Stereodynamic Analysis of New Atropisomeric 4,7-Di(naphthalen-1-yl)-5,6-dinitro-1H-indoles
Received: 15 May 2018
Accepted after revision: 21 June 2018
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.
Key wordsatropisomerism - electronic circular dichroism - benzannulation - DFT calculations - X-ray spectroscopy - indole
References and Notes
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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.
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