New Ring Formations Using Ni-Photoredox Catalysis for Organic Synthesis

利用 Ni-光氧化还原催化有机合成新环的形成

• 批准号: 426788634
• 负责人: Dr. Dorothée Ziegler
• 金额: --
• 依托单位: Frick Chemistry Laboratory
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/426788634?language=en
• 关键词: New; Ring; Formations; Using; Ni

In recent years, photoredox catalysis has evolved to a powerful methodology in organic synthesis. Typically, photocatalysts absorb light, convert it into chemical energy and perform selective molecule activations, which allow new synthetic transformations. Thus, photoredox catalysis offers new tools to apply in many fields of synthesis such as cycloadditions, C-H functionalizations or hydrofunctionalization. Furthermore, unusual reaction patterns are often observed with photoredox chemistry in comparison to traditional reaction manifolds. Noteworthy are the economical, environmentally friendly and mild reaction conditions that are tolerated by a broad range of functional groups. As a consequence of these benefits, numerous researchers have contributed to develop the transformations in photoredox systems further. Despite the significant advances, there are many opportunities for further investigations. Recently, Abigail Doyle at Princeton developed a promising Ni-photoredox catalytic method to directly carboxylate sp3-carbon-hydrogen bonds, a rare reaction type with great potential in organic synthesis. Thus, the aim of this research is to expand Ni-photoredox catalysis for new ring formations in organic synthesis. Since there are no examples of intramolecular C(sp3)-H acylations, the following questions should be addressed: (1) Can ring formations and ring annulations be achieved in the course of catalytic, intramolecular C(sp3)-H acylations? and (2) Could these new ring formations provide a basis for conceiving new approaches to challenging problems in target-directed synthesis? During the postdoctoral research, we will develop intramolecular C-H acylations into efficient reactions and demonstrate their ability to impact the planning of organic syntheses. We planned nine concise syntheses of target natural products such as fredericamycin, mitomycin and tremelin or further compounds that chemists have desired in the past. The synthesis strategy comprises the tactic of ring formation via C-H acylation, together with the application of known and/or commercially available starting materials, which may be used to accomplish short step syntheses of the required cyclization substrates. The proposed research will directly address the gap in the current state of dual-catalytic C-H acylations and generate powerful new strategies for synthesizing cyclic ketones and lactones, both of which are ubiquitous structural elements in nature and organic chemistry.

近年来，光氧化还原催化已发展成为有机合成中的一种强有力的方法。通常，光催化剂吸收光，将其转化为化学能并进行选择性分子活化，从而允许新的合成转化。因此，光氧化还原催化提供了新的工具，应用于许多领域的合成，如环加成，C-H官能化或氢官能化。此外，与传统的反应歧管相比，光氧化还原化学经常观察到不寻常的反应模式。值得注意的是，经济，环境友好和温和的反应条件，是由广泛的官能团容忍。由于这些益处，许多研究人员为进一步开发光氧化还原系统中的转化做出了贡献。尽管取得了重大进展，但仍有许多进一步调查的机会。最近，普林斯顿大学的Abigail Doyle开发了一种很有前途的Ni光氧化还原催化方法，直接羧酸sp3-碳-氢键，这是一种在有机合成中具有巨大潜力的罕见反应类型。因此，本研究的目的是扩大镍光氧化还原催化在有机合成中的新的环的形成。由于没有分子内C（sp3）-H酰化反应的例子，因此应解决以下问题：（1）在催化的分子内C（sp3）-H酰化反应过程中能否实现成环和成环？以及（2）这些新的环的形成是否可以为构思新的方法来解决靶向合成中的挑战性问题提供基础？在博士后研究期间，我们将把分子内C-H酰化发展成有效的反应，并展示它们影响有机合成规划的能力。我们计划了九个简明的目标天然产物的合成，如fredericamycin，丝裂霉素和tremelin或进一步的化合物，化学家们希望在过去。合成策略包括通过C-H酰化形成环的策略，以及应用已知的和/或可商购的起始材料，其可用于完成所需环化底物的短步骤合成。该研究将直接解决目前双催化C-H酰化反应中的差距，并为合成环酮和内酯产生强大的新策略，这两者都是自然界和有机化学中普遍存在的结构元素。