Functional Hexafluoroisopropyl\nGroup Used in the Construction\nof Biologically Important Pyrimidine Derivatives

A series of versatile 4-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)pyridine\nintermediates have been developed to efficiently produce biaryls,\namines,\nethers, and thioethers. These hydrolysis-stable ether intermediates\nexhibit reactivity toward electron-donating groups and nucleophiles\nin cross-coupling and nucleophilic substitution reactions while surpassing\nthe stability of corresponding aryl halides. In comparison to conventional\ncoupling methods, this protocol offers an alternative pathway for\naccessing natural product and drug-like compounds without the need\nfor metal catalysts. With assistance of this approach, we successfully\nobtained a potent P-glycoprotein inhibitor <b>4k</b> (YS-370),\na potent epidermal growth factor receptor inhibitor <b>4l</b> (YS-363), and a promising lysine-specific demethylase 1 inhibitor <b>5g</b>.