Copper-Catalyzed Radical Reductive Arylation of Styrenes with Aryl

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Copper-Catalyzed Radical Reductive Arylation of Styrenes with Aryl Iodides Mediated by Zinc in Water Feng Zhou, Xiaoyun Hu, Wanying Zhang, and Chao-Jun Li J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00278 • Publication Date (Web): 27 Apr 2018 Downloaded from http://pubs.acs.org on April 27, 2018

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The Journal of Organic Chemistry

Copper-Catalyzed Radical Reductive Arylation of Styrenes with Aryl Iodides Mediated by Zinc in Water Feng Zhou [a,+], Xiaoyun Hu [a,b,+], Wanying Zhang[a] and Chao-Jun Li[a] * a

Department of Chemistry and FQRNT Center for Green Chemistry and Catalysis, McGill

University, 801 Sherbrooke Street West, Montreal, Quebec, H3A 0B8, Canada. [+]These authors contributed equally to this work. *[email protected] b

College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, 430074, PR China TOC Table

Abstract A copper/aniline catalyst system enables the radical arylation of styrenes using aryl iodides mediated by zinc in water. This transformation provides an efficient synthetic methodology for the convenient synthesis of diarylethane.

INTRODUCTION Environmental concerns and resource depletion have given rise to the increased attentions in developing novel chemistry that could lead to more sustainable chemical syntheses,1 among which is

the development of organic reactions by using water as solvent.2 Many types of reactions that are traditionally conducted exclusively in organic solvents can now be carried out in water with additional interesting features.2c-e, 3 In particular, there has been considerable progress in the development of various transition-metal-catalyzed reactions in water, 2a, 2b, 2e, 4 among which one of the most attractive and practical studies is the radical chemistry catalyzed by transition metals.5 Radical reactions are generally triggered by either the irradiation of a radical initiator 6 (e.g. benzoyl peroxide or AIBN) or by means of SET (single-electron transfer) between the lowvalent transition metal (or transition metal complex) and organic molecules, typically alkyl

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halides.7 On one hand, since being charge-neutral, these radical reactions not only can tolerate aqueous conditions but also are particularly effective in water, as have been shown by Oshima8 and others.9 Furthermore, the resulting radicals might also be incorporated into the formation of metal-carbon bond via redox process involved in catalytic cycle. As the exemplary reactions that combine the transition-metal catalysis and radical reaction, the atom-transfer radical polymerization (ATRP)10 and atom-transfer radical addition (ATRA)11 are among the most widely used and recognized transformations (Scheme 1, a). Despite myriad reports regarding the efficient generation of alkyl radical species from the reaction of copper salt with an alkyl halides,10b, 12 including ATRP and ATRA, the generation of aryl radical from aryl halide has been relatively less investigated13 except for the tin hydridemediated method14 and photo-induced SET,15 largely due to the high-dissociation-energy of a non-activated C(sp2)-halogen bond. To the best of our knowledge, there has been no report on the copper-catalyzed intermolecular radical arylation of olefin with aryl halides,16 especially in water. Therefore, it is highly desirable to develop the radical alkene arylation, analogous to the ATRP alkene alkylation process, and explore its application. Herein, we report the first copper/aniline-catalyzed radical reductive arylation of styrenes17 mediated by zinc in water (Scheme 1, b).

Scheme 1. a) Cu/ligand-catalyzed atom-transfer-radical-polymerization. b) This work, Cu/aniline-catalyzed radical reductive arylation of styrenes with aryl iodides mediated by zinc in water


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RESULTS AND DISCUSSION Our initial studies were focused on the copper-catalyzed reaction of iodobenzene (1a) and 4chlorostyrene (2a). We were delighted to find that a small amount of desired product 3aa was observed when the reaction was treated with IiPrS-CuCl/zinc in 1% of BrijC10 (Table 1, entry 1). The yield was further increased to 20% with 3.9 equiv of Zn (Table 1, entry 2). When 10 mol% of catalyst complex IiPrS-CuCl was used, the reaction afforded 3aa in 30% yield (Table 1, entry 3). Switching catalyst from IiPrS-CuCl to Cu(acac)2 resulted in lower yields with BrijC10 (polyoxyethylene (10) cetyl ether) and CTAS (cetyltrimethylammonium hydrogensulfate) as surfactants

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respectively (Table 1, entries 4 and 5). Then a series of ligands were investigated,

and interestingly, a significant amount of product 3aa was obtained with p-anisidine being the ligand (Table 1, entries 6-9). The even more electron-rich 3, 4-dimethoxyaniline proved to be a better ligand, providing 3aa in 58% yield after 26 h (Table 1, entry 10). Conducting the reaction with the ratio of catalyst and ligand tuned from 1/1 to 1/2 further improved the yield to 64% (Table 1, entries 11-13). It is worth noting that the reaction could be carried out at room temperature under extended reaction time (36 h) without significantly compromising the yield (Table 1, entry 14). Subsequently, electron-rich ligands 3, 4-(methylenedioxy)aniline and 3, 4, 5trimethoxyaniline were subjected to further evaluation (Table 1, entries 15 and 16), neither of which afforded better yields than 3,4-dimethoxyaniline. Finally, 63% yield of the corresponding product was obtained with water as the sole solvent (Table 1, entry 17). Table 1. Conditions for Cu-catalyzed and zinc-mediated arylation of styrene in water a

Entry

Cat. (mol%)

Zinc (equiv)

1 2 3 4 5 6 7 8

IiPrS-CuCl (5) IiPrS-CuCl (5) IiPrS-CuCl (10) Cu(acac)2 (10) Cu(acac)2 (10) Cu(acac)2 (10) Cu(acac)2 (10) Cu(acac)2 (10)

1.2 3.9 3.9 3.9 3.9 3.9 3.9 3.9

Ligand (mol%)

DMAP (10) 2,2’-bipyridine (10) 2,3-diaminopyridine (10)


Solvent (surfactant 1%) BrijC10 BrijC10 BrijC10 BrijC10 CTAS CTAS CTAS CTAS

Time (h)

Yield (%)b

12 12 12 12 12 16 16 16

5 20 30(27) 5 13 17 16 43


9 Cu(acac)2 (10) 3.9 p-anisidine (10) CTAS 16 49 10 Cu(acac)2 (10) 3.9 3,4-dimethoxyaniline (10) CTAS 26 58 11 Cu(acac)2 (5) 3.9 3,4-dimethoxyaniline (10) CTAS 26 64(59) 12 Cu(acac)2 (10) 3.9 3,4-dimethoxyaniline (20) CTAS 22 61(63) 13 Cu(acac)2 (10) 3.9 3,4-dimethoxyaniline (20) CTAS 26 62 14c Cu(acac)2 (10) 3.9 3,4-dimethoxyaniline (20) CTAS 36 49 15 Cu(acac)2 (10) 3.9 3,4-(methylenedioxy)aniline (20) CTAS 26 52 16 Cu(acac)2 (10) 3.9 3,4,5-trimethoxyaniline (20) CTAS 26 60 17 Cu(acac)2 (10) 3.9 3,4-dimethoxyaniline (20) H2O 16 63 a Reaction conditions: 1a (0.60 mmol), 2a (0.20 mmol), Zn dust, surfactant (1%) in H2O (W/V) (0.5 mL), 70 oC. bYields were determined by 1H NMR analysis with 1,3,5-trimethoxybenzene as an internal standard. cThe reaction was conducted at room temperature. Isolated yields in brackets. BrijC10 = polyoxyethylene (10) cetyl ether. CTAS = cetyltrimethylammonium hydrogensulfate.

With the optimized reaction conditions in hand, the scope of this arylation chemistry was then investigated and the results were shown in Table 2. The reactions of iodobenzene (1a) and 3methyliodobenzene (1b) proceeded smoothly to give the corresponding products in 63% and 56% yields, respectively (Table 2, 3aa and 3ba). Substrates 1c-e bearing electron-donating groups could also react successfully to provide the products in yields ranging from 36-45% (Table 2, 3ca-3ea), among which the lower yield of the substrate bearing o-methoxyl (1e) is probably due to both electronic and steric effects. Interestingly, in the case of 4-fluoroiodobenzene (1f), the reaction was completed in 16 h and the yield declined dramatically to 34% (Table 2, 3fa). The reactions of 1g bearing a strong electron-withdrawing group trifluoromethyl group with styrenes 2a-c afforded the arylated products in good to excellent yields (Table 2, 3ga-3gc). Surprisingly, when heterocyclic substrates, 2-bromopyridine (1h) and 2-iodothiophene (1i), were subjected to the standard conditions, only trace amounts of products were detected, along with the corresponding dehalogenated heterocycles as major byproducts (Table 2, 3ha and 3ia). Then the arylation on styrene 2a gave rise to the corresponding product in 63% yield (Table 2, 3ab).


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Subjecting 4-tert-butylstyrene (2c) to the standard conditions, the reactions of 1a and 1f gave the corresponding arylation products in 72% and 34% yields, respectively (Table 2, 3ac and 3fc). Furthermore, electron-rich styrene 2d, bearing 3, 4-dimethoxyl groups, reacted smoothly with iodobenzene (1a) and 3-trifluoroiodobenzene (1g) to furnish the corresponding products in moderate yields (Table 2, 3ad and 3gd). Then the standard reaction was applied to 4trifluorostyrene (2e) and a series of iodoarenes bearing electron-donating and electronwithdrawing groups, affording the desired products in 34-62% yields (3ae-3ce and 3fe). Notably, 4-phenylstyrene (2f) was also accommodated, providing the corresponding product 3af in 40% yield, albeit with a slight modification of the reaction conditions. Additionally, the reaction protocol was also successfully applied to trans-β-methylstyrene, giving rise to desired product in 27% yield (Table 2, 3ag). Table 2. Cu-catalyzed and zinc-mediated arylation of styrenes in water a, b



a

Reaction conditions: 1 (0.40 mmol), 2 (0.20 mmol), Cu(acac)2 (10 mol%), 3, 4-dimethoxyaniline (20 mmol%), Zn dust (0.78 mmol), H2O (0.5 mL) at 70 o for 16 h. b All yields are those for isolated products. c

Copper-Catalyzed Radical Reductive Arylation of Styrenes with Aryl

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