New Robust Olefin Metathesis Catalysts Based on Non-Toxic and Abundant Low-Valent Molybdenum

 描述（由申请人提供）：迫切需要基于无毒且丰富的金属的新型稳健的烯烃复分解催化剂，但很少有人致力于解决这个问题。有机金属化学这一领域缺乏报道与制备低价过渡金属亚烷基配合物相对困难有关。这种未满足的需求代表了一个重要问题：在发现此类催化剂之前，烯烃复分解药物的开发、生产和商业化仍将受到金属污染和经济问题的阻碍。我们的长期目标是为合成化学家提供廉价、无毒、高效、稳健和选择性（例如对映选择性、E/Z-非对映选择性）的烯烃复分解催化剂。该应用的总体目标是开发基于低价钼金属的烯烃复分解催化剂。这项研究背后的基本原理是，此类催化剂的发现将为制药行业提供一个强大的工具，最终将产生更实惠、更安全、更可靠的药物。 更清洁的方法来生产治疗药物。这项工作的中心工作假设如下：已证明在齐格勒-纳塔烯烃聚合中具有活性的配体-金属系统在烯烃复分解中具有很高的活性潜力。为了达到总体目标并检验中心假设，将追求以下三个具体目标。在具体目标1中，将合成并表征由双（亚氨基）吡啶（或NNN）、双（膦基）吡啶（PNP）、双（膦基）吡啶和双（膦基）吡啶（PONOP）配体支持的钼（0）二氮配合物和三氯化钼配合物。这些钼络合物将用作制备亚烷基钼化合物的前体。在具体目标2中，将研究将具体目标1中制备的钼前体转化为亚烷基钼化合物LMo=CHR和/或LMo(=CHR)(CH2R)的不同方法。其中一种方法是基于当前 SC3 奖项期间完成的工作。另一种方法涉及用重氮烷试剂处理二氮钼(0)络合物，而第三种方法包括使三氯化钼(III)络合物与不同的大烷基格氏试剂反应。最后，具体目标 3 将重点测试新型金属亚烷基配合物在不同烯烃复分解反应中的催化活性，并将包括制备真正感兴趣的生物医学相关支架。这项工作的完成将产生基于廉价且无毒金属的新型稳健的烯烃复分解催化剂，以及制备低价过渡金属亚烷基配合物的新通用方法。这项研究意义重大，因为它将促进烯烃复分解药物的发现和商业化。

 DESCRIPTION (provided by applicant): There exists a critical need for new robust olefin metathesis catalysts based on innocuous and abundant metals, but little effort has been applied toward addressing it. The lack of reports in this area of organometallic chemistry is related to th relative difficulty in preparing alkylidene complexes of low-valent transition metals. This unmet need represents an important problem: until such catalysts are discovered, the development, production, and commercialization of olefin metathesis-enabled drugs will remain hampered by metal-contamination and economic concerns. Our long-term goal is to provide inexpensive, non-toxic, highly efficient, robust and selective (e.g., enantioselective, E/Z-diastereoselective) olefn metathesis catalysts to the community of synthetic chemists. The overall objective of this application is to develop olefin metathesis catalysts based on low-valent molybdenum metals. The rationale behind this research is that the discovery of such catalysts will equip the pharmaceutical industry with a powerful tool that will ultimately yield more affordable, safer, and cleaner methods to produce therapeutics. The central working hypothesis for this proposed work is the following: ligand-metal systems that have proven active in Ziegler-Natta olefin polymerization have a high potential to be active in olefin metathesis. The following three specific aims will be pursued in order to reach the overall objective and test the central hypothesis. In specific aim 1, Molybdenum(0) dinitrogen complexes and molybdenum(III) trichloride complexes supported by bis(imino)pyridine (or NNN), bis(phosphino)pyridine (PNP), bis(phosphinito)pyridine and bis(phosphito)pyridine (PONOP) ligands will be synthesized and characterized. These molybdenum complexes will serve as precursors for the preparation of molybdenum alkylidene compounds. In specific aim 2, different methods to turn the molybdenum precursors prepared in specific aim 1 into molybdenum alkylidene compounds LMo=CHR and/or LMo (=CHR) (CH2R) will be investigated. One of these methods is based on work completed during the current SC3 award. Another method will involve the treatment of molybdenum(0) dinitrogen complexes with diazoalkane reagents, while a third method will consist in reacting molybdenum(III) trichloride complexes with different bulky alkyl Grignard reagents. Finally, specific aim 3 will focus on testing the catalytic activity of the new metal alkylidene complexes in different olefin metathesis reactions and will include the preparation of a bio medically relevant scaffold of genuine interest. The completion of this work will yield new robust olefin metathesis catalysts based on inexpensive and innocuous metals and a new general method for preparing alkylidene complexes of low-valent transition metals. This research is significant, because it will facilitate the discovery and the commercialization of olefn metathesis-enabled drugs.