Two-Step Synthesis, Structure, and Optical Features of a Double Hetero[7]helicene

A novel double aza-oxa[7]helicene was synthesized from the commercially available N1,N4-di(naphthalen-2-yl)benzene-1,4-diamine and p-benzoquinone in two steps. Combining the acid-mediated annulation with the electrochemical sequential reaction (oxidative coupling and dehydrative cyclization) afforded this double hetero[7]helicene. Moreover, the structural and optical features of this molecule have been studied using X-ray crystallographic analysis, and the absorption and emission behaviors were rationalized based on DFT calculations.

Notably, these examples ( Figure 1c) represent a quantum leap in the short-step synthesis of double hetero [7]helicenes via the tandem process of nucleophilic substitution with BBr 3 followed by C-H aryl borylation [44,45]. As part of our effort to explore the Molecules 2022, 27, 9068 3 of 12 electrochemical domino syntheses, we were interested in designing effective sequential reactions to access double helicene motifs [46,47]. Herein, a facile preparation of a double aza-oxa [7]helicene with a phenylene linker has been established through acid-mediated annulation with the electrochemical sequential reaction (oxidative coupling and dehydrative cyclization). We also studied the structural and optical features via x-ray crystallographic analysis, spectrophotometric analysis, and DFT calculations.

Results and Discussion
2.1. Synthesis of Double Aza-oxa [7]helicene 3 Recently, Zhang reported a facile acid-mediated synthesis of carbazole in which aniline derivatives react with p-benzoquinone to produce 3-hydroxycarbazoles [48]. Combining this approach with our unprecedented electrochemically enabled synthesis of hetero [7]helicenes and dehydro-hetero [7]helicenes [46,47], herein, we achieved the two-step synthesis of double aza-oxa [7]helicenes as depicted in Scheme 1. The acid-mediated annulation of the commercially available substrates; N 1 ,N 4 -di(naphthalen-2-yl)benzene-1,4diamine 1 and p-benzoquinone afforded the corresponding bis-3-hydroxy-benzo[c]carbazole 2 in 54% yield via a tandem process of double Michael addition and subsequent double ring closure. Next, a DCM solution of 2, β-naphthol, and tetrabutylammonium hexafluorophosphate(V) as an electrolyte, was utilized to a constant current of 1.5 mA in an undivided electrolysis cell with platinum electrodes for 3.5 h at room temperature, affording double aza-oxa [7]helicene 3 in 26% yield. The electrochemical sequential synthesis of 3 proceeds through the oxidative hetero-coupling of arenols to produce a diol intermediate that can readily undergo a subsequent dehydrative cyclization to 3. All compounds showed good chemical and thermal stabilities and no decomposition was observed upon purification on silica column chromatography and heating at 100 • C in air. Notably, these examples ( Figure 1c) represent a quantum leap in the short-step syn thesis of double hetero [7]helicenes via the tandem process of nucleophilic substitutio with BBr3 followed by C-H aryl borylation [44,45]. As part of our effort to explore th electrochemical domino syntheses, we were interested in designing effective sequenti reactions to access double helicene motifs [46,47]. Herein, a facile preparation of a doub aza-oxa [7]helicene with a phenylene linker has been established through acid-mediate annulation with the electrochemical sequential reaction (oxidative coupling an dehydrative cyclization). We also studied the structural and optical features via x-ra crystallographic analysis, spectrophotometric analysis, and DFT calculations.

Synthesis of Double Aza-oxa[7]helicene 3
Recently, Zhang reported a facile acid-mediated synthesis of carbazole in which an line derivatives react with p-benzoquinone to produce 3-hydroxycarbazoles [48]. Combin ing this approach with our unprecedented electrochemically enabled synthesis of he ero [7]helicenes and dehydro-hetero [7]helicenes [46,47], herein, we achieved the two-ste synthesis of double aza-oxa [7]helicenes as depicted in Scheme 1. The acid-mediated an nulation of the commercially available substrates; N 1 ,N 4 -di(naphthalen-2-yl)benzene-1, diamine 1 and p-benzoquinone afforded the corresponding bis-3-hydroxy-benzo[c]carb zole 2 in 54% yield via a tandem process of double Michael addition and subsequent dou ble ring closure. Next, a DCM solution of 2, β-naphthol, and tetrabutylammonium he afluorophosphate(V) as an electrolyte, was utilized to a constant current of 1.5 mA in a undivided electrolysis cell with platinum electrodes for 3.5 h at room temperature, afford ing double aza-oxa [7]helicene 3 in 26% yield. The electrochemical sequential synthesis 3 proceeds through the oxidative hetero-coupling of arenols to produce a diol intermed ate that can readily undergo a subsequent dehydrative cyclization to 3. All compound showed good chemical and thermal stabilities and no decomposition was observed upo purification on silica column chromatography and heating at 100 °C in air.

Structure and Packing Mode of 3
The double aza-oxa [7]helicene structure of 3 was definitely confirmed by X-ray cry tallography using a single crystal, grown from its racemic solution. We used the liquid/li uid diffusion technique between ethyl acetate and n-hexane to prepare this crystal slow over three days in a dark environment at -20 °C. As expected, the two helicene moieti Scheme 1. The synthesis of a double aza-oxa [7]helicenes 3.

Structure and Packing Mode of 3
The double aza-oxa [7]helicene structure of 3 was definitely confirmed by X-ray crystallography using a single crystal, grown from its racemic solution. We used the liquid/liquid diffusion technique between ethyl acetate and n-hexane to prepare this crystal slowly over three days in a dark environment at −20 • C. As expected, the two helicene moieties are connected via a phenylene linker (Figure 2a,b). The dihedral angles between the phenylene linker's plane and the pyrrole (ring B') are −41.86 • for (C 1 -C 6 -N 7 -C 8 ), and 54.38 • for (C 5 -C 6 -N 7 -C 9 ). Although the experimental values of (C 5 -C 6 -N 7 -C 9 ) dihedral angle (54.38 • ) is comparable to that of the optimized structure using DFT calculations at MN15/6-311G(d,p) level of theory (54.72 • ), (C 1 -C 6 -N 7 -C 8 ) dihedral angle was smaller than optimized structures at various levels (Table 1). This can be attributed to the intermolecular interactions between the double helicene molecules 3 in the packed structure. Only meso isomer (P,M)-3 was observed in the crystal packing with achiral molecules packed along the b-axis (Figure 2c,d). The packing of 3 shows a herringbone pattern with π-π distance of 4.458 A • . This characteristic arrangement is optimum for many material-based applications, especially semiconductors [49][50][51]. In addition, it maximizes the optical and electronic properties of the obtained double helicene upon self-assembly [49,[52][53][54]. Most of these larger or multiple helicenes showed significant variations during DFT calculations owing to the long-range conjugation and the effects of charge transfer [55,56]. Among the functions we screened, Minnesota 15 (MN15) function was found to be the most suitable parameters for our molecules (Table 1) [57].
are connected via a phenylene linker (Figure 2a,b). The dihedral angles between the phenylene linker's plane and the pyrrole (ring B') are −41.86° for (C1-C6-N7-C8), and 54.38° for (C5-C6-N7-C9). Although the experimental values of (C5-C6-N7-C9) dihedral angle (54.38°) is comparable to that of the optimized structure using DFT calculations at MN15/6-311G(d,p) level of theory (54.72°), (C1-C6-N7-C8) dihedral angle was smaller than optimized structures at various levels (Table 1). This can be attributed to the intermolecular interactions between the double helicene molecules 3 in the packed structure. Only meso isomer (P,M)-3 was observed in the crystal packing with achiral molecules packed along the b-axis (Figure 2c,d). The packing of 3 shows a herringbone pattern with π-π distance of 4.458 A°. This characteristic arrangement is optimum for many material-based applications, especially semiconductors [49][50][51]. In addition, it maximizes the optical and electronic properties of the obtained double helicene upon self-assembly [49,[52][53][54]. Most of these larger or multiple helicenes showed significant variations during DFT calculations owing to the long-range conjugation and the effects of charge transfer [55,56]. Among the functions we screened, Minnesota 15 (MN15) function was found to be the most suitable parameters for our molecules (Table 1) [57].

Figure 2.
Single crystal structure of the double helicene 3: (a,b) ORTEP drawing structure of (P,M)-3 obtained by X-ray crystal analysis with ellipsoids at 50% probability (H atoms were omitted for clarity); (c) crystal packing of (P,M)-3 with ellipsoids at 30% probability; (d) packing structure of (P,M)-3 is viewed along the c-axis to show the herringbone arrangement. Single crystal structure of the double helicene 3: (a,b) ORTEP drawing structure of (P,M)-3 obtained by X-ray crystal analysis with ellipsoids at 50% probability (H atoms were omitted for clarity); (c) crystal packing of (P,M)-3 with ellipsoids at 30% probability; (d) packing structure of (P,M)-3 is viewed along the c-axis to show the herringbone arrangement. Nucleus-independent chemical shift (NICS) calculations revealed the low aromaticity of the central phenylene linker with a NICS (0) value of −5.8 ppm (Figure 3a), much lower than that of benzene −7.6 ppm calculated at the same level of theory. The largest NICS (0) values (between −7.3 ppm and −8.6 ppm) were found on the benzene of 6H-furo[3,2e]indole (ring C ), pyrrole (ring B ) and naphthalene (rings F' and H'). While the lowest NICS (0) values (around −5.8 ppm) were found on the phenylene linker (ring A') and furan rings (D') which is consistent with the aromatic character of this ring. Generally, symmetric double hetero[n]helicenes (n ≥ 4) have three isomers, those being two chiral enantiomers (P,P) and (M,M), and one meso diasteromer (P,M) [30]. All three isomers of 3 were afforded under our reaction conditions which was confirmed by HPLC separation using DAICEL CHIRALPAK IA column (eluent: n-hexane/i-PrOH = 20/1) (Figure 3b). The experimental ratio among the three isomers was found to be around (1:2:1) with the meso isomer (P,M)-3 as the major formed product (confirmed by the absence of optical rotation). After HPLC chiral resolution, the epimerization rate of 3 was studied at three different temperatures (See SI). Eyring plot (Figure 3c) (Figure 3d).

Photophysical Properties
Our double aza-oxa [7]helicene 3 shows high luminescence upon photo-irradiation, which can be attributed to the rigid scaffold that hinders the thermal energy loss upon structural changes. The UV/vis absorption of 3 was recorded in different solvents to show its high solubility in most of the organic solvents which increases the potential for some applications that require good solubility such as solution-processed electronics [58][59][60]. In all measured solvents, compound 3 showed similar UV/vis absorption patterns (Figure 4a). The maximum absorbance exhibited in chloroform was shown at 407 nm (absorption coefficient: 7.5 × 10 4 M −1 cm −1 ) corresponding to an optical energy gap of (2.18 eV). According to TD-DFT calculations at the MN15/6-311G(d,p) level of theory, this lowenergy absorption can be accountable to the HOMO→LUMO transition. The absorption band at 385 nm possibly attributed to the equal contribution of both HOMO−1→LUMO and HOMO→LUMO+1 transitions. The band at 368 nm is estimated to be due to the HOMO−1→LUMO+1 transition, while the higher energy absorption band at 328 nm would be attributed to HOMO−2→LUMO corresponding to an optical energy gap of (2.58 eV). Molecular orbital calculations indicated that the HOMO is spread mainly over the phenylene linker (ring A ) and pyrroles (rings B') and LUMO is spread over the whole scaffold rather than the phenylene linker (ring A ), accounting for the substantial stability. Photoluminescence PL spectrum of 3 was recorded in a pure chloroform solution exhibiting emission maxima shifted in a bathochromic way at 415 nm and 440 nm.

Photophysical Properties
Our double aza-oxa [7]helicene 3 shows high luminescence upon photo-irradiation, which can be attributed to the rigid scaffold that hinders the thermal energy loss upon structural changes. The UV/vis absorption of 3 was recorded in different solvents to show its high solubility in most of the organic solvents which increases the potential for some applications that require good solubility such as solution-processed electronics [58][59][60]. In all measured solvents, compound 3 showed similar UV/vis absorption patterns ( Figure  4a). The maximum absorbance exhibited in chloroform was shown at 407 nm (absorption coefficient: 7.5 × 10 4 M −1 cm −1 ) corresponding to an optical energy gap of (2.18 eV). According to TD-DFT calculations at the MN15/6-311G(d,p) level of theory, this low-energy absorption can be accountable to the HOMO→LUMO transition. The absorption band at 385 nm possibly attributed to the equal contribution of both HOMO−1→LUMO and HOMO→LUMO+1 transitions. The band at 368 nm is estimated to be due to the HOMO−1→LUMO+1 transition, while the higher energy absorption band at 328 nm would be attributed to HOMO−2→LUMO corresponding to an optical energy gap of (2.58 eV). Molecular orbital calculations indicated that the HOMO is spread mainly over the phenylene linker (ring A′) and pyrroles (rings B') and LUMO is spread over the whole scaffold rather than the phenylene linker (ring A′), accounting for the substantial stability. Photoluminescence PL spectrum of 3 was recorded in a pure chloroform solution exhibiting emission maxima shifted in a bathochromic way at 415 nm and 440 nm.

Energetic Characterization by Cyclic Voltammetry
Cyclic voltammetry (CV) measurements of our double aza-oxa [7]helicene 3 showed reversible redox peaks in both negative and positive regions indicating the chemical stability of its anion/cation pairs and how they can be reduced or oxidized readily to the neutral form ( Figure 5). Using ferrocene and ferrocenium as internal references, the HOMO energy level of 3 was calculated using Bredas empirical equation to be around (-7.83 eV) which is comparable to the DFT-calculated HOMO energy (−7.90 eV) [61]. ELUMO could be estimated after considering the gap between EHOMO and ELUMO (3.04 eV) from the

Energetic Characterization by Cyclic Voltammetry
Cyclic voltammetry (CV) measurements of our double aza-oxa [7]helicene 3 showed reversible redox peaks in both negative and positive regions indicating the chemical stability of its anion/cation pairs and how they can be reduced or oxidized readily to the neutral form ( Figure 5). Using ferrocene and ferrocenium as internal references, the HOMO energy level of 3 was calculated using Bredas empirical equation to be around (-7.83 eV) which is comparable to the DFT-calculated HOMO energy (−7.90 eV) [61]. E LUMO could be estimated after considering the gap between E HOMO and E LUMO (3.04 eV) from the λ max or excitation energy (407 nm) to be around (−4.79 eV) showing little higher energy than the DFT-calculated LUMO (−5.72 eV).

General Experimental Details
1 H-, and 13 C-NMR were recorded via JNM ECA600 FT NMR ( 1 H-NMR 600 MHz, 13 C-NMR 151 MHz). 1 H-NMR spectra are reported as follows: a chemical shift in ppm downfield of tetramethylsilane (TMS) and referenced to residual solvent peak (CDCl 3 ) at 7.26 ppm, or ((CD 3 ) 2 CO) at 2.05 ppm, multiplicities (s = singlet, d = doublet, dd = doublet of doublets, t = triplet, q = quartet, m = multiplet), and coupling constants (Hz). 13 C-NMR spectra reported in ppm relative to the central line of triplet for CDCl 3 at 77.16 ppm, or the central line of septet for ((CD 3 ) 2 CO) at 29.84 ppm. APCI-MS spectra were obtained with JMS-T100LC (JEOL). FT-IR spectra were recorded on a JASCO FT-IR system (FT/IR4100). Photoluminescence (PL) spectra were recorded on JASCO FP-8550 Spectrofluorometer. UV spectra were recorded on a JASCO v-770 spectrophotometer. Column chromatography on SiO 2 was performed with Kanto Silica Gel 60 (63-210 µm). Commercially available organic and inorganic compounds were used without further purification. The electro-oxidation was carried out using sing ElectraSyn ® 2.0 (designed by IKA) at a constant current of 1.5 mA, under air (1 atm.) [62].

DFT Calculations
All DFT calculations were performed using the Gaussian 16 package of programs [63]. The geometries of the model compounds were optimized using three DFT functions: B3LYP, wB97XD, and MN15 at 6-311G(d,p) basis set. All stationary points were identified as stable minima by frequency calculations. Geometry optimization was achieved using the normal criteria defined in Gaussian 16. TD-DFT calculations were performed using two different levels of theory B3LYP/6-311G(d,p) and MN15/6-311G(d,p) in both chloroform and gas-phase. All structures were optimized without any symmetry assumptions. For further computational details, see Supplementary Materials.

Conclusions
In summary, we introduced a two-step protocol to synthesize double aza-oxa [7]helicene 3 using an electrochemical approach. This novel double hetero [7]helicene shows interesting structural features that were reflected in its excellent optical properties. We have studied the photophysical characteristics of this compound and correlated its absorption and fluorescence behavior based on DFT calculations. Further development for this two-step protocol towards the preparation of other multiple helicenes and PHAs and study their photophysical and chiroptical features are currently under investigation.