Synthesis of Janus All- Cis Tetrafluorocyclohexanes Carrying 1,4-Diether Motifs

J Org Chem. 2024 Dec 20;89(24):18445-18451. doi: 10.1021/acs.joc.4c02345. Epub 2024 Nov 27.

Abstract

Nucleophilic aromatic substitutions (SNAr) of alkoxides on pentafluoroaryl ethers are explored as a first step in a synthesis sequence to generate all-cis 2,3,5,6-tetrafluorocyclohexyl-1,4-dialkyl ethers 1. The SNAr reaction was explored both experimentally and theoretically to rationalize ortho/para/meta selectivities. tert-Butyl deprotection of products followed by phenol alkylations introduces versatility to the synthesis. The final Rh(CAAC) 3 catalyzed aryl hydrogenation step of intermediate tetrafluoroaryl-1,4-diethers generated cyclohexane products 1. This chemistry introduces a new class of Janus fluorocyclohexane derivatives with ether substituents placed 1,4- to each other.