New Methods for Asymmetric Carbon-Carbon and Carbon-Heteroatom Bond Formation

功能化分子的制备是有机化学的中心课题，也是医学、生物技术等相关应用科学的核心。大量具有生物活性的有机分子，包括市场上的几种药物，可以以两种不同的结构形式存在，这两种结构形式是不可重叠的镜像。这些被称为对映体。有趣的是，两种可能的对映体中只有一种具有预期的生物活性，而另一种不具有活性或有毒。因此，化学方法制备单一对映体具有重要的现实意义。这项提议的中心主题是开发这种制备方法，这些方法被广泛描述为有机化合物的不对称合成方法。制造有机分子的重要方法之一是通过在小的、容易获得的积木中的碳原子之间建立新的连接(键)来连接这些积木。拟议的研究将研究以一种优先形成一个对映体的方式形成碳-碳键的新方法。此外，许多生物活性分子都被含有氧和氮原子的基团所修饰。这些基团通常对生物活性至关重要，它们必须在三维空间中定向到特定的方向。因此，我们还将研究制造碳氧键和碳氮键的方法，目标是制造单一对映体的产品。可持续性和对环境的最小影响是开发新技术时的重要考虑因素，特别是在化学科学方面。为了与这些目标保持一致，我们将为我们的成键反应研究新的催化方法。新方法可能只需要少量促进反应所需的关键试剂，而且还将使用无毒溶剂。因此，与目前的做法相比，新程序将更加环保和经济。预计新方法将应用于制备治疗疾病的药物化合物，以及开发应用于健康科学的传感器。从拟议的调查中获得的知识将对化学和制药工业的持续发展、创新研究和有助于提高国家竞争力和生产力的新技术的开发至关重要。

The preparation of functionalized molecules is a central theme in organic chemistry and it is at the core of the related applied sciences such as medicine and biotechnology. A large number of biologically active organic molecules, including several medicinal agents on the market, can exist in two distinct structural forms which are non-superimposable mirror images. These are known as enantiomers. Interestingly, only one of the two possible enantiomers has the desired biological activity whereas the other is either inactive or toxic. Consequently, chemical methods for the preparation of single enantiomers are of great practical significance. The central theme of this proposal is the development of such preparative methods, and these are broadly described as methods for 'asymmetric synthesis' of organic compounds. One of the important methods of making organic molecules involves the joining of small, readily available building blocks by making new connections (bonds) between carbon atoms in these building blocks. The proposed investigations will examine new methods for making carbon-carbon bonds in such a way that one enantiomer is formed preferentially. In addition, many biologically active molecules are decorated with groups containing oxygen and nitrogen atoms. These groups are often crucial for bioactivity and they must be oriented in a specific direction in three dimensional space. Hence, we will also investigate methods for making carbon-oxygen and carbon-nitrogen bonds with the goal of making products that are single enantiomers. Sustainability and minimum environmental impact are important considerations when developing new technology, especially in the chemical sciences. In keeping with these objectives, we will investigate new catalytic methods for our bond forming reactions. The new methods will potentially require only small amounts of key reagents that are necessary for facilitating the reaction and will also use non-toxic solvents. Hence the new procedures will be environmentally friendly and more economical as compared to current practices. The new methods are anticipated to have applications in the preparation of medicinal compounds for the treatment of disease, and in the development of sensors with applications in the health sciences.The knowledge gained from the proposed investigations will be essential for the sustained development of the chemical and pharmaceutical industry, for innovative research and for the development of new technologies that contribute to our national competitiveness and productivity.