Synthetic Methods for Heterocycles and Carbocycles Bearing Fluorinated One-Carbon Units (=CF₂, CHF₂, or CF₃): Intramolecular Reaction of 2-Trifluoromethyl-1-alkenes

Abstract

Fluorine-containing heterocyclic and carbocyclic compounds attract widespread attention as important components of agrochemicals, pharmaceuticals, materials, and catalysts. To provide a general route to these compounds, we have developed a new methodology to construct fluorocarbon-bearing cyclic systems based on ring closure of functionalized 2-trifluoromethyl-1-alkenes, readily obtained from commercially available CH₂=C(CF₃)Br or CF₃CO₂Et. Their intramolecular reactions, such as nucleophilic substitution or addition, alkene insertion, and electrocyclization, provide a wide variety of five- and six-membered heterocycles and carbocycles bearing a fluorinated one-carbon unit (a =CF₂, CHF₂, or CF₃ group). To construct five-membered rings, we successfully accomplished a nucleophilic 5-endo-trig cyclization and 5-endo alkene insertion, normally disfavored processes, as well as fluorine-directed Nazarov cyclization.