Fier Patrick S, Hartwig John F
Department of Chemistry, University of California , Berkeley, California 94720, United States.
J Am Chem Soc. 2014 Jul 16;136(28):10139-47. doi: 10.1021/ja5049303. Epub 2014 Jul 1.
We report the late-stage functionalization of multisubstituted pyridines and diazines at the position α to nitrogen. By this process, a series of functional groups and substituents bound to the ring through nitrogen, oxygen, sulfur, or carbon are installed. This functionalization is accomplished by a combination of fluorination and nucleophilic aromatic substitution of the installed fluoride. A diverse array of functionalities can be installed because of the mild reaction conditions revealed for nucleophilic aromatic substitutions (S(N)Ar) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution versus the rates for competitive processes provides a framework for planning this functionalization sequence. This process is illustrated by the modification of a series of medicinally important compounds, as well as the increase in efficiency of synthesis of several existing pharmaceuticals.
我们报道了多取代吡啶和哒嗪在氮原子α位的后期官能团化反应。通过该过程，一系列通过氮、氧、硫或碳与环相连的官能团和取代基得以引入。这种官能团化反应是通过氟化反应以及对所引入氟化物进行亲核芳香取代反应相结合来实现的。由于2-氟杂芳烃亲核芳香取代反应（S(N)Ar）所显示的温和反应条件，能够引入各种各样的官能团。对取代反应速率与竞争过程速率的评估为规划该官能团化反应序列提供了一个框架。一系列具有重要药用价值的化合物的修饰以及几种现有药物合成效率的提高都说明了这一过程。
