Department of Medicinal Chemistry, Biotherapeutic and Medicinal Sciences, Biogen, Cambridge, Massachusetts 02142, United States.
Biogen Postdoctoral Scientist Program, Biogen, Cambridge, Massachusetts 02142, United States.
J Org Chem. 2020 May 15;85(10):6747-6760. doi: 10.1021/acs.joc.0c00870. Epub 2020 Apr 28.
Transannular C-H heteroarylation of amines provides rapid access to complex scaffolds that are otherwise difficult to synthesize. Wide adaptation of this emerging reaction for medicinal chemistry requires a broad understanding of substrate scope and more robust experimental conditions. In this article, we report a new ligand to promote the transannular reaction of a range of fused- and bridged-bicyclic secondary amines with a broad set of heteroarenes. The method was also successfully applied to the arylation of one spiro-bicyclic amine, a class of substrates that has not been studied in the context of transannular C-H activation reactions. The broad application of this transannular C-H heteroarylation methodology is currently hampered by the difficulty of removing the directing group. The development of a new directing group that is easier to remove will expand the utility of this reaction.
胺的环间 C-H 杂芳基化反应为快速构建复杂支架提供了途径，而这些复杂支架通常难以合成。为了将这种新兴的反应广泛应用于药物化学，需要广泛了解底物范围和更稳健的实验条件。在本文中，我们报道了一种新的配体，用于促进一系列稠环和桥环双环仲胺与广泛的杂芳烃的环间反应。该方法还成功地应用于一个螺环双环胺的芳基化，这一类底物在环间 C-H 活化反应中尚未得到研究。目前，这种环间 C-H 杂芳基化方法的广泛应用受到去除导向基团的困难的阻碍。开发一种更容易去除的新导向基团将扩大该反应的用途。
