Geminal/Vicinal Amino‐ and Oxy‐Trifluoromethylation of ortho‐Ethynyl Anilines and Phenols by Cu(III)−CF3 Compounds

Abstract

AbstractThis study reports geminal amino‐ and oxy‐trifluoromethylation of ortho‐ethynyl anilines/phenols by phenCu(III)(CF3)3 (phen denotes 1,10‐phenanthroline), which constructs indole and benzofuran skeleton with concurrent incorporation of a CF3 group to the C2 position. Sequential trifluoromethylation of the terminal alkyne followed by 5‐endo‐trig cyclization of amino/hydroxyl with alkyne is involved. This method addresses the troublesome regioselectivity issue in C−H trifluoromethylation of arenes/heteroarenes wherein complicated mixtures of regioisomers were often obtained. A competing vicinal fluoro‐trifluoromethylation of terminal alkynes is suppressed under the optimal conditions wherein the Cu(III)−CF3 compound acts as a bifunctional reagent to provide both CF3 and F. Interestingly, when an acylamino group is present at the ortho‐position of phenylacetylene, vicinal syn‐amidate‐trifluoromethylation of the alkyne group occurs preferentially through 6‐exo‐trig cyclization to produce benzoxazines with a trifluoroethylidene at the C4‐position. The controllable and concise synthesis of valuable trifluoromethylated N‐ and O‐heterocyclic compounds shows the synthetic value of Cu(III)−CF3 compounds in medicinal chemistry.magnified image