Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Size-Selective Synthesis of Large Cycloparaphenyleneacetylene Carbon Nanohoops Using Alkyne Metathesis Xin Zhou, Richard R. Thompson, Frank R. Fronczek, and Semin Lee* Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70810, United States
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S Supporting Information *
ABSTRACT: Size selective synthesis of large cycloparaphenyleneacetylene carbon nanohoops was achieved using alkyne metathesis. The large nanohoops were stable in ambient conditions due to their reduced strain. The nanohoops exhibited blue fluorescence with high quantum yields.
Scheme 1. Previously Reported Synthesis of [3]CPP3Aa
C
arbon nanohoops1,2 are fully conjugated macrocycles with radially oriented aromatic groups. Due to their curved aromatic structure, carbon nanohoops have unique photophysical,3,4 electronic,5 and supramolecular properties.6−8 Cycloparaphenyleneacetylenes (CPPA) were first synthesized by Kawase and Oda.9 Synthetic breakthoughs by Jasti,1 Itami,10 and Yamago11 enabled the preparation of cycloparaphenylenes (CPP). Following such achievements, the field of carbon nanohoop has vastly matured in the past two decades. Numerous nanohoop derivatives12 have been reported, and various synthetic approaches13,14 have been proposed. Furthermore, potential applications in organic electronics,15,16 sensing,17 and bioimaging18 have been explored. Additionally, Lee, Moore,19 and Jasti20 have demonstrated that strained alkynes within the nanohoops can undergo strain-promoted cycloadditions. Preparation of carbon nanohoops consists of two core steps: (a) macrocyclization to construct the cyclic backbone, (b) reactions that induce fullconjugation and build up strain. In recent years, macrocyclization with Pd- or Ni-catalyzed cross-coupling reactions,21 followed by reductive aromatization using H2SnCl4, has become the optimized method for preparing carbon nanohoops.22 Another effective method requires the synthesis of platinum (Pt)-coordinated macrocycles followed by reductive elimination.11 We previously addressed that the macrocyclization step was the major bottleneck for achieving overall high yields in preparing carbon nanohoops.19 The major reason was due to its reliance on cross-coupling reactions that are irreversible in nature and compete with a number of nonproductive side reactions. Therefore, we proposed Mo(VI)-catalyzed alkyne metathesis23−26 as an efficient dynamic covalent method for macrocyclization.19 Alkyne metathesis allowed us to prepare a trimeric macrocycle (2, Scheme 1) in a one-pot reaction with quantitative yields from a dipropynyl building block (1). The reductive aromatization successfully provided carbon nanohoop [3]CPP3A. While [3]CPP3A could be stored under an © XXXX American Chemical Society
a [Mo]: tris(tert-butyl(3,5-dimethylphenyl)amino)-(propylidyne)molybdenum(VI) with 6 equiv of Ph3SiOH. MS: molecular sieves. TCB: 1,2,4-trichlorobenzene. NaNaph: sodium naphthalenide.
inert atmosphere, it was extremely unstable upon exposure to ambient conditions, decomposing instantly while in the solid state. Stability of the nanohoop was only improved upon C70 complexation to form the 1:1 adduct.19 Such instability with [3]CPP3A was due to the strained alkynes within the nanohoop. Similarly, Jasti and co-workers attempted to prepare an extremely strained CPPA derivative with four phenylenes and one alkyne.21 However, they were not able to isolate the product, presumably due to its instability. On the other hand, larger CPPA derivatives with one alkyne were isolated in moderate yields.20 Here, in order to alleviate the strain and expand the synthetic scope of [3]CPPnA, we prepared large nanohoops [3]CPP4A and [3]CPP5A (Scheme 2). Compared to [3]CPP3A, larger nanohoops, [3]CPP4A and [3]CPP5A, require macrocyclic precursors with three and six additional phenylene groups, respectively. However, we recognized that the macrocyclic precursor 2, with six methoxy (−OMe) groups, was poorly soluble in common organic solvents. The reductive aromatization yield was highly dependent on sonication, which dispersed the aggregates into small particulates. Therefore, it was reasonable to assume that Received: May 3, 2019
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DOI: 10.1021/acs.orglett.9b01563 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 2. Synthesis of [3]CPP4A and [3]CPP5Aa
biphenyl groups selectively form alkynyl bonds with the phenylenes with no evidence of scrambling (Supporting Information). Such directional macrocyclization clearly highlights the benefits of dynamic covalent chemistry through alkyne metathesis.31 The macrocyclic precursor 8 was prepared in a similar manner starting from the symmetric dibromobuilding block 6.15,20 The dipropynyl-monomer 7 was prepared using Kumada coupling. The subsequent alkyne metathesis resulted in the macrocyclic precursor 8 in 95% yield. Both macrocycles 5 and 8 were moderately soluble in CHCl3, CH2Cl2, and THF. With macrocyclic precursors 5 and 8 at hand, we initially attempted reductive aromatization using H2SnCl4.22,27 After successful desilylation using TBAF, aromatization via H2SnCl4 (SnCl2 with 2 equiv of HCl) was performed. Unfortunately, this reaction resulted in intractable yellow solids that were insoluble in organic solvents. This is contrasted by reports from Jasti,20 Miki and Ohe,32,33 who showed that other CPPA derivatives can be prepared in good yields using this method. In a separate experiment, we added SnCl2 or H2SnCl4 to a solution of [3]CPP4A or [3]CPP5A in THF. Both nanohoops decomposed instantly under these conditions. It was evident that [3]CPPnA nanohoops, in particular, are not compatible with either SnCl2 or H2SnCl4, unlike other CPPA derivatives. After the failed attempts using H2SnCl4, we returned to using NaNaph as the reducing agent. In a previous report by Jasti and co-workers,21 TES groups were converted to methyl groups before being subjected to NaNaph reduction.21 On the other hand, reductive aromatization directly on TES protected macrocycles has not been reported. Fortunately, TESprotected macrocycles 5 and 8 were soluble in THF at −78 °C and were able to undergo reductive aromatization smoothly with NaNaph to give [3]CPP4A and [3]CPP5A, respectively, in good yields. We note that good yields (≥80%) were only achieved in small scale (≤100 mg of 5 or 8) reactions. Regardless of concentration (1, 5 mM) or temperature (−78 °C, −100 °C), larger scale (>200 mg) reactions resulted in significantly lower yields (5−50%) of the desired products and large amounts of insoluble byproducts. Szwarc34,35 and Daley36 previously showed that tolan (diphenylacetylene) can be converted to stilbene, bibenzyl, or tolan dimers upon reduction with lithium or sodium in THF. While further investigation is required, we envision that these undesired reactions produced insoluble byproducts during the reductive aromatization. As hypothesized, both nanohoops [3]CPP4A and [3]CPP5A were significantly more stable in ambient conditions compared to [3]CPP3A. It is noteworthy that [3]CPP5A did not show any noticeable decomposition on the bench for more than a year. The strain energies37,38 for [3]CPP4A and [3]CPP5A were calculated to be 8.2 and 14.4 kcal/mol less than [3]CPP3A, respectively (Table 1). In perspective, [3]CPP4A and [3]CPP5A have similar diameters as [13]CPP39 and
a [Mo]: tris(tert-butyl(3,5-dimethylphenyl)amino)-(propylidyne)molybdenum(VI) with 6 equiv of Ph3SiOH. MS: molecular sieves. NaNaph: sodium naphthalenide
macrocyclic precursors with extended phenylene groups would show even poorer solubility compared to macrocycle 2. Here, we employed triethylsilyl (TES) groups27 to provide sufficient solubility for the macrocyclic precursors of [3]CPP4A and [3]CPP5A. In addition, reductive aromatization22 using H2SnCl4 after desilylation was initially anticipated as an improved method compared to using sodium naphthalenide (NaNaph). Nanohoop [3]CPP4A (Scheme 2) has 12 phenylene groups within its structure. Therefore, a nonsymmetric dipropynyl monomer (4) was required for alkyne metathesis in order to prepare macrocycle 5. The disilylether-cyclohexadiene building block 3 was synthesized using previously reported methods27,28 (Supporting Information). The following Pdcatalyzed Kumada coupling reaction with 1-propynylmagnesium bromide29 afforded the dipropynyl monomer 4 in good yields. Mo(VI)-catalyzed alkyne metathesis30 of 4 resulted in a C3-symmetric macrocycle 5 selectively in 82% yield. Single crystals of 5 were obtained from CH2Cl2 and ether. Unfortunately, crystals of 5 were very weakly diffracting (θmax = 61.3°), and thus a satisfactory refinement model could not be fit for the data. Furthermore, the molecule exhibited whole molecule disorder, as well as disorder about the siloxide groups, and thus we cannot comment on precise bond metrics. Nevertheless, the bulk structure could be confirmed, as well as the directionality of the macrocyclization such that the
Table 1. Calculated Diameter, Average Alkyne Bond Angle (∠C−CC), Strain Energy (DFT B3LYP 6-31G*), and Experimental CC 13C NMR Chemical Shift of [3]CPP3A,19 [3]CPP4A, and [3]CPP5A
[3]CPP3A [3]CPP4A [3]CPP5A B
diameter (nm)
C−CC angle (deg)
strain energy (kcal/mol)
CC 13C NMR (ppm)
1.4919 1.91 2.31
164.619 167.7 169.7
47.7619 39.60 33.33
98.019 95.3 94.0
DOI: 10.1021/acs.orglett.9b01563 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters [16]CPP,40 respectively. Enlarging the size of [3]CPPnA increased the alkyne bond angles (∠C−CC), reduced the strain, and thereby stabilized the nanohoops. [3]CPP4A and [3]CPP5A were both characterized using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (Supporting Information). The 1H NMR spectra (Figure 1) show that aromatic protons shift downfield as the
symmetric monomer to prepare [3]CPP4A. The large nanohoops were stable at ambient conditions and exhibited high fluorescence quantum yields. While we have improved the macrocyclization yields and found that TES-groups are compatible with NaNaph-reductive aromatization, achieving overall high yields in large scale is still a challenge to overcome.
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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.9b01563.
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Synthetic procedures, compound characterization, 1H and 13C NMR spectra, fluorescence quantum yield, Xray crystallographic, computational analysis details (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Figure 1. 1H NMR spectra of [3]CPP4A and [3]CPP5A.
Frank R. Fronczek: 0000-0001-5544-2779 Semin Lee: 0000-0003-0873-9507
size increases. Such shift is consistent with the trend observed in [7−13]CPP3,4 and [6−9]CPPA41 nanohoops. 13C NMR chemical shifts of alkynyl carbons move downfield as the nanohoops become smaller in diameter (Table 1). This observation is identical to the trend observed in [6−9]CPPA41 where more bent and strained alkynes become more sp2-like and deshielded. UV−vis absorption and fluorescence spectra of [3]CPP4A and [3]CPP5A were collected in CH2Cl2 (Figure 2). Both nanohoops had maximum UV−vis absorption at 345
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This research was supported by the College of Science and the Office of Research and Economic Development at Louisiana State University.
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REFERENCES
(1) Jasti, R.; Bhattacharjee, J.; Neaton, J. B.; Bertozzi, C. R. J. Am. Chem. Soc. 2008, 130, 17646−17647. (2) Lewis, S. E. Chem. Soc. Rev. 2015, 44, 2221−2304. (3) Darzi, E. R.; Jasti, R. Chem. Soc. Rev. 2015, 44, 6401−6410. (4) Fujitsuka, M.; Cho, D. W.; Iwamoto, T.; Yamago, S.; Majima, T. Phys. Chem. Chem. Phys. 2012, 14, 14585−14588. (5) Iwamoto, T.; Watanabe, Y.; Sakamoto, Y.-I.; Suzuki, T.; Yamago, S. J. Am. Chem. Soc. 2011, 133, 8354−8361. (6) Kawase, T.; Tanaka, K.; Fujiwara, N.; Darabi, H. R.; Oda, M. Angew. Chem., Int. Ed. 2003, 42, 1624−1628. (7) Iwamoto, T.; Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S. Angew. Chem., Int. Ed. 2011, 50, 8342−8344. (8) Xia, J.; Bacon, J. W.; Jasti, R. Chem. Sci. 2012, 3, 3018−3021. (9) Kawase, T.; Darabi, H. R.; Oda, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 2664−2666. (10) Takaba, H.; Omachi, H.; Yamamoto, Y.; Bouffard, J.; Itami, K. Angew. Chem., Int. Ed. 2009, 48, 6112−6116. (11) Yamago, S.; Watanabe, Y.; Iwamoto, T. Angew. Chem., Int. Ed. 2010, 49, 757−759. (12) Majewski, M. A.; Stepien, M. Angew. Chem., Int. Ed. 2019, 58, 86−116. (13) Hayase, N.; Miyauchi, Y.; Aida, Y.; Sugiyama, H.; Uekusa, H.; Shibata, Y.; Tanaka, K. Org. Lett. 2017, 19, 2993−2996. (14) Huang, C.; Huang, Y.; Akhmedov, N. G.; Popp, B. V.; Petersen, J. L.; Wang, K. K. Org. Lett. 2014, 16, 2672−2675. (15) Kayahara, E.; Sun, L.; Onishi, H.; Suzuki, K.; Fukushima, T.; Sawada, A.; Kaji, H.; Yamago, S. J. Am. Chem. Soc. 2017, 139, 18480− 18483. (16) Lin, J. B.; Darzi, E. R.; Jasti, R.; Yavuz, I.; Houk, K. N. J. Am. Chem. Soc. 2019, 141, 952−960.
Figure 2. UV−vis absorption (1 μM, CH2Cl2) and emission (1 μM, CH2Cl2, λex = 320 nm) spectra of [3]CPP4A and [3]CPP5A.
nm and exhibited violet-blue fluorescence. [3]CPP4A has emission peaks at 418 and 440 nm (fluorescence quantum yield, ΦF = 0.98), and [3]CPP5A has peaks at 412 and 433 nm (ΦF = 0.96). Overall, the fluorescence showed a 6−7 nm blue shift as the [3]CPPnA size increases, which also follows the trend observed in [n]CPP nanohoops.42,43 In summary, we demonstrated that alkyne metathesis can be used to effectively prepare a variety of cycloparaphenyleneacetylene nanohoops. The strength of this method is highlighted in size-selective macrocyclization in a nonC
DOI: 10.1021/acs.orglett.9b01563 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters (17) Van Raden, J. M.; White, B. M.; Zakharov, L. N.; Jasti, R. Angew. Chem., Int. Ed. 2019, 58, 7341−7345. (18) White, B. M.; Zhao, Y.; Kawashima, T. E.; Branchaud, B. P.; Pluth, M. D.; Jasti, R. ACS Cent. Sci. 2018, 4, 1173−1178. (19) Lee, S.; Chenard, E.; Gray, D. L.; Moore, J. S. J. Am. Chem. Soc. 2016, 138, 13814−13817. (20) Schaub, T. A.; Margraf, J. T.; Zakharov, L.; Reuter, K.; Jasti, R. Angew. Chem., Int. Ed. 2018, 57, 16348−16353. (21) Darzi, E. R.; White, B. M.; Loventhal, L. K.; Zakharov, L. N.; Jasti, R. J. Am. Chem. Soc. 2017, 139, 3106−3114. (22) Patel, V. K.; Kayahara, E.; Yamago, S. Chem. - Eur. J. 2015, 21, 5742−5749. (23) Zhang, W.; Kraft, S.; Moore, J. S. Chem. Commun. 2003, 832− 833. (24) Furstner, A. Angew. Chem., Int. Ed. 2013, 52, 2794−2819. (25) Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93−120. (26) Ehrhorn, H.; Tamm, M. Chem. - Eur. J. 2018, 25, 3190−3208. (27) Kayahara, E.; Patel, V. K.; Yamago, S. J. Am. Chem. Soc. 2014, 136, 2284−2287. (28) Jackson, E. P.; Sisto, T. J.; Darzi, E. R.; Jasti, R. Tetrahedron 2016, 72, 3754−3758. (29) Woody, K. B.; Bullock, J. E.; Parkin, S. R.; Watson, M. D. Macromolecules 2007, 40, 4470−4473. (30) Finke, A. D.; Gross, D. E.; Han, A.; Moore, J. S. J. Am. Chem. Soc. 2011, 133, 14063−14070. (31) Sisco, S. W.; Moore, J. S. J. Am. Chem. Soc. 2012, 134, 9114− 9117. (32) Miki, K.; Matsushita, T.; Inoue, Y.; Senda, Y.; Kowada, T.; Ohe, K. Chem. Commun. 2013, 49, 9092−9094. (33) Miki, K.; Saiki, K.; Umeyama, T.; Baek, J.; Noda, T.; Imahori, H.; Sato, Y.; Suenaga, K.; Ohe, K. Small 2018, 14, No. 1870120. (34) Levin, G.; Jagur-Grodzinski, J.; Szwarc, M. J. Am. Chem. Soc. 1970, 92, 2268−2275. (35) Levin, G.; Jagur-Grodzinski, J.; Szwarc, M. Trans. Faraday Soc. 1971, 67, 768−771. (36) Dadley, D. A.; Evans, A. G. J. Chem. Soc. B 1968, 107−111. (37) Ali, M. A.; Krishnan, M. S. Mol. Phys. 2009, 107, 2149−2158. (38) Segawa, Y.; Omachi, H.; Itami, K. Org. Lett. 2010, 12, 2262− 2265. (39) Ishii, Y.; Nakanishi, Y.; Omachi, H.; Matsuura, S.; Matsui, K.; Shinohara, H.; Segawa, Y.; Itami, K. Chem. Sci. 2012, 3, 2340−2345. (40) Omachi, H.; Matsuura, S.; Segawa, Y.; Itami, K. Angew. Chem., Int. Ed. 2010, 49, 10202−10205. (41) Kawase, T.; Ueda, N.; Tanaka, K.; Seirai, Y.; Oda, M. Tetrahedron Lett. 2001, 42, 5509−5511. (42) Segawa, Y.; Fukazawa, A.; Matsuura, S.; Omachi, H.; Yamaguchi, S.; Irle, S.; Itami, K. Org. Biomol. Chem. 2012, 10, 5979−5984. (43) Camacho, C.; Niehaus, T. A.; Itami, K.; Irle, S. Chem. Sci. 2013, 4, 187−195.
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DOI: 10.1021/acs.orglett.9b01563 Org. Lett. XXXX, XXX, XXX−XXX
