Development of Catalytic Enantioselective Intermolecular Diene Hydrofunctionalization Reactions

化学部化学合成计划支持史蒂文·马尔科姆森教授的项目。马尔科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于包括材料、农业和制药在内的一些重要技术的持续进步至关重要。开发合成方法的需要包括使用廉价和丰富的原料，同时产生最少的化学废物。一种有趣的反应被称为催化氢功能化，它增加了新的能力，可以改变为容易获得的分子。目前，氢化功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。为了解决这些局限性，马尔科姆森实验室正在开发一些形成碳-碳和碳-氮键的新的氢功能化反应。这些反应利用了市场上可获得的试剂和容易获得的起始材料，它们将所有试剂中的所有原子合并到产品中(原子经济性)，同时使用最少的溶剂。因此，这些反应产生的化学废物非常少。这些反应产生的产品很有价值，因为它们可以用作精细化工、农用化学和药物化学行业的合成构件。除了这项工作，马尔科姆森博士和他的团队还在开发一系列在线短视频，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现代世界。这一努力提高了公众的科学素养，并在预科和大学生中培养了对科学的兴趣，同时也扩大了研究生教育，从而有助于培养下一代科学家。在化学系化学合成计划的资助下，杜克大学马尔科姆森实验室正在开发一些催化部位和对映选择性1，3-二烯的氢胺化和氢烷基化反应，包括具有挑战性的内部双烯。具有手性配位性P，N-配体的钯基催化剂可以在较短的反应时间内，在室温下对廉价的、丰富的和商业上可用的胺和β-二酮基亲核试剂进行高效的对映选择性反应。二烯烃的氢化功能化为构建具有烯丙基立体中心的化合物提供了一种方便且100%原子经济的方法，这些化合物是组装精细化学品、农用化学品和药物的宝贵构件。在该项目下获得的高价值产品并不容易通过诸如烯丙基取代等竞争技术来制备。本申请中概述的方法开发以及随之而来的机理研究可能开始解决对映体选择性水力功能化技术的长期挑战，并为未来的相关研究奠定基础。教育宣传的重点是通过制作和分发一系列短片来增加公众对催化的理解和欣赏，这些短片讲述了合成催化化学如何塑造现代世界。这些视频可以在YouTube上找到。这个奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.