Laboratory of Organic Chemistry, ETH Zurich, D-CHAB, Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland.
J Org Chem. 2020 Jun 19;85(12):7633-7640. doi: 10.1021/acs.joc.0c00665. Epub 2020 May 5.
Despite intense interest in amine-catalyzed stereoselective reactions, high catalyst loadings of ≥10 mol % are still common and either due to low reactivity or catalyst deactivation. Yet, few deactivation pathways are well understood. Here, we unraveled the deactivation of secondary amines by undesired aldol reaction. Mechanistic studies with peptide and prolinol silyl ether catalysts showed the generality of this so-far underappreciated catalyst deactivation pathway. The insights enabled conjugate addition reactions between aldehydes and nitroolefins on a multigram scale in the absence of solvent-conditions that are attractive as environmentally benign processes-with excellent product yields and stereoselectivities in the presence of as little as 0.1 mol % of a chemoselective peptidic catalyst.
尽管人们对胺催化的立体选择性反应非常感兴趣，但仍普遍使用高达 10 mol%的高催化剂负载量，这要么是由于反应活性低，要么是由于催化剂失活。然而，人们对失活途径的了解甚少。在这里，我们揭示了次级胺通过不希望的醛醇缩合反应失活。用肽和脯氨醇硅醚催化剂进行的机理研究表明，这种迄今为止未被充分认识的催化剂失活途径具有普遍性。这些见解使得在没有溶剂的条件下（作为环境友好的过程具有吸引力），在多克规模上进行醛和硝基烯烃之间的共轭加成反应成为可能，在使用低至 0.1 mol%的选择性肽催化剂的情况下，获得了优异的产物收率和立体选择性。
