Development of Catalytic Enantioselective Intermolecular Diene Hydrofunctionalization Reactions

化学部的化学合成项目支持Steven Malcolmson教授的项目。马尔科姆森教授是杜克大学化学系的一名教员。新化学反应的发展对包括材料、农业和制药在内的许多重要技术的持续进步至关重要。发展合成方法的需要包括使用廉价和丰富的起始材料，同时产生最少的化学废物。我们感兴趣的一种反应被称为催化氢功能化，它为现成的分子增加了新的变化能力。目前，氢化官能化反应在可使用的分子类型以及整个过程的速度和选择性方面受到限制。为了解决这些限制，马尔科姆森实验室正在开发一些新的氢化反应，形成碳-碳和碳-氮键。该反应利用了市售试剂和易于获取的起始材料，并且在使用最少溶剂的情况下，将所有试剂中的所有原子合并到产物中（原子经济）。因此，这些反应产生的化学废物很少。这些反应产生的产物是有价值的，因为它们可以作为精细化学、农业化学和药物化学工业中使用的合成基石。除了这项工作，Malcolmson博士和他的团队正在开发一系列简短的在线视频，以教育公众、本科生和研究生，让他们了解催化反应的发展如何通过工业应用塑造了现代世界。这一努力提高了公众的科学素养，培养了大学预科生和大学生对科学的兴趣，同时也扩大了研究生教育，从而有助于培养下一代科学家。在化学合成项目的资助下，杜克大学的Malcolmson实验室正在开发一些催化位点和对映选择性的1,3-二烯的氢胺化和氢烷基化反应，包括具有挑战性的内二烯。具有手性螯合P， n配体的钯基催化剂允许在室温下在短的反应时间内进行廉价，丰富和市售的胺和β -二羰基亲核原试剂的高效和对映选择性反应。二烯的加氢功能化提供了一种方便和100%原子经济的方法来构建具有烯丙基立体中心的化合物，这是组装精细化学品，农用化学品和药品的宝贵基石。在这个项目下获得的高价值产品不容易通过竞争技术，如烯丙基替代制备。本应用程序中概述的方法发展以及随之而来的机制研究可能开始解决对映选择性氢化技术中长期存在的挑战，并为相关的未来研究奠定基础。教育外展的重点是通过制作和分发一系列短视频，提高公众对催化的理解和欣赏，这些视频讲述了合成催化化学如何塑造了现代世界。这些视频可以在YouTube上找到。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。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Steven Malcolmson. Professor Malcolmson is a faculty member in the Department of Chemistry at Duke University. The development of new chemical reactions is critical to continued progress within a number of vital technologies, including materials, agriculture, and pharmaceuticals. The needs for the development of synthetic methods include the use of cheap and abundant starting materials while generating minimal chemical waste. One reaction of interest, called a catalytic hydrofunctionalization, adds new abilities to change to readily available molecules. Hydrofunctionalization reactions are currently limited in terms of the types of molecules that can be used and the speed and selectivity of the overall process. To address these limitations, the Malcolmson laboratory is developing a number of new hydrofunctionalization reactions that form carbon-carbon and carbon-nitrogen bonds. The reactions take advantage of commercially available reagents and easily accessed starting materials, and they incorporate all of the atoms from all reagents into the products (atom economy) while using minimal solvent. As such, the reactions generate very little chemical waste. The products generated from the reactions are valuable in that they can serve as synthetic building blocks for use in the fine chemical, agrochemistry, and medicinal chemistry industries. In addition to this work, Dr. Malcolmson and his team are developing a series of short online videos to educate the public and undergraduate and graduate students about how the development of catalytic reactions has shaped the modern world through industrial applications. This effort increases public scientific literacy and fosters an interest in science among precollege and college students while also broadening graduate education, thereby helping to train the next generation of scientists.With funding from the Chemical Synthesis Program of the Chemistry Division, the Malcolmson laboratory at Duke University is developing a number of catalytic site- and enantioselective hydroamination and hydroalkylation reactions of acyclic 1,3-dienes, including challenging internal dienes. Palladium-based catalysts with chiral chelating P,N-ligands allow for efficient and enantioselective reactions of cheap, abundant, and commercially available amines and beta-dicarbonyl pronucleophiles at room temperature within short reaction times. Hydrofunctionalization of dienes offers an expedient and 100% atom economical way to construct compounds with allylic stereogenic centers, valuable building blocks for assembling fine chemicals, agrochemicals, and pharmaceuticals. The high-value products garnered under this project are not easily prepared through competing technologies such as allylic substitution. The methods development outlined in this application along with the accompanying mechanistic investigations may begin to address long-standing challenges in enantioselective hydrofunctionalization technologies and lay the groundwork for related future studies. The educational outreach focuses on increasing public understanding and appreciation for catalysis via production and distribution of a collection of short videos, relating how synthetic catalytic chemistry has shaped the modern world. These videos are available on YouTube.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.