Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Nat Chem. 2015 Dec;7(12):1009-16. doi: 10.1038/nchem.2367. Epub 2015 Nov 2.
Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.
脂肪族伯胺是一类对合成高阶含氮分子至关重要的化学原料，在生物活性化合物和药物制剂中普遍存在。新型复杂胺类化合物的合成方法一直是合成化学家面临的持续挑战。在这里，我们概述了一种钯催化的在氨基醇中脂肪族 C-H 键官能化的通用策略，氨基醇是一类重要的小分子。该策略的核心是将催化不相容的伯氨基醇暂时转化为位阻仲胺，使其能够进行空间促进的钯催化 C-H 活化。此外，胺和催化剂之间的氢键增强了钯周围的相互作用，并使脂肪族胺取代基以适合 C-H 活化的理想几何形状取向。这种催化方法可以直接将简单、易于获得的胺转化为高度取代、功能集中和结构多样的产物，并可以简化生物重要含胺分子的合成。
