Trifluoroacetic Anhydride Promoted Copper(I)-Catalyzed Interrupted Click Reaction: From 1,2,3-Triazoles to 3-Trifluoromethyl-Substituted 1,2,4-Triazinones.

ABSTRACT

A copper(I)-catalyzed interrupted click reaction in the presence of trifluoroacetic anhydride has been developed, wherein an N-trifluoroacetyl group is used to accelerate the ring-opening of the putative 5-copper(I) triazolide intermediate. Under the optimized reaction conditions, a broad range of azides and alkynes were found to participate in this transformation, thus affording 3-trifluoromethyl-substituted 1,2,4-triazinones in moderate to excellent yields. The reaction has proven to be compatible with a variety of electron-withdrawing and electron-donating groups, halogens, and nitrogen- and sulfur-containing heterocycles, as well as pharmaceutically relevant molecules.