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Axial Chirality of 4-Arylpyrazolo[3,4-b]pyridines. Conformational Analysis and Absolute Configuration

Author:
Gunasekaran, Pethaiah, Perumal, Subbu, Menéndez, J. Carlos, Mancinelli, Michele, Ranieri, Silvia, Mazzanti, Andrea
Source:
Journal of organic chemistry 2014 v.79 no.22 pp. 11039-11050
ISSN:
1520-6904
Subject:
circular dichroism spectroscopy, diastereomers, enantiomers, enantioselectivity, energy, high performance liquid chromatography, moieties, molecular conformation, nuclear magnetic resonance spectroscopy, optical isomerism, organic chemistry, pyridines
Abstract:
The stereodynamic behavior of a series of pyrazolo[3,4-b]pyridines was studied. The restricted rotations of the aryl substituent in position 4 of the heteroaromatic ring and of the benzoyl group in position 5 generated conformational enantiomers or conformational diastereoisomers depending on the local symmetry of the aryl substituent, with very high rotational barriers despite the absence of ortho-substituents. The energy barriers for the rotation of the 5-benzoyl group and the 4-aromatic ring were measured by dynamic NMR and rationalized by DFT calculations. When the aryl substituent at position 4 was 1-naphthyl, the resulting atropisomeric pair was resolved by means of enantioselective HPLC and the absolute configuration was determined by TD-DFT simulations of electronic circular dichroism spectra.
Agid:
5503007