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)acetonitrile with (COCl)(2) in toluene or chlorobenzene afforded the atropisomeric 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, CH(3), CF(3), OCH(3)) on the aromatic ring, mixtures of atropisomers were obtained from the cyclization reaction. All of the individual atropisomers prepared were stable at room temperature. All but the o-fluoro-substituted atropisomers were stable at elevated temperatures. This paper describes a stereoselective synthesis of pyrazinones and suggests a mechanism for formation via an interesting transfer of chirality.
Tulinsky
John
J
Structural, Analytical and Medicinal Chemistry, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001-0199.
Cheney
B. Vernon
BV
Mizsak
Stephen A.
SA
Watt
William
W
Han
Fusan
F
Dolak
Lester A.
LA
Judge
Thomas
T
Gammill
Ronald B.
RB