Aliphatic Effects in Transition Metal Catalysis

过渡金属催化中的脂肪族效应

基本信息

批准号：
10459387
负责人：
Bradley Carrow
金额：
$ 38.75万
依托单位：
UNIVERSITY OF HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-15 至 2024-06-30
项目状态：
已结题

项目摘要

Project Summary. An incredible diversity of transition metal-catalyzed methods has been developed around a small subset of elementary organometallic reactions. The overarching goal of our research program is to expand this tool box to include new organometallic mechanisms that can in turn be integrated into many new catalytic transformations to generate new organic structures. A central hypothesis of this proposal is that enforcing persistent coordinative-unsaturation in catalyst structures can enable unique organometallic mechanisms, such as in the transmetalation step common to all carbon- carbon and carbon-heteroatom cross-coupling reactions – some of the most practiced reactions at all levels of pharmaceutical research. Our approach is inspired by the potential for substantial attractive van der Waals forces in large aliphatic groups, which we are able to incorporate into metal catalysts structures using large organophosphorus ligands. A primary focus of this work will be to understand the mechanisms of, and to leverage, an unusual series of transmetalation reactions we have observed with mixtures of low-coordinate palladium complexes and protic nucleophiles, such as organoboronic acids. These reactions can occur under very mild conditions even in the absence of strong base, which has been historically necessary in many cross-coupling reactions yet also compromises the compatibility with sensitive compounds. The unique influence of diamondoids, such as in tri(1-adamantyl)phosphine, in promoting this chemistry may reflect the large polarizability and dispersion forces manifested in large aliphatic molecules. In order to generalizing these aliphatic effects, we will concurrently pursue new, modular methods to construct congested C(sp3)−P bonds, which are common motifs in both catalytic structures and also many biologically active compounds. Furthermore, we will expand these aliphatic effects to promote historically challenging transmetalation and oxidative addition reactions in iron and copper catalysis, respectively, which are general problems that have hindered efforts hindered to develop more sustainable cross-coupling methods using abundant base metals Together the catalytic and organophosphorus synthetic efforts of this proposal will generate new biologically active molecular structures through novel carbon-element bond forming reactions.

项目摘要过渡金属催化方法的多样性令人难以置信。围绕基本有机金属反应的一小部分发展起来。我们研究计划的目标是扩展这个工具箱以包括新的有机金属这些机制又可以整合到许多新的催化转化中该提案的一个中心假设是强制执行。催化剂结构中持久的配位不饱和度可以实现独特的有机金属机制，例如所有碳原子共有的金属转移步骤碳和碳-杂原子交叉偶联反应——一些最常用的反应我们的方法受到药物研究潜力的启发。对于大型脂肪族中具有大量吸引力的范德华力，我们能够使用大型有机磷配体纳入金属催化剂结构中。这项工作的重点将是了解一种不寻常的机制并利用它我们用低配位混合物观察到一系列金属转移反应钯配合物和质子亲核试剂，例如有机硼酸这些反应。即使没有强碱，也可以在非常温和的条件下发生，这已被证实在许多交叉偶联反应中历史上是必要的，但也损害了与敏感化合物的相容性，例如金刚烷烃的独特影响。三(1-金刚烷基)膦在促进这种化学反应中可能反映了大的极化率和分散力表现在大的脂肪族分子中为了概括这些。脂肪族效应，我们将同时寻求新的模块化方法来构建拥挤的 C(sp3)−P 键，这是催化结构和许多催化结构中的常见基序此外，我们还将这些脂肪族效应扩展到生物活性化合物。促进铁和金属中历史上具有挑战性的金属转移和氧化加成反应铜催化分别是阻碍努力的普遍问题阻碍利用丰富的贱金属开发更可持续的交叉耦合方法该提案的催化和有机磷合成努力将共同产生通过新型碳元素键形成形成新的生物活性分子结构反应。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Diverted Aerobic Heck Reaction Enables Selective 1,3-Diene and 1,3,5-Triene Synthesis through C-C Bond Scission.

DOI：
10.1021/jacs.8b10007
发表时间：
2018-10-24
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
McAlpine NJ;Wang L;Carrow BP
通讯作者：
Carrow BP

Visible light-induced palladium-carbon bond weakening in catalytically relevant T-shaped complexes.

DOI：
10.1039/d3sc02588h
发表时间：
2023-12-13
期刊：
CHEMICAL SCIENCE
影响因子：
8.4
作者：
Waddell, Peter M.;Tian, Lei;Scavuzzo, Anthony R.;Venigalla, Lalu;Scholes, Gregory D.;Carrow, Brad P.
通讯作者：
Carrow, Brad P.

Aryl Amination Using Soluble Weak Base Enabled by a Water-Assisted Mechanism.