Brusoe Andrew T, Hartwig John F
Department of Chemistry, University of California, Berkeley, California 94720, United States.
J Am Chem Soc. 2015 Jul 8;137(26):8460-8. doi: 10.1021/jacs.5b02512. Epub 2015 Jun 29.
We report the synthesis of fluorinated anilines by palladium-catalyzed coupling of fluoroalkylamines with aryl bromides and aryl chlorides. The products of these reactions are valuable because anilines typically require the presence of an electron-withdrawing substituent on nitrogen to suppress aerobic or metabolic oxidation, and the fluoroalkyl groups have steric properties and polarity distinct from those of more common electron-withdrawing amide and sulfonamide units. The fluoroalkylaniline products are unstable under typical conditions for C-N coupling reactions (heat and strong base). However, the reactions conducted with the weaker base KOPh, which has rarely been used in cross-coupling to form C-N bonds, occurred in high yield in the presence of a catalyst derived from commercially available AdBippyPhos and [Pd(allyl)Cl]2. Under these conditions, the reactions occur with low catalyst loadings (<0.50 mol % for most substrates) and tolerate the presence of various functional groups that react with the strong bases that are typically used in Pd-catalyzed C-N cross-coupling reactions of aryl halides. The resting state of the catalyst is the phenoxide complex, (BippyPhosPd(Ar)OPh); due to the electron-withdrawing property of the fluoroalkyl substituent, the turnover-limiting step of the reaction is reductive elimination to form the C-N bond.
我们报道了通过钯催化氟代烷基胺与芳基溴化物和芳基氯化物的偶联反应来合成氟化苯胺。这些反应的产物很有价值，因为苯胺通常需要在氮上存在吸电子取代基以抑制需氧或代谢氧化，并且氟代烷基具有与更常见的吸电子酰胺和磺酰胺单元不同的空间性质和极性。氟代烷基苯胺产物在典型的C-N偶联反应条件（加热和强碱）下不稳定。然而，使用较弱的碱KOPh进行的反应（该碱很少用于交叉偶联形成C-N键），在由市售的AdBippyPhos和[Pd(烯丙基)Cl]2衍生的催化剂存在下高产率地发生。在这些条件下，反应在低催化剂负载量（大多数底物<0.50 mol%）下进行，并且能够容忍各种与通常用于芳基卤化物的钯催化C-N交叉偶联反应中的强碱发生反应的官能团的存在。催化剂的静止状态是酚盐配合物(BippyPhosPd(Ar)OPh)；由于氟代烷基取代基的吸电子性质，反应的周转限制步骤是还原消除以形成C-N键。
