Four-layer folding framework: design, GAP synthesis, and aggregation-induced emission

The design and synthesis of a type of [1 + 4 + 2] four-layer framework have been conducted by taking advantage of Suzuki–Miyaura cross-coupling and group-assisted purification (GAP) chemistry. The optimized coupling of double-layer diboronic esters with 1-bromo-naphth-2-yl phosphine oxides resulted in a series of multilayer folding targets, showing a broad scope of substrates and moderate to excellent yields. The final products were purified using group-assisted purification chemistry/technology, achieved simply by washing crude products with 95% EtOH without the use of chromatography and recrystallization. The structures were fully characterized and assigned by performing X-ray crystallographic analysis. UV–vis absorption, photoluminescence (PL), and aggregation-induced emission (AIE) were studied for the resulting multilayer folding products.

In the past several years, our group has reported new multi-layer folding chirality of a series of molecules, including oligomers and polymers with structural flexibility, displaying physical properties on UV/Vis absorption, fluorescence, electrochemical performance, aggregation-induced emission (AIE) (Wu et al., 2019;Wu et al., 2019;Liu et al., 2020;Wu et al., 2020;Wu et al., 2021a;Jin et al., 2022a;Tang et al., 2022a;Tang et al., 2022b;Wang et al., 2022), and aggregation-induced polarization (AIP) (Tang et al., 2022c;Tang et al., 2022d).Among them are three-layer compounds (Scheme 1), in which electron-rich (Tang et al., 2022b) and electron-deficient (Jin et al., 2022a) bridges showed distinct impacts on UV-vis absorption and fluorescence behaviors.It is worth noting that many of these compounds showed fluorescence not only in solutions but also in solid states.Very recently, we have established the asymmetric catalytic approach to a [1 + 3+1] type of multi-layer 3D chirality containing the phosphine oxide moiety (Wu et al., 2021a) via chiral amide-phosphine ligands for Suzuki-Miyaura cross-couplings, in which a single asymmetric C-C bond formation led to the efficient control of three-layer chirality.
After achieving the synthesis of three-layer folding chiral targets, our attention is now focused on the design and assembly of four-layered compounds, starting from their racemic counterparts.In the new molecular framework, there are three planar units, including one naphthyl ring, four packed phenyl rings, and two parallel naphthyl rings, which are categorized as a type of [1 + 4 + 2] framework.This is inspired by our early work on the [1 + 3 + 1] framework, in which one packed plane is provided by the (P=O)Ph 2 group (Wu et al., 2021a).Herein, we report our preliminary results on this endeavor based on new designs and modifications to reaction conditions (Scheme 1).
The synthesis of another key precursor is represented by the generation of (1-bromonaphthalen-2-yl)diarylphosphine oxides 7 by the following literature procedures (Wu et al., 2021a).It was started with the protection of 1-bromo-2-naphthol with Tf 2 O to yield 1-bromonaphthalen-2-yl trifluoromethanesulfonate in the presence of pyridine.The second step was conducted through the C-P coupling with diaryl phosphine oxide by taking advantage of Pd 2 (dba) 3 and 1,3-bis(diphenylphosphino)propane (DPPP) as the catalytic combination (Ji et al., 2020).In addition, substrates 7b-7o were synthesized starting with the nucleophilic substitution of diethyl phosphite with arylmagnesium bromide to yield bisaryl phosphine oxides, followed by subjecting to the catalytic coupling with 1-bromonaphthalen-2-yl trifluoromethanesulfonate.
Frontiers in Chemistry frontiersin.org04 catalysts, solvents, and bases were screened, and the results are shown in Table 1 (entries 1-9).In the beginning, the reaction of 6a and 7a in a 1:2.5 mol ratio was carried out in the presence of 10 mol % Pd(PPh 3 ) 4 and 3.0 equiv of K 2 CO 3 in THF/H 2 O (5:1, v/v) at 90 °C for 48 h, and the desired [1 + 4+1] multilayered 3D product 8a was obtained in 86% yield through dual Suzuki-Miyaura couplings (entry 1).Other Pd catalysts, including Pd 2 (dba) 3 , PdCl 2 , and Pd(OAc) 2 , were then examined together with K 2 CO 3 in this transformation, but all yielded unsatisfactory results (entries 2-4).Similarly, experimentation with various solvent systems, such as toluene/H 2 O, DME/H 2 O, and 1,4-dioxane/H 2 O did not produce satisfactory results either (entries 5-7).We next attempted to optimize conditions by exploiting K 3 PO 4 and Cs 2 CO 3 as bases and found that both attempts did not show poor chemical yields of 37% and 40%, respectively (entries 8 and 9).
Since there are two polar -POPh 2 groups existing in the products, the purification of resulting crude products at this step can be readily obtained through the group-assisted purification (GAP) (Kaur et al., 2010;Kaur et al., 2011;An et al., 2015) chemistry/technology, eliminating the need for chromatography and recrystallization.The pure product 8a and its derivatives 8b-8p were conveniently obtained by simply washing the crude products with 95% EtOH, making this synthesis much greener and environmentally friendly.
Having established the optimal reaction conditions, we next investigated the scope of the double Suzuki-Miyaura cross-coupling reaction by using a variety of preformed 2-diarylphosphinyl-1-naphthyl bromide 7.As shown in Scheme 3, the influence of substituents in the aryl moiety of 7 was first evaluated.The reactions of 2diarylphosphinyl-1-naphthyl bromide 7 with either electron-rich groups (Me 7b, OMe 7c, Ph 7d, SMe 7e, and NMe2 7f) or electron-poor groups (F 7g, Cl 7h, and OCF 3 7i) at the para position of the aryl moiety of 7 could tolerate this reaction system, leading to the corresponding products 8b-8i in 54%-91% yield.Similarly, the meta-substituent of the aryl unit of 7 (Me 7j, OMe 7k, and F 7l) still showed a high reactivity profile, providing access to the corresponding multilayered 3D products 7j-7l in 62%-93% yield.It is noteworthy that the ortho-methyl substituted analog 7m was a suitable surrogate for this coupling reaction, which could work smoothly to deliver the product 8m in 52% yield.To our delight, both 3,5-dimethylsubstituted arylphosphine oxide 7n and 1-naphthyl-substituted phosphine oxide 7o were adopted to demonstrate the compatibility of this protocol and furnished the target products 8n-8o in 88% and 64% yields, respectively.Furthermore, the dihydroacenaphthylenederived double-layer diboronic ester 6b was then allowed to react with 2-diphenylphosphinyl-1-naphthyl bromide 7a under standard conditions.As anticipated, the reactions proceeded smoothly, enabling the Pd-catalyzed coupling to yield the corresponding product 8p in 87% yield.The structures of all products were fully characterized by carbon and proton NMR spectroscopic and HRMS analyses.
Furthermore, the resulting multilayer framework has been unambiguously assigned by X-ray structural analysis of one of the products, 8a (Figure 2).This structure clearly presents two groups of nearly parallel units: four phenyl rings in the middle and two naphthyl rings at one end.These two planar units plus a single naphthyl ring anchor consist of a [1 + 4+2] multilayer framework, which added one more layer in the middle, as compared with our previous [1 + 3+1] type of multi-layer counterparts in the middle columns of their structures.It should be noted that our preliminary results on assembling a maximum of five-layer counterparts show promising results, leading to a [2 + 5+2] multilayer framework.

UV-vis absorption, PL, and AIE determinations
Among the products listed in Figure 3 and Figure 4, several representatives, 8a, 8c, 8g, 8i, and 8n, were examined for their behaviors on UV-vis absorption, photoluminescence (PL), and aggregation-induced emission (AIE).As shown in Figure 3A, UV-vis absorption spectra were recorded for these compounds with the same concentration in THF (Figure 3A).The highest absorptions of four samples (8a, 8g, 8i, and 8n) displayed wide absorption between 280 nm and 360 nm, except for molecule 8c.The wide absorption of 8c was observed to be between 260 and 210 nm; the highest position appeared at 280 nm, and the second highest position was around 340 nm.The photoluminescence spectra of these compounds upon excitation exhibit bands at slightly different curves with regard to emission strengths and wavelengths (Figure 3B).Excitation wavelengths at 344 nm for 8a, 8c, 8i, and 8g and at 352 nm for 8n were utilized for measuring their photoluminescence.As shown in the spectrum, 8c displays its maximum emission at 400 nm.As compared with 8c, 8a displays its maximum emission at 430 nm shifted downfield and 8a, 8g, and 8i at 344 nm shifted upfield, respectively.The PL performance seems complicated, being attributed to solvent-target interactions and electronic and conformational steric effects of aromatic rings attached to the phosphorus center.Compared with 8a, which has no functional group on its two phenyl rings of the P=O center, the presence of both the electron-donating (OMe in 8c) and electron-withdrawing groups (CF 3 O and F in 8g and 8i, respectively) and the steric effect (two methyl groups in 8n) all resulted in upfield emission.
Fluorescence spectroscopic analysis was conducted using 8n as a representative for aggregation-induced emission (AIE).As shown in Figure X, the water fractions (f w ) were increased from 0% to 60%, resulting in a steady emission enhancement from 352 nm to 555 nm.This emission change is attributed to the intermolecular packing of the molecular matrix, indicating the existence of aggregationinduced emission (AIE) by this four-layer compound.Although an obvious GAP exists between emission in f w = 0% (in pure THF) SCHEME 3 Substrate scope for forming products 8. and the other four fw slots, the emission at the later four curves (10%-60%) does not display obvious differences.
As usual, the intermolecular aggregation largely suppresses the rotational motions of aromatic rings so that the exciton energy cannot be depleted by the radiation-less decay, thus making the present AIE observation possible.The intermolecular packing process would have an impact on the intramolecularly layered framework, but in a diluted environment, the movements between molecules would diminish as the poor solvent (water) became more prevalent.The intramolecular stacking would become more regular and predominantly controlled by suppressing the whole framework while water was added to the solvent mixture as soon as the acceptable saturation value of f w = 60% was reached.The partial AIE activities could also exist because of this compressed packing model's contribution to more efficient through-space interactions.This result is in accordance with our earlier research on multilayer molecules (Wu et al., 2021a;Wu et al., 2021b;Wang et al., 2022).
An interesting shape of emission appeared in pure and transparent THF, which indicates some degrees of molecular aggregation exist in this system.This observation would benefit organic synthesis during condition modifications by taking advantage of aggregates.It should be noted that THF is among the most common solvents in organic synthesis, particularly in asymmetric synthesis and catalysis.Our laboratory has recently proven that chiral aggregates can enhance asymmetric control and can even switch the stereo configuration of resulting chiral products (Rouh et al., 2022;Tang et al., 2023).Chiral aggregates were directly confirmed by AIE, AIP (aggregation-induced polarization) (Tang et al., 2022c;Tang et al., 2022d), and dynamic light scattering (DLS) experiments in THF-water and THF-ethanol co-solvents.Both stoichiometric and catalytic asymmetric reactions have been carried out successfully, defined as aggregation-induced asymmetric synthesis (AIAS) (Tang et al., 2023) and aggregationinduced asymmetric catalysis (AIAC) (Jin et al., 2022b).

Summary
In summary, a new [1 + 4+2] framework of multilayer targets has been successfully designed and synthesized.Starting from commercial starting materials, more than 40 steps were performed for generating 16 multilayer folding products bearing various phosphine oxides.The synthesis takes advantage of modified dual Suzuki-Miyaura cross-couplings and GAP chemistry/ technology simply by washing with 95% EtOH without the use of chromatography and recrystallization.The structures were fully characterized by spectroscopic analysis and assigned by X-ray crystallographic determination.The physical properties of UV-vis absorption, photoluminescence (PL), and aggregation-induced emission (AIE) were studied for the resulting multilayer folding products.Further research on the asymmetric synthesis and catalysis for generating the chiral [1 + 4+2] framework of four-layer counterparts and its attachment onto orientational chirality (Jin et al., 2022b;Jin et al., 2022c) is currently being conducted in our laboratories, and the results will be reported in due course.

TABLE 1
Optimization of the reaction conditions a .
b Isolated yield based on 6a.Frontiers in Chemistry frontiersin.org