Synthesis and Analysis of (γ,γ’,γ’’‐Trifluoro)neopentyl (TFNP) Aryl Ethers as a Polar Fluoroaliphatic Motif

Abstract

A route is developed to (g,g’,g’’’’‐trifluoro)neopentyl (TFNP) aryl ethers to extend the methods for the introduction of the tert‐butyl group, carrying a fluorine on each of the methyl substituents. The route combines neopentyltosylate 3 with phenols and thiophenols to give efficient substitution reactions to the corresponding TFNP aryl ethers. The three C‐F bonds adopt a helical propeller conformation as revealed by computation and single crystal X‐ray structure analysis. The LogPs of TFNP ethers are lower (more hydrophilic) than their tert‐butyl analogues. The metabolism of selected TFNP ethers was explored in the fungus Cunninghamella elegans.