853577-87-4Relevant academic research and scientific papers
Palladium-mediated arylation of 3-aminopiperidines and 3-aminopyrrolidines
Jean, Ludovic,Rouden, Jacques,Maddaluno, Jacques,Lasne, Marie-Claire
, p. 8893 - 8902 (2007/10/03)
This paper describes the palladium-catalyzed arylation of 1-substituted 3-aminopyrrolidines or piperidines. Palladium(0) (1-2 mol %) in conjunction with "Buchwald's ligand" [2-(dimethylamino)-2′- (dicyclohexylphosphine)biphenyll was shown to be the catalyst of choice for the coupling with aryl bromides or chlorides. When bromobenzene was used, a strong temperature effect was noticed. Whereas no reaction occurred at 100 °C, yields higher than 85% were obtained at 130 °C for each substrate. Such an effect was not observed when diphosphines were used. Whereas Xantphos and, to a lesser extent BINAP, were moderately efficient in the coupling of all diamines, the palladium-mediated arylation in the presence of monophosphines was strongly dependent on the substrate. The results suggest the participation of both nitrogens of the aminoheterocycle in the reactive intermediate. This participation could also account for the highly selective arylation of the endocyclic nitrogen of unsubstituted 3-aminopyrrolidine or piperidine. Optimal conditions were found for the arylation using 2- or 4-substituted electron-poor or enriched aryl halides.
