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Controllable stepwise fluorine elimination strategy for the chemodivergent synthesis of pyrido[2,1-a]isoquinolines

Year: 2025

Type: article

Abstract: A controllable stepwise fluorine elimination strategy has been reported, and used to selectively produce fluoro-substituted pyrido[2,1- a ]isoquinolines and fluorine-free pyrido[2,1- a ]isoquinolines through transition-metal-free formal [3 + 3] cycloadditions of isoquinolinium ylides with gem -difluorocyclopropenes. Mechanistic studies revealed that the unstable allylic C(sp 3 )–F bond serves as the primary driving force for the second C–F bond cleavage, which is readily substituted by H 2 O and subsequently oxidized by t -butyl hydroperoxide (TBHP). This protocol shows several attractive characteristics, such as readily available and inexpensive substrates, step and atom economy, and mild reaction conditions without any transition-metal catalysts. A controllable stepwise fluorine elimination strategy is reported, chemoselectively producing fluoro-substituted pyrido[2,1- a ]isoquinolines and fluorine-free pyrido[2,1- a ]isoquinolines through transition-metal-free formal [3 + 3] cycloadditions.

Source: Green Synthesis and Catalysis

DOI: 10.1016/j.gresc.2025.03.007