Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

Novel carbazole-based [6]helicenes fused with an azine ring (pyridine, pyrazine or quinoxaline) have been prepared through a five-step synthetic sequence in good overall yields. Commercially available 2,3-dihaloazines were used as starting materials. To discern the effect of merging an azine moiety within a helical skeleton, the X-ray structures, UV–vis absorption and fluorescence spectra of the helicenes were investigated and compared to that of the parent carbazole-based [6]helicene (7H-phenanthro[3,4-c]carbazole).

In the cases of compounds 2a,b, the reaction was found to be very sensitive to the amount of ICl used. In the case of 2a, the use of a 1.5-fold excess of ICl led to a hardly separable mixture of compound 7a and diiodo derivative 8a (Table 3, entry 1, for the NMR spectrum of the mixture see Supporting Information File 1, Figure S13). Iodine chloride, taken in an equimolar amount, made it possible to obtain the required product 7a in 65% yield and to remove minor impurities of diiodo derivative 8a by chromatography (Table 3, entry 2). For the selective syn-  thesis of 7b, iodine chloride was taken in a small deficit ( Table 3, entries 3 and 4). Compound 8b was synthesized in 97% yield by the treatment with a 3-fold excess of ICl on monoiodide 7b. The ICl-induced cyclization of the pyridinebased starting compound 6 proceeded smoothly giving rise to product 7c in 62% (  The fourth step of the synthesis of the target helicenes, namely the Sonogashira coupling of iodides 7a and 7c with p-tolylacetylene, was carried out in the Pd(PPh 3 ) 2 Cl 2 /CuI/Et 3 N/THF catalytic system that proved itself well in the azine-fused [5]helicenes synthesis [72] ( Table 4, entries 1 and 3). The corresponding compounds 9a and 9c were obtained in 84 and 88% yields, respectively. In the case of 7b, the reaction was more selective without THF solvent producing alkyne 9b in 82% yield (Table 4, entry 2). The structure of 9c was unambiguously proved by X-ray structural analysis (see Supporting Information File 1, Figure S34). Earlier, at the final step of a similar synthesis of the azine-fused [5]helicenes, we used trifluoroacetic acid as a cyclizing agent [72]. Unfortunately, only in the case of compound 9c, heating in trifluoroacetic acid led to isomerization into the required carbazole-based [6]helicene 10c (Table 5, entry 3). Under these conditions, alkynes 9a and 9b produced an unseparable mixture of some products. To our delight, treating 9a and 9b with triflic acid in СH 2 Cl 2 solution at room temperature allowed us to obtain helicenes 10a and 10b in high yields ( Table 5, entries 1 and 2). Apparently, the presence of the aza group adjacent to the triple bond in compounds 9a and 9b causes the observed difference in the reactivity of compounds 9. Its protonation makes the formation of a key cyclization intermediate 11 difficult.
It is known that the [n]helicenes with at least one five-membered heteroaromatic ring need n ≥ 6 to become intrinsically chiral [9,10]. High-performance liquid chromatography on chiral stationary phases confirmed the presence of configurationally stable (P)-and (M)-enantiomers at room temperature in the samples of synthesized helicenes 10a-c. In all cases, separation of enantiomers of 10 was achieved using Kromasil 5-Cellucoat column (4.6 mm × 250 mm), acetonitrile as a mobile phase and UV-detection (see Supporting Information File 1, Figures  S38-S40).

X-ray molecular structures
The structures of the title compounds 10a-c were further explored by a single-crystal X-ray diffraction analysis ( Figure 1, see also Supporting Information File 1, Figures  S35-S37 and Table S1) and compared with that of the carbazole-based [6]helicene [42] (7-hexyl-7H-phenanthro[3,4c]carbazole, 12) to see the effect of the azine ring annelation (Table 6). The values of the torsion and interplanar angles make it possible to describe and compare the structural specificity of the synthesized [6]helicenes. From the data given in Table 6, it can be seen that the interplanar angle between the terminal rings A and F of the pyridine-fused [6]helicene 10c is the largest in the series (average value is 62°). The same value for [6]helicene 12 is equal to 56.7° [42]. The helicity of pyrazine-fused [6]helicene 10b and quinoxaline-fused hybrid 10a is intermediate (52.8°a nd 50.5°). Comparing the sum of the inner helix torsion angles of the helicenes 10a-c and 12 reveals the same patterns. Evidently, the repulsive interaction of the H (14) and H(g) atoms of 10c is the main reason for the observed extra twisting, whereas relative planarization of 10a and 10b is the result of attractive interactions of the aza groups N(f) and N(g) with the H(9) and H(14) atoms, respectively. The short intramolecular contacts H(9)···N(f) (2.457 Å for 10a, 2.454 Å for 10b) and H(14)···N(g) (2.517 Å for 10a, 2.477 Å for 10b) support this opinion. Apparently, interaction of this type is also realized in solution since the signal of the inner helix proton in the 1 H NMR spectra of azine-fused [6]helicenes appeared in the low field at δ 9.3-9.7 ppm. A similar pattern was observed by us in the structures of the azine-fused [5]helicenes [72].
It is well-known that the inner helix and outer helix C-C bonds of helicenes differ in their length [9]. Deviations of some of them from the standard aromatic C-C bond of benzene (1.393 Å) are significant. The length of the inner helix C-C bonds of [6] The X-ray analysis of quinoxaline-fused [6]helicene 10a revealed the presence of the face-to-face π-π interaction between the helicene aggregates. The racemic aggregation was composed by (P)-and (M)-enantiomers on the manner of embrace: π-deficient pyrazine ring of one enantiomer of 10a is located over the π-excessive pyrrole ring of another enantiomer (Figure 2a and Figure 2b). An intermolecular distance between the centroids of these rings was found to be equal to 3.74 Å making the π overlapping possible. In the case of helicene 10b, the enantiomeric molecules are aggregated into pairs differently: the pyrazine ring of one enantiomer is located over the E ring of another enantiomer and the distance between the layers is ca. 3.4 Å (Figure 2c and Figure 2d). The crystal packing of helicene 10c (Figure 2e) is peculiar: the alternating enantiomers form a screw along the a axis.

Optical properties
All helicenes 10 are well soluble in dichloromethane and chloroform. Solubility in other common solvents such as acetonitrile, DMSO, tetrahydrofuran, ethanol and hexane is markedly lower. Carbazole-based [6]helicene 12 was described as yellow  A dihedral angle between the four adjacent inner helix carbon atoms. b An angle between the two terminal aromatic rings A and F of a helicene. c There are two independent molecules in the unit cell. Data for the second molecule are marked with an asterisk *.  solid (the longest λ max 414 nm, CH 2 Cl 2 ) [42]. All azine-fused analogs of 12 are yellow-orange. The annelation of the pyridine or pyrazine ring to the skeleton of 12 only slightly changed the wavelength of the absorption maximum (the longest λ max 411 and 418 nm, respectively), whereas the absorption of quinoxaline-fused [6]helicene 10a was red-shifted by 19 nm (Table 7). Compounds 10 exhibited almost a solvent independence of UV-vis absorption spectra (Supporting Information File 1, Figure S41). The optical band gaps (E g opt ), estimated from the onset point of the absorption spectra, for [6]helicene 12 was equal to 2.92 eV [42]. The E g opt values for its π-extended analogs were 2.45 eV (10a), 2.76 eV (10b) and 2.85 eV (10c), suggesting a higher HOMO and lower oxidation potential, which are typically desired characteristics when designing organic materials. Unfortunately, for all azine-fused [6]helicenes 10 only weak fluorescence in the solution under UV irradiation was observed (Table 7, see also Supporting Information File 1, Figures S42-S45). Helicenes 10b and 10c exhibited blue emission with emission peaks at 481 and 440 nm, respectively. Quinoxaline-fused helicene 10a demonstrated a yellow emission with the highest in the series λ em = 561 nm and Stokes shift 128 nm.

Conclusion
In summary, novel carbazole-based [6]helicenes fused with an azine ring (pyridine, pyrazine or quinoxaline) have been prepared from commercially available 2,3-dihaloazines via a fivestep synthetic sequence. Two key steps of the method are electrophile-induced 6-endo-dig cyclizations of ortho-alkynylated biaryls. The overall yields of helicenes in five stages of the synthesis exceed 30%.
The single-crystal X-ray diffraction analysis revealed the nonplanar crystal structures of the synthesized helicenes responsible for reducing close-packing arrangement, though, in cases of pyrazine-and quinoxaline-fused helicenes, moderate π overlap in pairs of enantiomeric molecules was observed. Carbazolebased [6]helicene, fused with the pyridine ring, is more twisted than the parent carbazole-based [6]helicene (7Hphenanthro[3,4-c]carbazole). The interplanar angle between the two terminal benzene rings of the latter is equal to 56.7°, whereas the same value for the pyridine-fused analog is 62°. The pyrazine-fused [6]helicene demonstrates intermediate helicity (52.8°). In the case of the quinoxaline-fused analog the distortion angle of 50.5° is the smallest in the series.
The photophysical properties of the synthesized [6]helicenes were compared to the parent carbazole-based [6]helicene. A spectrophotometric analysis of the quinoxaline-fused helicene displayed a moderate absorption red-shift (19 nm) and reduced optical band gaps (by ≈0.5 eV). In cases of pyrazine and pyridine-fused analogs, differences are not so noticeable.

Experimental
The synthetic procedures, HPLC, X-ray studies and spectra ( 1 H and 13 C NMR) of all new compounds can be found in Supporting Information File 1.

Supporting Information
Supporting Information File 1 Experimental procedures and analytical data, copies of 1 H and 13 C NMR spectra of all new compounds, X-ray data for 9c and 10a-c, HPLC spectra of helicenes 10a-c, UV-vis and fluorescence spectra of 10a-c.