Letter Cite This: Org. Lett. 2018, 20, 1517−1520
pubs.acs.org/OrgLett
Unforeseen 1,2-Aryl Shift in Tetraarylpyrrolo[3,2‑b]pyrroles Triggered by Oxidative Aromatic Coupling Maciej Krzeszewski,† Keisuke Sahara,‡ Yevgen M. Poronik,† Takashi Kubo,*,‡ and Daniel T. Gryko*,† †
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan
‡
S Supporting Information *
ABSTRACT: Tetraarylpyrrolo[3,2-b]pyrroles (TAPPs) possessing [1,1′-biphenyl]-2-yl substituents attached to the pyrrolic nitrogen atoms undergo selective double dehydrogenative cyclization accompanied by twofold 1,2-aryl migration under oxidative aromatic coupling conditions. The structure of the product of the rearrangement has been unambiguously confirmed by X-ray crystallography, and the reaction pathway is supported by density functional theory (DFT) calculations. Six-membered ring formation (requiring rearrangement of aryl substituents around the core) is energetically preferred over seven-membered ring closure, and a 1,2-aryl shift occurs via arenium cation intermediate.
During our exploration of the synthesis of π-extended systems based on the pyrrolo[3,2-b]pyrrole scaffold possessing both planar (ladder-type)11a and nonplanar ([6]azahelicene)11e architectures, we initially employed sterically congested, orthosubstituted benzaldehydes as essential starting materials. In both cases, cyclodehydrogenation leads to the efficient formation of two new six-membered rings utilizing the FeCl3/MeNO2/CH2Cl2 system. To examine if seven-membered rings can be formed in similar fashion we designed synthesis leading to the model TAPP 4a possessing orthobiphenyl units attached to the pyrrolic nitrogen atoms. Indeed, the desired compound was formed in the condensation between p-tolualdehyde (1a), 2-aminobiphenyl (2), and diacetyl (3) in acetic acid in the presence of a catalytic amount of p-toluenesulfonic acid (Table 1). Synthesized product, however, was obtained in a significantly lower yield in comparison with analogical TAPP possessing biphenyl units at the C2 and C5 positions (18% vs 48%).11a In the next step we subjected dye 4a to intramolecular oxidative aromatic coupling. Our previous negative experience related to the interaction of pyrrolo[3,2-b]pyrroles with other oxidizing agents such as DDQ/TfOH and PIFA,11a,e prompting us to refrain from using them in this project. Thin layer chromatography (TLC) inspection revealed that, using a standard system, conversion is very low; therefore, harsher reaction conditions were employed. We conducted the reaction at elevated temperature in dichloroethane for a prolonged time of 16 h. Under revised reaction conditions substrate 4a is cleanly transformed into one new product. Tentative analysis of
P
olycyclic aromatic hydrocarbons1 and their heteroatomdoped analogs2,3 are of interest among the scientific community due to the wide range of their potential applications, including organic electronics, fluorescent imaging probes, photovoltaic devices, and dye-sensitized solar cells.4 Due to the ongoing demand for novel π-expanded dyes, the toolbox with organic reactions for their preparation is rapidly growing.5 Yet, oxidative aromatic coupling, being one of the oldest method among them, continues to play the key role.6 Elegant recent work, most predominantly by the groups of Müllen and Itami, has revealed that long graphene nanoribbons and large curved architectures can be synthesized using this methodology via formation of up to 100 biaryl linkages in one pot.7 Notwithstanding that oxidative aromatic coupling has been known for over a century, its mechanism is still under discussion and its output proves to be unpredictable in many cases due to the various activity of aryl C−H bonds as well as electronic parameters and steric factors.8 Needless to say, in order to obtain designed PAHs and nanographenes9 in highly selective and precise fashion, exhaustive understanding of these reactions is requisite. The discovery of one-pot synthesis of tetraarylpyrrolo[3,2-b]pyrroles (TAPPs)10 made it possible to obtain an ample library of unprecedented π-extended nitrogendoped polycyclic aromatic hydrocarbons in a concise manner.11 The exceptionally electron-rich character of the pyrrolo[3,2b]pyrrole’s core12 prompted us to attempt to synthesize their πextended analogs possessing two seven-membered rings. In this work, we present an unexpected tandem migration of aryl substituents across the pyrrolo[3,2-b]pyrrole’s core, followed by the cyclodehydrogenation under oxidative aromatic coupling conditions. © 2018 American Chemical Society
Received: January 22, 2018 Published: March 7, 2018 1517
DOI: 10.1021/acs.orglett.8b00223 Org. Lett. 2018, 20, 1517−1520
Letter
Organic Letters Table 1. Synthetic Pathway towards π-Extended Pyrrolo[3,2b]pyrroles 5a−g
aldehyde
R
TAPP
yield (%)
π-exp PP
yield (%)
1a 1b 1c 1d 1e 1f 1g
Me H CN NO2 CF3 Br Ph
4a 4b 4c 4d 4e 4f 4g
18 30 14 15 19 6 24
5a 5b 5c 5d 5e 5f 5g
70 54 60 66 33 64 53
We carried out DFT calculations to reveal the reaction mechanism of the 1,2-aryl shift and ring cyclization to afford the rearranged compounds 5a−5g from TAPPs 4a−4g. Scheme 1 and Scheme S1 show the computational results for the rearrangement mechanism. The oxidation of TAPP 4b with FeCl3 gives rise to a radical cation species 4b•+. The spin density map of 4b•+ indicates that an unpaired electron mostly resides on the pyrrolo[3,2-b]pyrrole core (Figure S1), and the carbon atoms bearing a phenyl group possess the largest spin density. Next oxidative cyclization between the pyrrolo[3,2b]pyrrole core and the terminal phenyl group of the biphenyl has two possibilities: six-membered ring formation (i.e., 6) or seven-membered ring formation (i.e., 11). The DFT calculation suggests the preferential formation of 6 over 11 because 6 is lower in energy than 11 by 12.5 kcal/mol. In the subsequent 1,2-aryl shift, two mechanisms seem likely. The first mechanism, which arises from the detachment of H• from the radical six-membered ring, is the “cation path”, in which the phenyl group migrates through the arenium cation transition state (7b). The second mechanism starts with the deprotonation from 6 and involves the radical phenyl migration (radical path). The radical cation species 6 would prefer the detachment of H• over deprotonation because the Meisenheimer-type sixmembered ring bears an unpaired electron from the spin density map of 6 (Figure S2). Moreover, according to the DFT calculation, the activation barrier for the 1,2-phenyl shift is lower in energy for the cation path (+23.9 kcal/mol) than for the radical path (+31.2 kcal/mol), indicating that the phenyl group migrates in the positively charged state and then the release of a proton leads to the half-rearranged compound 8. Rearrangement in the remaining half occurs in a similar manner: oxidative cyclization, a 1,2-phenyl shift in the cation state, and deprotonation, giving rise to the final product 5b. The overall difference in energy between initially expected compound 15 and dye 5b is 28.7 kcal/mol (Scheme 1). This mechanism is in partial agreement with results by Müllen and co-workers who suggested the 1,2-aryl shift preceding intramolecular oxidative aromatic coupling in the case of benzo[k]tetraphene.13f Parent TAPPs display featureless absorption bands typically located between λabs = 360 and 390 nm. Absorption is significantly red-shifted for compounds 4c and 4d (λabs = 412 and 470 nm) bearing substituents with strong electronwithdrawing character, namely CN and NO 2 groups, respectively. The molar extinction coefficient (εmax) varies from 34 000 up to 47 000 M−1 cm−1. These compounds emit blue light in the narrow range of λem = 406 to 451 nm. These observations follow earlier assessments of photophysical properties of TAPPs.11 The only exception is p-nitrophenyl substituted pyrrolo[3,2-b]pyrrole 4d which emit at 544 nm which corresponds to a green color (Table 2, Figure 2A). The fact that pyrrolo[3,2-b]pyrroles possessing 4-nitrophenyl substituents at positions C2 and C5 display strong fluorescence in nonpolar solvents has been observed earlier.11b,d At the same time, in this series, the fluorescence quantum yield (Φfl) appears to strongly depend on the nature of the peripheral substituent (Table 2). Extension of the π-conjugation in 5a−g leads to the bathochromic shift of both absorption and emission in comparison with their parent counterpart. Final dyes exhibit two major absorption bands, the first located between 320 and 340 nm and the second between 410 and 440 nm with apparent fine vibronic features (Table 2, Figure 2B). The lower-energy transitions display two separate peaks with
1
H NMR (a small number of signals indicating high symmetry of the analyte, lack of the “pyrrole singlet” in the 6.0−6.5 ppm region of the spectrum, and total integral which amounts to 30) as well as matching HRMS-EI (calculated for C44H30N2: 586.2409 [M]+, found: 586.2402) of the obtained compound supported our expectation of the formation of two new sevenmembered rings (Table 1). To our surprise, however, X-ray crystallography analysis proved us wrong (Figure 1). It turned
Figure 1. Molecular structure of 5a (left) and 4f (right) (CCDC 1815287 and 1824878).
out that the obtained compound comprises two hexagons fused to the central core. Formation of new six-membered rings occur via cyclization at already occupied positions C2/C5 with a consequent double aryl shift from position C2/C5 to C3/C6. The 1,2-aryl shift has been observed sometimes during attempted oxidative aromatic coupling of PAHs.13 This rearrangement also occurs during exposure of phenylsubstituted arenes to strong acids.14 The X-ray diffraction analysis proves that the rearrangement indeed occurs during the dehydrogenation as X-ray data for compound 4f, confirming the presence of biphenyl substituents at positions N1 and N4 (Figure 1). With established protocol in hand we obtained a series of parent TAPPs possessing various substituents at the periphery in 6−30% yield. The rearrangement reaction turned out to be general, and in all cases π-extended PPs 5a−g were formed in reasonable yields of 33−70% (Table 1). 1518
DOI: 10.1021/acs.orglett.8b00223 Org. Lett. 2018, 20, 1517−1520
Letter
Organic Letters Scheme 1. Computational Results for the Rearrangement Mechanism from 4b to 8
Fluorescence quantum yields are moderate, ca. 30%. Nitrosubstituted derivative 5d does not exhibit any measurable fluorescence. When compared to analogous π-expanded pyrrolo[3,2-b]pyrroles possessing a biaryl linkage between aryl rings at positions C2 and C3, compounds 5a−g have a significant bathochromic shift of absorption (typically ∼60 nm) and red-shifted (25−40 nm) emission. At the same time their Φfl are lower (∼30% vs ∼50%).11a We have demonstrated that easily accessible pyrrolo[3,2b]pyrroles, possessing ortho-biphenyl substituents attached to the pyrrolic nitrogen atoms, undergo twofold 1,2-aryl migration followed by cyclodehydrogenation upon treatment with iron(III) chloride, which is unprecedented for heterocyclic compounds. This study shows a strong preference for the formation of new six-membered over seven-membered rings under oxidative aromatic coupling conditions even if it entails the attack of a radical cation on the already occupied carbon atom accompanying a rare 1,2-aryl shift. The performed quantum chemical calculations fully support the experimental data. It has been proven that the 1,2-aryl shift occurs via an arenium cation pathway rather than by a radical mechanism. The fusion of benzene rings located at positions N1 and C2 triggers more significant change in both absorption and emission, shifting it bathochromically when compared to analogous π-expanded pyrrolo[3,2-b]pyrroles possessing fused rings at positions C2 and C3. These results bring us closer to fully comprehending the still elusive reaction mechanism.
Table 2. Spectroscopic Properties of All Synthesized Dyes Measured in Toluene compd 4a 4b 4c 4d 4e 4f 4g 5a 5b 5c 5d 5e 5f 5g
λabs [nm] 356 357 412 470 378 368 389 412; 411; 412; 386; 409; 410; 413;
437 435 435 418 432 433 436
εmax × 10−3 [M−1 cm−1] 38 34 47 42 40 44 46 26; 25; 22; 26; 28; 28; 28;
18 18 20 20 23 22 21
λem [nm]
ΔSa [cm−1]
Φflb
424 406 444 544 418 416 451 455 455 481 − 450 450 456
4500 3400 1700 2900 2500 3100 3500 900 1000 2200 − 900 900 1000
0.17 0.52 0.85 0.30 0.97 0.16 0.75 0.33 0.36 0.18 − 0.32 0.25 0.29
a ΔS = Stokes shift. bDetermined with quinine sulfate in H2SO4 (0.5 M) as a standard.
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ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00223. Experimental procedures, compound characterization data, 1H and 13C NMR spectra, absorption and emission spectra, cyclic voltammograms, computational data (PDF)
Figure 2. Absorption (solid) and emission (dotted) spectra of dyes 4b (blue line) and 4d (red line) (A) and 4e (blue line) and 5e (red line) (B) measured in toluene.
corresponding molar extinction coefficient values ca. 25 000 and 20 000 M−1 cm−1. Noticeably, unlike 4a−g possessing various substituents at positions C2 and C5, there is negligible influence on optical properties by substituents located at positions C3 and C6 of the pyrrolo[3,2-b]pyrrole core in 5a−g. These compounds emit in the range 450 to 480 nm.
Accession Codes
CCDC 1815287 and 1824878 contain the supplementary crystallographic data for this paper. These data can be obtained 1519
DOI: 10.1021/acs.orglett.8b00223 Org. Lett. 2018, 20, 1517−1520
Letter
Organic Letters
(8) (a) Zhang, X.; Xu, Z.; Si, W.; Oniwa, K.; Bao, M.; Yamamoto, Y.; Jin, T. Nat. Commun. 2017, 8, 15073−15080. (b) Ferguson, J. L.; Squire, M. A.; Fitchett, C. M. Org. Biomol. Chem. 2017, 15, 9293− ́ 9296. (c) Krzeszewski, M.; Swider, P.; Dobrzycki, Ł.; Cyrański, M. K.; Danikiewicz, W.; Gryko, D. T. Chem. Commun. 2016, 52, 11539− 11542. (9) (a) Segawa, Y.; Ito, H.; Itami, K. Nat. Rev. Mater. 2016, 1, 15002. (b) Narita, A.; Wang, X.-Y.; Feng, X.; Müllen, K. Chem. Soc. Rev. 2015, 44, 6616−6643. (c) Stępień, M.; Gońka, E.; Ż yła, M.; Sprutta, N. Chem. Rev. 2017, 117, 3479−3716. (10) (a) Janiga, A.; Głodkowska-Mrówka, E.; Stokłosa, T.; Gryko, D. T. Asian J. Org. Chem. 2013, 2, 411−415. (b) Krzeszewski, M.; Thorsted, B.; Brewer, J.; Gryko, D. T. J. Org. Chem. 2014, 79, 3119− 3128. (11) (a) Krzeszewski, M.; Gryko, D. T. J. Org. Chem. 2015, 80, 2893−2899. (b) Friese, D. H.; Mikhaylov, A.; Krzeszewski, M.; Poronik, Y. M.; Rebane, A.; Ruud, K.; Gryko, D. T. Chem. - Eur. J. 2015, 21, 18364−18374. (c) Tasior, M.; Gryko, D. T. J. Org. Chem. 2016, 81, 6580−6586. (d) Łukasiewicz, Ł.; Ryu, H. G.; Mikhaylov, A.; Azarias, C.; Banasiewicz, M.; Kozankiewicz, B.; Ahn, K. H.; Jacquemin, D.; Rebane, A.; Gryko. Chem. - Asian J. 2017, 12, 1736−1748. (e) Krzeszewski, M.; Kodama, T.; Espinoza, E. M.; Vullev, V. I.; Kubo, T.; Gryko, D. T. Chem. - Eur. J. 2016, 22, 16478−16488. (12) (a) Hemetsberger, H.; Knittel, D. Monatsh. Chem. 1972, 103, 194−204. (b) Kumagai, T.; Tanaka, S.; Mukai, T. Tetrahedron Lett. 1984, 25, 5669−5672. (c) Janiga, A.; Gryko, D. T. Chem. - Asian J. 2014, 9, 3036−3045. (d) Krzeszewski, M.; Gryko, D.; Gryko, D. T. Acc. Chem. Res. 2017, 50, 2334−2345. (13) (a) Müller, M.; Mauermann-Düll, H.; Wagner, M.; Enkelmann, V.; Müllen, K. Angew. Chem., Int. Ed. Engl. 1995, 34, 1583−1586. (b) Balaban, A. T.; Nenitzescu, C. D. Friedel-Crafts and Related Reaction; Olah, G. A., Ed.; Wiley & Sons: New York, 1964; Vol. 2, pp 979−1047. (c) Iyer, V. S.; Yoshimura, K.; Enkelmann, V.; Epsch, R.; Rabe, J. P.; Müllen, K. Angew. Chem., Int. Ed. 1998, 37, 2696−2699. (d) Pradhan, A.; Dechambenoit, P.; Bock, H.; Durola, F. J. Org. Chem. 2013, 78, 2266−2274. (e) Ormsby, J. L.; Black, T.; Hilton, C. L.; Bharat, B. T.; King, B. T. Tetrahedron 2008, 64, 11370−11378. (f) Liu, J.; Narita, A.; Osella, S.; Zhang, W.; Schollmeyer, D.; Beljonne, D.; Feng, X.; Müllen, K. J. Am. Chem. Soc. 2016, 138, 2602−2608. (14) (a) Skraba-Joiner, S. L.; McLaughlin, E. C.; Ajaz, A.; Thamatam, R.; Johnson, R. P. J. Org. Chem. 2015, 80, 9578−9583. (b) Ajaz, A.; McLaughlin, E. C.; Skraba, S. L.; Thamatam, R.; Johnson, R. P. J. Org. Chem. 2012, 77, 9487−9495.
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
Daniel T. Gryko: 0000-0002-2146-1282 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The work was financially supported by the Polish National Science Centre, Grants MAESTRO 2012/06/A/ST5/00216 and PRELUDIUM 2015/19/N/ST5/00826, and by the Global Research Laboratory Program (2014K1A1A2064569). M.K. thanks the Foundation for Polish Science for START Scholarship.
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REFERENCES
(1) (a) Tsefrikas, V. M.; Scott, L. T. Chem. Rev. 2006, 106, 4868− 4884. (b) Rabideau, P. W.; Sygula, A. Acc. Chem. Res. 1996, 29, 235− 242. (c) Pun, S. H.; Chan, C. K.; Luo, J.; Liu, Z.; Miao, Q. Angew. Chem., Int. Ed. 2018, 57, 1581−1586. (2) (a) Rudebusch, G. E.; Fix, A. G.; Henthorn, H. A.; Vonnegut, C. L.; Zakharov, L. N.; Haley, M. M. Chem. Sci. 2014, 5, 3627−3633. (b) Myśliwiec, D.; Stępień, M. Angew. Chem., Int. Ed. 2013, 52, 1713. (c) Caruso, A., Jr.; Tovar, J. D. Org. Lett. 2011, 13, 3106−3109. (3) (a) Hensel, T.; Andersen, N. N.; Plesner, M.; Pittelkow, M. Synlett 2016, 27, 498−525. (b) Watson, M. D.; Fechtenkötter, A.; Müllen, K. Chem. Rev. 2001, 101, 1267−1300. (c) Bendikov, M.; Wudl, F.; Perepichka, D. F. Chem. Rev. 2004, 104, 4891−4896. (d) Anthony, J. E. Chem. Rev. 2006, 106, 5028−5048. (4) (a) Wang, X.; Zhang, F.; Liu, J.; Tang, R.; Fu, Y.; Wu, D.; Xu, Q.; Zhuang, X.; He, G.; Feng, X. Org. Lett. 2013, 15, 5714−5717. (b) Kim, Y.; Hong, J.; Oh, J. H.; Yang, C. Chem. Mater. 2013, 25, 3251−3259. (c) Wang, C.; Dong, H.; Hu, W.; Liu, Y.; Zhu, D. Chem. Rev. 2012, 112, 2208−2267. (5) Ito, H.; Ozaki, K.; Itami, K. Angew. Chem., Int. Ed. 2017, 56, 11144−11164. (6) (a) King, B. T.; Kroulık, J.; Robertson, C. R.; Rempala, P.; Hilton, C. L.; Korinek, J. D.; Gortari, L. M. J. Org. Chem. 2007, 72, 2279− 2288. (b) Dohi, T.; Ito, M.; Itani, I.; Yamaoka, N.; Morimoto, K.; Fujioka; Kita, Y. Org. Lett. 2011, 13, 6208−6211. (c) Grzybowski, M.; Skonieczny, K.; Butenschön, H.; Gryko, D. T. Angew. Chem., Int. Ed. 2013, 52, 9900−9930. (d) Kita, Y.; Dohi, T. Chem. Rec. 2015, 15, 886−906. (e) Kita, Y.; Dohi, T. Chem. Rec. 2015, 15, 886−906. (f) Hensel, T.; Trpcevski, D.; Lind, C.; Grosjean, R.; Hammershøj, P.; Nielsen, C. B.; Brock-Nannestad, T.; Nielsen, B. E.; Schau-Magnussen, M.; Minaev, B.; Baryshnikov, G. V.; Pittelkow, M. Chem. - Eur. J. 2013, 19, 17097−17102. (7) (a) Dötz, F.; Brand, J. D.; Ito, S.; Gherghel, L.; Müllen, K. J. Am. Chem. Soc. 2000, 122, 7707−7717. (b) Narita, A.; Feng, X.; Hernandez, Y.; Jensen, S. A.; Bonn, M.; Yang, H.; Verzhbitskiy, I. A.; Casiraghi, C.; Hansen, M. R.; Koch, A. H. R.; Fytas, G.; Ivasenko, O.; Li, B.; Mali, K. S.; Tatyana, B.; Mahesh, S.; Feyter, S. D.; Müllen, K. Nat. Chem. 2014, 6, 126−132. (c) Kawasumi, K.; Zhang, Q.; Segawa, Y.; Scott, L. T.; Itami, K. Nat. Chem. 2013, 5, 739−744. (d) Cheung, K. Y.; Xu, X.; Miao, Q. J. Am. Chem. Soc. 2015, 137, 3910−3914. (e) Kato, K.; Segawa, Y.; Scott, L. T.; Itami, K. Angew. Chem., Int. Ed. 2018, 57, 1337−1341. 1520
DOI: 10.1021/acs.orglett.8b00223 Org. Lett. 2018, 20, 1517−1520
