Indolizin-1-ols with Charged Electron Acceptors: A Direct Way to 3 H -Indolizinium-1-olates with Donor Functions.

The reaction of cyclopropenones with pyridines, having an attached integer-charged electron-withdrawing group (pyridinium, imidazolium, and phosphonium) was discovered to afford novel indolizin-1-ol derivatives in high yields with no chromatographic purification required. While being stable as solids, these indolizin-1-ols have a limited lifetime in solution. The study of reasons for such instability uncovered an aerobic oxidative pathway, eventually resulting in indolizine-1,7-dione dimers. The exploration of N -(1-hydroxyindolizin-7-yl)pyridinium salts' chemistry led to a reaction discovery, affording a new type of rare pseudo-cross-conjugated mesomeric betaines (3 H -indolizin-4-ium-1-olates with an electron-donating function at C7 position) inaccessible by other means. In this reaction, a sequential introduction of nucleophiles takes place: the first one (Nu 1 ) is represented by simple anilines, whereas Nu 2 extends to primary, secondary, aliphatic, aromatic amines, and phenols. For the obtained betaines having unsymmetrical aliphatic amino groups at C7 position an increased order of the C7-Nu 2 bond resulting in existence of amide type E/Z-forms (∼1:1 at room temperature) was demonstrated. For aryl amino groups, with typically reduced nitrogen's lone-pair donation, the barrier of rotation around the C7-Nu 2 bond was lower, and for the C7-oxy betaines, no such E/Z-isomerism was revealed. Although primary amines (as Nu 2 ) introduce a hydrogen atom in the conjugated betaine system, allowing prototropic tautomerism in this way, non-zwitterionic tautomers (3-amino-7-iminoindolizin-1-ones) were rejected by nuclear Overhauser effect spectroscopy experiments.