Zhang Jiadi, Bellomo Ana, Trongsiriwat Nisalak, Jia Tiezheng, Carroll Patrick J, Dreher Spencer D, Tudge Matthew T, Yin Haolin, Robinson Jerome R, Schelter Eric J, Walsh Patrick J
Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
J Am Chem Soc. 2014 Apr 30;136(17):6276-87. doi: 10.1021/ja411855d. Epub 2014 Apr 21.
Although the past 15 years have witnessed the development of sterically bulky and electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings with aryl chlorides, examples of palladium catalysts based on either triarylphosphine or bidentate phosphine ligands for efficient room temperature cross-coupling reactions with unactivated aryl chlorides are rare. Herein we report a palladium catalyst based on NiXantphos, a deprotonatable chelating aryldiphosphine ligand, to oxidatively add unactivated aryl chlorides at room temperature. Surprisingly, comparison of an extensive array of ligands revealed that under the basic reaction conditions the resultant heterobimetallic Pd-NiXantphos catalyst system outperformed all the other mono- and bidentate ligands in a deprotonative cross-coupling process (DCCP) with aryl chlorides. The DCCP with aryl chlorides affords a variety of triarylmethane products, a class of compounds with various applications and interesting biological activity. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of aryl chloride substrates bearing heteroaryl groups and sensitive functional groups that are known to undergo 1,2-addition, aldol reaction, and O-, N-, enolate-α-, and C(sp(2))-H arylations. The advantages and importance of the Pd-NiXantphos catalyst system outlined herein make it a valuable contribution for applications in Pd-catalyzed arylation reactions with aryl chlorides.
尽管在过去15年里，空间位阻大且富电子的烷基膦配体已被用于钯催化的与芳基氯的交叉偶联反应，但基于三芳基膦或双齿膦配体的钯催化剂用于与未活化芳基氯进行高效室温交叉偶联反应的例子却很少。在此，我们报道了一种基于NiXantphos（一种可去质子化的螯合芳基二膦配体）的钯催化剂，它能在室温下对未活化芳基氯进行氧化加成。令人惊讶的是，对大量配体的比较表明，在碱性反应条件下，所得的异双金属Pd-NiXantphos催化剂体系在与芳基氯的去质子化交叉偶联过程（DCCP）中优于所有其他单齿和双齿配体。与芳基氯的DCCP可得到多种三芳基甲烷产物，这是一类具有各种应用和有趣生物活性的化合物。此外，在存在带有杂芳基和已知会发生1,2-加成、羟醛反应以及O-、N-、烯醇盐-α-和C(sp(2))-H芳基化的敏感官能团的芳基氯底物时，DCCP表现出显著的化学选择性。本文所述的Pd-NiXantphos催化剂体系的优点和重要性使其在钯催化的与芳基氯的芳基化反应应用中做出了有价值的贡献。
