Sweeney Joseph B, Doulcet Julien, Thapa Bimod
Department of Chemistry, Lancaster University, Lancaster LA1 4YB, UK.
Department of Chemical Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK.
iScience. 2018 Nov 30;9:328-336. doi: 10.1016/j.isci.2018.10.025. Epub 2018 Nov 1.
Metal-catalyzed reactions have revolutionized synthetic chemistry, allowing access to unprecedented molecular architectures with powerful properties and activities. Nonetheless, some transformations remain sparse in number, or out of reach, even with the diverse modern catalytic chemical arsenal, including bimolecular alkene hydroarylation reactions. We report here a broad-scope, palladium-catalyzed pyrroline hydroarylation process that gives 3-aryl pyrrolidines, a class of small molecules with potency in a diverse range of biological scenarios. Thus, whereas N-acyl pyrrolines usually undergo palladium-catalyzed arylation to give alkene products, the corresponding reactions of N-alkyl pyrrolines deliver products of hydroarylation, pyrrolidines. The process has broad substrate scope and can be used to directly deliver drug-like molecules in a single step from readily available precursors.
金属催化反应彻底改变了合成化学，使人们能够获得具有强大性能和活性的前所未有的分子结构。尽管如此，即使拥有多样的现代催化化学手段，包括双分子烯烃氢芳基化反应，一些转化反应的数量仍然稀少，或者难以实现。我们在此报告一种范围广泛的钯催化吡咯啉氢芳基化过程，该过程可生成3-芳基吡咯烷，这是一类在多种生物场景中具有活性的小分子。因此，虽然N-酰基吡咯啉通常会发生钯催化的芳基化反应生成烯烃产物，但N-烷基吡咯啉的相应反应则生成氢芳基化产物吡咯烷。该过程具有广泛的底物范围，可用于从易得的前体一步直接合成类药物分子。
