MIRA: C(sp3)-H Heteroatom Incorporation Using Photoexcited Nitroarenes

项目摘要 杂原子单元，如C(SP3)-OH和C(SP3)-NH2，是许多药学中普遍存在的基序 相关药品和天然产物。将这些重要的官能团整合在一起的方法 C-H键依赖于非商业性杂原子转移剂、贵重过渡金属、 和/或昂贵的工程酶。此外，这些方法通常需要苛刻的外源氧化剂来促进 C-杂原子成键事件，极大地限制了衬底范围。在这项建议中，我们强调 使用经济的硝基芳烃作为多功能试剂，可用作C(SP3)-H键激活剂和 在良性可见光照射下，脂肪族体系C-H羟化反应的氧原子源。 值得注意的是，杂原子转移事件以厌氧方式发生，从而允许显著扩展 与以前最先进的方法相比，衬底范围更广。不对称C-H羟基化方案可以 通过使用可回收的光激发硝基芳烃异构体来实现，从而实现可持续的方法 用于手性醇基的后期安装。C-H通用平台的开发 在这种反应范式下，脂肪族体系的杂原子掺入可以通过形式 极地交叉事件和与亲核试剂的耦合。手性氢键供体催化剂或手性的合并 以磷酸为催化剂的这种方法可以使不对称杂原子成为通用的平台 直接从C-H键并入，不需要离开基团，这是一个不发达的领域 在合成中。对于C-N键的形成，硝基芳烃中氮原子的化学选择性转移 部分脂肪族体系可以在光照射下实现亚胺的容易形成 直接来自亚甲基装置。形成的亚胺产物的原位加氢反应正式生成胺 从C-H键；因此，从光激发的多重反应中产生C-H胺化事件 硝基芳烃。所提出的方案的综合效用表明，晚期的C-H杂原子 光激发硝基芳烃促进的掺入活动可以提供经济有效的手段 复合分子支架的合成。总体而言，新的C-H杂原子事件可以在温和的， 通过利用光诱导的硝基芳烃的多功能作用，以普遍、可持续的方式。它是 预计光激发的硝基芳烃将作为厌氧杂原子掺入的有用工具 有机分子。

Project Summary Heteroatom units, such as C(sp3)–OH and C(sp3)–NH2, are prevalent motifs in many pharmaceutically relevant drugs and natural products. Methods to incorporate these important functional groups at the expense of C–H bonds rely on the use of non-commercial heteroatom transfer agents, precious transition metals, and/or costly engineered enzymes. Also, these methods often require harsh exogenous oxidants to promote the C–heteroatom bonding event, which greatly limits substrate scope. In this proposal, we highlight the employment of economical nitroarenes as versatile reagents that can serve as the C(sp3)–H bond activator and the oxygen atom source for the C–H hydroxylation of aliphatic systems under benign visible-light irradiation. Notably, the heteroatom transfer event occurs anaerobically, thereby allowing for significant expansion of substrate scope compared to previous state-of-the-art methods. Asymmetric C–H hydroxylation protocols can be achieved with the use of recyclable photoexcited nitroarene atropisomers, leading to a sustainable approach for the late-stage installation of chiral alcohol groups. The development of a universal platform for C–H heteroatom incorporation of aliphatic systems can be engendered under this reaction paradigm via a formal polar crossover event and coupling with nucleophiles. The merger of chiral H-bond donor catalysts or chiral phosphoric acid catalysts to this approach can enable a general platform for asymmetric heteroatom incorporation directly from C–H bonds without the need for a leaving group, which is an underdeveloped area in synthesis. For C–N bond formation, chemoselective transfer of the nitrogen atom from the nitroarene moiety to aliphatic systems can be achieved under photoirradiation empowering facile formation of imines directly from methylene units. In-situ hydrogenation of the formed imine products generates amines formally from C–H bonds; thus, resulting in a C–H amination event from the multi-fold reactivity of photoexcited nitroarenes. The synthetic utility of the proposed protocols illustrates that late-stage C–H heteroatom incorporation events promoted by photoexcited nitroarenes can provide a cost-effective means for the synthesis of complex molecular scaffolds. Overall, novel C–H heteroatom events can be achieved in a mild, general, and sustainable manner by exploiting the multifunctional role of photoinduced nitroarenes. It is anticipated that photoexcited nitroarenes will serve as useful tools for the anaerobic heteroatom incorporation of organic molecules.