氟代芳基的合成Efficient Synthesis of Aryl Fluorides.pdf

Angewandte Chemie DOI: 10.1002/anie.200905855 Selective Fluorination Efficient Synthesis of Aryl Fluorides** Pazhamalai Anbarasan, Helfried Neumann, and Matthias Beller* Dedicated to Professor Michael Drscher on the occasion of his 60th birthday Selective functionalization reactions of aromatic and hetero- aromatic halides with carbon, oxygen, and nitrogen nucleo- philes have attracted much attention in the last decades.[1] In addition to typical metal-catalyzed coupling reactions, direct functionalization of aryl halides through the formation of Grignard reagents offer new ways for the efficient construc- tion of biologically interesting carbo- and heterocycles.[2,3] Recent elegant examples include the development of LiCl- mediated preparation of Grignard reagents by Knochel and co-workers.[4] Inspired by their work and our interest in functionalization reactions of aryl halides,[5] we have been fascinated in the direct synthesis of aryl fluoride compounds from aryl Grignard reagents. Although a large number of known pharmaceutical and agrochemical products contain fluorinated arenes (Scheme 1), which enhance solubility, bioavailability, and metabolic stability compared with non-fluorinated ana- logues,[6,7] there is no convenient and general synthetic method available for their synthesis. Commonly known methods for the introduction of a fluorine atom to arenes require relatively harsh r