Copper-Catalyzed Three-Component Carboiminolactonization of Electron-Deficient Olefins.

Herein we report the three-component copper-catalyzed carboiminolactonization of α,ß-unsaturated carbonyl derivatives. In the presence of a Cu(I) catalyst, α-haloesters, electron-deficient alkenes, and primary amines couple to generate γ-iminolactones in a single step. The scope of the reaction is explored with respect to the three coupling partners. Nineteen examples are presented with yields of these hydrolytically labile heterocycles of up to 69%. Mechanistic investigations support the formation of an oxocarbenium by way of an atom transfer radical addition (ATRA) intermediate.

Copper-Catalyzed Three-Component 1,5-Carboamination of Vinylcyclopropanes.

The 1,5-copper-catalyzed carboamination of vinylcyclopropanes is presented. A carbon-centered radical, formed upon reduction of an alkyl halide by Cu(I), adds across the alkene of a vinylcyclopropane, triggering ring opening to generate a benzylic radical, which, finally, undergoes copper-mediated amination to afford a homoallylic amine. The reaction occurs with outstanding regio- and good to very good diastereoselectivities. The scope of the reaction is demonstrated with respect to all three components: alkyl halide, vinylcyclopropane, and amine nucleophile. A total of 38 examples are presented with an average yield of 60%.

Cu-Catalyzed Three-Component Carboamination of Electron Deficient Olefins.

The copper-catalyzed three-component carboamination of atropates for the synthesis of α-aryl amino acid derivatives is presented. The scope of the reaction is explored with respect to all three coupling partners: the alkyl halide, the atropate, and the aryl amine. A total of 41 examples are included, with yields of ≤92%. Both primary and secondary aryl amines participate in the carboamination along with α-haloesters, nitriles, and perfluoroiodoalkanes. Mechanistic investigations support a radical mechanism involving Cu-mediated C-N bond formation with the radical adduct.