Design, Synthesis and Evaluation of Radical-Based Catalysts for the Direct Anti-M

描述(申请人提供)：伯醇是商品和医药化学工业中的重要分子。目前，它们的大规模生产要么使用有毒和危险的高压一氧化碳和氢气，要么使用化学计量金属和过氧化氢试剂。以现成的烯烃前体为原料，通过反马尔可夫尼科夫水合反应直接催化合成它们的新方法，将有利于合成具有生物活性的小分子，以及有益于人类健康和生活质量的聚合物和商品化学品。目前对这一问题的解决方案要么需要多个步骤，要么需要化学计量的氧化剂和/或还原剂，要么范围有限。提出了一种反Markovnikov水合反应的一般方法，即通过与烯烃的自由基加成反应提供更多取代度更高的自由基中间体。开发了一种新的催化循环，其中氢原子从金属-羟基物种转移产生新的碳氢键，并通过再生金属-氧催化剂来促进自由基反应。这个循环涉及两种有机金属物种的互换氧化态，允许反应进行，而不需要外源氧化剂或还原剂。这种双模式催化将通过设计双核有机金属骨架来促进，其中金属-氧和金属-羟基组分紧密地存在。这种方法允许氢原子转移被加速，因为它是一个分子内过程，并在双核氧化还原转移中创建形式对称性。由于锰氧配合物在氧原子转移反应和氢原子转移反应中都具有已知的自由基型反应活性，因此已被确定为本研究的理想起点。根据这一建议开发的烯烃水合催化剂由于通常具有较高的官能团对自由基反应的耐受性，因此有望具有广泛的应用范围，从而允许从容易获得的烯烃原料合成各种醇。 与公共健康相关：商品和制药化学工业每年生产100多万吨初级酒精。这些产品是合成许多生物活性化合物的重要中间体，但从普通的烯烃前体合成它们需要高压有毒和有害气体，或使用含有大量废气的工艺。这项建议旨在解决有害反应条件和废物产生的健康问题，方法是开发一种利用底物、催化剂和水作为唯一试剂将末端烯烃转化为伯醇的新方法。

DESCRIPTION (provided by applicant): Primary alcohols are important molecules in both the commodity and pharmaceutical chemical industries. Currently, their large-scale production involves the use of either high pressures of toxic and hazardous carbon monoxide and hydrogen gasses, or stoichiometric metal and peroxide reagents. A new method for their direct, catalytic synthesis by anti-Markovnikov hydration from readily available olefin precursors would be beneficial for the synthesis of bioactive small molecules, as well as polymers and commodity chemicals that benefit human health and quality of life. Current solutions to this problem either require multistep procedures, stoichiometric amounts of oxidant and/or reductant, or are limited in scope. A general approach to anti- Markovnikov hydration is proposed to proceed through radical addition to olefins, which provide the more highly substituted radical intermediate. A new catalytic cycle is developed where hydrogen atom transfer from a metal-hydroxo species generates the new carbon-hydrogen bond and propagates the radical reaction be regenerating the metal-oxo catalyst. This cycle involves two organometallic species of interchanging oxidation states, allowing reaction to proceed without the need for exogenous oxidants or reductants. This dual-mode catalysis will be facilitated by the design of dinuclear organometallic frameworks where the metal-oxo and the metal-hydroxo components are present in close proximity. This approach allows for hydrogen atom transfer to be accelerated by nature of it being an intramolecular process, and creates formal symmetry in the dinuclear redox transfer. Manganese oxo complexes have been identified as the ideal starting point for this investigation due to their known radical-type reactivity in both oxygen atom transfer and hydrogen atom transfer reactions. Olefin hydration catalysts developed from this proposal are anticipated to have general scope due to the typically high functional-group tolerance of radical reactions, allowing a wide range of alcohols to be synthesized from readily available olefin feedstocks. PUBLIC HEALTH RELEVANCE: Over one million tons of primary alcohols are produced by the commodity and pharmaceutical chemical industries every year. These products are important intermediates in the synthesis of many bioactive compounds, but their synthesis from common olefin precursors requires either high pressures of toxic and hazardous gasses, or the use of processes with heavy waste streams. This proposal seeks to address the health issues of hazardous reaction conditions and waste production by developing a new method for the conversion of terminal olefins to primary alcohols utilizing substrate, catalyst and water as the only reagents.