Practical Strategies for Controlling Selectivity in Organic Reactions

描述（由申请人提供）：根本需要开发高度选择性和原子经济性的化学转化。定向基团在一系列有机转化中控制区域和立体化学方面发挥了关键作用。然而，通常导向基团策略需要将化学计量量的合成上不期望的官能团（如膦）引入有机底物中。该计划的长期目标是通过开发能够同时可逆地结合金属催化剂和常见有机官能团（如醇，胺和羧酸）的配体来解决这一限制。通过使用配体作为支架将催化剂和底物临时连接在一起，引导基团控制选择性的能力将与催化的实用性相结合。支架策略的价值在于，我们可以应用合成上有用的官能团与配体结合，然后定制配体以在所需的转化中获得最佳性能。这一概念将适用于区域，非对映体，和对映体选择性加氢的一系列基板。这一策略的成功应用将显着拓宽化合物的范围可从加氢，一个有效的和实用的金属催化反应，并将提供生物相关的杂环。一旦这一概念通过应用于催化加氢反应而建立起来，我们将把这一思想应用于其他重要的过渡金属催化反应。 公共卫生相关性：2002年，单一对映体药物占全球药物销售的40%。在过去的二十年中，全世界批准的对映体纯药物的数量稳步增加，而非手性药物的百分比从所有批准药物的43%下降到34%。这些趋势产生了对有效地和选择性地制备单一立体异构体产物的方法的需要。提出的研究直接解决这一需要，通过开发一种新的策略，控制有机转化的立体选择性。

DESCRIPTION (provided by applicant): There is a fundamental need to develop chemical transformations that are highly selective and atom-economical. Directing groups have played a pivotal role in controlling regio- and stereochemistry in a range of organic transformations. However, often directing-group strategies require the introduction of stoichiometric quantities of synthetically undesirable functional groups (such as phosphines) into the organic substrates. The long-term goal of this program is to address this limitation by developing ligands that have the ability to simultaneously and reversibly bind to a metal catalyst and common organic functional groups (such as alcohols, amines, and carboxylic acids). By using a ligand as a scaffold to temporarily join the catalyst and substrate together, the power of directing groups to control selectivity will be coupled to the practicality of catalysis. The value of the scaffolding strategy is that we can apply a synthetically useful functional group to bind to the ligand, and then tailor the ligand for optimal performance in the desired transformation. This concept will be applied towards the regio-, diastereo-, and enantioselective hydroformylation of a range of substrates. Successful application of this strategy will significantly broaden the scope of compounds accessible from hydroformylation, an efficient and practical metal-catalyzed reaction, and will provide access to biologically relevant heterocycles. Once this concept is established through application to catalytic hydroformylation, we will apply this idea to other significant transition metal- catalyzed reactions. PUBLIC HEALTH RELEVANCE: In 2002, single enantiomer pharmaceuticals made up 40% of worldwide drug sales. Over the last twenty years the number of enantiopure drugs approved worldwide has steadily increased, while the percentage of achiral drugs decreased from 43 to 34% of all approved drugs. These trends have created a need for methods that efficiently and selectively make single stereoisomer products. The proposed studies directly address this need by developing a new strategy for controlling stereoselectivity in organic transformations.