[1H]/[2H] discriminated bianthryl atropisotopomers: enantiospecific syntheses from BINOL and direct multi-spectroscopic analyses of their isotopic chirality

Abstract

The synthesis of two [¹H]/[²H] discriminated bianthryl atropisotopomers (i.e., isotopically chiral atropisomers, vide infra) with ≥97% enantiomeric excess (ee) from the atropisomers of commercial (aS)- and (aR)-1,1′-bi-2-naphthol (BINOL, >99% ee) is described. The approach is based on enantiospecific [4 + 2] cycloaddition reactions of aryne atropisomer intermediates with [²H₄]-furan. Overall, the six-step (from enantiopure BINOL) reaction sequence to the bianthryl atropisotopomers described herein occurs without significant erosion of the molecular stereogenic information. This is substantiated experimentally by three direct spectroscopic methods that do not necessitate chemical derivatization: (i) mirrored specific optical rotations as a proof of optical activity as well as of their equivalent ee, (ii) mirrored vibrational circular dichroism (VCD) spectra as a proof of their equivalent ee and for the confirmation of their absolute configurations (AC), and (iii) for the first time, anisotropic ²H/¹³C NMR in lyotropic chiral liquid crystals for the determination of the ee of one of them. In a broader and foreseeable perspective, the enantiospecific synthetic approach considered in this work to access bianthryl atropisotopomers from BINOL is simple and scalable, which should enable the production of a diverse range of atropisotopomers in the near future, possibly utilizing never-examined isotopes (e.g., [³H]). The availability of this class of isotopically chiral compounds in high isotopic and enantiomeric purity is a real asset for the development of precision chiral spectroscopies.