Centre for Catalysis Research and Innovation (CCRI), Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N6N5, Canada.
AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery Research, Knollstrasse, 67061, Ludwigshafen, Germany.
Chemistry. 2021 Sep 1;27(49):12535-12539. doi: 10.1002/chem.202101617. Epub 2021 Jul 29.
NaBHT (sodium 2,6-di-tert-butyl-4-methylphenolate), a strong, but hindered and lipophilic base, has been effectively paired with similarly lipophilic, high-reactivity Pd-NHC (N-heterocyclic carbene) catalysts to produce an ideal combination for performing solvent-free (melt) cross-coupling amination. The mild nucleophilicity of NaBHT, coupled with the anti-oxidant properties of its conjugate acid byproduct, BHT means the process seems to have no functional group incompatibilities. Highly effective coupling of base-sensitive and redox-active functional groups was observed in all cases with only 0.1-0.2 mol percent catalyst. Comparisons using the standard base for this reaction, KOtBu, led to poor couplings or complete degradation in most applications - only NaBHT works.
NaBHT（2,6-二叔丁基-4-甲基苯酚钠盐）是一种强碱性物质，但位阻较大且亲脂性较强，它与同样具有亲脂性和高反应性的 Pd-NHC（N-杂环卡宾）催化剂有效配对，形成了一种理想的组合，可以在无溶剂（熔融）条件下进行交叉偶联胺化反应。NaBHT 的亲核性较弱，其共轭酸副产物 BHT 具有抗氧化性能，这意味着该过程似乎没有官能团不相容性。在所有情况下，仅使用 0.1-0.2 mol%的催化剂就能实现高效偶联，即使是对碱敏感和氧化还原活性的官能团也是如此。使用该反应的标准碱 KOtBu 进行比较，在大多数情况下导致偶联效果不佳或完全降解——只有 NaBHT 有效。
