Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL), ISIC-LSCI, BCH 3305, 1015, Lausanne, Switzerland.
Angew Chem Int Ed Engl. 2018 Jul 20;57(30):9501-9504. doi: 10.1002/anie.201804873. Epub 2018 Jun 28.
Alkyl amines are an important class of organic compounds in medicinal and materials chemistry. Until now very have been very few methods for the synthesis of alkyl amines by metal-catalyzed cross-coupling of alkyl electrophiles with nitrogen nucleophiles. Described here is an approach to employ tandem photoredox and copper catalysis to enable the cross-coupling of alkyl N-hydroxyphthalimide esters, readily derived from alkyl carboxylic acids, with benzophenone-derived imines. Hydrolysis of the coupling products furnish alkylated primary amines. Primary, secondary, and tertiary alkyl groups can be transferred, and the coupling tolerates a diverse set of functional groups. The method allows rapid functionalization of natural products and drugs, and can be used to expedite syntheses of pharmaceuticals from readily available chemical feedstocks.
烷基胺是药物和材料化学中一类重要的有机化合物。到目前为止，通过金属催化的烷基亲电试剂与氮亲核试剂的交叉偶联合成烷基胺的方法非常少。本文描述了一种通过串联光氧化还原和铜催化来实现烷基 N-羟基邻苯二甲酰亚胺酯与二苯甲酮衍生亚胺的交叉偶联的方法，烷基 N-羟基邻苯二甲酰亚胺酯可由烷基羧酸容易得到。偶联产物的水解得到烷基化伯胺。伯、仲和叔烷基可以进行转移，而且该偶联反应可以耐受多种官能团。该方法允许对天然产物和药物进行快速功能化，并且可以用于从易得的化学原料快速合成药物。
