Discrimination of Axial and Central Stereogenic Elements in Chiral Bis(oxazolines) Based on Atropisomeric 3,3′-Bithiophene Scaffolds Through Chiroptical Spectroscopies

Two diastereoisomeric pairs of bis-oxazolines, provided with a stereogenic center
at carbon 4 and based on the 3,3′-bithiophene atropisomeric scaffold, were synthesized and
structurally characterized. They differ in the substituents at positions 2 and 5 of the thiophene
rings, which are functionalized with methyl (1) or phenyl (2) groups, respectively. In vibrational
circular dichroism (VCD) spectra, recorded in CCl4 solutions, it is possible to distinctly recognize
the characteristic features of axial and central stereogenic elements. In tandem with Density
Functional Theory (DFT) calculations, the absolute configuration (AC) of the diastereoisomers
was safely established. In this case, VCD was shown to be superior to ECD (electronic circular
dichroism) in the assignment of AC. The normal modes, evaluated from DFT calculations, show
that the VCD signals in correspondence with the stereogenic axis of the bithiophene unit are different
for 1 and 2. The VCD spectra of a molecular analog of 1, the (S)-2,2′,5,5′-tetramethyl-4,4′-
bis-(diphenylphosphino)-3,3′-bithiophene oxide (3), characterized by the same 3,3′-bithiophene
scaffold, but devoid of stereogenic centers, exhibits signals similar to those observed in the case
of diastereoisomer (aS,R,R)-1a, associated with almost identical normal modes.