Streamlining Fluoroalkenyl Arene Synthesis Illuminated with Mechanistic Insights

Abstract

Fluorinated compounds are a staple of modern-day chemical innovation, and efficient strategies for their synthesis are highly valuable. In this chemical space, fluoroalkenes continue to be the object of much interest across diverse fields, including drug development and pharmaceuticals with active roles as bioisosteres. Herein, in expanding chemists' synthetic toolbox for constructing valuable organofluorine compounds, we report a "pipeline" strategy for the synthesis of fluorinated olefins, viz., gem-difluoroalkenyl and monofluoroalkenyl arenes with high E-isomeric selectivity. The advantages of this streamlined synthetic protocol include mild reaction conditions, operational simplicity, broad substrate scope, and good to excellent yields, even at gram scales. Critical to this robust procedure is the use of widely available and inexpensive "scavenger" solid-support Merrifield peptide resin for removing phosphine impurities. Further computational investigations offering clarity into this reactivity are disclosed.