Watson Donald A, Su Mingjuan, Teverovskiy Georgiy, Zhang Yong, García-Fortanet Jorge, Kinzel Tom, Buchwald Stephen L
Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Science. 2009 Sep 25;325(5948):1661-4. doi: 10.1126/science.1178239. Epub 2009 Aug 13.
Despite increasing pharmaceutical importance, fluorinated aromatic organic molecules remain difficult to synthesize. Present methods require either harsh reaction conditions or highly specialized reagents, making the preparation of complex fluoroarenes challenging. Thus, the development of general methods for their preparation that overcome the limitations of those techniques currently in use is of great interest. We have prepared [LPd(II)Ar(F)] complexes, where L is a biaryl monophosphine ligand and Ar is an aryl group, and identified conditions under which reductive elimination occurs to form an Ar-F bond. On the basis of these results, we have developed a catalytic process that converts aryl bromides and aryl triflates into the corresponding fluorinated arenes by using simple fluoride salts. We expect this method to allow the introduction of fluorine atoms into advanced, highly functionalized intermediates.
尽管含氟芳香有机分子在药学上的重要性日益增加，但它们的合成仍然困难。目前的方法要么需要苛刻的反应条件，要么需要高度专业化的试剂，这使得复杂氟代芳烃的制备具有挑战性。因此，开发能够克服现有技术局限性的通用制备方法备受关注。我们制备了[LPd(II)Ar(F)]配合物，其中L是联芳基单膦配体，Ar是芳基，并确定了发生还原消除以形成Ar-F键的条件。基于这些结果，我们开发了一种催化过程，该过程通过使用简单的氟化物盐将芳基溴化物和芳基三氟甲磺酸酯转化为相应的氟代芳烃。我们期望这种方法能够将氟原子引入到先进的、高度官能化的中间体中。
