Letter pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Pd-Catalyzed Denitrative Intramolecular C−H Arylation Kitty K. Asahara,†,§ Toshimasa Okita,†,§ Ami N. Saito,† Kei Muto,† Yoshiaki Nakao,‡ and Junichiro Yamaguchi*,† †
Department of Applied Chemistry, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo 169-8555, Japan Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
‡
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S Supporting Information *
ABSTRACT: A Pd-catalyzed intramolecular C−H arylation of nitroarenes has been developed. Nitroarenes bearing tethered aryl groups at the ortho-position can be readily prepared in one step from 2-halonitroarenes by a nucleophilic aromatic substitution (SNAr). Under Pd/BrettPhos catalysis, activations of the C−NO2 bond as well as the C−H bond on arenes generated the corresponding biaryl linkage in moderate to excellent yields.
N
itroarenes are produced in the petrochemical industry from simple arenes and are a source of haloarenes and functionalized aromatic compounds.1 For example, haloarenes, which are well-known aryl electrophiles for metal-catalyzed cross-coupling reactions, have frequently been synthesized in four steps: (1) nitration of arenes, (2) reduction of nitroarenes, (3) diazotization of anilines, and (4) halogenation of diazonium aromatics. Including the cross-coupling reaction, this involves a multistep reaction of five steps. Therefore, the direct coupling of a more “synthetically upstream” nitroarene instead of a haloarene would lead to a facile access to functionalized aromatics. Furthermore, this could reduce the number of steps as well as the manufacturing cost of the aromatic products. However, the coupling of nitroarenes with nucleophiles has rarely been reported.2 Recently, our group successfully developed palladium-catalyzed coupling reactions of nitroarenes with external nucleophiles, which include Suzuki−Miyaura coupling,3a amination,3b and reductive hydrogenation (Figure 1A).3c A Pd/BrettPhos catalytic system has also been known to activate a C−NO2 bond, with the formed complex reacting with nucleophiles.3d Meanwhile, C−H arylation using (hetero)arenes as aryl nucleophiles instead of metalloarenes is also quite effective in reducing the number of steps.4 Recently, C−H arylation of (hetero)arenes with various aryl electrophiles (i.e., aryl pseudohalides, arenols, aryl carboxylic acids, aromatic esters, and aromatic amides) has been reported.4,5 However, the C− H nucleophile component has been limited, and the use of simple arenes continues to be a challenging issue. To circumvent this problem, an internal nucleophile can be used, changing the reaction mode from intermolecular to intramolecular. Similarly, intramolecular C−H arylations of various “tethered” aryl electrophiles and arenes have been developed,6 but the use of a nitro group as a formal leaving group has not been previously reported. We hypothesized that the nitro group and the C−H bond of an aromatic compound can be simultaneously activated using Pd/BrettPhos or a new catalytic system, leading to a significant reduction in the number of steps in the synthesis of biaryl linkages such as © XXXX American Chemical Society
Figure 1. (A) Catalytic denitrative functionalization. (B) Catalytic denitrative intramolecular C−H arylation.
dibenzofurans, carbazoles, and fluorenones (Figure 1B). Herein, we report the first intramolecular coupling reaction between a nitroarene and an aromatic C−H bond. Our study began by optimizing the reaction between 1-nitro2-phenoxybenzene (1A) as the model substrate, particularly focusing on the ligand structure (Table 1).7 The reaction was conducted using 1A with 5 mol % Pd(acac)2 and a variety of ligands (15−30 mol %), along with K3PO4 (3.0 equiv) as an additive in toluene at 150 °C. First, we screened several electron-rich alkyl phosphine ligands, but the reaction did not Received: May 7, 2019
A
DOI: 10.1021/acs.orglett.9b01593 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Screening of Ligands and Other Reaction Parametersa
entry
ligand (X mol %)
recovery of 1A (%)b
yield of 2A (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
P(n-Bu)3 (30) PCy3·HBF4 (30) dcype (15) dppp (15) Xantphos (15) 2,9-dmphen (15) phen L1 (15) phen L2 (15) BrettPhos (15) t BuBrettPhos (15) JohnPhos (15) XPhos (15) JackiePhos (15) BrettPhos (12)c BrettPhos (12)d
81 95 77 86 64 81 53 50 25 0 76 72 88 6 0
0 0 0 0 0 22 15 24 50 54 0 0 3 71 89 (70)e
Scheme 1. Substrate Scope of Denitrative Intramolecular C−H Arylationa
a
Conditions: 1A (0.20 mmol), Pd(acac)2 (5 mol %), ligand (15−30 mol %), K3PO4 (3.0 equiv), toluene (1.0 mL), 150 °C, 24 h.
b1
H NMR yield determined by using CH2Br2 as an internal standard. Toluene (2.5 mL) was used. d160 °C. eIsolated yield.
c
work at all (Table 1, entries 1 and 2). Diphosphines were also completely ineffective, for example, with dcype, dppp, and Xantphos (Table 1, entries 3−5). Delightfully, when 2,9dimethylphenanthroline(2,9-dimephen) was used, the desired coupling product 2A was produced in 22% yield (Table 1, entry 6). However, after extensive screening of phenanthroline derivatives, a result that exceeds that of 2,9-dimephen was not obtained (Table 1, entries 7 and 8).7 In the end, BrettPhos or t BuBrettPhos were the most effective ligands to give 2A in 50% and 54% yields, respectively (Table 1, entries 9 and 10), whereas other Buchwald ligands gave almost no reaction (Table 1, entries 11−13). Finally, slightly decreasing the amount of the ligand and changing the reaction concentration from 0.2 to 0.08 M increased the yield of 2A (71%); elevating the temperature from 150 to 160 °C afforded 2A in 89% yield. With the optimal conditions (Table 1, entry 15) in hand, we then investigated the substrate scope (Scheme 1). The starting materials can be readily prepared in one step from ohalonitroarenes and arenols. At first, we modified the arenol unit (Ar2) to check the generality. Diarylethers bearing a substituent on the para position of the arenol unit, such as methoxy and phenyl, afforded the corresponding biaryls 2B (95% yield) and 2C (57% yield). The reaction proceeded
a
Conditions: 1 (0.20 mmol), Pd(acac)2 (5 mol %), BrettPhos (12 mol %), toluene (1.0 mL), K3PO4 (3.0 equiv), 160 °C, 24 h; (a) 150 °C.
smoothly even if one ortho position of the arenol was blocked, such as with a t-Bu and a methoxy group, giving the products 2D and 2E in moderate yields. meta-Substituted arenols (e.g., with a methoxy group) afforded 2F and 2F′ (2F/2F′ = 87/13) in a good yield (66%) Diarylethers derived from 1- or 2naphthols gave the corresponding products 2G and 2H, along with a regioisomer 2H′ (2H/2H′ = 69/31) in moderate yields. Next, we investigated applicable nitroarene units (Ar1). Methoxy (1B), methoxycarbonyl (1I), dimethylaminocarbonyl (1J), trifluoromethyl (1K), and methylsulfonyl (1L) groups were tolerated under the standard conditions to furnish the corresponding products 2B−2L in moderate to good yields.8 Additionally, although the esters on the aromatic rings were changed to different positions, the products (2M−2O) were formed in excellent yields. Subsequently, the “tether” which connects the aromatic rings was changed (Scheme 2). For example, when 1P (changed B
DOI: 10.1021/acs.orglett.9b01593 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Detailed experimental procedures, spectral data for all compounds, and 1H, and 13C NMR spectra (PDF)
Scheme 2. Carbonyl Tether (Instead of an Oxygen Atom)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] ORCID
from an oxygen atom to a carbonyl group) was used, the desired fluorenone 2P was obtained in 44% yield. On the other hand, when the arenol oxygen atom was changed to a nitrogen atom (NH), carbazole was obtained, albeit in a low yield.7 Although there remains room for further improvement, these results indicate that this reaction is not restricted to diarylether formation and that various denitrative intramolecular C−H arylations proceed under the catalytic conditions. Finally, the denitrative C−H arylation reaction was combined with a state-of-the-art cross-coupling reaction (Scheme 3). 4-Fluoro-3-nitrobenzoic acid (3) was converted
Kei Muto: 0000-0001-8301-4384 Yoshiaki Nakao: 0000-0003-4864-3761 Junichiro Yamaguchi: 0000-0002-3896-5882 Author Contributions §
These authors contributed equally.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by JSPS KAKENHI grant no. JP19H02726, JP18H04272 (to J.Y.), JP15H05799 (to Y. N.), and JP19K15573 (to K.M.). We thank Myuto Kashihara (Kyoto University) for fruitful discussion and critical comments. The Materials Characterization Central Laboratory in Waseda University is acknowledged for HRMS measurement.
Scheme 3. Denitrative C−H Arylation/Decarbonylative Alkynylationa
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a Conditions: (a) 3, (COCl)2 (1.0 equiv), cat. DMF; phenol (2.0 equiv), NEt3 (3.0 equiv), CH2Cl2, RT, 3 h (58%). (b) 1Q, Pd(acac)2 (5 mol %), BrettPhos (12 mol %), K3PO4 (3.0 equiv), toluene, 160 °C, 24 h, 56%. (c) 2Q, TIPS−acetylene (5.0 equiv), Pd(acac)2 (5 mol %), dcypt (10 mol %), CuI (10 mol %), Et2NH (6.0 equiv), MS3A, 1,4- dioxane, 17 0 ° C, 16 h (33 %) dcy pt = 3, 4-bis(dicyclohexylphosphino)thiophene.
to an acid chloride, and then phenol was reacted to synthesize 1Q in one step. Subsequent denitrative C−H arylation gave dibenzofuran 2Q in 56% yield. Furthermore, a Pd-catalyzed decarbonylative alkynylation reaction, which was developed in our group, was carried out:9 the reaction proceeded in moderate yield, and the desired alkynylated product 4 was synthesized. In summary, we have achieved an intramolecular C−H arylation of nitroarenes by a Pd/BrettPhos catalyst. This is the first example of an intramolecular reaction that simultaneously activates a C−H bond and a C−NO2 bond. The development of more efficient catalysts and the expansion of the substrate scope are currently under investigation in our laboratories.
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REFERENCES
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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.9b01593. C
DOI: 10.1021/acs.orglett.9b01593 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters 2011, 133, 18566. (i) Muto, K.; Yamaguchi, J.; Itami, K. J. Am. Chem. Soc. 2012, 134, 169. (j) Song, W.; Ackermann, L. Angew. Chem., Int. Ed. 2012, 51, 8251. (k) Amaike, K.; Muto, K.; Yamaguchi, J.; Itami, K. J. Am. Chem. Soc. 2012, 134, 13573. (l) Meng, G.; Szostak, M. ACS Catal. 2017, 7, 7251. (6) For representative examples of intramolecular (hetero)biaryl synthesis, see: (a) Campeau, L.-C.; Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7, 1857. (b) Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581. (c) Wang, J.; Ferguson, D. M.; Kalyani, D. Tetrahedron 2013, 69, 5780. (d) Ferguson, D. M.; Rudolph, S. R.; Kalyani, D. ACS Catal. 2014, 4, 2395. (e) Panda, N.; Mattan, I.; Nayak, D. K. J. Org. Chem. 2015, 80, 6590. (f) Hong, F.; Chen, Y.; Lu, B.; Cheng, J. Adv. Synth. Catal. 2016, 358, 353. (g) Maetani, S.; Fukuyama, T.; Ryu, I. Org. Lett. 2013, 15, 2754. (h) Okita, T.; Komatsuda, M.; Saito, A. N.; Hisada, T.; Takahara, T. T.; Nakayama, K. P.; Isshiki, R.; Takise, R.; Muto, K.; Yamaguchi, J. Asian J. Org. Chem. 2018, 7, 1358. (7) For details, see the Supporting Information. (8) Any halogens were incompatible, occurring dehalogenation prior to the denitrative reaction. (9) (a) Takise, R.; Muto, K.; Yamaguchi, J. Chem. Soc. Rev. 2017, 46, 5864. (b) Okita, T.; Kumazawa, K.; Takise, R.; Muto, K.; Itami, K.; Yamaguchi, J. Chem. Lett. 2017, 46, 218.
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DOI: 10.1021/acs.orglett.9b01593 Org. Lett. XXXX, XXX, XXX−XXX
