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

Author(s):Show less -

Dobson, Luca S. ; Zhang, Qingzhi ; Mckay, Benjamin A. ; Oke, Oluwayinka ; Isanbor, Chukwuemeka ; Khan, Mohd Faheem ; Piscelli, Bruno A. ; Cordes, David B. ; Cormanich, Rodrigo A. ; Murphy, Cormac D. ; O'Hagan, David

• Document type: Journal article
• Source: ORGANIC LETTERS; v. 25, n. 37, p. 6-pg., 2023-09-08.

Abstract

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. (AU)

• FAPESP's process: 22/10156-7 - Experimental and Theoretical study of stereoelectronic effects and supramolecular assembly of organofluorinated compounds
• Grantee: Bruno de Almeida Piscelli
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/03910-1 - Physicochemical studies of fluorinated organic compounds: experimental and theoretical approaches
• Grantee: Rodrigo Antonio Cormanich
• Support Opportunities: Research Grants - Young Investigators Grants