Triazoliptycenes: A Twist on Iptycene Chemistry for Regioselective

Letter pubs.acs.org/OrgLett

Triazoliptycenes: A Twist on Iptycene Chemistry for Regioselective Cross-Coupling To Build Nonstacking Fluorophores Taewon Kang, Hongsik Kim, and Dongwhan Lee* Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea S Supporting Information *

ABSTRACT: Triazoliptycene fluorophores have been designed and synthesized, in which a three-dimensional propeller-like iptycene motif is employed to suppress intermolecular π−π stacking in the solid state. Key to the success of this modular synthesis is a stereoelectronic bias imposed by the iptycene scaffold, which assists the desired regioselectivity in the C−N cross-coupling step as the laststage structure diversification from a common precursor.

uminescent molecules are finding wide applications as lightemitting diodes,1 vapor sensors,2 and encryption materials.3 Flat and rigid organic molecules developed for such a purpose, however, tend to engage in extensive intermolecular π−π interactions upon solidification.4 This structural property often perturbs intrinsic molecular photophysical properties in the solid state.5,6 An intuitive solution to this problem is building steric shields to isolate fluorogenic molecular motifs.2,7,8 Toward this objective, we have devised and implemented a last-stage cross-coupling strategy to construct a new class of organic solid-state fluorophores, N-aryl triazoliptycenes (1) (Figure 1). Formally considered as a hybrid between a flat N-aryl

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propeller-shaped architecture have subsequently been exploited in various applications including crystal engineering, host−guest chemistry, conformationally rigid ligands, and polymers having internal free volume.2,10 As the fluorophores to be fused with the iptycene system, we chose N-aryl functionalized triazoles (Figure 1, in red). This decision was made for the following reasons. First, the electrondeficient triazole ring could function as an acceptor in chargetransfer (CT) type transitions, which respond sensitively to changes in the local environment.6 Second, without close orbital overlap between neighboring arene units, the intrinsic photophysical properties of the fluorophore would be maintained even after being fused with the iptycene scaffold. Third, the iptycene scaffold offers a rather unconventional yet viable solution for regioselective C−N cross-coupling reactions, as discussed below. Transition metal-catalyzed C−N cross-coupling reactions have widely been employed to construct structurally elaborate molecules from nitrogen-containing precursors.11 When such precursor has multiple nitrogen atoms to react, however, the problem of isomerism could arise. For N-arylation reactions of 1,2,3-triazoles via direct C−N coupling (Scheme 1),12,13 a mixture of nonfluorescent N1- (2) and fluorescent N2-arylated (3) products are typically obtained with poor to moderate selectivity (1:1−4.3).13a−c Since the photophysical properties of 3 can be tuned by varying the N-aryl substituent,13c,e,14 diversity-oriented synthesis by late-stage C−N bond-making should significantly expand the scope of this chemistry. This strategy, however, requires a high N2-selectivity in cross-coupling, which is difficult to achieve. Previous efforts to realize this goal have focused on triazoles having special substituents,13d or bulky and electron-rich ligands for the metal catalyst.13a

Figure 1. Chemical structure of N2-aryl triazoliptycene (1), and a schematic representation of the design concept to suppress close and contiguous π−π contacts of the N-aryl triazole fluorophores (in red) in the solid state.

triazole fluorophore and iptycene-based three-dimensional scaffold, these molecules are designed specifically to avoid close and contiguous π−π contacts upon aggregation. The chemistry of iptycenes has evolved from the parent triptycene system (Figure 1), which was invented originally to study the exceptional stability of bridgehead C−X bonds in substitution reactions.9 The unique structural properties of such © 2017 American Chemical Society

Received: October 17, 2017 Published: November 16, 2017 6380

DOI: 10.1021/acs.orglett.7b03239 Org. Lett. 2017, 19, 6380−6383

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Organic Letters Scheme 1. Tautomeric Triazoles To Produce Isomeric N-Aryl Triazoles by Metal-Catalyzed C−N Cross-Coupling Reactions

Scheme 2. Synthetic Route to Triazoliptycene

In order to assess the effects of iptycene scaffold on the chemistry outlined in Scheme 1, we first investigated the tautomer equilibrium by DFT computational studies (Figure 2).

removal of the temporarily installed N-aryl appendage to unveil the desired triazoliptycene 5 as the newest addition to heterocycle-fused iptycenes (Scheme 2). A simplified 1H NMR spectral pattern of 5 (Figure S2), in particular, a single resonance of the bridgehead C−H protons at δ = 5.55 ppm, is consistent with the presence of a mirror plane that bisects the molecule. The dominance of the 2H-tautomer 5, as predicted by DFT computational studies (Figure 2), has thus been confirmed experimentally. Starting from 5 as a common synthetic precursor, various arylsubstituted triazoliptycenes 1-H, 1-CN, 1-NMe2, 1-NPh2, and 1NaphNMe2 were readily prepared by straightforward C−N cross-coupling reactions with the corresponding aryl bromides or iodides (Scheme 3, Route A).

Figure 2. Thermodynamic preference between the 2H- and 1Htautomer of the parent triazole (4 and 4′), and the corresponding triazoliptycene system (5 and 5′) probed by DFT computational studies (B3LYP/6-31G(d) level; in DMSO solvent at t = 120 °C to simulate the reaction conditions for C−N cross-coupling). Shown next to the chemical structure of 5′ is an NBO representation of the nN → πCC* donor−acceptor interaction plotted with an isovalue of 0.05.

Scheme 3. Synthesis of N-Aryl Triazoliptycenes

For the simple triazole, both isomers are essentially isoenergetic ( ΔGcalc = 0.67 kcal mol−1), with 4 slightly favored (K = [4′]/[4] = 4.26 × 10−1). Once integrated into the iptycene scaffold, however, a dramatic change is observed in the thermodynamic preference. For triazoliptycene, the 1H-isomer (5′) becomes significantly destabilized over the 2H-isomer (5) by as much as ΔGcalc = 3.06 kcal mol−1. Our NBO analysis (Figure 2) based on the Wiberg bond index (Figure S1) revealed that the C−C double bond character of the iptycene-fused triazole fragment is significantly diminished for the triazoliptycene. With strong nN → πCC* donor−acceptor type orbital interaction (Figure 2, bottom right), the electron density at the N1 position (and thus its affinity toward proton) is reduced, which promotes tautomerization of 5′ to 5. It still remained an open question whether such electronically driven thermodynamic bias (Figure 2) would somehow translate to the desired regiochemical preference, thereby producing the desired N2-aryl product 3 (Scheme 1). We were intrigued by such possibility, and proceeded to carry out experimental studies. The first step was making the hitherto unknown triazoliptycene 5. A typical entry point for the iptycene chemistry is direct [4 + 2]-cycloaddition reactions between anthracenes and appropriate dienophiles, such as benzynes, to construct the three-bladed architecture.15 For triazoles, however, no such heteroaryne equivalent is available. We thus devised a synthetic detour that commenced with the known dione 6 (Scheme 2).16 Sequential condensation reactions of 6 with 4-methoxyphenylhydrazine and hydroxylamine, followed by dehydration, produced 1-OMe. Oxidation with CAN at rt cleanly effected

With standard protocols using a combination of a copper(I) precatalyst and proline ligand,13c−e the reactions proceeded cleanly to produce the desired N2-arylated triazoliptycenes. The cross-coupling reaction of 5 with 1,4-dibromobenzene to produce 1-Br, however, suffered from decomposition of the substrate under the reaction conditions. For the reaction of 5 with 4-iodonitrobenzene to produce 1-NO2, we had difficulty in separating the N-aryl triazoliptycene product from the dehalogenative homocoupling byproduct. Preparatory-scale synthesis of 1-Br and 1-NO2 thus resorted to stepwise functional group transformations from 6 (Scheme 3, Route B). Compound 1-NH2 was prepared by reduction of 1-NO2 with SnCl2. The products were fully characterized by a combination of 1H/13C NMR spectroscopic and X-ray crystallographic analysis (Figure 3; Figures S4−S22). 6381

DOI: 10.1021/acs.orglett.7b03239 Org. Lett. 2017, 19, 6380−6383

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Figure 3. ORTEP diagrams of (a) 1-H (prepared by Route A in Scheme 3) and (b) 1-NO2 (prepared by Route B in Scheme 3) with thermal ellipsoids at 50% probability.

One salient feature of the triazole-based fluorophores is the tunability of their photophysical properties by the N2-aryl substituent.13c,e,14 Indeed, the emission of triazoliptycenes in MeCN spans a wide spectral window (λmax,em = 340−495 nm; Figure 4a) with visually discernible purple (for 1-H, 1-Br, 1-CN,

Figure 5. (a) Normalized fluorescence spectra of (a) 1-H, (b) 1-CN, (c) 1-Br, and (d) 7 in MeCN solution, powder, drop-cast film, and spin-cast film samples (t = 298 K; λexc = 280 nm). See the figure legend (top) for sample designations.

shifts are observed upon going from solution to solid state (Figures 5b and 5c), but their solid-state fluorescence spectra also overlap nicely. Donor−acceptor (D−A) type triazoliptycenes also display similar longer-wavelength CT-type emissions across differently prepared solid samples (Figure S26).18 In stark contrast to the context-insensitive emission properties of triazoliptycenes, the simple triazole 7 (Figure 5d), used as a reference system prone to π−π stacking, suffers from large red shifts and spectral broadenings in the condensed phase. Moreover, different sample preparation methods (i.e., powder, drop-cast film, or spin-cast film) produced widely different spectra with varying and unpredictable degrees of energy shifts and spectral broadening, as shown in Figure 5d. According to our empirical observations described above, triazoliptycene aggregates behave as if they were discrete molecules in solution, as far as the emission energy windows and spectral line shapes are concerned. What structural features are responsible for the apparent lack of strong interchromophore interactions in the condensed phase? As shown in Figures 6 and S27, triazoliptycenes adopt either (i) slipped face-to-face dimeric pairs (Figures 6a and 6b; Figure S27; two N-aryl triazole units pointing in opposite directions to minimize dipole moment) or (ii) edge-to-face interaction between the N-aryl triazole units (Figure 6c). The latter spatial arrangement is reinforced by an electrostatic attraction between one end of the molecule and the aryl ring of the neighboring molecule. The crystallographic 4-fold rotational symmetry maximizes such edge-to-face interactions by establishing a cyclic array. While their positioning varies depending on the electronic and steric demand of the aryl group, the distance between two adjacent π-faces of N-aryl triazole fluorophore ranges as 3.9−5.9 Å (Table S2). These metric parameters are significantly longer than the ∼3.4 Å spacing anticipated for typical π−π contacts.4 Moreover, the steric shield afforded by the iptycene scaffold does not allow parallel stacking of π-faces beyond the simple dimer stage (Figure 6; Figure S27). Without intimately spaced π-faces to form a continuous array for exciton delocalization or hopping, as typically observed for flat rigid aromatics, triazoliptycene aggregates seem to behave as discrete molecules in solution as far as light-emitting properties are concerned (Figure 5).

Figure 4. Fluorescence spectra of N-aryl triazoliptycenes in MeCN (t = 298 K; λexc = 280 nm). The emission intensities were rescaled by dividing with the absorbance at λ = 280 nm, so that they are proportional to the fluorescence quantum yields (ΦF). (b) Emission energy (in cm−1) of 1-H (light blue), 1-NPh2 (red), 1-NMe2 (orange), and 1-NaphNMe2 (green) plotted vs solvent polarity (ET(30) parameter). Overlaid linear lines are obtained by least-squares fitting.

1-OMe), blue (for 1-NH2, 1-NMe2, 1-NPh2), and green (for 1NaphNMe2) colors. The fluorescence quantum yield also changes as the N-aryl substituent is varied (Table S1). Notably, a large red shift in fluorescence is observed for compounds having electron-donating N-aryl groups (Figure 4a), implicating the involvement of charge-transfer (CT) type emission; the electron-deficient triazole group promotes the evolution of charge-separated excited states upon photoexcitation. In support of this notion, 1-NMe2, 1-NPh2, and 1-NaphNMe2 show systematic red shifts in the emission wavelength with increasing solvent polarity (Figure S25). A good linear relationship (R2 = 0.94−1.00) is observed between the emission energy (in cm−1) and the ET(30) value (Figure 4b);17 such an effect is less pronounced for 1-H having an unsubstituted phenyl group, which serves as a control (Figure 4b). Due to intermolecular electronic coupling, light-emitting properties of molecular aggregates often deviate significantly from those of solution samples. To demonstrate that the threeblade shaped iptycene scaffold could be a viable solution to this problem, we prepared three different types of solid samples of triazoliptycenes (powder, drop-cast film, and spin-cast film) and compared their emission spectra (Figure 5). For the iptycene-appended fluorophores 1-H, 1-CN, and 1-Br, both the energy (λmax,em) and spectral width (fwhm) remain largely invariant upon changing from solution to solid environments. Notably, the normalized emission spectra of 1-H are essentially superimposable (Figure 5a), regardless of whether the molecule is in solution or solidified as a powder, drop-cast film, or spin-cast film. For 1-CN and 1-Br, slight (Δλ = 6−11 nm) red 6382

DOI: 10.1021/acs.orglett.7b03239 Org. Lett. 2017, 19, 6380−6383

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ACKNOWLEDGMENTS This work was supported by the Basic Research Grant (2017R1A2B2006605), Creative Materials Discovery Program (2017M3D1A1039558), and NRF-2016-Global Ph.D. Fellowship Program (2016H1A2A1906550 to T.K.) through the National Research Foundation of Korea (NRF).

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Figure 6. X-ray structures of triazoliptycenes in the (a) P21/c space group (1-H), (b) P1̅ space group (1-OMe), and (c) I4/m space group (1-NO2). Capped-stick models were constructed with crystallographically determined atomic coordinates, and overlaid with spacefilling models to highlight closest intermolecular contacts in the crystal packing.

In summary, our work described here convincingly showcases the conceptual appeal and practical utility of the iptycene scaffold as an electronic controller group in synthesis and steric controller group in assembly. To suppress interchromophore electronic coupling or to enhance solid-state fluorescence, previous work elsewhere focused on the following: (i) introducing bulky substituents,2,7 or spiro-junctions to the fluorogenic core;19 (ii) encapsulating fluorophores within hosts;8 (iii) appending peripheral groups for aggregation-induced emission (AIE).20 It is yet to be seen whether our approach based on this “pluggable” iptycene could be extended and generalized for other types of fluorophores. Efforts are underway in our laboratory to refine and expand the scope of this chemistry.

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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.7b03239. Synthesis and characterization; additional spectroscopic data (PDF) Accession Codes

CCDC 1579227−1579231 and 1579233−1579234 contain 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 Author

*E-mail: [email protected]. ORCID

Dongwhan Lee: 0000-0001-6683-9296 Notes

The authors declare no competing financial interest. 6383

DOI: 10.1021/acs.orglett.7b03239 Org. Lett. 2017, 19, 6380−6383