Axially chiral pyridine compounds: Synthesis, chiral separations and determination of protonation dependent barriers to hindered rotation

Axially chiral enantiomeric 2-pyridylimino-3-pyridyl-thiazolidine-4-ones and -thiones have been synthesized and their rotational barriers around the N-3C_(pyridyl) bond have been determined by variable temperature NMR or by thermal racemization of the micropreparatively resolved enantiomers. Rotational barriers of the unprotonated compounds ranged from 46 to 116 kJ/mol, depending on the substituent on the N-3-pyridyl ring and on the exocyclic oxygen or sulfur atoms of the thiazolidine ring. Protonation of the pyridine nitrogens by TFA caused a decrease in the barrier to the rotation by stabilizing the transition state of the rotations via hydrogen bonding interactions.