Synlett 2018; 29(16): 2161-2166
DOI: 10.1055/s-0037-1609908
© Georg Thieme Verlag Stuttgart · New York

Stereodynamic Analysis of New Atropisomeric 4,7-Di(naphthalen-1-yl)-5,6-dinitro-1H-indoles

Angela Pagano
b  Department of Chemistry and Industrial Chemistry, University of Genova, Via Dodecaneso 31, 16146 Genova, Italy
Emanuela Marotta
a  Department of Industrial Chemistry “Toso Montanari”, University of Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy   Email:
Andrea Mazzanti
a  Department of Industrial Chemistry “Toso Montanari”, University of Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy   Email:
Giovanni Petrillo*
b  Department of Chemistry and Industrial Chemistry, University of Genova, Via Dodecaneso 31, 16146 Genova, Italy
Cinzia Tavani
b  Department of Chemistry and Industrial Chemistry, University of Genova, Via Dodecaneso 31, 16146 Genova, Italy
Michele Mancinelli*
a  Department of Industrial Chemistry “Toso Montanari”, University of Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy   Email:
› Author Affiliations
Further Information

Publication History

Received: 15 May 2018

Accepted after revision: 21 June 2018

Publication Date:
20 July 2018 (online)

Published as part of the Cluster Atropisomerism


A series of atropisomeric molecules containing the indole ring and two stereogenic axes were prepared. The four atropisomers were resolved by enantioselective HPLC. The rotational barriers of the indole–naphthyl axes were evaluated by means of kinetic analysis either by NMR or enantioselective HPLC. The absolute configuration of the ­atropisomers was determined by a combination of X-ray spectroscopy and TD-DFT simulation of electronic circular dichroism spectra.

Supporting Information

  • References and Notes

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  • 19 To compare the diastereoisomerization barriers, the kinetic experiments were run by keeping the samples of 1, 2, and 5 in the same oil bath, in order to avoid any temperature difference between the experiments. Within this framework the error due to the temperature is ruled out and any difference in the rate constants is meaningful.
  • 20 Molecular formula: C23H24N3O6Br·CH2Cl2 M r = 317.43, triclinic, space group P1, a = 9.61(3), b = 11.83(3), c = 15.19(4), α = 104.22(5), β = 92.04(4), γ = 107.90(5) Å, V = 1581(7) Å3, T = 298(2) K, Z = 2, ρc = 1.430 g cm–3, F(000) = 694, graphite-monochromated Mo radiation (λ = 0.71073 Å), μ(Mo) = 1.433 mm–1, colorless needle (0.40 × 0.20 × 0.2 mm3), empirical absorption correction with SADABS (transmission factors: 0.598–0.763), 2400 frames, exposure time 25 s, 1.88 ≤ θ ≤ 25.00, –11≤ h ≤ 11, –14 ≤ k ≤ 14, –18 ≤ l ≤ 18, 17236 reflections collected, 10797 independent reflections (R int = 0.0379), solution by intrinsic phasing (SHELXT) and subsequent Fourier syntheses, full-matrix least-squares on F o 2 (SHELXL-2014/7), hydrogen atoms refined with a riding model, data/restraints/parameters = 10797/0/809, S(F 2) = 1.026, R(F) = 0.0765 and wR(F 2) = 0.1485 on all data, R(F) = 0.0511 and wR(F 2) = 0.1447 for 7850 reflections with I > 2σ (I), weighting scheme w = 1/[σ2(F o 2) + (0.0420P)2 + 0.4393P] where P = (F o 2 + 2F c 2)/3, largest difference peak and hole 0.572 and –0.378 e Å–3. Flack parameter for 4P,7M and 4P,7P absolute configuration: 0.094(7). The crystal cell contains both the diastereoisomers 4b and 4c. Crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC-1843183 (https://www.ccdc.
  • 21 Here the 5a and 5d labels are not related to the elution order. As in the case of 1, CSP-HPLC separation of the four stereoisomers of 5 could not be obtained.
  • 22 The ECD spectra were acquired in HPLC-grade acetonitrile (about 1·10–4 M in order to have a maximum absorbance between 0.8 and 1) with a cell path of 0.2 cm in the 190–400 nm region by the sum of 8 scans at 50 nm min–1 scan rate.

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  • 29 See Scheme S1 in the Supporting Information: To a stirred suspension of dinitrobutadiene 6 (100 mg, 0.25 mmol) in TFE (5 mL) at room temperature was added pyrrole (35 μL, 0.50 mmol). After 24 h, a second aliquot of pyrrole (35 μL, 0.50 mmol) was added and the mixture was stirred for 48 h. The reaction was monitored by TLC (petroleum ether/EtOAc 7:3) until the disappearance of the dinitrobutadiene. The solvent was removed under reduced pressure and the residue was dissolved in toluene (5 mL). DDQ (114 mg, 0.50 mmol) was added and the reaction mixture was stirred at reflux for 15 h. The solvent was removed under reduced pressure and then the residue was purified by flash chromatography on silica gel, eluting with petroleum ether/EtOAc 7:3, to afford compound 1 (73 mg, 0.16 mmol, 63%) as a yellow solid. The diastereomeric ratio of compound 1 was 3:7. The spectroscopic characterization of 1a and 1b was carried out starting from the deprotection of 3a and 3b as reported in the Supporting Information.
  • 30 Experimental procedures and spectroscopic characterization of compounds 2, 3, 4, and 5 are reported in the Supporting Information.
  • 31 Ground state optimizations and transition states were obtained by DFT computations performed by the Gaussian 09 rev D.01 series of programs by using standard parameters. The calculations for ground states and transition states employed the B3LYP hybrid functional and the 6-31G (d) or the 6-311G(d,p) basis set. Optimizations for 1, 2, and 5 were also run at the PCM-B3LYP/6-311G(d,p) level. The analysis of the vibrational frequencies for the optimized structures showed the absence of imaginary frequencies for the ground states, and the presence of one imaginary frequency for each transition state. Visual inspection of the corresponding normal mode validated the identification of the transition states. The ECD spectra of compounds were calculated with TD-DFT by using BH&HLYP, M06-2X, ωB97XD, CAM-B3LYP, and the 6-311++G(2d,p) basis set. TD-DFT calculation including the solvent acetonitrile were run at the PCM-CAM-B3LYP/6-311++G(2d,p) level. 70 to 90 discrete transitions were calculated for each conformation (lowest calculated wavelength about 160 nm) and the ECD spectrum was obtained by convolution of Gaussian shaped lines (0.25 eV line width). The simulated spectra resulting from the Boltzmann averaged sum of the conformations were vertically scaled and red-shifted by 10–18 nm to obtain the best comparison with the experimental spectra.