Aryl (β,β',β″-Trifluoro)--butyl: A Candidate Motif for the Discovery of Bioactives.

The (β,β',β″-trifluoro)--butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a -butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log (increasing hydrophilicity), ultimately by 1.7 Log units in the TFTB group relative to that of -butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.