Synthesis of Pyrrole Derivatives via Ordered Isocyanide Insertion Reaction Driven by Ring Strain Mediated by Non-covalent Bond Interactions

Abstract

An efficient synthesis of pyrrole derivatives is achieved via ordered isocyanide insertion reaction, driven by ring strain and mediated by intramolecular non-covalent bonds. This method harnesses the strategic design of precursors to control reactivity, ensuring selectivity and high yields. The strategy is noteworthy for its innovative utilization of α, β-unsaturated ketone, which concurrently serves as both a directing group and an integral reaction substrate. Additionally, we have demonstrated the sequential de-tert-butylation of the same substrate under alkaline or acidic conditions. The plausible mechanism has been further corroborated through DFT theoretical calculations, providing a solid foundation for our proposed route.