Indolizines electrophilic substitution: acylation

Indolizine is much more basic than indole (p Ta = 3.9 vs. —3.5), and the stability of the cation makes it less reactive and resistant to acid-catalyzed polymerization. Protonation occurs at C-3, although 3-methylindolizine protonates also at C-l. Introduction of methyl groups raises the basicity of indolizines. Electrophilic substitutions such as acylation, Vilsmeyer formylation, and diazo-coupling all take place at C-3. Nitration of 2-methylindolizine under mild conditions results in substitution at C-3, but under strongly acidic conditions it takes place at C-l, presumably via attack on the indolizinium cation. However, the nitration of indolizines often can provoke oxidation processes. 

Electrophilic substitution on indolizine takes place at C-3, such as acylation (e.g., AC2O/ACOH), ViLSMEiER formylation (DMF/POCI3), or diazo coupling (Ar — N ). 

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