Chichibabin indolizine synthesis revisited: synthesis of indolizinones by solvolysis of 4-alkoxycarbonyl-3-oxotetrahydroquinolizinium ylides.

Solvolysis of 4-alkoxycarbonyl-(or 4-acyl)-3-oxo-1,2,3,4-tetrahydroquinolizinium ylides (1-4) was studied and three types of reactions were found to proceed competitively. Thus, alcoholysis afforded the Chichibabin rearrangement products, 2,3-dihydro-2-indolizinones (5-8), solvolysis in trifluoroethanol or in aqueous methanol caused ring opening (and subsequent ester cleavage) to 2-alkoxycarbonylethylpyridinium-1-acetates 10, 15, and 16, and hydrolysis resulted in ring opening to 1-alkoxycarbonylmethylpyridinium-2-propionates 11 or 13 (and subsequently to 12 or 14). Characteristically, all the types of reactions proceeded significantly faster with t-butoxycarbonyl substituted ylides than with smaller alkoxycarbonyl substituted ones. The general mechanism for the solvolysis, involving a ketene intermediate, is proposed based on kinetic measurements.