Nature Catalysis ( IF 37.8 ) Pub Date : 2018-02-07 , DOI: 10.1038/s41929-017-0023-z Runze Mao , Adrian Frey , Jonathan Balon , Xile Hu
Amines are a quintessential moiety in bioactive molecules, pharmaceuticals and organic materials. Transition-metal-catalysed C–N coupling of aryl electrophiles has been established as a powerful and reliable method for amine synthesis. However, the analogous C–N coupling of alkyl electrophiles is largely under-developed due to the decomposition of metal alkyl intermediates by β-hydrogen elimination and difficulty in C(sp3)–N reductive elimination. Here, we provide a general strategy for amination of alkyl electrophiles by merging photoredox and copper catalysis. Photoredox catalysis allows the use of alkyl redox-active esters, recently established as a superior class of alkyl electrophiles, whereas copper catalysis enables C(sp3)–N cross-coupling. Decarboxylative amination can be used for the synthesis of a diverse set of alkyl anilines with high chemoselectivity and functional-group compatibility. Rapid functionalization of amino acids, natural products and drugs is demonstrated.
中文翻译:
协同光氧化还原和铜催化脱羧C(sp 3)–N交叉偶联
胺是生物活性分子,药物和有机材料中的一个重要组成部分。过渡金属催化的芳基亲电试剂的C–N偶联已被确立为一种强大而可靠的胺合成方法。但是,由于烷基金属中间体被β-氢消除而分解,并且难以进行C(sp 3)-N的还原消除,烷基亲电试剂的类似的C-N偶联在很大程度上尚未得到开发。在这里,我们提供了通过合并光氧化还原和铜催化来胺化烷基亲电试剂的一般策略。光氧化还原催化作用允许使用烷基氧化还原活性酯(最近被确立为烷基亲电试剂的上等类别),而铜催化可以使C(sp 3)–N交叉耦合。脱羧胺化可用于合成具有高化学选择性和官能团相容性的各种烷基苯胺。证明了氨基酸,天然产物和药物的快速功能化。