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

MIRA：使用光激发硝基芳烃引入 C(sp3)-H 杂原子

基本信息

批准号：
10714687
负责人：
Marvin Parasram
金额：
$ 38.41万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-05-31
项目状态：
未结题

项目摘要

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.

项目概要杂原子单元，例如 C(sp3)–OH 和 C(sp3)–NH2，是许多药物中普遍存在的基序。相关药物和天然产物的方法，以牺牲这些重要的官能团为代价。 C-H 键依赖于使用非商业杂原子转移剂、贵重过渡金属、而且，这些方法通常需要苛刻的外源氧化剂来促进。 C-杂原子键合事件，极大地限制了底物范围。在本提案中，我们强调了这一点。使用经济的硝基芳烃作为多功能试剂，可作为 C(sp3)–H 键活化剂和良性可见光照射下脂肪族体系 C-H 羟基化的氧原子源。值得注意的是，杂原子转移事件在厌氧条件下发生，从而允许显着扩展与之前最先进的方法相比，底物范围更广。通过使用可回收的光激发硝基芳烃阻转异构体来实现，从而形成可持续的方法用于手性醇基团的后期安装。开发C-H通用平台。在这种反应范式下，可以通过正式的反应范式产生脂肪族系统的杂原子结合极性交叉事件以及与亲核试剂的偶联。手性氢键供体催化剂或手性的合并。这种方法的磷酸催化剂可以为不对称杂原子提供通用平台直接由C-H键结合，无需离去基团，这是一个欠发达的领域在合成过程中，氮原子从硝基芳烃中化学选择性转移，形成 C-N 键。在光照射下可以实现脂肪族系统的部分，从而能够容易地形成亚胺直接由亚甲基单元原位氢化形成胺。来自C-H键；因此，光激发的多重反应性导致C-H胺化事件所提出的方案的合成效用说明了后期 C-H 杂原子。光激发硝基芳烃促进的掺入事件可以为总体而言，新的 C-H 杂原子事件可以在温和的情况下实现。通过利用光诱导硝基芳烃的多功能作用，以通用且可持续的方式。预计光激发硝基芳烃将成为厌氧杂原子掺入的有用工具的有机分子。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Photoinduced Nitroarenes as Versatile Anaerobic Oxidants for Accessing Carbonyl and Imine Derivatives.

DOI：
10.1021/acs.orglett.3c02292
发表时间：
2023-09-08
期刊：
ORGANIC LETTERS
影响因子：
5.2
作者：
Mitchell, Joshua K.;Hussain, Waseem A.;Bansode, Ajay H.;O'Connor, Ryan M.;Wise, Dan E.;Choe, Michael H.;Parasram, Marvin
通讯作者：
Parasram, Marvin