Synthesis of Atropisomeric Quinazolin-4-one Derivatives Based on Remote H/D and C/C Discrimination.

Both enantiomers of 2-ethylquinazolin-4-ones bearing -CHO/CDO and CHO/CHO phenyl groups at the N3 position were prepared. These are isotopic atropisomeric compounds based on a remote and conformationally flexible H/D and C/C discrimination, and it was found that a CHCl solution of -CHO/CDO derivative shows a slight specific optical rotation. Furthermore, diastereomeric quinazolinone derivatives bearing a chiral carbon were prepared, and their stereochemical purities and rotational stability as well as the isotopic atropisomerism were verified by H NMR and chiral high-performance liquid chromatography (HPLC) analyses.

Synthesis of Isotopic Atropisomers Based on C/C Discrimination.

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

Asymmetric Synthesis of Isotopic Atropisomers based on -CH/CD 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 -CH/CD discrimination and were revealed to possess a slight optical rotation and high rotational stability.