Abstract

Comprehensive Summary Indolizine is a nitrogen‐containing heterocycle with strong aromaticity, possessing a delocalized 10π‐electron system. Based on the indolizine scaffolds, numerous molecules with biological activity and organic functional materials have been synthesized. Since 2016, over 110 papers have been published on the synthesis of indolizine scaffolds, but the reviews on synthesizing indolizine scaffolds have been incomplete and not up‐to‐date. Herein, from the perspective of the structure of indolizine with the combination of pyrrole and pyridine ring, we focus on the construction of indolizine scaffolds through the diversity of starting substrates, including pyridine derivatives (N1‐substituted pyridinium salt derivatives, C2‐substituted pyridine derivatives, N1‐ and C2‐free substituted pyridine derivatives), pyrrole derivatives and unoriginal ring substrates. Furthermore, the corresponding reaction mechanisms of synthetic methodologies are also elaborated. Therefore, this review not only paves the way for indolizine synthesis but also provides insight into exploring new reaction modes for constructing nitrogen‐containing heterocycles. Key Scientists Indolizine was discovered by Angeli in 1890 and first prepared by Scholtz in 1912 from α‐picoline and acetic anhydride. A general approach was developed by Chichibabin in 1927, that is of practical value for the preparation of 2‐alkyl‐ or 2‐arylindolizines. The Chichibabin reaction was the ring closure of quaternary pyridinium halides. At the begining of the 21st century, Basavaiah introduced a new dimension in the Baylis‐Hillman chemistry leading to a novel facile convenient methodology for synthesis of indolizine scaffolds in one‐pot operation. In 2010, Barluenga reported Cu(I)‐catalyzed regioselective [3+2] cyclization of unsubstituted pyridines toward alkenyldiazoacetates leading to functionalized indolizine derivatives, that was the first successful example of metal‐catalyzed cyclization of a π‐deficient heterocyclic system with alkenyldiazo compounds. In 2019 and 2022, Xi and Liu exploited the methods of non‐pyridine derivatives as starting materials to synthesize indolizines, respectively. In 2022, Guo developed an environmentally benign electrooxidative approach for constructing formyl‐ and acyl‐substituted indolizines.