Non-Organometallic Partners as Radical Precursors for the Diversification of Dual Catalytic Cross-Coupling Processes

非有机金属伙伴作为双催化交叉偶联过程多样化的自由基前体

• 批准号: 9041110
• 负责人: Christopher B. Kelly
• 金额: $ 5.25万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-05 至 2019-02-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9041110
• 关键词: Biological Availability; Carbon; Catalysis; Chemicals; Clinical; Coupling; Development; Drug Industry; Electrons; Event; Failure; Goals; Grant; Hydrazines; Industry; Ligands; Metals; Methods; Pathway interactions; Probability; Process; Protocols documentation; Rationalization; Reaction; Reagent; Regulation; Research; Role; Salts; Solubility; Source; System; Technology; Toxic effect; Work; base; cost effective; drug discovery; enzyme substrate; functional group; improved; novel; panacea; programs; public health relevance; small molecule; success

 DESCRIPTION (provided by applicant): The goal of the research proposed is to facilitate the construction of organic molecules by exploring unconventional reagents for cross-coupling and exploiting the unique attributes of such reagents. This will be accomplished by employing a recently developed, paradigm-shifting approach to cross-coupling involving a dual catalytic cycle. The two cycles, a photoredox catalytic cycle and a cross-coupling cycle, working in concert, will facilitate a single electron transmetalation protocol, allowing cross-coupling under mild conditions and, with the appropriate ligand, high levels of enantioselectivity via stereoconvergent transformations. In particular, methods to do so from inexpensive, bench-stable, commodity nonmetallic organic precursors will be sought. A process using such materials would be robust, cost-effective, and scalable, leading to a facile transition from the academic setting to a process development facility. Employing the dual catalytic systems that have proven effective in studies on the cross-coupling of organotrifluoroborates, the protocol will be extended to non-organometallic bulk source materials, namely hydrazines and sulfinate salts. Studies on these commodity materials will focus on practical methods of effecting radical formation under photoredox conditions and assessing their viability in being funneled into the base metal catalytic cycle. Organocatalysts and inexpensive inorganic materials will be explored as potential photocatalysts to enhance the sustainable profile of developed processes. Photoflow-based technologies and strategies will be examined as a means of enhancing scalability and effectivity. Diverse electrophilic coupling partners will be examined, and stereoconvergent processes will be developed to access enantioenriched alkyl substructures. This protocol will be transformative in enabling unprecedented C-C bond construction via cross-coupling from nonconventional, inexpensive coupling partners.

 描述（由申请人提供）：拟议研究的目标是通过探索用于交叉偶联的非常规试剂和利用此类试剂的独特属性来促进有机分子的构建。这将是通过采用最近开发的，范式转换的方法，涉及一个双催化循环的交叉耦合。这两个循环，光氧化还原催化循环和交叉偶联循环，协同工作，将促进单电子transmetalation协议，允许交叉偶联在温和的条件下，并与适当的配体，高水平的对映体选择性通过立体会聚转化。 特别地，将寻求从廉价的、工作台稳定的、商品非金属有机前体这样做的方法。使用这种材料的过程将是强大的，具有成本效益的，可扩展的，导致从学术环境到过程开发设施的轻松过渡。采用双催化系统，已被证明有效的交叉偶联的有机三氟硼酸盐的研究，该协议将扩展到非有机金属散装源材料，即肼和亚磺酸盐。对这些商品材料的研究将集中于在光氧化还原条件下实现自由基形成的实用方法，并评估它们在被引入贱金属催化循环中的可行性。有机催化剂和廉价的无机材料将被探索作为潜在的光催化剂，以提高开发过程的可持续性。将研究基于光电流的技术和战略，作为提高可扩展性和有效性的一种手段。不同的亲电耦合合作伙伴将被检查，立体收敛过程将开发访问对映体富集的烷基亚结构。该协议将是变革性的，通过非传统的，廉价的偶联伙伴的交叉偶联，使前所未有的C-C键的建设。