Reusser Esaïe, Aeschlimann Michael, Albrecht Martin
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern Freiestrasse 3 3012 Bern Switzerland
Catal Sci Technol. 2024 Dec 18;15(3):867-877. doi: 10.1039/d4cy01337a. eCollection 2025 Feb 3.
Even though α-arylation of ketones is attractive for direct C-H functionalization of organic substrates, the method largely relies on phosphine-ligated palladium complexes. Only recently, efforts have focused on developing nitrogen-based ligands as a more sustainable alternative to phosphines, with pyridine-functionalized pyridinium amidate (pyr-PYA) ,'-bidentate ligands displaying good selectivity and activity. Here, we report on a second generation set of catalyst precursors that feature a 5-membered N-heterocycle instead of a pyridine as chelating unit of the PYA ligand to provide less steric congestion for the rate-limiting transmetalation of the enolate. To this end, new heterocycle-functionalized PYA palladium(ii) complexes containing an oxazole (5b), -phenyl-triazole (5c), -methyl pyrazole (5d), -phenyl-pyrazole, (5e), -xylyl-pyrazole (5f), and -isopropyl-pyrazole (5g) were synthesized compared to the parent pyr-PYA complex 5a. Less packing of the palladium coordination sphere was evidenced from solid state X-ray diffraction analysis. While the catalytic activity of the oxazole system was lower, all other complexes showed higher activity. In particular, complex 5g comprised of an electron-donating and sterically demanding iPr-pyrazole chelating PYA ligand is remarkably stable towards air and moisture and shows outstanding catalytic activity with complete selectivity (>99% yield) and turnover frequencies up to 1200 h, surpassing that of parent 5a by one order of magnitude and rivalling the most active phosphine-based palladium systems. Kinetic studies demonstrate a first order rate-dependence on palladium and the substrate. Some deviation of linearity together with poisoning experiments suggest a mixed homogeneous/heterogeneous pathway, though the reproducible kinetics of catalyst recycling experiments strongly point to a molecularly defined active species, demonstrating the high potential of PYA-based ligands.
尽管酮的α-芳基化对于有机底物的直接C-H官能化很有吸引力，但该方法在很大程度上依赖于膦配位的钯配合物。直到最近，人们才致力于开发氮基配体作为膦的更可持续替代品，吡啶官能化的吡啶酰胺（pyr-PYA）双齿配体表现出良好的选择性和活性。在此，我们报道了第二代催化剂前体，其特征是具有一个5元氮杂环而非吡啶作为PYA配体的螯合单元，从而为烯醇盐的限速转金属化提供更少的空间位阻。为此，与母体pyr-PYA配合物5a相比，合成了含有恶唑（5b）、苯基三唑（5c）、甲基吡唑（5d）、苯基吡唑（5e）、二甲苯基吡唑（5f）和异丙基吡唑（5g）的新型杂环官能化PYA钯（II）配合物。固态X射线衍射分析证明了钯配位球的堆积较少。虽然恶唑体系的催化活性较低，但所有其他配合物都表现出更高的活性。特别是，由供电子且空间位阻较大的异丙基吡唑螯合PYA配体组成的配合物5g对空气和水分具有显著的稳定性，并表现出出色的催化活性，具有完全的选择性（产率>99%）和高达1200 h的周转频率，比母体5a高出一个数量级，可与最具活性的膦基钯体系相媲美。动力学研究表明反应速率对钯和底物呈一级依赖关系。线性关系的一些偏差以及中毒实验表明存在均相/非均相混合途径，尽管催化剂循环实验中可重复的动力学强烈表明存在分子定义的活性物种，这证明了基于PYA的配体具有很高的潜力。
