Fluorinated cyclopropanes for 2-heterosubstituted electron-rich indolizine synthesis

Abstract

Fluorinated cyclopropanes were proven to be valuable precursors for a wide range of 2-heterosubstituted electron-rich indolizines, hardly accessible by other methods due to their instability. Copper(I) activation of C–X bonds permits disubstituted fluorocyclopropanes to undergo ring opening in the presence of pyridines, yielding (2-fluoroallyl)pyridinium salts. These intermediates were found to undergo base-promoted cyclization, either retaining the fluorine atom or undergoing intermolecular fluorine substitution with additional NuH, producing two- or three-component-derived 2-F,N,S,O-subtituted indolizines. This strategy allows 2-heterosubsituted indolizines with different 1,3-substitutition and nucleophilic parts to be prepared, including ones with functional groups capable of coupling with biologically relevant structures. The 2-heteroindolizines obtained exhibit blue-light emission with high intensity in DMSO, good Stokes shift and notable quantum yields.