Design of Imidazo[1,2- a ]pyridine-Based Donor–Acceptor Chromophores through a Multicomponent Approach

A series of donor-acceptor chromophores was synthesized bearing a 3-aminoimidazo[1,2-a]pyridine donor motive. Through DFT-calculations, different combinations of the ImPy donor motive and different electron acceptors were assessed. In combination with an anthraquinone acceptor, the calculated ΔEST values were in range to suggest that these compounds would emit via thermally activated delayed fluorescence. Based on these findings, a series of ImPy-Aq emitters with different geometries and substitution patterns was synthesized through GBB-3CR and Suzuki coupling reactions. According to preliminary experimental data, the compounds were only slightly emissive at ambient temperatures due to a combination of low radiative rates and competing non-radiative deactivation pathways.

Imidazo [1,2-a]heterocyclic scaffolds are well-explored substrates in medicinal chemistry while examples of their application in material science remain relatively scarce. 1 However, the intrinsic fluorescence of imidazopyridine (ImPy) and related fused systems is quite intriguing and could be very promising for the development of novel fluorophores. 2ImPys are easily accessible through an isonitrilebased multicomponent reaction (MCR), the Groebke-Black-burn-Bienaymé reaction (GBB-3CR). 3The modular nature of MCRs would also allow for easy assembly, customization and fine-tuning of the optoelectronic properties of these compounds. 4However, possible applications of the GBB-3CR and its products for the design of functional chromophores have not been explored thoroughly.One of the few examples of the synthesis of chromophores based on the GBB-3CR was reported by Burchak et al. in 2011. 5Shahrisa et al. reported a library of donor-acceptor fluorophores consisting of imidazo [1,2-a]pyridines as donors in combination with tetrazole, dihydropyridine or dihydropyrimidones acceptors via sequential GBB-3CR-Ugi-azide-4CR/Hantzsch-4CR/Biginelli-3CR synthesis. 6Balijapalli and Iyer also designed imidazo [1,2-a]pyridine fluorophores exhibiting excited-state intramolecular proton transfer (ESIPT) properties, which were accessed in a copper-catalyzed three-component reaction rather than a GBB-3CR. 7ue to their luminescence properties, we targeted the exploration of imidazo [1,2-a]heterocycles for different applications; e.g., pH sensing or DNA-staining. 8To expand on these results, we envisioned imidazo[1,2-a]heterocycles acting as donor motifs in donor-acceptor chromophores that would emit via thermally activated delayed fluorescence (TADF). 9In 2020, Lee et al. reported on the first series of TADF-emitters containing the imidazopyridine motif. 10itrile groups were grafted onto the scaffold to enhance their electron-withdrawing properties and it was combined as an acceptor with two different donors.As the secondary amino substituent originating from the isonitrile employed in the GBB-3CR increases the electron density of the imidazopyridine, we expected that this moiety would be very

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well suited as a donor rather than an acceptor.We thus targeted the design of donor-acceptor TADF-emitters featuring an ImPy-based donor.
Prior to synthesis, we assessed the feasibility of our design using density functional theory by partnering the 3-(tert-butylamino) imidazo[1,2-a]pyridine moiety with a range of electron-accepting groups that had previously been studied in donor-acceptor TADF emitters.We first modelled a set of potential structures with 3-tert-butyl imidazo[1,2-a]pyridine as the donor, a 2,6-dimethylphenylene bridge that is coupled at the 4-position to the acceptor motif (ImPy*).The results are listed in Table 1.
According to the calculations, the dihedral angle between the ImPy* unit and the 2,6-dimethylphenylene bridging unit is ca.29°.The smallest ΔE ST value was obtained for the combination of ImPy and anthraquinone (Aq).The ImPy-group acts as a relatively weak donor, thus pairing it with the strong acceptor anthraquinone was necessary to stabilize the S 1 energy into the visible regime and decrease the singlet-triplet energy gap, ΔE ST , to a value where TADF may be possible.Coupling ImPy to weaker electron acceptors would yield a weaker charge-transfer state that would place the likely emission in the UV region.
Based on these results, we envisaged that incorporating multiple ImPy residues attached to a central phenylene spacer would effectively increase the strength of the charge-transfer S 1 state, red-shifting the emission and decreasing further ΔE ST .A series of target emitters with different configurations of donors and the Aq acceptor was designed: o-, m-, and p-ImPyAq.The differing regiochemistry of the donor was expected to influence the exchange ener-gy of the emitter and thus ΔE ST .The energy levels of the frontier orbitals of the three isomers and their localization in the optimized structures are presented in Figure 1.
For all three proposed compounds, the estimated ΔE ST values are moderately small, with p-ImPyAq* exhibiting the largest ΔE ST of 0.18 eV while the bis-ImPyAq isomers both have predicted ΔE ST of 0.10 eV.The LUMOs of each of the three structures are almost exclusively located on the anthraquinone acceptor, while the HOMOs span over the imidazo [1,2-a]pyridine moiety and the central phenylene ring.In the case of p-ImPyAq*, the greater extension of the LUMO onto the bridge explains the higher ΔE ST for this compound.The HOMO-LUMO gaps were calculated to range from 2.78 to 3.11 eV.However, the singlet oscillator strength of all compounds is relatively low, reflecting the poor overlap of the electron densities of the HOMO and LUMO in each molecule.
To access the proposed structures starting from a set of donors and acceptors, a modular synthesis approach was developed by dissecting the emitters into individual building blocks.The donor building blocks, comprising the ImPy moiety and the phenylene spacer, were prepared via a GBB-3CR from the respective brominated benzaldehydes (Scheme 1).For the para-emitter, the location of the methyl groups on the phenylene spacer was inverted because the respective aldehyde component for the GBB-3CR synthesis of this building block is more easily available.The yield of the mono-imidazo[1,2-a]pyridine donor 4a was significantly better than for the bis-imidazo[1,2-a]pyridines due to their additional reactive site and because of the steric congestion in the case of 4c.

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The acceptor building block, anthraquinone pinacol borate was prepared via Miyaura borylation according to a procedure by Liu et al. using a Pd(dppf)Cl 2 catalyst and potassium acetate as the base. 11The desired product 6 was obtained in quantitative yield (Scheme 2).

Scheme 2 Synthesis of anthraquinone pinacol borate 6 via Miyaura borylation
We next optimized the Suzuki-Miyaura conditions for the coupling of the individual building blocks to form the targeted donor-acceptor compounds.To find the best reaction conditions for this key step, we first optimized the synthesis of p-ImPyAq as a model system.The conversion of 4a into 7 was calculated from the 1 H NMR spectra of the crude products to identify the most effective reaction conditions.For this, the ratio of the signals' integrals corresponding to the methyl residues of the phenyl spacer of both starting material and product were used.As no internal standard was employed, the conversion does not reflect the actual isolated yield.The results are displayed in Table 2.Among the tested Pd sources, palladium(II) acetate performed the best.Potassium acetate and potassium carbonate were used for the optimization of the Pd source and the ligand.The best results were obtained using RuPhos and SPhos (entries 9 and 11); without any ligand, only traces of the product could be detected (entry 12).Using stronger bases like potassium tert-butoxide, potassium hydroxide or cesium carbonate led to a significantly improved conversion as, in all three cases, no residual starting material was present (entries 13-15).Considering the overall purity of the product based on its 1 H NMR spectrum from each of the various entries, cesium carbonate was chosen.Using these optimized conditions, the target ortho-, meta-and para-emitters were synthesized from the respective building blocks (Scheme 3).
After flash chromatography, p-ImPyAq (7) was obtained in a yield of 61%. 12 The notable difference between the quantitative conversion of 4a into 7 (see Table 2) and the isolated yield of 7 is due to losses during the compound's purification.For m-BisImPyAq (8), the yield was even high-

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er, at likely due to the reduced steric hindrance of the bromide.13a The structure of 8 was confirmed unambiguously through single-crystal X-ray crystallography (Figure 2).13b On the other hand, o-BisImPyAq (9) could not be obtained.Instead, protodeboronation of the anthraquinone pinacol borate was observed while the ImPy building block remained unconverted.Addressing positions between sterically hindered residues is quite challenging and only a few procedures have been reported; e.g., using AntPhos as a ligand.While this catalytic system is feasible for adjacent phenyl substituents, no reaction was observed for imidazo[1,2-a]pyridines.Hence, o-BisImPyAq needed to be accessed via a different route.Therefore, the acceptor unit was attached to the bridging aldehyde prior to the synthesis of the imidazo[1,2-a]pyridine moieties.The synthetic approach is depicted in Scheme 4.
2-Bromoisophthalaldehyde 2c was coupled to anthraquinone pinacol borate 6 in a Suzuki-Miyaura reaction.The desired coupling product 10 was obtained in a yield of 19%.Presumably, the losses are due to side reactions like decarbonylation of the neighboring formyl groups as a significant evolution of gas was observed during the reaction.Subsequently, the formyl groups were transformed into 3-aminoimidazo [1,2-a]pyridines in a GBB-3CR.Initially, standard conditions were applied.However, even after a prolonged reaction time of ten days, the conversion remained incomplete.Thus, the solvent was changed to chloroform and the temperature was increased to 60 °C to accelerate the reaction.Through this modification to the reaction conditions, an excellent yield of 92% for 9 could be achieved. 14he synthesized compounds were studied to assess their photophysical properties and to evaluate whether the emitters exhibit TADF properties.For this, absorption and

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emission spectra of the compounds were recorded at ambient (Figure 3a, Table 3), and emission at 77 K over different time scales (Figure 3b).The absorption spectra of all derivatives show similar profiles, with the highest intensity bands located at 290 nm, followed by lower intensity shoulders at 320-370 nm and a varying intensity lowenergy band at >380 nm.Isomeric differences among the derivatives are most notably reflected in the energy and intensity of this lowest energy absorption band, with 9 showing the highest intensity.The DFT-predicted absorption spectra follow a similar trend (Figure S19), except that they are considerably red-shifted compared to the experimental results.The molar absorptivity values, , of the band located at 320-370 nm for 9, 8 and 7 are 13,664, 15,717 and 11,424 M -1 cm -1 , respectively.Turning to emission in toluene, the spectra were acquired at a considerably high concentration (1 × 10 -4 M) due to their weak fluorescence intensity.Hence, all the samples showed weak, broad emission bands in the sky-blue region, with peak maxima,  PL , of 463, 460, and 455 nm for 9, 8 and 7, respectively.The weak emission correlates with DFT-predicted low oscillator strength values.In o-ImPyAq 9, we noticed what appears to be dual emission with the second higher-energy peak at 394 nm.We have excluded its origin as being due to solvent Raman

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scattering as the scattering peak appeared at a higher energy, therefore this high-energy peak could be attributed to LE emission from one of the chromophores.There is a progressing bathochromic shift of the  PL from para-to metato ortho-isomers that is consistent with the trends predicted by TD-DFT; however, the experimentally observed emission red-shift is rather moderate (max.8 nm).Low-temperature measurements were performed to investigate the fundamental luminescent mechanisms of the samples.For o-ImPyAq 9, the signal-to-noise ratio remained poor, showing almost no emission at all.For m-ImPyAq 8, a bathochromic shift was observed for the prompt fluorescence at 77 K.No delayed luminescence was observed.In contrast to this, the emission intensity of p-ImPyAq 7 was significantly increased upon cooling to 77 K.While at room temperature the compound was barely emissive, an intense green-yellowish prompt emission was observed at 77 K. Aside from the prompt fluorescence, a delayed luminescence was also observed.Surprisingly, the maximum emission wavelength of the delayed fluorescence showed a hypsochromic shift.A potential reason might be that the sample was flash-frozen, thus the conformations of the individual molecules are not in equilibrium. 15The broad and structureless singlet emission shape hints at emission occurring from a charge-transfer state, while the structured phosphorescence is consistent with a locally excited emission from anthraquinone individual chromophores. 16Similar behavior in flash-freeze luminescence experiments was also observed in other donor-acceptor systems.15a In summary, a series of donor-acceptor chromophores bearing a 3-aminoimidazo[1,2-a]pyridine donor motif was synthesized through a GBB-3CR/Suzuki-Miyaura coupling sequence.While multicomponent methods are still underrepresented in the synthesis of functional materials, this study showcases the advantages of such modular approaches.The GBB-3CR offers facile access to the imidazo[1,2a]scaffold, which can easily be derivatized through combinatorial variation of the individual components.This way, a series of ImPy-based building blocks with different geometries and substitution patterns were synthesized in overall good yields.Subsequently, these ImPy-building blocks can be coupled to a variety of acceptor moieties.With the optic of designing new TADF emitters, DFT calculations were used to assess a family of ImPy-acceptor compounds possessing different acceptors.This study revealed that in combination with an anthraquinone acceptor moiety, the calculated ΔE ST values of the ImPy-based compounds were in a range suitable for TADF.However, spectroscopic and optoelectronic characterization only show very weak emission at ambient temperatures for the series of synthesized ImPyAq emitters.This is likely due to a combination of very low oscillator strength and competing non-radiative deactivation pathways.The detailed origin of this behavior is the subject of further studies.Thus, adjustments and optimizations of the structures are necessary to improve the optoelectronic properties of this class of emitters.Therefore, our modular approach lends itself perfectly to assess different combinations of donor and acceptor motifs.Overall, the ImPy-donor motive and the MCR-based synthesis concept provide a versatile synthetic platform for the development of new types and architectures of fluorescent emitters.

Scheme 3 Figure 2 F
Scheme 3 Synthesis the ortho-, meta-, and para-ImPyAq through Suzuki-Miyaura coupling of the donor and acceptor building blocks

Scheme 4
Scheme 4 Synthesis of (a) 10 and (b) 9 and 9′. a The reaction was performed in MeOH at r.t. for 3 days.

Table 1
Chemical Structures and DFT-Predicted Singlet-Triplet Energy Gaps and Vertical S 1 Energy Levels of the ImPy* Donor with Different Acceptor Types using the PBE0/6-31G(d,p) Method In Vacuum a a Top row: ΔE ST , bottom row: S 1 energy

Table 3
Photophysical Properties of the Synthesized Emitters a