Extended π-Conjugated Structures via Dehydrative C–C Coupling

Article Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

pubs.acs.org/JACS

Extended π‑Conjugated Structures via Dehydrative C−C Coupling Constantin-Christian A. Voll and Timothy M. Swager* Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States

J. Am. Chem. Soc. Downloaded from pubs.acs.org by YORK UNIV on 12/14/18. For personal use only.

S Supporting Information *

ABSTRACT: We describe a methodology for the synthesis of extended aromatic structures through dehydrative C−C coupling from readily accessible diols. Treatment of the diols with a Brønsted acid (para-toluenesulfonic acid) induces the nucleophilic addition of an arene or heteroarene, yielding fully aromatic products in high to quantitative yields with thiophenes, furan, indole, and N,N-dimethylaniline as coupling partners. The C−C coupling reactions proceed under mild, open flask conditions and offer high atom economy, while providing an attractive alternative approach to metal-catalyzed cross-coupling.

■

INTRODUCTION Extended conjugated structures are ubiquitous in the field of organic semiconductive materials because of their favorable optical and electronic properties.1 Conjugation can promote stronger optical absorption, smaller band gaps, and increased emission efficiencies, thereby explaining the prevalence of these structures in chromophores2,3 and organic emitters4 as well as polymers for photovoltaics,5,6 organic light-emitting diodes (OLEDs),7 and organic field effect transistors (OFETs)1 and in emerging applications derived from magneto-optical Faraday rotation.8 Most of these structures are synthesized by transition-metal cross-coupling reactions (Suzuki, Stille, Negishi, Kumada, etc.) (Scheme 1). Despite the undisputed synthetic utility of transition-metal cross-coupling, inherent drawbacks exist. For example, prefunctionalization is usually needed, which adds synthetic steps and produces stoichiometric waste, with tin waste from Stille couplings being particularly toxic. Hence, many of these syntheses are not atom-efficient. Additionally, cross-coupling reactions typically require organometallic catalysts, which often use precious metals and necessitate anhydrous or oxygen-free environments. Direct (hetero)arylation, where the organometallic substrate is replaced by a (hetero)arene, has emerged as an alternative to traditional cross-coupling, requiring only one functionalized substrate.9−11 This results in improved atom economy and the generation of only benign byproducts. Direct (hetero)arylation reactions have demonstrated efficiencies that rival traditional cross-coupling methodologies, and these reactions are used to produce high-molecular-weight, low-defect polymers.12,13 Whereas this minimizes some drawbacks, reactions still require palladium, an anaerobic environment, and high reaction temperatures. Furthermore, palladium nanoparticles have been shown to be difficult to remove from high-molecularweight molecules and polymers, sometimes with detrimental effects on device performance.14 Organic trace impurities, for example resulting from incomplete selectivity in Stille coupling, © XXXX American Chemical Society

can also be very challenging to separate. Even when highly diluted, these contaminants have been shown to cause drastic differences in device performance.15 To facilitate the widespread adoption of conjugated molecules in organic electronics, it is vital to develop scalable and sustainable methods for both small molecules and polymers. Dehydrative couplings are a preferred reaction class because the only byproduct, water, is an easily removed and environmentally friendly thermodynamic sink. Although dehydrative polymerizations are used on a vast scale for nonconjugated polymers such as nylon-6,6 and polyesters, examples of the construction of conjugated materials for optoelectronic or semiconductive applications by dehydrative couplings are scarce. There has been some work on super-acidcatalyzed cyclizations16−18 and intermolecular reactions, with a narrow focus on furans with potential use in drug discovery,19,20 as well as axially chiral naphthyl-indole skeletons.21 Schipper and coworkers recently demonstrated an elegant intermolecular dehydrative coupling based on thiazole N-oxide motifs. They demonstrate a dehydrative coupling of small molecules and an analogous polymerization.22 Although their work is an important step toward a robust, atom-efficient method for the scalable synthesis of extended π-conjugated structures, there is still a need for additional methods to access a more diverse array of conjugated architectures. Herein we report a high-yielding dehydrative C−C coupling methodology to prepare π-extended structures in two steps from readily available quinone starting materials. These coupling reactions are run under ambient conditions (open flask), with fast reaction times and complete conversion using relatively mild reaction conditions. Received: September 4, 2018

A

DOI: 10.1021/jacs.8b09337 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Article

Journal of the American Chemical Society Scheme 1. Synthetic Approaches to Highly Conjugated Molecules

■

RESULTS AND DISCUSSION Proof of Concept. With the idea of dehydrative C−C coupling in mind, we decided to focus on motifs that are

Table 1. Reaction Optimization Using 2-Methylthiophene

Scheme 2. Preparation of the Key Intermediate Diol 1 entry 1 2 3 4 5 6 7 8

Scheme 3. Proof of Concept Reaction: 1:3 Condensation of 1 with EDOT Yields Dimer 4 as the Major Product

a

acid

2 5.0 2.5 1.2 1.2 1.2 1.2 1.2 1.2

equiv equiv equiv equiv equiv equiv equiv equiv

4.0 2.0 1.0 0.1 0.1 1.0 1.0 1.0

equiv equiv equiv equiv equiv equiv equiv equiv

p-TsOH p-TsOH p-TsOH p-TsOH p-TsOH p-TsOH HCl TFA

solvent

T/°C

yielda

toluene toluene toluene toluene toluene CH2Cl2 toluene toluene

40 40 40 40 60 40 40 40

quant. 95% 94% 86% 52% quant. trace trace

NMR yields. p-TsOH was used as the monohydrate.

chromatography on silica gel, but a mixture was used for subsequent reactions. We hypothesized that either a strong acid or the introduction of a good leaving group such as a triflate would lead to the formal elimination of water via a delocalized carbocation intermediate. With no acidic sp3 proton proximate to the carbocation, we anticipated that this intermediate will persist to allow for a bimolecular reaction with an electron-rich hetero(arene). We chose para-toluenesulfonic acid (p-TsOH) in toluene as the initial reaction conditions because it has been shown to promote quantitative dehydrations of benzylic tertiary alcohols;27 furthermore, p-TsOH is inexpensive, nonoxidizing, easily handled, and weighed. Initially, we chose 3,4-ethylenedioxythiophene (EDOT) as the coupling partner because it is a popular, readily available building block in electrooptical materials, and its electron-rich character should facilitate reactivity with a carbocation.28 We were pleased to see that reacting the diol 1 with excess EDOT gave 3 as a minor product (13%) and 4 as the major product in 59% yield (Scheme 3). This indicated that the hypothesized

commonly found in organic materials: thiophenes and anthracene, an example of an acene. Materials including these groups have been investigated in solar cells23 and fieldeffect transistors24,25 and have shown promise for singlet fission materials.26 The key intermediate 1 was prepared in 87% yield, by the addition of lithiated thiophene to anthraquinone at −78 °C (Scheme 2). These carbonyl additions of thiophenes were high-yielding starting from either 2-bromothiophene or unfunctionalized thiophene. Both the cis and trans isomers of 1 are produced in a ratio of about 1.5:1. The isomers were easily separable by flash column B

DOI: 10.1021/jacs.8b09337 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Article

Journal of the American Chemical Society Table 2. Substrate Scopea

a

All yields are isolated.

reagents provided the expected product in quantitative yield at 40 °C (Table 1, entry 1). The faster reaction time (minutes) suggests that water is adventitious, likely by facilitating efficient proton transfers. After optimizing, we found that 1.2 equiv of nucleophile and 1 equiv of acid provided the desired product in 94% yield. Using 10 mol % of acid still gave the product in a relatively high yield of 86%, but the reaction suffered from increased byproducts, and slow kinetics required a day to reach completion. Increasing the temperature to 60 °C under catalytic conditions led to increased byproduct formation and lowered the yield to 52% (Table 1, entry 5). Running the reaction in dichloromethane instead of toluene also gave the product in quantitative yield (Table 1, entry 6). The presence of oxygen does not seem to have an effect on the reaction. pTsOH appears to be an excellent Brønsted acid, as other strong acids result in either no product, low yields, or a mixture of products (Table 1, entries 7 and 8). Interestingly, one of the diol isomers is more reactive than the other one. This became evident when running this reaction at room temperature, where one isomer reacted exclusively within minutes, whereas the other persisted. We suspect that the orientation of the trans diol allows for anchimeric assistance. However, we are unsure as to whether this promotes elimination, allowing for faster kinetics, or whether this forms an endoxide-type kinetic sink. Heating the reaction to 40 °C rendered both diols susceptible to the desired

Scheme 4. When Substituted with Phenyl or Naphthyl, Diols Produce Anthraquinone

dehydrative coupling is indeed feasible and that the initially formed product 3 is more nucleophilic than EDOT itself. Reaction Optimization. EDOT is very electron-rich, so we investigated reactions with the less nucleophilic 2methylthiophene (Table 1). The steric bulk of the methyl group should also suppress dimerization. Initially, we ran the reaction under air-free and anhydrous conditions, evaluating different strategies to remove water from the reaction mixture, which might promote side reactions. However, using anhydrous p-TsOH, refluxing the reaction in toluene with a Dean−Stark apparatus fitted, or adding ground molecular sieves all gave moderate yields. We were pleased to discover that the wet, open-flask conditions using superstoichiometric C

DOI: 10.1021/jacs.8b09337 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Article

Journal of the American Chemical Society Scheme 5. Proposed Reaction Mechanism

reaction, and we were able to find a rough nucleophilicity cutoff for this reaction (−1.0 < N < 1.3, ignoring the SN parameter due to small differences for five- and six-membered aromatic rings).30−34 This helps to predict if a particular substrate may be suitable for this reaction. Limitations. As one might intuitively expect, π-donating aromatics are crucial for this reaction. Replacing them with phenyl or naphthyl groups has detrimental effects on the outcome. Instead, they furnish trace amounts of the desired product and mostly give anthraquinone as the product. We suspect that without a moderately strong π-donor such as thiophene the elimination of water becomes slow, rendering the phenyl/naphthyl moiety susceptible to protonation, followed by elimination as shown in Scheme 4. The second limitation involves the stability of the diol. One can imagine how diols resulting from benzoquinone and naphthoquinone would undergo an analogous reaction. However, these diols are prone to irreversible rearrangements. As a result, we suspect that suitable core substrates should not feature protons in the α-position of the carbonyl/alcohol. Rearrangements of the diols are thereby suppressed. Reaction Mechanism. For the successful coupling reactions, we propose the reaction mechanism shown in Scheme 5. The protonated diol (1+) eliminates water, leaving a delocalized carbocation. The nucleophile, in this case, 2methylthiophene, attacks the five-position at the thiophene. Rearomatization of the thiophenes occurs by deprotonation and as part of the elimination of a second equivalent of water. This proposed reaction mechanisms is reminiscent of the indophenin reaction, originally discovered by Adolf von Baeyer in the 19th century, which served as a colorimetric test for thiophene.35,36 Similar to this dehydrative coupling approach, the reaction is initiated through an electrophilic attack of the protonated isatin to form extended conjugated structures. The difference in reaction mechanism arises from the structural differences. The diols in this study have two leaving groups and furnish fully aromatic structures. In the indophenin reaction,

reaction. We did not observe this phenomenon for any other substrate we subsequently tested. Nucleophile Scope. With the optimized conditions in hand, 1.2 equiv of nucleophile and 1.0 equiv of p-TsOH, we evaluated the scope of this dehydrative coupling reaction and the results are summarized in Table 2. This method is successful in coupling a range of aromatic nucleophiles, including 2-MeEDOT (97% yield), 2-methylfuran (87% yield), indole (95% yield), and N,N-dimethylaniline (62% yield). Even the sterically demanding nucleophile 1,3,5trimethoxybenzene coupled in 81% yield. Guaiazulene coupled in excellent yields as well, furnishing 87% yield after column chromatography and a recrystallization to remove excess guaiazulene. We were also able to obtain the product resulting from a double condensation to EDOT in 67% yield. We find that this method is intuitively predictable: Electron-rich substrates such as indole react at room-temperature within minutes, whereas less electron-rich substrates such as N,Ndimethylaniline require higher temperatures (70 °C) and longer reaction times (18 h). All reaction temperatures were lower than typical Pd-catalyzed C−H arylations of EDOT.10 The simplicity and robustness of this method is noteworthy. At insufficient temperatures or in the absence of a suitable nucleophile, diol 1 remains stable in solution without appreciable decomposition. This makes choosing the reaction temperature easy, as one can start at room-temperature, monitor the reaction by thin layer chromatography (TLC), and increase the temperature until the reaction proceeds. It is worth mentioning that the reactions can proceed with catalytic amounts of acid, as exemplified with 2-methylthiophene. This option might be useful when working with acid-labile compounds. However, some nucleophiles yielded no or very little product. These included benzothiophene, dibenzothiophene, and thiophene, the latter two of which we had anticipated would undergo the analogous double condensation observed for EDOT. By consulting Mayr’s database of reactivity parameters,29 we developed a better understanding of this D

DOI: 10.1021/jacs.8b09337 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Article

Journal of the American Chemical Society

(6) Wu, J. S.; Cheng, S. W.; Cheng, Y. J.; Hsu, C. S. Donor-Acceptor Conjugated Polymers Based on Multifused Ladder-Type Arenes for Organic Solar Cells. Chem. Soc. Rev. 2015, 44 (5), 1113−1154. (7) Voll, C.-C. A.; Engelhart, J.; Einzinger, M.; Baldo, M. A.; Swager, T. M. Donor-Acceptor Iptycenes with Thermally Activated Delayed Fluorescence. Eur. J. Org. Chem. 2017, 2017, 4846−4851. (8) Wang, P.; Jeon, I.; Lin, Z.; Peeks, M. D.; Savagatrup, S.; Kooi, S. E.; Van Voorhis, T.; Swager, T. M. Insights into Magneto-Optics of Helical Conjugated Polymers. J. Am. Chem. Soc. 2018, 140 (20), 6501−6508. (9) Schipper, D. J.; Fagnou, K. Direct Arylation as a Synthetic Tool for the Synthesis of Thiophene-Based Organic Electronic Materials. Chem. Mater. 2011, 23 (6), 1594−1600. (10) Liu, C. Y.; Zhao, H.; Yu, H. H. Efficient Synthesis of 3,4Ethylenedioxythiophene (EDOT)-Based Functional π-Conjugated Molecules through Direct C-H Bond Arylations. Org. Lett. 2011, 13 (15), 4068−4071. (11) Satoh, T.; Miura, M. Catalytic Direct Arylation of Heteroaromatic Compounds. Chem. Lett. 2007, 36 (2), 200−205. (12) Grenier, F.; Goudreau, K.; Leclerc, M. Robust Direct (Hetero)Arylation Polymerization in Biphasic Conditions. J. Am. Chem. Soc. 2017, 139 (7), 2816−2824. (13) Pouliot, J. R.; Grenier, F.; Blaskovits, J. T.; Beaupré, S.; Leclerc, M. Direct (Hetero)Arylation Polymerization: Simplicity for Conjugated Polymer Synthesis. Chem. Rev. 2016, 116 (22), 14225−14274. (14) Krebs, F. C.; Nyberg, R. B.; Jørgensen, M. Influence of Residual Catalyst on the Properties of Conjugated Polyphenylenevinylene Materials: Palladium Nanoparticles and Poor Electrical Performance. Chem. Mater. 2004, 16 (7), 1313−1318. (15) Leong, W. L.; Welch, G. C.; Kaake, L. G.; Takacs, C. J.; Sun, Y.; Bazan, G. C.; Heeger, A. J. Role of Trace Impurities in the Photovoltaic Performance of Solution Processed Small-Molecule Bulk Heterojunction Solar Cells. Chem. Sci. 2012, 3 (6), 2103−2109. (16) Olah, G. A.; Klumpp, D. A.; Neyer, G.; Wang, Q. The Preparation of Substituted Phenanthrenes from Aryl Pinacols in Superacid. Synthesis 1996, 1996, 321−323. (17) Klumpp, D. A.; Baek, D. N.; Prakash, G. K. S.; Olah, G. A. Preparation of Condensed Aromatics by Superacidic Dehydrative Cyclization of Aryl Pinacols and Epoxides 1a Depending on the Strength of the Acid Catalyst, Ben-. J. Org. Chem. 1997, 62, 6666− 6671. (18) Vanveller, B.; Schipper, D. J.; Swager, T. M. Polycyclic Aromatic Triptycenes: Oxygen Substitution Cyclization Strategies. J. Am. Chem. Soc. 2012, 134 (17), 7282−7285. (19) Xu, J.; Luo, Y.; Xu, H.; Chen, Z.; Miao, M.; Ren, H. CatalystControlled Chemodivergent Modification of Indoles with 2Furylcarbinols: Piancatelli Reaction vs Cross-Dehydrative Coupling Reaction. J. Org. Chem. 2017, 82 (7), 3561−3570. (20) Miao, M.; Luo, Y.; Li, H.; Xu, X.; Chen, Z.; Xu, J.; Ren, H. Lewis Acid Catalyzed Regiospecific Cross-Dehydrative Coupling Reaction of 2-Furylcarbinols with β-Keto Amides or 4-Hydroxycoumarins: A Route to Furyl Enols. J. Org. Chem. 2016, 81 (12), 5228− 5235. (21) Zhang, H. H.; Wang, C. S.; Li, C.; Mei, G. J.; Li, Y.; Shi, F. Design and Enantioselective Construction of Axially Chiral NaphthylIndole Skeletons. Angew. Chem., Int. Ed. 2017, 56 (1), 116−121. (22) Mirabal, R. A.; Vanderzwet, L.; Abuadas, S.; Emmett, M. R.; Schipper, D. Dehydration Polymerization for Poly(Hetero)Arene Conjugated Polymers. Chem. - Eur. J. 2018, 24 (47), 12231−12235. (23) Gorodetsky, A. A.; Cox, M.; Tremblay, N. J.; Kymissis, I.; Nuckolls, C. Solar Cells from a Solution Processable Pentacene with Improved Air Stability. Chem. Mater. 2009, 21 (18), 4090−4092. (24) Miao, Q.; Chi, X.; Xiao, S.; Zeis, R.; Lefenfeld, M.; Siegrist, T.; Steigerwald, M. L.; Nuckolls, C. Organization of Acenes with a Cruciform Assembly Motif. J. Am. Chem. Soc. 2006, 128 (4), 1340− 1345. (25) Wang, J.; Liu, K.; Liu, Y. Y.; Song, C. L.; Shi, Z. F.; Peng, J. B.; Zhang, H. L.; Cao, X. P. New Oligothiophene-Pentacene Hybrids as

there is no such driving force. With only one leaving group, the indophenin products cannot fully aromatize. Future Outlook. This method represents a new versatile route to the construction of extended conjugated structures. In addition to being a robust method, the starting materials are readily available simple aromatics. In principle, these diols could also undergo homocoupling and potentially form conjugated polymers. However, we did not observe homocoupling with these diols, even under more forcing conditions such as refluxing in toluene. We are currently exploring other scaffolds as well as conditions other than Brønsted acids to promote polymerization.

■

CONCLUSIONS We have disclosed a dehydrative C−C coupling methodology using para-toluenesulfonic acid (p-TsOH) in toluene for the preparation of highly conjugated molecules. Starting from simple quinones, unsymmetrically substituted conjugated molecules that are cumbersome to access through typical cross-coupling methodologies are obtained in up to 97% isolated yield. Products are obtained in two-steps, and the C− C forming reactions are run under ambient conditions, at room temperature or slightly elevated temperatures, rendering this method extremely user-friendly.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.8b09337. Experimental procedures and methods, 1H and 13C NMR spectra, and UV−vis spectra (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Constantin-Christian A. Voll: 0000-0003-2769-3321 Timothy M. Swager: 0000-0002-3577-0510 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was funded by the Air Force Office of Scientific Research Grant No. 17RT0904. We thank Dr. Nathan A. Romero for insightful discussions.

■

REFERENCES

(1) Wang, C.; Dong, H.; Hu, W.; Liu, Y.; Zhu, D. Semiconducting πConjugated Systems in Field-Effect Transistors: A Material Odyssey of Organic Electronics. Chem. Rev. 2012, 112 (4), 2208−2267. (2) Malytskyi, V.; Simon, J. J.; Patrone, L.; Raimundo, J. M. Thiophene-Based Push-Pull Chromophores for Small Molecule Organic Solar Cells (SMOSCs). RSC Adv. 2015, 5 (1), 354−357. (3) Schleper, A. L.; Voll, C.-C. A.; Engelhart, J. U.; Swager, T. M. Iptycene-Containing Azaacenes with Tunable Luminescence. Synlett 2017, 28 (20), 2783−2789. (4) Nielsen, C. B.; Holliday, S.; Chen, H.-Y.; Cryer, S. J.; McCulloch, I. Non-Fullerene Electron Acceptors for Use in Organic Solar Cells. Acc. Chem. Res. 2015, 48 (11), 2803−2812. (5) Li, G.; Chang, W. H.; Yang, Y. Low-Bandgap Conjugated Polymers Enabling Solution-Processable Tandem Solar Cells. Nat. Rev. Mater. 2017, 2 (8), 17043. E

DOI: 10.1021/jacs.8b09337 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Article

Journal of the American Chemical Society Highly Stable and Soluble Organic Semiconductors. Org. Lett. 2009, 11 (12), 2563−2566. (26) Yost, S. R.; Lee, J.; Wilson, M. W. B.; Wu, T.; McMahon, D. P.; Parkhurst, R. R.; Thompson, N. J.; Congreve, D. N.; Rao, A.; Johnson, K.; Sfeir, M. Y.; Bawendi, M. G.; Swager, T. M.; Friend, R. H.; Baldo, M. A.; Van Voorhis, T. A Transferable Model for Singlet-Fission Kinetics. Nat. Chem. 2014, 6 (6), 492−497. (27) He, X. S.; Raymon, L. P.; Mattson, M. V.; Eldefrawi, M. E.; de Costa, B. R. Synthesis and Biological Evaluation of 1-[1-(2Benzo[b]Thienyl)Cyclohexyl]Piperidine Homologs at DopamineUptake and Phencyclidine-, and σ-Binding Sites. J. Med. Chem. 1993, 36 (9), 1188−1193. (28) Roncali, J.; Blanchard, P.; Frère, P. 3,4-Ethylenedioxythiophene (EDOT) as a Versatile Building Block for Advanced Functional πConjugated Systems. J. Mater. Chem. 2005, 15 (16), 1589−1610. (29) Mayr’s Database of Reactivity Parameters. http://www.cup.lmu. de/oc/mayr/reaktionsdatenbank/. (30) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. Reference Scales for the Characterization of Cationic Electrophiles and Neutral Nucleophiles. J. Am. Chem. Soc. 2001, 123 (39), 9500− 9512. (31) Ammer, J.; Nolte, C.; Mayr, H. Free Energy Relationships for Reactions of Substituted Benzhydrylium Ions: From Enthalpy over Entropy to Diffusion Control. J. Am. Chem. Soc. 2012, 134 (33), 13902−13911. (32) Kȩdziorek, M.; Mayer, P.; Mayr, H. Nucleophilic Reactivities of Azulene and Fulvenes. Eur. J. Org. Chem. 2009, 2009 (8), 1202−1206. (33) Lakhdar, S.; Westermaier, M.; Terrier, F.; Goumont, R.; Boubaker, T.; Ofial, A. R.; Mayr, H. Nucleophilic Reactivities of Indoles. J. Org. Chem. 2006, 71, 9088−9095. (34) Mayr, H.; Kempf, B.; Ofial, A. R. Π-Nucleophilicity in CarbonCarbon Bond-Forming Reactions. Acc. Chem. Res. 2003, 36 (1), 66− 77. (35) Baeyer, A. Ueber Die Einwirkung Des Fünffachchlorphosphors Auf Isatin Und Auf Verwandte Substanzen. Ber. Dtsch. Chem. Ges. 1879, 12, 456−461. (36) Steinkopf, W.; Roch, J. Studien in Der Thiophenreihe. XXI. Zur Kenntnis Des Indophenins. Justus Liebigs Ann. Chem. 1930, 482 (1), 251−264.

F

DOI: 10.1021/jacs.8b09337 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX