Development of Catalysts for Asymmetric Synthesis

不对称合成催化剂的开发

• 批准号: 7009556
• 负责人: VIRESH H. RAWAL
• 金额: $ 21.87万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7009556
• 关键词: Diels Alder reaction; alcohols; carbonyl group; catalyst; chemical reaction; chemical structure; chemical synthesis; chromium; cobalt; drug design /synthesis /production; electron crystallography; heavy metals; hydrogen bond; stereoisomer; technology /technique development

DESCRIPTION (provided by applicant): The importance of methods for the synthesis of chiral compounds in high enantiomeric purity cannot be overstated. In 2001, single enantiomer drugs comprised 36% ($147 billion) of the total market of $410 billion. This number is projected to increase steadily, such that chiral drugs will constitute a market of over $200 billion by 2008. The growing economic importance of chiral compounds has spurred major research efforts from many laboratories, academic and industrial, directed at the selective preparation of chiral compounds. A recent report from the PI's laboratory described the development of chiral metal-salen complexes that are exceptional catalysts for enantioselective Diels-AIder (DA) reactions, one of the most useful reactions for organic synthesis. A major focus of the proposed activity will be to investigate these catalysts and to develop related complexes for use in DA and other C-C bond forming reactions. The high efficiency of these catalysts (record low catalyst loading) makes them attractive for various applications in complex molecule synthesis, even for industrial uses. In conjunction with this work, additional heteroatom-substituted dienes will be developed for use in DA reactions. Also presented in the proposal are plans for the development of metal-free catalysts that use hydrogen bonding rather than Lewis acids to promote the enantioselective process. This metal-free acceleration of reactions is not only of fundamental interest, but is also of potential industrial importance, since metal impurities, especially transition metals, are undesirable in precious chemicals such as pharmaceutical drugs. Effort will be directed at the use of hydrogen bonding for the enantioselective catalysis of various C-C bond-forming reactions. The asymmetric catalysis capabilities of numerous chiral alcohols as well as other hydrogen bond donors will be examined. Both of the major subprojects (metal salen complexes and hydrogen bonding catalysis) will integrate crystallographic studies and computational modeling in order to develop models to rationalize the observed enantioselectivities. Overall, the investigations described in this proposal are expected to lead to useful new methodology advances for the asymmetric synthesis of complex molecules. The projects described herein will provide excellent training for undergraduate students, graduate students, and postdoctoral associates in asymmetric catalysis methodology development and complex molecule synthesis, experience that will prepare them well for independent research careers, either in industry or academics.

描述（由申请人提供）：在高对映体纯度中合成手性化合物的方法的重要性不能被夸大。 2001年，单一对映异构体药物占4100亿美元的总市场的36％（1,470亿美元）。预计该数字将稳定增加，因此，手性药物到2008年将构成超过2000亿美元的市场。手性化合物的经济重要性促使许多实验室（学术和工业）的重大研究工作促进了选择性准备手性化合物。 PI实验室的最新报告描述了手性金属盐络合物的发展，这些复合物是对映选择性Diels-aider（DA）反应的特殊催化剂，这是有机合成的最有用的反应之一。拟议活动的主要重点是研究这些催化剂，并开发相关的复合物，以用于DA和其他C-C键形成反应。这些催化剂的高效率（创纪录的低催化剂负载）使它们对于复杂分子合成中的各种应用，即使是工业用途也很有吸引力。结合这项工作，将开发出其他杂原子取代的二enes，以用于DA反应。该提案中还提出的是开发无金属催化剂的计划，这些催化剂使用氢键而不是刘易斯酸来促进对映选择过程。这种无金属反应的加速不仅具有根本利益，而且具有潜在的工业意义，因为金属杂质（尤其是过渡金属）在诸如药品等珍贵化学物质中是不受欢迎的。努力将致力于将氢键用于各种C-C键形成反应的对映选择性催化。将检查许多手性醇和其他氢键供体的不对称催化能力。两种主要的子运动（金属沙子络合物和氢键催化）将整合晶体学研究和计算模型，以开发模型以合理化观察到的对映射性。总体而言，预计该提案中描述的研究将导致复杂分子不对称合成的有用的新方法。本文所述的项目将为本科生，研究生和博士后伴侣提供出色的培训，这些培训在不对称催化方法论开发和复杂的分子综合方面，这将为他们在工业或学者中的独立研究职业做好准备。