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.

项目摘要杂原子单元，例如C（SP3）–OH和C（SP3）–NH2，在许多药物上都是普遍的主题相关药物和天然产品。以费用为代价合并这些重要官能团的方法 C – H债券的依赖于使用非商业杂种转移代理，宝贵的过渡金属，和/或昂贵的工程酶。同样，这些方法通常需要危害外源氧化物来促进 C – Heteroatom键合事件，大大限制了基板范围。在此提案中，我们强调了经济硝酸作为多功能试剂的使用，可以用作C（SP3） - H键激活剂和在良性可见光照射下，脂肪族系统C-H羟基化的氧原子源。值得注意的是，杂原转移事件在厌氧上发生，从而大大扩展与以前的最新方法相比，底物范围。不对称C – H羟基化方案可以可以通过使用可回收的光激发硝化阿托蛋白体来实现，从而实现可持续的方法用于手性酒精组的晚期安装。开发C – H的通用平台脂肪族系统的杂原剂掺入可以通过正式形式产生此反应范式极性跨界事件，并与核pholipses结合。手性H键供体催化剂或手性的合并这种方法磷酸催化剂可以使一个不对称杂原子的一般平台直接从C – H债券合并而无需离开组，这是一个欠发达的地区在合成中。对于C – N键的形成，将氮原子从硝基苯烯中的化学选择性转移可以在赋予脂肪剂的脂肪系统中获得脂肪族系统的一部分直接来自甲基单元。形成的亚胺产物的原位氢化正式产生胺来自C – H键；因此，从光激发的多重反应性导致C – H胺化事件氮气。提议的协议的合成效用说明了后期C – H杂原子由光激发硝化碳促进的合并事件可以为复杂分子支架的合成。总体而言，新型的C – H杂种事件可以在温和的通过利用光诱导的硝酸的多功能作用，一般和可持续的方式。这是预计光激发的硝化烯烃将作为厌氧杂种就业的有用工具有机分子。

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