N-杂环化合物的合成对制药工业至关重要。它们通常是通过原子经济和不利于环境的方法合成的，产生大量的废物。一种探索较少但更环保的替代方法是利用有机叠氮化合物通过直接分子内C–H胺化进行合成。使用该方法的示例很少，但由于需要使用化学计量量的Boc2O，许多示例受到限制。
该文中，研究人员报道了一种同质C，O-螯合中离子卡宾-铁络合物，其实第一种不需要添加任何保护基团的铁基络合物，并且在强供体溶剂（如THF或甚至DMSO）中也具有活性。实现的周转数比任何其他报告的催化系统都高一个数量级。多种C–H键被激活，包括苄基键、一级键、二级键和三级键。
通过跟踪反应时间，研究人员确定了起始期的存在。动力学研究表明，底物浓度和催化剂浓度分别为一级和半级。与氘化底物的分子间竞争反应显示没有KIE，而与氘标记底物的单独反应导致KIE为2.0。此外，使用氘化底物显著缩短了催化起始时间。初步的机理研究表明，一种独特的机制涉及二聚铁物种作为催化剂的静止状态。
附：英文原文
Title: An Iron–Mesoionic Carbene Complex for Catalytic Intramolecular C–H Amination Utilizing Organic Azides
Author: Wowa Stroek, Martin Keilwerth, Daniel M. Pividori, Karsten Meyer, Martin Albrecht
Issue&Volume: November 28, 2021
Abstract: The synthesis of N-heterocycles is of paramount importance for the pharmaceutical industry. They are often synthesized through atom economic and environmentally unfriendly methods, generating significant waste. A less explored, but greener, alternative is the synthesis through the direct intramolecular C–H amination utilizing organic azides. Few examples exist by using this method, but many are limited due to the required use of stoichiometric amounts of Boc2O. Herein, we report a homoleptic C,O-chelating mesoionic carbene–iron complex, which is the first iron-based complex that does not require the addition of any protecting groups for this transformation and that is active also in strong donor solvents such as THF or even DMSO. The achieved turnover number is an order of magnitude higher than any other reported catalytic system. A variety of C–H bonds were activated, including benzylic, primary, secondary, and tertiary. By following the reaction over time, we determined the presence of an initiation period. Kinetic studies showed a first-order dependence on substrate concentration and half-order dependence on catalyst concentration. Intermolecular competition reactions with deuterated substrate showed no KIE, while separate reactions with deuterium-labeled substrate resulted in a KIE of 2.0. Moreover, utilizing deuterated substrate significantly decreased the initiation period of the catalysis. Preliminary mechanistic studies suggest a unique mechanism involving a dimeric iron species as the catalyst resting state.
DOI: 10.1021/jacs.1c07378
Source: https://pubs.acs.org/doi/10.1021/jacs.1c07378
