Nickel-Catalyzed Electrochemical Phosphorylation of Aryl Bromides

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Nickel-Catalyzed Electrochemical Phosphorylation of Aryl Bromides Ya Bai,†,§ Nian Liu,†,§ Shutao Wang,† Siyu Wang,† Shulin Ning,† Lingling Shi,† Lili Cui,*,‡ Zhuoqi Zhang,† and Jinbao Xiang*,† †

The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, P.R. China ‡ School of Chemistry and Environmental Engineering, Changchun University of Science and Technology, 7989 Weixing Road, Changchun, Jilin 130022, P.R. China Downloaded via NEWCASTLE UNIV on August 22, 2019 at 18:26:56 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: A nickel-catalyzed electrochemical cross-coupling reaction of aryl bromides with dialkyl phosphites, ethyl phenylphosphinate, and diphenylphosphine oxide has been developed. This reaction utilizes a simple undivided cell with inexpensive carbon electrodes to synthesize aryl phosphonates, aryl phosphinates, and arylphosphine oxides at room temperature. This protocol provides a mild and efficient route for the construction of C−P bond in moderate to high yields with broad substrate scope.

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suffered from limited scope of aryl bromides and poor tolerance of functional groups. For example, 5-bromopyrimidine and cyano/oxo-containing substrates were not successful under this reaction system. Recently, Baran’s group disclosed the nickel-catalyzed electrochemical amination where anodic and cathodic processes are reconciled to synergistically generate reactive catalyst species in different oxidation states.11 Inspired by the important work and as part of our continuing interest for the synthesis of organophosphorus compounds, we envisioned that phosphorus 3 could be readily prepared from aryl bromide 1 and compound 2 via a nickel-catalyzed electrochemical C−P bond formation using a nonsacrificial anode in an undivided cell (Scheme 1). Herein, the details of these studies are presented.

ransition metal-catalyzed cross-coupling reactions are among the most important and attractive methods for both academia and industry.1 Among them, transition-metalcatalyzed phosphorylation of aryl halides is an efficient way to synthesize aryl phosphorus compounds,2 which could be widely applied to pharmaceuticals, biochemistry, organic synthesis, and material science. 3 At present, for the construction of C−P bonds, a number of catalytic systems based on palladium,4 copper,5 and nickel6 have been developed by several groups. For example, Herzon’s group reported the palladium-mediated P-arylation of secondary phosphine oxides at room temperature;4c Fu’s group disclosed the proline/ pipecolinic acid-promoted copper-catalyzed P-arylation of organophosphorus compounds at 110 °C for 20−36 h;5a and Han’s group described the formation of C−P bond through the cross-coupling of aryl halides with H−phosphonates by using [NiCl2(dppp)] as catalyst at 100−120 °C.6b Very recently, Che’s group7 and Li’s group8 reported the photoinduced phosphinylation of aryl halides in the presence of strong base (tBuOK or tBuONa), respectively. Despite being interesting, these methods have some drawbacks, such as limited substrate scope, the requirement of a noble catalyst, high reaction temperature, long reaction time, and/or strong base, which likely limit their application in organic synthesis. Consequently, the development of more concise and universal methods to solve the aforementioned deficiencies is highly desirable and presents considerable challenges. Organic electrosynthesis, which achieves redox reactions with traceless electric current, is accepted to be an environmentally friendly and enabling synthetic tool.9 In 2018, Léonel’s group reported the synthesis of arylphosphonates via an interesting nickel-catalyzed electrochemical reaction of aryl bromides with dialkyl phosphites under high current (200 mA) using a sacrificial iron anode.10 However, the substrates © XXXX American Chemical Society

Scheme 1. Nickel-Catalyzed Electrochemical C−P Bond Formation

We first identified the optimal reaction conditions for the electrochemical cross-coupling reaction of 1-bromo-4(trifluoromethyl)benzene 1a with diethyl phosphite 2a, which involved constant-current electrolysis using RVC as anode and cathode in an undivided cell containing NiBr2· 3H2O (catalyst), di-tBubpy (ligand), phthalimide (additive), Cs2CO3 (base), Et4NPF6 (electrolyte), and DMA (solvent) at Received: July 16, 2019

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DOI: 10.1021/acs.orglett.9b02475 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Table 2. Synthesis of Arylphosphonates 3a,b

room temperature for 3 h (Table 1) (see the Supporting Information for an extensive sampling). Under these mild Table 1. Optimization of the Reaction Conditionsa

entry

variation from standard conditions

yieldb (%)

c

none graphite as anode Ni foam as cathode no phthalimide or 0.2 equiv of phthalimide DBU instead of Cs2CO3 CH3CN instead of DMA under air no NiBr2·3H2O no di-tBubpy no electric current

90 62 53 50/64 69 37 69 0 5 0

1 2 3 4 5 6 7 8 9 10

a Standard conditions: RVC anode, RVC cathode, 1a (0.4 mmol), 2a (0.8 mmol), NiBr2·3H2O (0.08 mmol), di-tBubpy (0.08 mmol), phthalimide (0.4 mmol), Cs2CO3 (0.5 mmol), Et4NPF6 (0.4 mmol), DMA (6.25 mL), undivided cell, constant current = 10 mA, N2 protection, room temperature, 3 h (2.8 F/mol). bIsolated yield. c94% yield of phthalimide was recovered. DMA = N,N′-dimethylacetamide, RVC = reticulated vitreous carbon, di-tBubpy = 4,4′-di-tert-butyl-2,2′bipyridine, DBU = 1,8-diazabicyclo(5.4.0)undec-7-ene.

a

Standard conditions (except where designated): RVC anode, RVC cathode, 1 (0.4 mmol), 2a (0.8 mmol), NiBr2·3H2O (0.08 mmol), di-tBubpy (0.08 mmol), phthalimide (0.4 mmol), Cs2CO3 (0.5 mmol), Et4NPF6 (0.4 mmol), DMA (6.25 mL), undivided cell, constant current = 10 mA, N2 protection, room temperature, 3 h (2.8 F/mol). bIsolated yield. c1-Chloro-4-(trifluoromethyl)benzene was used. d6 h (5.6 F/mol). e27% yield of 1-(4-hydroxyphenyl)ethan-1one 3g′ was isolated. f24% yield of 2-methylbenzo[d]thiazol-5-ol 3r′ was isolated.

conditions, the desired phosphonate 3a was isolated in 90% yield (entry 1). In comparison, reduced yields were obtained when the reaction conditions were modified in one of the following manners: changing the anode to graphite (entry 2) or changing the cathode to Ni foam (entry 3), removing or reducing the amount of phthalimide (entry 4), using other base such as DBU (entry 5), or changing the solvent to CH3CN (entry 6). Although optimal results were obtained when the reaction was set up under a protective atmosphere of nitrogen, rigorous deoxygenation was unnecessary. The coupling product was afforded in 69% yield even under air (entry 7). NiBr2·3H2O, di-tBubpy, and electrical current are necessary for this reaction on the basis of control experiments (entries 8−10). Having optimized the reaction conditions, we next examined the scope of the cross-coupling reaction by testing a series of aryl bromides (Table 2). To our satisfaction, a variety of functional groups, including alkoxy (OMe), alkyl (Me and CF3), halogen (F and Cl), cyano, carbonyl (COMe), and ester substituents in the phenyl ring, were well tolerated in the reaction system (3a−j). Bromobenzene substituted with a mild electron-donating group (Me) gave the best yield of coupling product 3d. When R = COMe, a lower yield (39%) of product 3g was obtained, and the corresponding hydrolysis product 3g′ was also isolated in 27% yield. It is noteworthy that inert chlorobenzene derivative is also compatible in our electrochemical conditions, albeit in moderate yield (3a). Moreover, other aryl bromides, such as 1- or 2-bromonaphthalene, 9bromophenanthrene, and even oxidation-prone 2-bromo-9Hfluorene, underwent a smooth reaction with diethyl phosphite 2a, furnishing the coupled products 3k−n in moderate to good yields (Table 2). Finally, heterocyclic products 3o−r were also easily prepared from corresponding 2-bromoquinoline, 5-

bromopyrimidine, 2-bromothiophene, and 5-bromo-2methylbenzo[d]thiazole by this method (Table 2). The successful synthesis of aryl phosphonates 3 from aryl bromide and diethyl phosphite under the above mild electrochemical conditions encouraged us to investigate other phosphorus-based nucleophiles. As shown in Table 3, ethyl phenylphosphinate and diphenylphosphine oxide participated in the current reaction effectively to produce the desired products aryl phosphinates 4a−e and arylphosphine oxides 5a−e in moderate to high yields. In most cases, ethyl phenylphosphinate and diphenylphosphine oxide showed higher coupling reactivity than diethyl phosphite.6b Control experiments indicated that the desired product 3a was completely suppressed when radical scavenger TEMPO was added in the standard reaction conditions, suggesting that a radical process should be involved in the cross-coupling reaction (Scheme 2). On the basis of the observations above and a literature report,12 a possible mechanism for the electrochemical crosscoupling reaction was proposed (Scheme 3). As a start, diethyl phosphite loses a proton and an electron on the anode to generate the radical intermediate 6. Meanwhile, the [Ni0] species is formed from [NiII] by cathodic reduction. Oxidative addition of [Ni0] to an aryl bromide generates [ArNiIIBr] 7, which traps the radical 6 to furnish a Ni(III) complex 8. B

DOI: 10.1021/acs.orglett.9b02475 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters

method offers an alternative to conventional methods and provides an efficient tool for oxidative C−P bonds formation.

Table 3. Synthesis of Arylphosphinates 4 and Arylphosphine Oxides 5a,b

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b02475.

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Experimental procedures, full characterization data, copies of NMR spectra for all products (PDF)

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Shutao Wang: 0000-0003-4895-2687 Lingling Shi: 0000-0002-8641-1657 Jinbao Xiang: 0000-0002-2628-3075 Author Contributions §

Y.B. and N.L. contributed equally to this work.

a

Standard conditions: RVC anode, RVC cathode, 1 (0.4 mmol), 2b/ 2c (0.8 mmol), NiBr2·3H2O (0.08 mmol), di-tBubpy (0.08 mmol), phthalimide (0.4 mmol), Cs2CO3 (0.5 mmol), Et4NPF6 (0.4 mmol), DMA (6.25 mL), undivided cell, constant current = 10 mA, N2 protection, room temperature, 3 h (2.8 F/mol). bIsolated yield.

Notes

The authors declare no competing financial interest.

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Scheme 3. Proposed Reaction Mechanism

ACKNOWLEDGMENTS This work was supported by the Natural Science Foundation of China (No. 21273024), the Sci-Tech Development Project of Jilin Province in China (No. 20170101095JC), the Foundation of Jilin Educational Committee (Nos. JJKH20180244KJ and JJKH20181091KJ), the China Postdoctoral Science Foundation (NO. 2016M601355), and the Norman Bethune Program of Jilin University (No. 2015330). Additional support was provided by Changchun Discovery Sciences, Ltd.

Reductive elimination from resulting 8 delivers the product 3 and [NiI] species followed by cathodic reduction to regenerate [Ni0] for the next cycle. Other possible paths, which involve Ni(I/III) or Ni(0/II) cycles, could not be ruled out at this stage.11b,13 In summary, we have successfully developed an electrochemical cross-coupling reaction of aryl bromides with dialkyl phosphites, ethyl phenylphosphinate, and diphenylphosphine oxide at room temperature. The anodic and cathodic processes are reconciled to synergistically generate reactive nickel species of different oxidation states in an undivided cell unit. This

(1) (a) Magano, J.; Dunetz, J. Chem. Rev. 2011, 111, 2177−2250. (b) Dong, Z.; Ren, Z.; Thompson, S. J.; Xu, Y.; Dong, G. Chem. Rev. 2017, 117, 9333−9403. (c) Fu, G. C. ACS Cent. Sci. 2017, 3, 692− 700. (2) (a) Baillie, C.; Xiao, J. L. Curr. Org. Chem. 2003, 7, 477−514. (b) Schwan, A. L. Chem. Soc. Rev. 2004, 33, 218−224. (c) Li, Y.-M.; Yang, S.-D. Synlett 2013, 24, 1739−1744. (3) (a) Moonen, K.; Laureyn, I.; Stevens, C. V. Chem. Rev. 2004, 104, 6177−6216. (b) Troev, K. D. Chemistry and Application of HPhosphonates; Elsevier: Amsterdam, 2006. (c) George, A.; Veis, A. Chem. Rev. 2008, 108, 4670−4693. (d) Van der Jeught, S.; Stevens, C. V. Chem. Rev. 2009, 109, 2672−2702. (e) Demmer, C. S.; Krogsgaard-Larsen, N.; Bunch, L. Chem. Rev. 2011, 111, 7981−8006. (4) (a) Schwan, A. L. Chem. Soc. Rev. 2004, 33, 218−224. (b) Kalek, M.; Jezowska, M.; Stawinski, J. Adv. Synth. Catal. 2009, 351, 3207− 3216. (c) Bloomfield, A. J.; Herzon, S. B. Org. Lett. 2012, 14, 4370− 4373. (d) Xu, K.; Yang, F.; Zhang, G.; Wu, Y. Green Chem. 2013, 15, 1055−1060. (5) (a) Huang, C.; Tang, X.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2006, 71, 5020−5022. (b) Rao, H.; Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Chem. - Eur. J. 2006, 12, 3636−3646. (c) Stankevič, M.; Włodarczyk, A. Tetrahedron 2013, 69, 73−81. (6) (a) Zhang, X.; Liu, H.; Hu, X.; Tang, G.; Zhu, J.; Zhao, Y. Org. Lett. 2011, 13, 3478−3481. (b) Zhao, Y.-L.; Wu, G.-J.; Li, Y.; Gao, L.X.; Han, F.-S. Chem. - Eur. J. 2012, 18, 9622−9627. (c) Łastawiecka,

Scheme 2. Control Experiment

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REFERENCES

DOI: 10.1021/acs.orglett.9b02475 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters E.; Flis, A.; Stankevič, M.; Greluk, M.; Słowik, G.; Gac, W. Org. Chem. Front. 2018, 5, 2079−2085. (7) Yuan, J.; To, W.-P.; Zhang, Z.-Y.; Yue, C.-D.; Meng, S.; Chen, J.; Liu, Y.; Yu, G.-A.; Che, C.-M. Org. Lett. 2018, 20, 7816−7820. (8) Zeng, H.; Dou, Q.; Li, C.-J. Org. Lett. 2019, 21, 1301−1305. (9) (a) Francke, R.; Little, R. D. Chem. Soc. Rev. 2014, 43, 2492− 2521. (b) Horn, E. J.; Rosen, B. R.; Baran, P. S. ACS Cent. Sci. 2016, 2, 302−308. (c) Yan, M.; Kawamata, Y.; Baran, P. S. Chem. Rev. 2017, 117, 13230−13319. (d) Jiang, Y.; Xu, K.; Zeng, C. Chem. Rev. 2018, 118, 4485−4540. (e) Deng, L.; Wang, Y.; Mei, H.; Pan, Y.; Han, J. J. Org. Chem. 2019, 84, 949−956. (f) Mei, H.; Yin, Z.; Liu, J.; Sun, H.; Han, J. Chin. J. Chem. 2019, 37, 292−301. (10) Sengmany, S.; Ollivier, A.; Le Gall, E.; Léonel, E. Org. Biomol. Chem. 2018, 16, 4495−4500. (11) (a) Li, C.; Kawamata, Y.; Nakamura, H.; Vantourout, J. C.; Liu, Z.; Hou, Q.; Bao, D.; Starr, J. T.; Chen, J.; Yan, M.; Baran, P. S. Angew. Chem., Int. Ed. 2017, 56, 13088−13093. (b) Kawamata, Y.; Vantourout, J. C.; Hickey, D. P.; Bai, P.; Chen, L.; Hou, Q.; Qiao, W.; Barman, K.; Edwards, M. A.; Garrido-Castro, A. F.; deGruyter, J. N.; Nakamura, H.; Knouse, K.; Qin, C.; Clay, K. J.; Bao, D.; Li, C.; Starr, J. T.; Garcia-Irizarry, C.; Sach, N.; White, H. S.; Neurock, M.; Minteer, S. D.; Baran, P. S. J. Am. Chem. Soc. 2019, 141, 6392−6402. (12) Wang, Y.; Deng, L.; Wang, X.; Wu, Z.; Wang, Y.; Pan, Y. ACS Catal. 2019, 9, 1630−1634. (13) (a) Amatore, C.; Jutand, A.; Mottier, L. J. Electroanal. Chem. Interfacial Electrochem. 1991, 306, 125−140. (b) Cannes, C.; Labbé, E.; Durandetti, M.; Devaud, M.; Nédélec, J. Y. J. Electroanal. Chem. 1996, 412, 85−93.

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DOI: 10.1021/acs.orglett.9b02475 Org. Lett. XXXX, XXX, XXX−XXX