On the racemization of chiral imidazolines.
Racemization of chiral imidazolines with base has been studied for the first time following an unexpected finding in the synthesis of chiral imidazoline ligands. Amine bases do not cause racemization. Strong inorganic bases can induce racemization, yet this occurs only when the nitrogen is unsubstituted, in agreement with a symmetry-allowed thermal disrotatory ring opening and closure from a diazapentadienyl anion. Surprisingly, even with electron-withdrawing N-substituents, no racemization is observed. Conditions which allow for the racemization-free manipulations of this important compound class have been defined and developed.
Busacca
Carl A
CA
Department of Chemical Development, Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877, USA. carl.busacca@boehringer-ingelheim.com
Bartholomeyzik
Teresa
T
Cheekoori
Sreedhar
S
Grinberg
Nelu
N
Lee
Heewon
H
Ma
Shengli
S
Saha
Anjan
A
Shen
Sherry
S
Senanayake
Chris H
CH
D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004121:Dimethyl Sulfoxide; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D007536:Isomerism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D012997:Solvents; D013237:Stereoisomerism
D007093:Imidazoles; D008024:Ligands; D012997:Solvents; D004121:Dimethyl Sulfoxide