Synthesis of Isotopic Atropisomers Based on 12C/13C Discrimination.

Quinazolin-4-one derivatives possessing an isotopic atropisomerism (isotopic N-C axial chirality) based on ortho-12CH3/13CH3 discrimination were prepared. The diastereomeric quinazolin-4-ones bearing an asymmetric carbon as well as an isotopic atropisomerism were clearly discriminated by 1H and 13C NMR spectra and revealed to possess high rotational stability and stereochemical purity.

Asymmetric Synthesis of Isotopic Atropisomers based on ortho-CH3/CD3 Discrimination and Their Structural Properties.

N-C axially chiral 3-(2-trideuteriomethyl-4,6-dimethylphenyl)-2-ethylquinazolin-4-ones and 3-(2-trideuteriomethyl-4,6-dimethylphenyl)-2-(1-phenylpropan-2-yl)quinazolin-4-ones were prepared in high enantio- and diastereomeric purities (98% ee). These quinazolinone derivatives are isotopic atropisomers based on ortho-CH3/CD3 discrimination and were revealed to possess a slight optical rotation and high rotational stability.

Detection of Isotopic Atropisomerism Based on ortho-H/D Discrimination.

Racemic and optically active 3-(2-deuteriophenyl)-2-(1-phenylpropan-2-yl)quinazoline-4-thiones were prepared. The nuclear magnetic resonance spectra clearly show that they exist as a 1:1 mixture of diastereomers due to the isotopic atropisomerism based on ortho-H/D discrimination (N-C axial chirality) and a chiral carbon.