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Synlett 2021; 32(16): 1633-1636
DOI: 10.1055/a-1457-2399
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Modern Nickel-Catalyzed Reactions

Nickel-Catalyzed Photodehalogenation of Aryl Bromides

Bradley Higginson
a   Institute of Chemical Research of Catalonia (ICIQ), Av. Paisos Catalans 16, 43007, Tarragona, Spain
b   Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, c/Marcel·lí Domingo, 1, 43007 Tarragona, Spain
,
Jesus Sanjosé-Orduna
a   Institute of Chemical Research of Catalonia (ICIQ), Av. Paisos Catalans 16, 43007, Tarragona, Spain
,
Yiting Gu
a   Institute of Chemical Research of Catalonia (ICIQ), Av. Paisos Catalans 16, 43007, Tarragona, Spain
,
Ruben Martin∗
a   Institute of Chemical Research of Catalonia (ICIQ), Av. Paisos Catalans 16, 43007, Tarragona, Spain
c   ICREA, Passeig Lluís Companys, 23, 08010 Barcelona, Spain
› Author Affiliations

We thank Institut Català d’Investigació Química (ICIQ) and the Fondo Europeo de Desarrollo Regional (FEDER/MCI, AEI/PGC2018-096839-B-I00) for financial support. B. H. thanks ‘La Caixa’ Foundation (ID 100010434 and LCF/BQ/DI18/11660031) for a predoctoral fellowship.
› Further Information
 
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Nickel-Catalyzed Photodehalogenation of Aryl BromidesSynlett 2021; 32(16): e1-e1
DOI: 10.1055/s-0040-1720893

Abstract

Herein, we describe a Ni-catalyzed photodehalogenation of aryl bromides under visible-light irradiation that utilizes tetrahydrofuran as hydrogen source. The protocol obviates the need for exogeneous amine reductants or photocatalysts and is characterized by its simplicity and broad scope, including challenging substrate combinations


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Key words

nickel - photochemistry - dehalogenation - reduction - deuteration

Aryl halides rank amongst the most versatile synthetic handles in organic chemistry. Whilst a myriad of C–C and C–heteroatom bond-forming reactions have been developed using aryl halides as coupling counterparts, the protodehalogenation reaction remains a much less-explored endeavor.[1] These processes are of significant industrial relevance, as polyhalogenated entities such as polybrominated diphenyl ethers (PBDE) are known persistent organic pollutants, flame retardants, and health hazards that have been banned by the Stockholm convention.[2] Therefore, the synthetic community has been challenged to design efficient, reliable, and practical catalytic dehalogenation techniques. Whilst radical pathways based on the utilization of tin hydride or metal–halogen exchange techniques with stoichiometric amounts of metal complexes have become routine in the dehalogenation arena (Scheme [1], top left),[3] the formation of toxic byproducts, the need for stoichiometric reductants, and/or the poor functional group compatibility reinforce a change in strategy. In recent years, transition-metal-catalyzed reductions of aryl halides have offered an alternative solution for promoting protodehalogenation reactions. Unfortunately, however, these techniques make use of expensive noble-metal catalysts, exogenous reductants, and/or high temperatures (Scheme [1], top right).[4] Electrochemistry has also made some significant progress in this arena, however, it is not without its limitations.[5] Driven by the renewed interest in photoredox reactions and its unique ability to access open-shell reaction intermediates via photoinduced electron-transfer events,[6] it comes as no surprise that catalytic photodehalogenation reactions have recently gained considerable momentum (Scheme [1], middle). However, the disparity between the reduction potential of aryl halides and the available portfolio of photocatalysts makes these techniques not as trivial as one might initially anticipate.[1] [3]

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Scheme 1 Catalytic photodehalogenation techniques

In recent years, high-energy UV or powerful blue lamps,[7] dual-catalytic platforms,[8] or novel photocatalysts designed to reach the appropriate range of redox potentials of aryl halides have been employed to trigger catalytic photodehalogenation reactions.[9] In most instances, however, an exogenous amine reductant is required to maintain the reductive quenching cycle of these techniques (Scheme [1], middle). Recently, Chen has shown the viability for enabling a photocatalytic reduction of aryl halides using noble palladium catalysts in combination with i-PrOH via hydrogen atom transfer (HAT).[10] Given the inherent ability of nickel catalysts to trigger single-electron-transfer processes and the ability to merge its unique properties within the realm of photoredox catalysis, we wondered whether a Ni-catalyzed photodehalogenation technique of aryl halides in the absence of sacrificial reductants or stoichiometric metal sources might be implemented (Scheme [1], bottom). If successful, we anticipated that such a technique might not only offer a complementary approach to related photodehalogenation scenarios and/or Pd-catalyzed approaches, but also provide new knowledge in synthetic design.

We began our study with the debromination of 4-bromoanisole by using THF both as solvent and as hydrogen donor. Judicious screening of the reaction conditions revealed that a combination of NiI2, 1,4-bis(dicyclohexylphosphino)butane (L1), Na2CO3, and CsI under blue light irradiation (451 nm) provided the best results, obtaining 2a in 90% isolated yield (Table [1], entry 1).[11] Ni(COD)2 and Ni(II) salts other than NiI2 had a deleterious impact on reactivity (entries 2–4). The latter is particularly interesting, thus revealing a non-negligible influence of the counterion in the reaction outcome. As shown in entries 5 and 6, L1 provided better results than its corresponding L2 or L3 analogues, this could possibly be due to the increased flexibility of L1 in comparison to L2 and the greatly increased electron density over L3. In addition, lower yields were found when employing PCy3 (entry 8) whereas nitrogen-containing ligands did not afford even traces of 2a. Interestingly, the utilization of additives other than CsI was detrimental for the reaction to occur. While control experiments showed that the inclusion of both light and ligand was critical for success (entry 8), it is worth noting that significant amounts of 2a were also observed in the absence of CsI (entry 10). Note, however, that traces of 2a were observed for reactions employing either dcye or dppe in the absence of CsI, thus not only showing the subtleties of our system, but also suggesting a complex behavior exerted by CsI.

Table 1 Screening of Reaction Conditionsa

a Standard conditions: 1a (0.2 mmol), Na2CO3 (0.3 mmol), Ni catalyst (0.02 mmol), ligand (0.03 mmol), CsI (0.03 mmol), THF (1 mL) under blue LED irradiation (451 nm) at 35 °C for 48 h. GC yields using decane as internal standard.

b Isolated yield.

Next, we turned our attention to evaluating the scope of the reaction. As evident from the results compiled in Scheme [2], our photodehalogenation could be applied across a wide number of aryl halides independently of whether electron-rich or electron-poor substituents were located at either meta, para, or ortho positions. Likewise, aryl bromides containing esters (2b, 2e, 2m, 2p, 2t), ketones (2d), amides (2i, 2s), or nitriles (2o) posed no problems. Importantly, the reaction could be executed on gram scale, obtaining 2n in 78% yield. Particularly interesting was the ability to extend our reaction to heterocyclic cores such as 2q, 2r, or even 2s possessing basic nitrogen donors, as these motifs might compete with L1 for metal binding. In addition, the presence of free carboxylic acids (2c) or alcohols (2l) does not interfere with productive photodehalogenation of the sp2 C–Br site. Importantly, aryl pivalates (2e), aryl tosylates (2f), or boronic esters (2j) could perfectly be tolerated, hence providing an additional handle for further functionalization via classical Pd- or Ni-catalyzed manifolds. Attempts to debrominate aryl rings containing iodo or chloro substituents did not lead to any reduced product. As illustrated by the successful preparation of 2t and 2u, our protocol could be applied to low bromine count polybrominated compounds, including the corresponding PBDE with equal ease. This result is particularly interesting given the growing interest in promoting efficient and reliable catalytic dehalogenation techniques of polyhalogenated ethereal entities.

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Scheme 2 Scope of (hetero)aryl bromides. Reagents and conditions: as for Table [1], entry 1 for 72 h. a LiOt-Bu (1 equiv); b NiI2 (5 mol%), dcyb (6 mol%), 1n (5 mmol); c CsI (0.08 mmol); d ArBr (0.10 mmol), NiI2 (0.02 mmol), L1 (0.022 mmol), Na2CO3 (0.3 mmol), CsI (0.04 mmol).

Encouraged by these results, we next evaluated whether complex mixtures of mono-, di-, and tribrominated diphenyl ethers could be accomplished with similar ease. As shown in Scheme [3] (top), this was indeed the case, obtaining the targeted 2u in 51% yield at 5 mol% catalyst loading. Following up our initial hypothesis of THF being both solvent and hydrogen donor, we anticipated that the utilization of THF-d 8 might not only provide a useful entry to incorporate deuterium atoms into arene backbones, but also offer a complementary approach to previously reported procedures employing other deuterated entities.[12] As shown in Scheme [3] (bottom), this turned out to be the case, and 2f-D, 2n-D, and 2v-D were easily within reach by promoting our photodehalogenation under otherwise identical reaction conditions, but using THF-d 8 instead.

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Scheme 3 Synthetic application

In conclusion we have developed a simple, efficient, and reliable catalytic photodehalogenation of aryl bromides under visible-light irradiation with THF both as solvent and as hydrogen donor. The transformation is distinguished by its broad applicability to a wide range of aryl halides including challenging substrate combinations. This protocol has shown to be particularly useful for promoting dehalogenation events on persistent organic pollutants and for incorporating deuterium atoms into arene backbones. Further investigations aimed at unravelling the mechanistic intricacies of this reaction and extending this concept to other coupling partners are currently underway.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We thank ICIQ for institutional support and the members of the Martin group for useful feedback during the execution of the project.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1457-2399.
  • Supporting Information

Corresponding Author

Ruben Martin
Institute of Chemical Research of Catalonia (ICIQ)
Av. Paisos Catalans 16, 43007, Tarragona
Spain   

Publication History

Received: 23 February 2021

Accepted after revision: 21 March 2021

Accepted Manuscript online:
21 March 2021

Article published online:
14 April 2021

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Zoom Image
Scheme 1 Catalytic photodehalogenation techniques
Zoom Image
Scheme 2 Scope of (hetero)aryl bromides. Reagents and conditions: as for Table [1], entry 1 for 72 h. a LiOt-Bu (1 equiv); b NiI2 (5 mol%), dcyb (6 mol%), 1n (5 mmol); c CsI (0.08 mmol); d ArBr (0.10 mmol), NiI2 (0.02 mmol), L1 (0.022 mmol), Na2CO3 (0.3 mmol), CsI (0.04 mmol).
Zoom Image
Scheme 3 Synthetic application