Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 36, 48149 Münster, Germany.
J Am Chem Soc. 2021 Oct 13;143(40):16370-16376. doi: 10.1021/jacs.1c08233. Epub 2021 Sep 28.
We describe a palladium-catalyzed nondirected late-stage deuteration of arenes. Key aspects include the use of DO as a convenient and easily available deuterium source and the discovery of highly active N,N-bidentate ligands containing an -acylsulfonamide group. The reported protocol enables high degrees of deuterium incorporation via a reversible C-H activation step and features extraordinary functional group tolerance, allowing for the deuteration of complex substrates. This is exemplified by the late-stage isotopic labeling of various pharmaceutically relevant motifs and related scaffolds. We expect that this method, among other applications, will prove useful as a tool in drug development processes and for mechanistic studies.
我们描述了一种钯催化的芳烃无导向晚期氘代反应。关键方面包括使用 DO 作为方便易得的氘源，以及发现含有 -酰基磺酰胺基团的高活性 N,N-双齿配体。所报道的方案通过可逆的 C-H 活化步骤实现了高度的氘掺入，并具有非凡的官能团耐受性，允许对复杂的底物进行氘代。这可以通过对各种药物相关的基序和相关支架的晚期同位素标记来例证。我们预计，除其他应用外，该方法还将作为药物开发过程和机理研究的工具非常有用。
