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.

Chart 1. Annulation with Terminal Styrenes

^aTwo equiv of styrene was used. ^bReaction run for 48 h. ^cReaction run at 95 °C.

Chart 2. Annulation with Di-substituted Styrenes

^aReaction run in anhydrous 1,4-dioxane at 120 °C. ^bReaction run for 36 h.

Scheme 1

Polar/radical pyrrolidine syntheses

Scheme 2

Reactions of Dienes and a Dienoate

Scheme 3

Reaction of Bexarotene Methyl Ester

Scheme 4

Proposed Reaction Mechanism

Scheme 5

Radical Clock Mechanism Probes