A General Platform for Copper-Catalyzed Atom Transfer Radical Addition with Electron-Deficient Olefins

Abstract

We disclose a broad platform for copper-catalyzed atom transfer radical addition (ATRA) of electron-deficient olefins. Catalytic Cu(dtbbpy)₂(OTf)₂ enables radical addition of electron-deficient alkyl halides to acrylates, acrylamides, and vinyl sulfones in fair to excellent yields. The resultant ATRA products can be used in a variety of telescoped reactions, including substitution with basic amine nucleophiles to afford α-amino esters. The synthetic utility of the products is further demonstrated through derivatization to give substituted cyclopropanes and a γ,δ-unsaturated ester.

Scheme 1.

Select previous examples of intermolecular ATRA

Scheme 2.. Scope of the Cu-Catalyzed ATRA.^a

^a Reactions run at 0.2 mmol scale in duplicate. ^b 20 mol % DIPEA in place of PhNHMe. ^c 2.0 mmol scale.

Scheme 3.. Synthetic Utility^a

^aTelescoped reaction sequence run at 0.2 mmol scale in duplicate; d.r. confirmed by crude GC analysis. ^b2.0 mmol scale

Scheme 4.. Ramberg-Bäcklund Reaction

Isolated yield of product at 0.2 mmol scale. ^ain-situ yield determined by GC analysis of the crude reaction mixture.