Facile Synthesis of Aryl-Substituted Cycloarenes via Bismuth(III) Triflate-Catalyzed Cyclization of Vinyl Ethers

Open AccessCCS ChemistryCOMMUNICATION1 May 2021Facile Synthesis of Aryl-Substituted Cycloarenes via Bismuth(III) Triflate-Catalyzed Cyclization of Vinyl Ethers Wei Fan, Yi Han, Shaoqiang Dong, Guangwu Li, Xuefeng Lu and Jishan Wu Wei Fan Department of Chemistry, National University of Singapore, Singapore 117543 , Yi Han Department of Chemistry, National University of Singapore, Singapore 117543 , Shaoqiang Dong Department of Chemistry, National University of Singapore, Singapore 117543 , Guangwu Li Department of Chemistry, National University of Singapore, Singapore 117543 , Xuefeng Lu Department of Materials Science, Fudan University, Shanghai 200438 and Jishan Wu *Corresponding author: E-mail Address: email protected Department of Chemistry, National University of Singapore, Singapore 117543 Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Fuzhou 350207 https://doi.org/10.31635/ccschem.020.202000356 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Cycloarenes are an essential class of polycyclic aromatic hydrocarbons with unique electronic structure, but their synthesis is very challenging. Herein, we report a facile synthetic strategy primarily involving macrocyclization by the Suzuki coupling reaction, followed by bismuth(III) triflate-catalyzed cyclization of vinyl ethers. By utilizing this approach, aryl-substituted soluble cycloarenes 7 and 8 with different sizes were obtained. X-ray crystallographic analysis revealed a slightly distorted backbone in the kekulene derivative 7 and a saddle-shaped skeleton in the octulene derivative 8. Bond length analysis suggested that both of the cycloarenes mainly complied with the Clar's bonding model with dominant local aromaticity, which was also in accord with our NMR measurements and the theoretical calculations nucleus-independent chemical shift [NICS, anisotropy of the induced current density (ACID), three-dimensional isochemical shielding surface (3D ICSS)]. The optical properties were investigated by UV–Vis absorption and fluorescence spectral measurements. Our method opens opportunities to access various expanded and core-modified cycloarenes in the future. Download figure Download PowerPoint Introduction Cycloarenes are a class of cata-condensed macrocyclic polyarenes with unique electronic structures (Figure 1).1,2 The initial report on cycloarenes could be dated as far back as 1951 when McWeeny3 discussed that the sixfold symmetric cycloarene cyclod.e.d.e.d.e.d.e.d.e.d.e.dodecakisbenzene, now known as "kekulene", has its π-electrons delocalized into only smaller benzene-type rings (local aromaticity) rather than globally delocalized throughout the entire molecule (global or superaromaticity).3 This provoked many experimental and theoretical studies on cycloarenes over several decades.2,4 Synthesis of cycloarenes is a very challenging task, and until 1978, Diederich et al.5–8 reported the first successful synthesis of kekulene, and the full study was published in 1983. The key strategy involves photocyclization of a macrocycle precursor containing two stilbene substructures, followed by oxidative dehydrogenation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (Figure 1a). The overall synthetic route was tedious, and the final product had very poor solubility. X-ray crystallographic analysis and 1H NMR spectra in high boiling point solvents indicated that kekulene contains six local aromatic sextets (the hexagons shaded in blue color) and six peripheral carbon-carbon (CC) double bonds (highlighted in the bold form) (Figure 1). Recently, Pozo et al.9 developed an efficient synthesis of the key intermediate, 5,6,8,9-tetrahydrobenzomtetraphene, via double Diels–Alder reaction between styrene and a benzodiyne synthon, which improved the synthesis of kekulene substantially. Importantly, by using the state-of-the-art noncontact atomic force microscopy (AFM) technique, they achieved single-molecule imaging of kekulene, and the bond order analysis provided additional support for the molecular structure, with a significant degree of bond localization. Enlighted by the precedent synthesis of kekulene, many efforts have been committed to obtaining other cycloarenes and their heterocyclic analogs.2 In 1986, cyclod.e.d.e.e.d.e.d.e.e.dekakisbenzene, a contracted kekulene molecule, was synthesized through a similar strategy.10 In 2012, Kumar et al.11 reported the synthesis of a higher homolog of kekulene, the septulene, through ring-closing metathesis reaction (Figure 1b). Like kekulene, the unsubstituted septulene has poor solubility. In 2016, Majewski et al.12 synthesized alkoxy group substituted kekulene and octulene by a fold-in strategy involving Ni(COD)2-mediated intramolecular Yamamoto coupling (Figure 1c). Recently, extended cycloarenes have been synthesized by both wet chemistry,13 and metal-mediated dehydrogenation reaction on metal surfaces,14 whereby, they displayed different electronic structures from that of cycloarenes. Despite this progress, the synthesis of soluble cycloarenes via a short synthetic route remains a significant challenge. In this study, we report a facile synthetic approach mainly by using bismuth(III) triflate Bi(OTf)3-catalyzed cyclization reaction of vinyl ethers (Figure 1d). This method provided efficient access to aryl-substituted soluble cycloarenes of different sizes. Figure 1 | (a–c) Previously reported methods and (d) current approach toward cycloarenes. Ar: aryl group. The Clar's sextets are shaded in blue color. Download figure Download PowerPoint Results and Discussion A conceptual synthetic strategy toward cycloarenes is to build up initially, the macrocyclic oligo(m-phenylene) precursors carrying alkyne/alkene groups on the outer periphery, followed by Brønsted acid or Lewis acid-catalyzed cyclization reaction.15–21 Our initial effort of using acid-catalyzed cyclization of alkyne precursors was not successful after many attempts. Fortunately, we found that the Bi(OTf)3-catalyzed cyclization reaction of vinyl ether developed by Murai et al.22 was efficient (Scheme 1). Two readily accessible building blocks, 3, containing two boronic ester groups and 4, bearing two bromo and 2-methoxyethenyl groups, were first synthesized from 123 and 2,24 respectively. The aryl (4-tert-butyl phenyl) group was introduced to improve the solubility of the intermediates, as well as the final products. Suzuki coupling between 3 and 4 under dilute condition using a catalytic system including Pd2(dba)3, (t-Bu)3PHBF4, and aqueous NaHCO325,26 gave the macrocyclic oligo(m-phenylene) intermediates 5 and 6 in 35% and 38% yield, respectively, after isolation by preparative gel permeation chromatography (GPC). Finally, Bi(OTf)3-catalyzed cyclization reaction of 5 and 6 in 1,2-dichloroethane, carried out at a high temperature of 90 °C afforded the aryl-substituted kekulene 7 and octulene 8 in 37% and 30% isolation yield, respectively. We found that cyclization at room temperature or 40 °C mainly gave partially cyclized products. Both compounds ( 7 and 8) were very stable and had sufficient solubility in common organic solvents for structural and spectroscopic characterization. Scheme 1 | Synthesis of aryl-substituted kekulene (7) and octulene (8): (a) bis(pinacolato)diboron, Pd(dppf)Cl2, KOAc, dioxane, 110 °C; (b) methoxymethyltriphenylphosphonium chloride, tBuOK, THF; (c) Pd2(dba)3, (tBu)3PHBF4, NaHCO3, THF/H2O, 80 °C; (d) Bi(OTf)3, 1,2-dichloroethane, 90 °C. THF, tetrahydrofuran. Download figure Download PowerPoint Single crystals of 7 and 8 were grown by slow solvent diffusion of methanol into their solutions in tetrahydrofuran (THF) and chloroform, respectively.a X-ray crystallographic analysis revealed a slightly distorted kekulene backbone in 7 (Figure 2a), which was different from the almost planar geometry of the parent kekulene.8 On the other hand, density functional theory (DFT) optimization gave a planar backbone ( Supporting Information Figure S10), and thus, the observed distortion could be ascribed to the crystal packing effect, as previously observed in septulene.11 The molecules were packed into a slipped one-dimensional (1D) chain via intermolecular π–π interactions with a distance of 3.394 Å (Figures 2b and 2c). The octulene skeleton in 8 shows a highly twisted saddle shape with negative curvature (Figure 2d). The geometry was previously predicted by calculation,9 but this is the first experimental evidence. The depth of the saddle (defined by the vertical distance between the two mean planes formed by the upmost and lowest six carbon atoms on the core, respectively) was 5.044 Å ( Supporting Information Figure S17). The molecules formed dimers via π–π interaction (with a distance of 3.354 Å), and each dimer could interact with other four dimers via short C–H•••π contacts (d = 3.252 Å), but there was no continuous π-staked column (Figures 2e–2g and Supporting Information Figure S17). Figure 2 | X-ray crystallographic structures of 7 and 8. (a and d) Top view of the whole molecules and side view of the backbones. (b and e) Overlap and close contacts of two neighboring molecules. (c, f, and g) 3D packing structures. Hydrogen atoms and 4-tert-butyl phenyl groups are omitted for clarity. Download figure Download PowerPoint Bond length analysis revealed the difference between each type of bond in 7 and 8 (Figure 3). In both cases, the bond lengths of the six nearly equivalent bonds a along the outer periphery were ∼1.32–1.36 Å, similar to that of typical olefins (∼1.35 Å). The CC bonds b and k linking these "double bonds" are much longer (1.42–1.45 Å), showing a typical C(sp2)–C(sp2) single-bond character. On the other hand, the CC bonds c, d, f, and g, at the inner and outer peripheries, exhibited typical lengths ranging from 1.37 to 1.43 Å for an aromatic benzene ring. Moreover, the radial bonds e and h were stretched (1.42–1.44 Å), and the bonds i linking these benzenoid rings became even longer (1.45–1.47 Å). All of these measurement outcomes indicated that both molecules had the characteristic dominant local aromaticity, with electrons mainly delocalized in six/eight benzene-type rings. Figure 3 | Selected bond lengths (in Å) from the X-ray structures, calculated NICS(1)zz values (the numbers in pink color), and the corresponding Clar's bonding models of the backbones for 7 (top) and 8 (bottom). NICS, nucleus-independent chemical shift. Download figure Download PowerPoint Nucleus-independent chemical shift (NICS),27 anisotropy of the induced current density (ACID),28 and three-dimensional isochemical shielding surface (3D ICSS)29 calculations were conducted to understand further the electronic structure and aromaticity of 7 and 8. Large negative NICS(1)zz values were calculated for the aromatic sextet rings, and the other six-membered rings containing the CC double bonds also showed significantly negative NICS values, indicating a dominant contribution from Clar's bonding model (Figure 3), but the contribution from globally delocalized structure could not be ignored. ACID plots of both 7 and 8 show diatropic and paratropic ring current circuits along the outer and inner periphery, respectively (Figure 4a and see magnified images in Supporting Information Figure S15). However, this was mainly due to the superposition of the diatropic ring currents of the individual aromatic benzene rings, and there was nearly zero current density along the radial bonds due to the cancelation effect. Nevertheless, significant current density was observed across the CC double bonds a, and a clockwise ring current circuit was formed along the outmost periphery, indicating that the π electrons on these CC double bonds could still delocalize along the whole skeleton, and the molecules were dominant with local aromaticity but with certain global aromaticity (or superaromaticity).4 Additionally, 3D ICSS maps indeed disclose that both the inner and outer areas of the macrocycle were deshielded (with negative ICSSzz values) (Figures 4b and 4c), again indicating a dominant local aromatic property. The 1H NMR spectra of 7 and 8 in C2D4Cl4 recorded at 373 K (Figure 4d) showed that the inner protons of the backbone appeared at low field (10.22 ppm for protons a/b in 7, 10.32 ppm for proton a and 10.0 ppm for proton b in 8). The assignment was based on two-dimensional (2D) Rotating frame nuclear Overhauser effect spectroscopy (ROESY) NMR technique ( Supporting Information Figures S3 and S6) and gauge-independent atomic orbital (GIAO) calculations ( Supporting Information Figure S16). This observation further supported that both 7 and 8 had a dominant local aromatic character. Upon lowering the temperature, the 1H NMR signals for the inner protons of 7 were shifted to a higher field ( Supporting Information Figures S1 and S2), presumably due to the enhanced aggregation. Below 243 K, the dynamic inversion of 8 became slower on the NMR timescale ( Supporting Information Figures S4 and S5), leading to NMR signal broadening. However, the coalescence temperature was lower than our experimental limit, which prevented detailed analyses of the thermodynamic parameters. Figure 4 | (a) Calculated ACID plots (π orbitals only) of 7 (left) and 8 (right), and the arrows indicate the ring current flow. Calculated 3D ICSSzz maps of (b) 7 and (c) 8 with an isovalue of 4 and 2.5, respectively; left: top view with the magnetic field perpendicular to the XY plane and pointing out through the paper, right: a side view and the red arrows represent the magnetic vector. The green color represents positive NICS values, whereas the blue color represents negative NICS values. (d) 1H NMR spectra (aromatic region) of 7 and 8 in CDCl2CDCl2 at 373 K, with the labeling, referred to Scheme 1. ACID, anisotropy of the induced current density; NICS, nucleus-independent chemical shift; 3D ICSS, three-dimensional isochemical shielding surface. Download figure Download PowerPoint Compound 7 in THF shows a major absorption band with three vibronic peaks at 327, 351, and 391 nm (Figure 5), which originated from a combination of several highest occupied molecular orbital (HOMO) − n → lowest unoccupied molecular orbital (LUMO) + m (n, m = 0–3) electronic transitions according to time-dependent DFT calculations (see Supporting Information). Noticeably, the symmetry-forbidden α-band for planar D6h symmetric molecules such as hexa-peri-hexabenzocoronene30 could then be observed partially in 7 with vibronic peaks at 413, 429, 440, and 457 nm, presumably due to its structural flexibility in solution. Compound 8 displayed a similar absorption spectrum but with a slight redshift due to more extended π-conjugation. Also, the spectrum was less resolved, compared with 7, which could be explained by the dynamic nature of the saddle-shaped structure. Compounds 7 and 8 showed a similar well-resolved fluorescence (FL) spectrum with the same emission maximum (460 nm), implying that they had the same electronic origin. The solid-state FL spectrum of 7 becomes less resolved and exhibits a slight redshift of the emission maximum to 470 nm, indicating the existence of aggregation ( Supporting Information Figure S7). Similarly, the spectrum of 8 was broader than that of 7, presumably due to its more flexible conformation. Both compounds exhibited moderate FL quantum yield, 31.4% for 7 and 34.8% for 8, by using our compound FZ1 reported previously as reference.31 One overlapped redox wave was observed in the cyclic voltammogram (CV) of 8 measured in dichloromethane, which was distinguished in four redox processes with E1/2°x = 1.29, 1.42, 1.62, and 1.89 V (vs Fc+/Fc) by differential pulse voltammetry (DPV) measurement ( Supporting Information Figure S8). Similarly, compound 7 showed a weak, overlapped redox wave with E1/2°x at ∼1.33 V in CV, but the peak could not be resolved distinctly by DPV, even under heating in a 1,2-dichlorobenzene solvent, presumably due to its aggregation ( Supporting Information Figure S8). Figure 5 | UV–Vis Abs and normalized FL spectra of 7 and 8 measured in THF (1 × 10−5 M) at room temperature. The excitation wavelength is 328 and 345 nm, respectively. Abs, absorption; FL, fluorescence; THF, tetrahydrofuran. Download figure Download PowerPoint Conclusion A facile synthetic strategy using Bi(OTf)3-catalyzed cyclization reaction of vinyl ethers was developed for the synthesis of aryl-substituted cycloarenes. The kekulene and octulene derivatives obtained were soluble and enabled full structural and electronic characterization. In accordance with previous studies on cycloarenes, our work further supports dominant local aromaticity. This synthetic method could likely be applicable for the synthesis of more expanded and core-modified cycloarenes by varying the structures of the building blocks 3 and 4. Moreover, it was possible to utilize the approach for the synthesis of otherwise more challenging carbon nanostructures such as nanobelts.32,33 Synthetic efforts along this way are undergoing in our laboratory. Footnotes a Crystallographic data with CCDC Number 1987820 ( 7) and 1987821 ( 8) are deposited in the Cambridge Crystallographic Data Center. Supporting Information Supporting Information is available. Conflict of Interest The authors declare no competing financial interests. Funding Information The authors acknowledge financial support from the MOE Tier 3 program (no. MOE2014-T3-1-004), Tier 2 grant (no. MOE2018-T2-2-094), and NRF Investigatorship (no. NRF-NRFI05-2019-0005). References 1. Miyoshi H.; Nobusue S.; Shimizu A.; Tobe Y.Non-Alternant Non-Benzenoid Kekulenes: The Birth of a New Kekulene Family.Chem. Soc. Rev.2015, 44, 6560–6577. Google Scholar 2. Buttrick J. C.; King B. T.Kekulenes, Cycloarenes, and Heterocycloarenes: Addressing Electronic Structure and Aromaticity Through Experiments and Calculations.Chem. Soc. Rev.2017, 46, 7–20. Google Scholar 3. McWeeny R.The Diamagnetic Anisotropy of Large Aromatic Systems: III Structures with Hexagonal Symmetry.Proc. Phys. Soc. A1951, 64, 921. Google Scholar 4. Aihara J.; Makino M.; Ishida T.; Dias J. R.Analytical Study of Superaromaticity in Cycloarenes and Related Coronoid Hydrocarbons.J. Phys. Chem. A2013, 117, 4688–4697. Google Scholar 5. Diederich F.; Staab H. A.Benzenoid Versus Annulenoid Aromaticity: Synthesis and Properties of Kekulene.Angew. Chem. Int. Ed. Engl.1978, 17, 372–374. Google Scholar 6. Krieger C.; Diederich F.; Schweitzer D.; Staab H. A.Molecular Structure and Spectroscopic Properties of Kekulene.Angew. Chem. Int. Ed. Engl.1979, 18, 699–701. Google Scholar 7. Staab H. A.; Diederich F.Cycloarenes, a New Class of Aromatic Compounds, I. Synthesis of Kekulene.Chem. Ber.1983, 116, 3487–3503. Google Scholar 8. Staab H. A.; Diederich F.; Krieger C.; Schweitzer D.Cycloarenes, a New Class of Aromatic Compounds, II. Molecular Structure and Spectroscopic Properties of Kekulene.Chem. Ber.1983, 116, 3504–3512. Google Scholar 9. Pozo I.; Majzik Z.; Pavliček N.; Melle-Franco M.; Guitián E.; Peña D.; Gross L.; Pérez D.Revisiting Kekulene: Synthesis and Single-Molecule Imaging.J. Am. Chem. Soc.2019, 141, 15488–15493. Google Scholar 10. Funhoff D. J. H.; Staab A.Cyclod.e.d.e.e.d.e.d.e.e.decakisbenzene, a New Cycloarene.Angew. Chem. Int. Ed. Engl.1986, 25, 742–744. Google Scholar 11. Kumar B.; Viboh R. L.; Bonifacio M. C.; Thompson W. B.; Buttrick J. C.; Westlake B. C.; Kim M.; Zoellner R. W.; Varganov S. A.; Mörschel P.; Teteruk J.; Schmidt M. U.; King B. T.Septulene: The Heptagonal Homologue of Kekulene.Angew. Chem. Int. Ed.2012, 51, 12795–12800. Google Scholar 12. Majewski M. A.; Hong Y.; Lis T.; Gregoliński J.; Chmielewski P. J.; Cybińska J.; Kim D.; Stępień M.Octulene: A Hyperbolic Molecular Belt that Binds Chloride Anions.Angew. Chem. Int. Ed.2016, 55, 14072–14076. Google Scholar 13. Beser U.; Kastler M.; Maghsoumi A.; Wagner M.; Castiglioni C.; Tommasini M.; Narita A.; Feng X.; Müllen K.A C216-Nanographene Molecule with Defined Cavity as Extended Coronoid.J. Am. Chem. Soc.2016, 138, 4322–4325. Google Scholar 14. Fan Q.; Martin-Jimenez D.; Werner S.; Ebeling D.; Koehler T.; Vollgraff T.; Sundermeyer J.; Hieringer W.; Schirmeisen A.; Gottfried J. M.On-Surface Synthesis and Characterization of a Cycloarene: C108 Graphene Ring.J. Am. Chem. Soc.2020, 142, 894–899. Google Scholar 15. Goldfinger M. B.; Swager T. M.Fused Polycyclic Aromatics via Electrophile-Induced Cyclization Reactions: Application to the Synthesis of Graphite Ribbons.J. Am. Chem. Soc.1994, 116, 7895–7896. Google Scholar 16. Mamane V.; Hannen P.; Fürstner A.Synthesis of Phenanthrenes and Polycyclic Heteroarenes by Transition-Metal Catalyzed Cycloisomerization Reactions.Chem. Eur. J.2004, 10, 4556–4575. Google Scholar 17. Feng X.; Pisula W.; Müllen K.From Helical to Staggered Stacking of Zigzag Nanographenes.J. Am. Chem. Soc.2007, 129, 14116–14117. Google Scholar 18. Yang W.; Lucotti A.; Tommasini M.; Chalifoux W. A.Bottom-Up Synthesis of Soluble and Narrow Graphene Nanoribbons Using Alkyne Benzannulations.J. Am. Chem. Soc.2016, 138, 9137–9144. Google Scholar 19. Yang W.; Monteiro J. H. S. K.; de Bettencourt-Dias A.; Catalano V. J.; Chalifoux W. A.Pyrenes, Peropyrenes, and Teropyrenes: and Chem. Int. Ed.2016, 55, Google Scholar Yang W.; S.; Lucotti A.; Tommasini M.; C.; Catalano V. J.; Varganov S. A.; Chalifoux W. and Am. Chem. Google Scholar Yang W.; Catalano V. J.; Chalifoux W. of to Chem. Int. Google Scholar Murai M.; N.; D.; Synthesis of Polycyclic Aromatic with a via Cyclization and of Google Scholar H. D.; A.; R. W.; of in the of Synthetic of with Chem. 4, Google Scholar Y.; T.; of a Helical of Kekulene: A with Large Helical as a Molecular Am. Chem. Google Scholar Lu X.; T. Y.; H.; T. S.; Q.; C.; Li J.; Wu Aromaticity in and Chem. Int. Google Scholar C.; M. E.; Hong Y.; T. Y.; H.; N.; T. S.; J.; H.; Kim D.; D.; Wu with Structure and 4, Google Scholar Z.; S.; C.; P. as an Aromaticity Google Scholar D.; K.; F.; of the (ACID), a to and Electronic Google Scholar W.; A.; Molecular Google Scholar New Google Scholar Y.; Wu X.; T. Y.; H.; Wu with Zigzag Chem. Int. Google Scholar Y.; T.; Y.; of a Google Scholar Y.; S.; C.; H.; Z.; Z.; L.; of and Google Scholar Information aromatic