Tarantino Kyle T, Miller David C, Callon Ted A, Knowles Robert R
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
J Am Chem Soc. 2015 May 27;137(20):6440-3. doi: 10.1021/jacs.5b03428. Epub 2015 May 13.
The ability of redox-active metal centers to weaken the bonds in associated ligands is well precedented, but has rarely been utilized as a mechanism of substrate activation in catalysis. Here we describe a catalytic bond-weakening protocol for conjugate amination wherein the strong N-H bonds in N-aryl amides (N-H bond dissociation free energies ∼100 kcal/mol) are destabilized by ∼33 kcal/mol upon by coordination to a reducing titanocene complex, enabling their abstraction by the weak H-atom acceptor TEMPO through a proton-coupled electron transfer process. Significantly, this soft homolysis mechanism provides a method to generate closed-shell, metalated nucleophiles under neutral conditions in the absence of a Brønsted base.
氧化还原活性金属中心削弱相关配体中化学键的能力已有充分先例，但在催化中很少被用作底物活化的机制。在此，我们描述了一种用于共轭胺化的催化键弱化方法，其中N-芳基酰胺中的强N-H键（N-H键解离自由能约为100 kcal/mol）在与还原性二茂钛配合物配位后，其稳定性降低约33 kcal/mol，从而能够通过质子耦合电子转移过程被弱氢原子受体TEMPO夺取。值得注意的是，这种温和的均裂机制提供了一种在中性条件下、无布朗斯特碱存在的情况下生成闭壳层金属化亲核试剂的方法。
