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
School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K.
Chemistry Department, University of Lagos, Akoka, Lagos 101245, Nigeria.
Org Lett. 2023 Sep 22;25(37):6802-6807. doi: 10.1021/acs.orglett.3c02236. Epub 2023 Sep 8.
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.
（β,β',β″-三氟）-丁基（TFTB）基团在文献中很少受到关注。这项工作展示了该基团的直接合成方法并探究了其性质。当丁基部分的甲基被氟甲基取代时，就会产生TFTB基团。连续的氟甲基化导致LogP降低（亲水性增加），相对于丁基苯本身，TFTB基团最终降低了1.7个LogP单位。在将TFTB基团作为生物活性物质发现的一个有利基序展示其优势的背景下，重点关注其合成转化、构象分析和代谢。
