Tandem Rh(III)-Catalyzed C–H Heteroarylation of ... - ACS Publications

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

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Tandem Rh(III)-Catalyzed C−H Heteroarylation of Indolyl Ketones and Cu(II)-Promoted Intramolecular Cyclization: One-Pot Access to Blue-Emitting Phenanthrone-Type Polyheterocycles Xingwen Pu, Mangang Zhang, Jingbo Lan,* Shuyou Chen, Zheng Liu, Wenbo Liang, Yudong Yang, Min Zhang, and Jingsong You* Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P.R. China

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ABSTRACT: Disclosed herein is a highly efficient one-pot synthetic strategy to phenanthrone-type polyheterocycles via tandem rhodium(III)-catalyzed ortho-C−H heteroarylation of indolyl ketones and copper(II)-promoted intramolecular cyclization. This protocol enables a library of blue-emitting fluorophores with high quantum yields and narrow full widths at half-maximum to be rapidly built from readily available substrates, among of which 6,6,7,9,12-pentamethyl-6,12-dihydro-5H-benzofuro[2,3-a]carbazol-5-one (4a) exhibits pure blue emission with Commission Internationale de I’Eclairage coordinates of (0.15, 0.09) and a high quantum yield of 85% in CH2Cl2 solution.

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Scheme 1. Molecular Design of Phenanthrone-Type Polyheterocycle Skeleton

i(hetero)aryl compounds, such as oxyluciferin, are an important class of fluorophores that have been widely used as organic electroluminescent materials and staining agents for cells and biotissues.1 Among organic electroluminescent materials with the three primary colors of red, green, and blue, the development of high-performance blue emitters is an appealing yet significantly challenging task. In recent years, various design tactics for bi(hetero)arene-based blue-emitting materials have been presented.2 However, some of the bi(hetero)arenes show relatively weak emissions, and moreover, their full widths at half-maximum (FWHM) of the radiation profile are relatively wide, mainly due to the excitedstate rotational relaxation and the resulting various metastable conformations with different energies.3,4 In general, ringbridged-model bi(hetero)arenes, such as fluorenes, in which the intramolecular rotation is blocked, usually exhibit higher fluorescence quantum yields and narrower FWHM than the corresponding unbridged biphenyls.3 Phenanthrone-type derivatives with a quaternary carbon center are a unique class of ring-bridged biarenes (Scheme 1). Their ketone groups are similar to the carbonyl group of fluorenones, which is advantageous to a red-shifted emission.5 The nonplanarity of the quaternary carbon center may compare favorably with that of 9,9-dimethyl-9H-fluorene, which can effectively inhibit intermolecular π−π interactions, leading to a high quantum yield.6 Phenanthrone-type skeletons are not readily accessible by conventional synthetic methods.7 Recently, using aryl trifluoroborates and aryl iodides as arylation reagents, the Pd(II)-catalyzed chelation-assisted ortho-C−H arylation of phenyl acetic acids and sec-alkyl aryl ketones and a subsequent cyclization reaction has been © XXXX American Chemical Society

accomplished, which enables a simple and highly efficient pathway to phenanthrones from readily available substrates.8 From the perspective of atom and step economy, transitionmetal-catalyzed oxidative C−H/C−H cross-coupling between two (hetero)arenes is doubtless one of the most attractive approaches to achieve various arylation reactions.9 However, the chelation-assisted ortho-heteroarylation of (hetero)aryl ketones through oxidative C−H/C−H cross-coupling and subsequent cyclization to construct phenanthrone structures remains unsolved. Our recent studies have focused on developing highly efficient C−H/C−H cross-coupling reactions to construct various bi(hetero)arenes and ring-bridged derivatives thereof.10,11 Following our continuing interest in Received: January 8, 2019

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DOI: 10.1021/acs.orglett.9b00089 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

(Table S2). To our surprise, trifluoromethanesulfonates, such as Zn(OTf)2, LiOTf, and NaOTf, could effectively promote the one-pot transformation (Table S3, entries 4−6). The optimal conditions were finalized as 1a (1.0 equiv) and 2a (3.0 equiv) in the catalysis of 5.0 mol % of [Cp*RhCl2]2 in combination with AgSbF6, with Cu(OAc)2 as an oxidant and a promoter of the intramolecular cyclization reaction and NaOTf as an additive in acetonitrile at 150 °C for 36 h under an N2 atmosphere (Table S3, entry 6). With the established tandem C−H heteroarylation/cyclization conditions in hand, the scope of indolyl ketones 1 was examined (Scheme 2). This protocol was amenable to both electron-donating and electron-withdrawing groups, which could be connected to the 4-, 5-, 6-, or 7-position of the indole substrates (3b−j). Fluoro and chloro substituents were also compatible, albeit in slightly lower yields (3f,g). 7Azaindolyl ketone gave the desired products in a moderate yield (3k). To our delight, 5-phenyl-substituted indolyl ketones with a strongly electron-withdrawing methylsulfonyl group and a strongly electron-donating diphenylamino group in the para-position of the 5-phenyl group could be also smoothly transformed into the desired products in 88% and 82% yields, respectively (3l−m). It is worth noting that 3a could be obtained not only in a yield of 67% by loading 0.2 mmol of 1a but also with a yield of 62% on a gram scale (4.0 mmol). The reaction efficiency of different heterocycles was also investigated. As shown in Scheme 3, substituted benzofurans and naphthofuran delivered the corresponding products smoothly in synthetically useful yields (4a−c). Benzothiophene was also found to be a suitable substrate for this reaction, affording the desired product 4d in moderate yield.

ring-bridged bi(hetero)arenes, we herein present a highly efficient one-pot synthetic protocol to phenanthrone-type polyheterocycles via tandem rhodium(III)-catalyzed ortho-C− H heteroarylation of indolyl ketones with furan and thiophene derivatives and copper(II)-promoted intramolecular cyclization for screening blue-emitting fluorophores. We initiated our investigations using isopropyl N-methylindol-3-yl ketone (1a) and benzofuran (2a) as model substrates to explore the reaction conditions (Table S1). Delightfully, the product of tandem ortho-C−H heteroarylation/cyclization (3a) was obtained with 30% yield in [Cp*RhCl2]2/AgSbF6 catalyst system using Cu(OAc)2 as an oxidant, CsOAc as an additive, and 1,4-dioxane as solvent (Table S1, entry 2). The structure of 3a was confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectra, highresolution mass spectrometry (HRMS), and single-crystal Xray diffraction analysis (CCDC 1888691; Scheme 2, 3a). Further optimization of the solvent showed that acetonitrile was a much better choice (Table S1, entry 4). Screening of oxidants showed that Cu(OAc)2 was superior to other oxidants Scheme 2. Scope of Indolyl Ketonesa

Scheme 3. Scope of Heterocyclesa

a

Reaction conditions: 1 (0.2 mmol), 2a (3.0 equiv), [Cp*RhCl2]2 (5.0 mol %), AgSbF6 (20 mol %), Cu(OAc)2 (5.0 equiv), NaOTf (50 mol %) in MeCN (0.5 mL) at 150 °C for 36 h under N2. Isolated yields. Emission maxima and fluorescence quantum yields in CH2Cl2 (1.0 × 10−5 M) are reported in parentheses. Absolute quantum yields were determined with a calibrated integrating sphere system. bGramscale reaction. c24 h.

a Reaction conditions: 1 (0.2 mmol), 2 (3.0 equiv), [Cp*RhCl2]2 (5.0 mol %), AgSbF6 (20 mol %), Cu(OAc)2 (5.0 equiv), NaOTf (50 mol %) in MeCN (0.5 mL) at 150 °C for 36 h under N2. Isolated yields. Emission maxima and fluorescence quantum yields in CH2Cl2 (1.0 × 10−5 M) are reported in parentheses. Absolute quantum yields were determined with a calibrated integrating sphere system.

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DOI: 10.1021/acs.orglett.9b00089 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters To our delight, various substituted thiophenes were compatible with the reaction, delivering the corresponding products in moderate to good yields (4e−i). To gain further insight into this tandem reaction, kinetic isotope effect (KIE) experiments were performed for both 1a and 2a. A KIE value of 1.09 was observed at the parallel reactions between 1a and [D1]-1a at the C2-position with 2a and a KIE value of 2.05 for the parallel reactions between 2a and [D1]-2a at the C2-position with 1a (Schemes S2 and S3). These results suggest that the chelation-assisted ortho-C−H activation of 1a may not be in a rate-determining step, while the C−H bond cleavage at the C2 site of 2a may be involved in the rate-determining step.12 Subsequently, the uncyclized intermediate 5a, which was observed in this catalytic system only in trace amounts, was synthesized according to our previously reported methods (Scheme S4).13 Then several control experiments were carried out to confirm the respective roles that the rhodium catalyst and the copper salt played in the tandem reaction. It was found that 5a can deliver the cyclization product 3a in 95% yield under standard conditions (eq 1). In the absence of [Cp*RhCl2]2/AgSbF6, 3a can also be

Scheme 4. Plausible Mechanistic Pathway

Subsequently, the photophysical properties of 3 and 4 were measured (Schemes 2 and 3, Table S5, and Figure S2). Most of these phenanthrone-type polyheterocycles emit blue fluorescence in CH2Cl2 solution with high quantum yields. While the uncyclized intermediate 5a exhibits a low fluorescence quantum yield of 0.12 and a wide FWHM of 79 nm, the corresponding cyclization product 3a shows a relatively high quantum yield of 0.67 and a relatively narrow FWHM of 66 nm (Table 1 and Figure 1a). It is noteworthy Table 1. Photophysical Properties of 3a, 4a, and 5a dye

λabsa (nm)

λemb (nm)

FWHMc (nm)

CIEd

ΦFe

3a 4a 5a

379, 400 367 311

446 428, 448 441

66 62 79

(0.16, 0.13) (0.15, 0.09) (0.14, 0.10)

0.67 0.85 0.12

Absorption maxima in CH2Cl2 (1.0 × 10−5 M). bEmission maxima in CH2Cl2 (1.0 × 10−5 M). cFull widths at half-maximum. dCIE coordinates measured in CH2Cl2 (1.0 × 10−5 M). eAbsolute quantum yields in CH2Cl2 (1.0 × 10−5 M) determined with an integrating sphere system. a

obtained in 90% yield (eq 2). However, only a trace amount of 3a was detected under the conditions without Cu(OAc)2 (eq 3). These results clearly demonstrate that the tandem reaction consists of Rh(III)-catalyzed ortho-C−H heteroarylation of indolyl ketones and Cu(II)-promoted intramolecular cyclization. In addition, the addition of radical inhibitors, such as 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 2,6-bis(tert-butyl)-4-methylphenol (BHT), displays a negligible effect on the reaction of 1a and 2a, ruling out a radical process of this tandem reaction (Table S4). A plausible pathway is proposed on the basis of the mechanistic studies described above (Scheme 4). First, [Cp*RhCl2]2 is transformed to a cationic Rh(III) species in the presence of AgSbF6, which reacts with 1a via chelationassisted ortho-C−H activation to form intermediate IM1. IM1 reacts with 2a to generate diarylrhodium complex IM2. The reductive elimination of IM2 delivers the uncyclized intermediate 5a. The generated Rh(I) is oxidized to Rh(III) by Cu(II) to accomplish the catalytic cycle. In the presence of Cu(OAc)2, 5a undergoes a keto−enol tautomerism and then coordinates with Cu(II) at the oxygen atom (path a) or at the α-carbon atom (path b) to form IM3 or IM4. Subsequently, the intramolecular C−H activation takes place, delivering IM5. IM5 is oxidized by Cu(OAc)2 to give Cu(III) complex IM6,14 which then undergoes reductive elimination, forming the product 3a.

that 4a exhibits pure blue emission with Commission Internationale de I’Eclairage (CIE) chromaticity coordinates of (0.15, 0.09) in solution and, moreover, with a fluorescence quantum yield of 85% and the most narrow FWHM (62 nm) in all these phenanthrone-type polyheterocycles (Table 1 and Figure 1). In addition, most of compounds 3 and 4 exhibit blue emissions in polystyrene film (c = 2.0 wt %) with fluorescence quantum yields from 4% to 36% (Table S5 and Figure S2), which may be potential candidates for organic optoelectronic devices. In summary, we have developed a highly efficient one-pot synthetic strategy to phenanthrone-type polyheterocycles via tandem rhodium(III)-catalyzed ortho-C−H heteroarylation of indolyl ketones with furan and thiophene derivatives and copper(II)-promoted intramolecular cyclization. This protocol enables a library of blue-emitting fluorophores to be rapidly built from readily available substrates. Compared with the uncyclized intermediate 5a, the corresponding cyclization product 3a shows a higher quantum yield with a narrower FWHM due to the restricted intramolecular rotation. It is noteworthy that 4a exhibits pure blue emission with CIE coordinates of (0.15, 0.09) and a very high fluorescence quantum yield of 85% in CH2Cl2 solution, which may be a potential candidate for organic optoelectronic devices. C

DOI: 10.1021/acs.orglett.9b00089 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

Yudong Yang: 0000-0002-7142-2249 Jingsong You: 0000-0002-0493-2388 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (Nos. 21871193, 21672154, 21502123, and 21432005) for financial support. We also thank the Comprehensive Training Platform Specialized Laboratory, College of Chemistry, Sichuan University.

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Figure 1. (a) Normalized absorption spectra (dotted lines) and fluorescence emission spectra (solid lines) in CH2Cl2 (1 × 10−5 M). (b) Emission color coordinates of 3a, 4a, and 5a in the CIE 1931 chromaticity diagram.

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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.9b00089. Detailed experimental procedures, characterization data, copies of 1H and 13C NMR spectra of products and Xray crystal structure of 3a (PDF) Accession Codes

CCDC 1888691 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Authors

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

Jingbo Lan: 0000-0001-5937-0987 D

DOI: 10.1021/acs.orglett.9b00089 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters (14) (a) Wu, X.; Zhao, Y.; Zhang, G.; Ge, H. Angew. Chem., Int. Ed. 2014, 53, 3706. (b) Guo, X.-X.; Gu, D.-W.; Wu, Z.; Zhang, W. Chem. Rev. 2015, 115, 1622.

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DOI: 10.1021/acs.orglett.9b00089 Org. Lett. XXXX, XXX, XXX−XXX