Diverse and Selective Catalytic P–C Bond Formation

在化学系化学催化项目的支持下，佛蒙特大学的Rory Waterman教授将研究促进磷碳键形成的催化作用。磷碳键存在于所有生物中，存在于消费品中，甚至存在于一些COVID-19疫苗中，以及其他药物制剂中。然而，制备含有该元素的分子的方法是有限的，特别是那些具有催化作用的分子。催化可以提高资源利用和合成的效率，这将有助于解决磷的挑战。因此，该项目旨在提供使用磷的新一代更快、更高效、更好控制的催化剂，使一系列领域的研究人员受益。这些努力有可能对生物医学和化学生物学相关的合成分子产生重大影响。该项目的另一个更雄心勃勃的目标是利用催化剂来推广一种罕见但非常有效的磷碳键形成反应。该项目还旨在建立光作为磷碳键形成催化的能量来源，即所谓的光催化，并了解这种光催化是如何运作的，以促进其与其他元素的催化反应。沃特曼教授在参与美国国家科学基金会资助的研究方面有着悠久的历史，他将利用这个项目来增加大学预科学生参与研究的能力，帮助实现长期的劳动力发展目标。在本研究中，佛蒙特大学的Rory Waterman教授将研究促进P（III）和P(I)形成P- c键的催化作用，提高氢磷化的对映体选择性，扩大光催化氢磷化。该项目建立在一个最初的发现，即光催化氢磷化是普遍的，旨在揭示早期和晚期过渡金属催化剂的机制。这项工作补充了稳定的氢膦化催化的创新。该项目还将结合这些努力来研究非活性底物的对端选择性氢磷化催化剂，潜在地利用氢磷化作为合成复杂分子结构的后期合成工具，特别是那些可能产生生物活性的支架。该项目的其他工作旨在通过催化利用环膦作为P(I)前体，以控制单线态膦的形成。环磷膦也可以是初级磷化氢前体，这一认识将有助于通过扩大磷化氢底物来扩大氢磷化氢催化。这些努力的目的是绕过氢磷化和膦烯转移的限制。这项工作有望推进对P-C键形成催化的基本理解，并有可能应用于其他催化体系。此外，本研究中针对的许多特定催化反应在更大的合成化学领域具有更广泛应用的潜力。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Rory Waterman of the University of Vermont will study catalysis that promotes formation of phosphorus-carbon bonds. Phosphorus-carbon bonds appear in all living things, are in consumer goods, and are even present in some of the COVID-19 vaccines, among other pharmaceutical agents. However, methods to prepare molecules containing this element are limited, particularly those that are catalytic. Catalysis can create efficiencies in both resource utilization and synthesis that would aid in the challenges with phosphorus. As such, this project aims to deliver a new generation of faster, more efficient, and better controlled catalysts that use phosphorus, benefitting researchers in a range of fields. These efforts have the potential to have a large impact for the synthesis molecules related to biomedical science and chemical biology. Another more ambitious aim of the project is to use catalysis to generalize a rare but very efficient phosphorus-carbon bond forming reaction. The project also aims to establish light as an energy source for phosphorus-carbon bond forming catalysis, so-called photocatalysis, and understand how this photocatalysis operates to facilitate its expansion to catalytic reactions with other elements. Professor Waterman has a strong history of involving high school students from historically underrepresented groups in NSF-funded research and will use this project to increase capacity to involve pre-college students in research, helping to meet long-standing workforce development goals. In this research, Professor Rory Waterman of the University of Vermont will study catalysis that promotes P-C bond formation from both P(III) and P(I), improved enantioselectivity in hydrophosphination, and expand photocatalytic hydrophosphination. The project builds on an initial discovery that photocatalytic hydrophosphination is general and aims to unravel the mechanisms that unfold for both early and late transition metal catalysts. This effort compliments innovations in bench-stable hydrophosphination catalysis. The project will also combine these efforts to investigate enantioselective hydrophosphination catalysts for unactivated substrates, potentially availing hydrophosphination as a late-stage synthetic tool in the synthesis of complex molecular architectures, particularly those scaffolds that are likely to engender biological activity. Additional efforts in the project aim to leverage cyclophosphines as P(I) precursors via catalysis with an eye toward controlling singlet phosphinidene formation. Cyclophosphines can also be primary phosphine precursors, and this understanding will aid in the expansion of hydrophosphination catalysis through expansion of phosphine substrates. These efforts are directed at making an end-run around limitations in hydrophosphination and phosphinidene transfer. This work holds promise to advance fundamental understanding of catalysis in P-C bond formation, with potential application to other catalytic systems. Additionally, many specific catalytic reactions targeted in this study have the potential for much broader application in the larger synthetic chemistry community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.