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

Abstract

Herein we report the three-component copper-catalyzed carboiminolactonization of α,β-unsaturated carbonyl derivatives. In the presence of a Cu(I) catalyst, α-haloesters, electron-deficient alkenes, and primary amines couple to generate γiminolactones 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

“…Furthermore, we do not observe any ATRA products in the absence of an amine nucleophile. Path (ii) seems less likely to occur in general: contrary to our previous reports, where the excellent scope with respect to the styrene coupling partner is attributed to the formation of an oxocarbenium intermediate, , the formation of an 8-membered oxocarbenium containing a trans -alkene is unlikely. Moreover, no Ritter adducts are detected with any of the VCPs, suggesting that a benzylic carbocation is not forming.…”

“…The mode of C–N bond formation remains unclear. Several mechanistic pathways are possible: (i) atom transfer radical addition (ATRA) followed by nucleophilic substitution at the benzylic carbon; − (ii) radical/polar crossover followed by nucleophilic trapping, or (iii.) a copper-mediated C–N formation .…”