Synthesis of 2-Aryl- and 2-Vinylpyrrolidines via Copper-Catalyzed Coupling of Styrenes and Dienes with Potassium β-Aminoethyl Trifluoroborates

Abstract

2-Arylpyrrolidines occur frequently in bioactive compounds and thus methods to access them from readily available reagents are valuable. We report a copper-catalyzed intermolecular carboamination of vinylarenes with potassium N-carbamoyl-β-aminoethyltrifluoroborates. The reaction occurs with terminal, 1,2-disubstituted and 1,1-disubstituted vinylarenes bearing a number of functional groups. 1,3-Dienes are also good substrates and their reactions give 2-vinylpyrrolidines. Radical clock mechanistic experiments are consistent with the presence of carbon radical intermediates and do not support participation of carbocations.

Stereoselective and Regioselective Synthesis of Heterocycles via Copper-Catalyzed Additions of Amine Derivatives and Alcohols to Alkenes

“…An exciting aspect of this work, however, also involved the fortuitous discovery of new reactions found during mechanistic probes, scope extensions and process optimizations. Immediate future directions involve additional intra/intermolecular reaction development including aerobic processes and those designed for larger ring synthesis as well as development of more fully intermolecular reaction sequences 83 using the reactivity concepts described in this Perspective and those yet to be developed.…”

Intermolecular radical carboamination of alkenes

“…Chemler and co-workers developed an efficient method for the preparation of pyrrolidines 170 through Cu-catalyzed radical coupling of alkenes with potassium N-carbamoyl-b-aminoethyltrifluoroborates 169 (Scheme 37). 97 Single electron oxidation of the trifluoroborate 169 by Cu(II) produces the corresponding C-radical 171, which reacts with an alkene to provide the adduct radical 172. Trapping of 172 by the Cu(II)-complex and ligand exchange afford the Cu(III) species 173 which undergoes reductive elimination to give the desired pyrrolidine 170.…”

Saturated oxygen and nitrogen heterocycles via oxidative coupling of alkyltrifluoroborates with alkenols, alkenoic acids and protected alkenylamines

“…We recently reported on the synthesis of 2-arylpyrrolidines via copper-catalyzed oxidative coupling of styrenes with potassium N-carbamolyl-b-aminoethyl triuoroborates (Scheme 1b). 13 In these reactions, the [Cu] salt oxidizes the alkyltri-uoroborate to a primary carbon radical. Addition of the radical to the styrene, followed by cyclization via addition of the pendant carbamate under the oxidative conditions generates the 2-arylpyrrolidine.…”

“…A radical clock experiment supported a mechanism involving primarily carbon radical intermediates (as opposed to carbocation). 13 Herein we present a new approach to the synthesis of a broad range of saturated heterocycles by addition of various potassium alkyltri-uoroborates to heteroatom-functionalized alkenes, primarily styrenes.…”