Enantioselective Functionalizations of Azomethines and Alkenes

描述(申请人提供)：这项提案的首要目标是开发新的反应和控制它们的试剂，以产生对映体丰富的有机化合物。这些产品是更精细的小分子药物和/或更复杂的生物活性天然产品的宝贵前体。所提出的方法专门针对作为单一立体异构体的仲胺、叔胺和邻二胺的简明合成。这些方法是基于双(酰胺)试剂的发展，当加入强酸或与酸性底物一起使用时，这些试剂会形成手性质子络合物(极性离子氢键)。还描述了一种新的变体的探索，当从相同的手性支架投射时，该变体包含一个非常接近氢键施主(极性共价氢键)的酰胺。这些研究继续成功地将双功能有机催化剂应用于立体控制的结构和功能基序的创建，这些结构和功能基序虽然常见，但很难使用传统替代品进行制备。这些研究还探索了一种全新的活化模式，涉及手性Bronsted酸介导的卤素-烯烃反应。利用手性质子催化作为控制对映体选择的手段，将开发一系列创新的多组分偶联反应。这些研究有可能影响小分子合成，并最终影响治疗剂的开发。此外，该方法能够无金属地生产功能稠密的单一对映体(和非对映异构体)有机化合物。

DESCRIPTION (provided by applicant): The overarching goal of this proposal is the development of new reactions, and the reagents that control them, to generate enantioenriched organic compounds. These products are valuable precursors to more elaborate small molecules that are medicinal agents and/or more complex biologically active natural products. The proposed methods specifically target the concise synthesis of secondary amines, tertiary amines, and vicinal diamines as single stereoisomers. These methods are based on the development of bis (amidine) reagents that form chiral proton complexes (a polar ionic hydrogen bond) when a strong acid is added, or when used with acidic substrates. Exploration of a new variant is also described, which contains a single amidine in close proximity to a hydrogen bond donor (polar covalent hydrogen bond) when projected from the same chiral scaffold. These studies continue the successful application of bifunctional organocatalysts to the stereocontrolled creation of structural and functional motifs that, while common, are otherwise difficult to prepare using conventional alternatives. These studies also explore an entirely new mode of activation that involves chiral Bronsted acid mediated halogen- alkene reactions. A range of innovative multicomponent coupling reactions will be developed using chiral proton catalysis as the means to control enantioselection. These studies have the potential to impact small molecule synthesis, and ultimately the development of therapeutic agents. Moreover, the methods enable the metal-free production of functionally dense, single enantiomer (and diastereomer) organic compounds.