Chemical and Synthetic Development, Bristol-Myers Squibb Company, One Squibb Drive , New Brunswick , New Jersey 08903 , United States.
Org Lett. 2018 Jul 20;20(14):4218-4222. doi: 10.1021/acs.orglett.8b01591. Epub 2018 Jun 29.
Challenging couplings of hindered carboxylic acids with non-nucleophilic amines to form amide bonds can be accomplished in high yields, and in many cases, with complete retention of the adjacent stereogenic centers using the combination of N, N, N', N'-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and N-methylimidazole (NMI). This method allows for in situ generation of highly reactive acyl imidazolium ions, which have been demonstrated to be intermediates in the reaction. The reagent delivers high reactivity similar to acid chlorides with the ease of use of modern uronium reagents.
使用 N, N, N', N'-四甲基氯代甲脒六氟磷酸盐（TCFH）和 N-甲基咪唑（NMI）的组合，可以高产率地将受阻羧酸与非亲核胺进行酰胺键偶联，在许多情况下，还可以完全保留相邻的立体中心。该方法允许在原位生成高反应性的酰基咪唑鎓离子，已经证明这些离子是反应的中间体。该试剂具有类似于酰氯的高反应性，同时具有现代翁试剂的易用性。
