Novel asymmetric synthesis of atropisomeric 6-aryl pyrazinones via an unusual chirality transfer process

Cyclization of (S,S)-alpha-[(1-phenylethyl)amino]-alpha-(2-iodophenyl)aceto nitrile with (COCl)(2) in toluene or chlorobenzene afforded the atropisomer ic pyrazinone (aS,S) 6-(2-alpha-iodophenyl)-3,5-dichloro-1-(1-phenylethyl)- 2-(1H)-pyrazinone in 57% yield. With smaller ortho substituents (F, Cl, CH3 , CF3, OCH3) on the aromatic ring, mixtures of atropisomers were obtained f rom the cyclization reaction. All of the individual atropisomers prepared w ere stable at room temperature. All but the o-fluoro-substituted atropisome rs were stable at elevated temperatures. This paper describes a stereoselec tive synthesis of pyrazinones and suggests a mechanism for formation via an interesting transfer of chirality.