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Thursday, March 30, 2023

Electrochemical Synthesis of Hetero[7]helicenes and Hetero-dehydro[7]helicenes

  • Electrochemical synthesis of straight[7]helicenes

Helicenes’ distinctive structure endowed them with optical and digital options that may be carried out in varied material-based functions, resembling natural light-emitting diodes (OLEDs) and field-effect transistors (FETs). Thus far, lots of artificial approaches for helicenes have been launched with [2+2+2] cycloaddition, alkyne cyclization, Friedel-Crafts, C−H activations, C−H arylations, metathesis, Diels-Alder, and cross-coupling reactions. Not too long ago, extra artificial advances have been achieved, increasing their various library and enabling uneven synthesis. In 2016, our group reported chiral vanadium(v)-catalyzed synthesis of oxa[9]helicenes through the oxidative coupling of arenol compounds adopted by intramolecular dehydrative cyclization.1,2 Regardless of all these profitable methods, there are some limitations associated to the low whole yields, harsh response circumstances, or overuse of oxidants.

Electrochemical syntheses have many benefits since no oxidant is required and oxidative transformation may be carried out below gentle response circumstances. To research the electrochemical synthesis of oxaza[7]helicenes 3, we chosen 3-hydroxybenzo[c]carbazole (1a) and 2-naphthol (2a) as mannequin substrates (Fig. 1). We assume that single electron switch (SET) from 1a would happen first to generate the electrophilic radical species on the anode as a result of 1a is extra simply oxidized than 2a.3 After radical-anion coupling between the novel cation species and 2a adopted by oxidative cyclization, oxaza[7]helicene 3aa can be fashioned. The differential redox potentials between coupling companions 1a and 2a play a key function within the chemoselectivity of the oxidative coupling step. After inspecting varied circumstances and performing sedulous optimization, we efficiently achieved a one-pot protocol with fluorine-doped tin oxide (FTO) electrodes and Bu4NPF6 as an electrolyte in CH2Cl2 for six h, at rt, giving oxaza[7]helicene 3aa in 82% yield.4,5

Fig. 1. Electrochemical synthesis of oxaza[7]helicene 3aa.

To ascertain the applicability of this methodology for concise synthesis of unsymmetrical helicenes from commercially out there substrates, a two-pot synthesis protocol was established: Acid-mediated annulation of p-benzoquinone (5) and N-aryl-2-naphthylamine 6 to afford 3-hydroxycarbazoles 1, that may bear with none additional purification an electrochemical domino response with 2-naphthol (2a) to afford the specified oxaza[7]helicenes 3aa-3ca in 43-45% total yields (Fig. 2). Varied mixtures of 2-naphthols 2 with a phenyl group or a (Bpin) group afforded the corresponding oxaza[7]helicenes 3 in 33–42% total yields. 2-Naphthols 2e with an electron-withdrawing substituent (e.g. methyl ester) at 3-position didn’t afford the specified oxaza[7]helicene 3ae in all probability attributable to a cause that may be attributed to the dearth of nucleophilicity of 2e and the alteration of its redox habits which interfered with the essential oxidative coupling step.6

Fig. 2. Two-pot synthesis of oxaza[7]helicene.

A two-step protocol to synthesize double oxaza[7]helicene 9 was additionally established through the use of our electrochemical strategy (Fig. 3). 

Fig. 3. Two-step synthesis of double oxaza[7]helicene 9.

The obtained novel double oxaza[7]helicene 9 exhibits attention-grabbing structural options that have been mirrored in its glorious optical properties. On this examine, an investigation of the photophysical traits of this compound and the correlation of its absorption and fluorescence habits based mostly on DFT calculations have been additionally carried out (Fig. 4).7

Fig. 4. UV/vis absorption and PL spectra of 9 in varied solvents (20 µM); Frontier Kohn-Sham molecular orbitals of 9 and TD-DFT calculated digital transitions at MN15/6-311G (d,p) degree of idea.

  • Electrochemical synthesis of straightdehydro[7]helicenes

    Hetero-dehydrohelicenes are a sort of polycyclic heteroaromatics (PHAs) characterised by their distinctive helical chirality, which ends from the connection of the 2 helical termini of a helicene by a sigma bond. Due to this distinctive chirality, dehydrohelicenes have extraordinary optical properties that may be utilized in numerous material-based functions. Regardless of the immense potential exhibited by dehydrohelicenes, to our information, there are not any reviews on their simple building together with uneven synthesis.

    To our delight, the electrochemical domino response was in a position to afford such attention-grabbing scaffolds upon utilizing particular substituted 2-naphthols 2. The electron-donating teams (e.g. OMe, OBn) on the 7-position of 2 will improve the electron density on the helical terminus enabling a further oxidative C-C bond-forming step within the sequence to offer finally oxaza-dehydro[7]helicenes 10 (Fig. 5). The design of those oxaza[7]helicene molecules with two heptagons (furan and pyrrole), and 5 hexagons made the gap between the 2 helical termini quick sufficient (< 3.0 A°) to allow the final oxidative C-C bond forming step upon rising the electron density on the helical termini therefore affording the corresponding oxaza-dehydrohelicenes 10.4

    Fig. 5. Electrochemical synthesis of oxaza-dehydro[7]helicene 10.

    Eyring plots indicated a big chiral stability of oxaza-dehydro[7]helicenes 10 (racemization barrier >140 kJ mol−1) (Fig. 6a); the t1/2 of compound 10aa was estimated to be better than 9.5 × 103 years at 25 °C. Dehydro[7]helicene 10aa confirmed larger chiral stability than that of corresponding oxaza[7]helicene 3aa (110 kJ mol−1). Subsequently, the chiroptical properties of the optically pure oxaza-dehydro[7]helicenes have been investigated. All of the helical dyes 10 confirmed absorption within the wavelength vary of 340–404 nm and fluorescence most at 450 nm; round dichroism (CD) and circularly polarized luminescence (CPL) alerts have been noticed in these areas. Oxaza-dehydro[7]helicenes, 10aa confirmed average quantum yield Φ = 0.25, and vital CPL exercise with glum = 2.5 × 10−3 at 433 nm (Fig. 6b).4

    Fig. 6. (a) Eyring plot for the racemization of dehydro[7]helicenes 10aa, and helicene 3aa; (b) Chiroptical properties (CD and CPL) of 10aa in CHCl3 (2×10-5  M).

    Having succeeded in growing a facile electrochemical synthesis of the dehydohelicenes, we subsequent targeted our consideration on the enantioselective synthesis of hetero-dehydro[7]helicenes (Fig. 7). Initially, diol (R)-4ba was readily obtained through the use of vanadium advanced (Ra,S)-11 through the enantioselective hetero-coupling. Subsequently, below electro-oxidation circumstances, (R)-4ba underwent a sequential dehydrative furan ring formation adopted by the coupling of the 2 helical termini to afford the corresponding oxaza-dehydro[7]helicene (M)-10ba in 87% yield sustaining the optical purity (Fig. 7).4

    Fig. 7. Stepwise building of (M)-10ba through chiral vanadium catalysis and electrochemical synthesis.

  • In the direction of larger sustainability

Though our sequential electrochemical protocol to synthesize oxaza[7]helicenes and oxaza-dehydro[7]helicenes from easy arenols contains a excessive yield below gentle circumstances (Fig. 8A), some limitations nonetheless stay to make these earlier circumstances much less sustainable, resembling the need of an extra quantity of the acidic additive BF3·OEt2 (50 equiv), larger present density (1.2 mA/cm2) that limits the compatibility with oxidatively-labile functionalities, the low recyclability of FTO electrodes (< 5 occasions), and low faradic effectivity (< 30%). With the intention to maximize the vitality effectivity and make this electro-synthetic strategy most sustainable, we additionally established the improved electrochemical circumstances that overcome these limitations by various some parameters (Fig. 8B).5

Fig. 8. New electrochemical circumstances for the synthesis of dehydro[7]helicenes and [7]helicenes.


  1. Sako, M., Takeuchi, Y., Tsujihara, T., Kodera, J., Kawano, T., Takizawa, S. & Sasai, H. Environment friendly enantioselective synthesis of oxahelicenes utilizing redox/acid cooperative catalysts. J. Am. Chem. Soc. 138, 11481–11484 (2016).
  2. Kumar, A., Sasai, H. & Takizawa, S. Atroposelective synthesis of C–C axially chiral compounds through mono- and dinuclear vanadium catalysis. Acc. Chem. Res. 55, 2949–2965 (2022).
  3. Sako, M., Higashida, Okay., Kamble, G. T., Kaut, Okay., Kumar, A., Hirose, Y., Zhou, D.–, Suzuki, T., Rueping, M., Maegawa, T. and Takizawa, S. & Sasai, H. Chemo-and enantioselective hetero-coupling of hydroxycarbazoles catalyzed by a chiral vanadium (v) advanced. Org. Chem. Entrance. 8, 4878–4885 (2021).
  4. Khalid, M. I., Salem, M. S. H., Sako, M., Kondo, M., Sasai, H. & Takizawa, S. Electrochemical synthesis of heterodehydro[7]helicenes. Commun. Chem. 5, 166 (2022).
  5. Salem, M. S. H., Khalid, M. I., Sako, M., Higashida, Okay., Lacroix, C., Kondo, M., Takishima, R., Taniguchi, T., Miura, M., Vo-Thanh, G., Sasai, H. & Takizawa, S. Electrochemical synthesis of straight[7]helicenes containing pyrrole and furan rings through an oxidative hetero-coupling and dehydrative cyclization sequence. Adv. Synth. Catal. in press, DOI: 10.1002/adsc.202201262.
  6. Salem, M. S. H., Khalid, M. I., Sasai, H. & Takizawa, S. Two-pot synthesis of unsymmetrical hetero[7]helicenes with intriguing optical properties. Tetrahedron in press, DOI: 10.1016/j.tet.2023.133266.
  7. Salem, M. S. H., Sabri, A., Khalid, M. I., Sasai, H. & Takizawa, S. Two-step synthesis, construction, and optical options of a double hetero[7]helicene Molecules 27, 9068 (2022).

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