Aryl (ß,ß′,ß.-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives

The (ss,ss ',ss ''-trifluoro)-tert-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 tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-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.

Automated summary

This work presents a direct synthesis of the (ss,ss ',ss ''-trifluoro)-tert-butyl (TFTB) group and explores its properties. The study focuses on synthetic transformations, conformational analysis, and metabolism of the TFTB group, providing insights for the discovery of bioactives.