Palladium-mediated arylation of 3-aminopiperidines and 3-aminopyrrolidines.
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)biphenyl] 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 degrees C, yields higher than 85% were obtained at 130 degrees 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.
Jean
Ludovic
L
Laboratoire de Chimie Moléculaire et Thioorganique, UMR CNRS 6507, ENSICAEN and Université of Caen-Basse Normandie, 6 Boulevard du Maréchal Juin, F14050 Caen Cedex, France.
Rouden
Jacques
J
Maddaluno
Jacques
J
Lasne
Marie-Claire
MC
D000478:Alkylation; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000138:chemical synthesis*
D000588:Amines; D010880:Piperidines; D011759:Pyrrolidines; D010165:Palladium