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

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.

Circular Dichroism and TDDFT Investigation of Chiral Fluorinated Aryl Benzyl Sulfoxides

“…As a final remark, we observe that range-separated functionals such as CAM-B3LYP, also including dispersion correction such as ωB97X-D, are emerging as the most accurate and versatile for the prediction of electronic CD spectra of different kinds of organic molecules. [46][47][48][49][50] …”

Enantioselective Preparation, Conformational Analysis and Absolute Configuration of Highly Substituted Aziridines

“…Simulations were performed using the B3LYP‐optimized geometries with CAM‐B3LYP that includes long‐range correction using the Coulomb Attenuating Method, with the hybrid functionals M06‐2X and BH&HLYP, and with ωB97XD that includes empirical dispersion . Given the result of the preliminary tests, the 6‐311++G(2d,p) basis set was employed for the calculations, as it is computationally cheaper than def2TZVPP and usually provides good accuracy . The rotational strengths were calculated in both length and velocity representation, the resulting values being very similar (RMS difference < 5%).…”

“…61 Given the result of the preliminary tests, the 6-311++G(2d,p) basis set was employed for the calculations, as it is computationally cheaper than def2TZVPP and usually provides good accuracy. [61][62][63][64][65] The rotational strengths were calculated in both length and velocity representation, the resulting values being very similar (RMS difference < 5%).…”

Pyrazolo-fused 4-azafluorenones as key reagents for the synthesis of fluorescent dicyanovinylidene-substituted derivatives

“…Numerous approaches for the synthesis of PP 11,12 and their fused derivatives have been reported, 13,14 those reactions involved the interaction of 1,3-bis-electrophilic compounds with N-substituted 5-aminopyrazoles. [11][12][13][14] Moreover, multicomponent reactions (MCRs) are used in the synthesis of these compounds by the formation in situ of the bis-electrophilic intermediate. This approach has been widely used in diversity-oriented synthesis (DOS) of biologically active heterocyclic compounds.…”