Diastereomeric preference of a triply axial chiral binaphthyl based molecule: a concentration dependent study by chiroptical spectroscopies

Abstract

We have examined the effects of environmental perturbations, specifically solvents and concentrations, on axial chirality of a recently synthesized axially chiral binaphthyl fluorene based salen ligand, named AFX-155, {[2,2'-(1E,1'E)-(R)-1,1'-binaphthyl-2,2'-diylbis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(4-((7-(diphenylamino)-9,9-dihexyl-9H-fluoren-2-l)ethynyl)-phenol)]}. Chirality and dominant conformations of AFX-155 in CDCl3 solvent have been characterized using vibrational absorption (VA) and vibrational circular dichroism (VCD) spectroscopy in combination with DFT calculations. AFX-155 exhibits triple axial chirality: one is at the binaphthyl ring and the other two are related to the axes of chirality along the -C-N bonds where Cs are part of the binaphthyl group. To evaluate solvent and concentration dependence, complementary VA and VCD experiments in both THF-d8 and CDCl3 have been performed, as well as the optical rotatory dispersion (ORD) and electronic CD (ECD) measurements in CDCl3 under much diluted conditions. While the binaphthyl chirality is determined by the synthetic route, the results show that the latter two axial chirality labels of the dominant diastereomers are concentration dependent. Under much diluted conditions, R-binaphthyl, R_intra_HB//R_extra_HB (R-RR) is favoured, whereas R-binaphthyl, S_intra_HB//S_extra_HB (R-SS) is the dominant species in a concentrated solution. This diastereomeric interconversion is found to be independent of the two solvents used. To provide insights into this interesting finding, conformational searches and the related spectral simulations have been carried out at the DFT/B3LYP/6-31G(d) level.

Stereochemistry of the Brivaracetam Diastereoisomers

“…The method became much more popular when algorithms appeared that allowed the interpretation of the spectra through comparison with theoretically obtained ones . The number of applications of VCD for the determination of the AC of diastereoisomers increases every year, and in many cases the relative stereochemistry is already known. The purpose of the present paper is to show the strength of VCD to determine the ACs of all stereoisomers of brivaracetam with no prior knowledge of their relative stereochemistry.…”