. 2018, 140 (47), 1636016367,  DOI: 10.1021/jacs.8b11218
      (c) Dam, P.; Zuo, K.; Azofra, L. M.; El-Sepelgy, O. Biomimetic Photoexcited Cobaloxime Catalysis in Organic Synthesis. Angew. Chem., Int. Ed. 2024, 63 (33), e202405775  DOI: 10.1002/anie.202405775
    22. 22
      (a) Fang, X.; Yu, P.; Morandi, B. Catalytic reversible alkene-nitrile interconversion through controllable transfer hydrocyanation. Science 2016, 351 (6275), 832836,  DOI: 10.1126/science.aae0427
      (b) Yu, P.; Morandi, B. Nickel-Catalyzed Cyanation of Aryl Chlorides and Triflates Using Butyronitrile: Merging Retro-hydrocyanation with Cross-Coupling. Angew. Chem., Int. Ed. 2017, 56 (49), 1569315697,  DOI: 10.1002/anie.201707517
      (c) Bhawal, B. N.; Morandi, B. Catalytic Transfer Functionalization through Shuttle Catalysis. ACS Catal. 2016, 6 (11), 75287535,  DOI: 10.1021/acscatal.6b02333
      (d) Bhawal, B. N.; Morandi, B. Shuttle Catalysis─New Strategies in Organic Synthesis. Chem. Eur. J. 2017, 23 (50), 1200412013,  DOI: 10.1002/chem.201605325
  • Supporting Information

    Supporting Information


    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.4c04701.

    • Experimental procedures, characterization data for all compounds, 1H, 11B, 13C, and 19F NMR spectra, and DFT calculations (PDF)


    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.