自然13885克服杂环定向化局限性1 1 1.pdfVIP

LETTER :10.1038/nature13885 Overcoming the limitations of directed C–H functionalizations of heterocycles 1 1 1 1 1 1,2 Yue-Jin Liu *, Hui Xu *, Wei-Jun Kong , Ming Shang , Hui-Xiong Dai Jin-Quan Yu In directed C H activation reactions, anynitrogen or sulphuratoms approaches has found limited success in terms of substrate scope and present inheterocyclic substrates will coordinate strongly with metal efficiency19 26. catalysts. This coordination, which can lead to catalyst poisoning or Here we report an aerobic C H functionalization reaction that ef C H functionalization at an undesired position, limits the application fectively overcomes catalyst poisoning by heterocycles and overrides of C H activation reactions in heterocycle based drug discovery1 5, the commonly observed positional selectivity dictated by heterocycles. in which regard they have attracted much interest from pharmaceu The catalytic cycle begins with the on site generation of a reactive Pd(II) tical companies3 5. Here we report a robust and synthetically useful species (Fig. 1b). To this end, a Pd(0) precursor coordinates with a method that overcomes the complications associated with perform simple, carboxylic acid derived N methoxy amide directing group ing C H functionalization reactions on heterocycles. Our approach (CONHOMe)27, which promotes subsequent oxidation of Pd(0) to Pd(II) employs a simple N methoxy amide group, which serves as both a by air present in the reaction mixture28. The directin