Jean Ludovic, Rouden Jacques, Maddaluno Jacques, Lasne Marie-Claire
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.
J Org Chem. 2004 Dec 10;69(25):8893-902. doi: 10.1021/jo0487193.
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.
本文描述了1-取代的3-氨基吡咯烷或哌啶的钯催化芳基化反应。钯(0)(1 - 2摩尔%)与“布赫瓦尔德配体”[2-(二甲基氨基)-2'-(二环己基膦基)联苯]结合，被证明是与芳基溴化物或氯化物偶联的首选催化剂。当使用溴苯时，观察到强烈的温度效应。在100℃时不发生反应，而在130℃时，每种底物的产率均高于85%。当使用双膦时未观察到这种效应。虽然Xantphos以及在较小程度上的BINAP在所有二胺的偶联中具有中等效率，但在单膦存在下钯介导的芳基化反应强烈依赖于底物。结果表明氨基杂环的两个氮原子都参与了反应中间体。这种参与也可以解释未取代的3-氨基吡咯烷或哌啶的内环氮的高度选择性芳基化。使用2-或4-取代的贫电子或富电子芳基卤化物进行芳基化反应时发现了最佳条件。
