Enantioselective Catalytic Boronate Reactions

对映选择性催化硼酸酯反应

• 批准号: 8818674
• 负责人: Scott Edward Schaus
• 金额: $ 28.94万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8818674
• 关键词: Acetals; Acids; Address; Aldehydes; Area; Biological Factors; Boron; Boronic Acids; Boxing; Breathing; Carbon; Carboxylic Acids; Catalysis; Chemicals; Chemistry; Collection; Coupling; Cyanides; Development; Diels Alder reaction; Drug Compounding; Glycols; Goals; Health; Isomerism; Ligands; Methodology; Methods; Modality; Natural Product Drug; Organic Synthesis; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Physical condensation; Process; Property; Reaction; Reagent; Research; Seminal; carbanion; carbon compound; catalyst; design; enantiomer; human disease; improved; innovation; insight; interest; novel; organic acid; prevent; programs; quinone methide

DESCRIPTION (provided by applicant): The development of new chemical methodologies is an important objective of organic synthesis. An area that continues to inspire chemists is the chemistry of organoboranes and boronates. The unique properties of boron and the ability to activate organic boronates to deliver carbon nucleophiles has yielded an impressive array of chemical methods and processes. We will extend the ability of organoboranes and boronates to deliver carbanion equivalents in novel condensation reactions including chemoselective carbonyl condensations and multicomponent reactions. The reactions will be rendered asymmetric through the development of asymmetric catalysts and chiral boronate reagents and the utility of the methods developed demonstrated by the asymmetric synthesis of pharmaceuticals and natural products. Significant advances have been made in the mechanistic understanding of boronate activation via ligand exchange with chiral diols. We will use the mechanistic insight we have obtained to expand the repertoire of reactions catalyzed by dynamic ligand exchange processes to include acyl cyanides as electrophiles, borono-Petasis reactions, and ortho-quinone methide chemistry. Our continued interest in reaction discovery has led to the identification of chiral diol acid catalysts capable of promoting the enantioselectie addition reactions to acetals. We seek to explore this reactivity and expand it to include types of functionalized nucleophiles in additions to oxoniums and iminiums and boronate hetero-Diels-Alder reactions. Goals of the research program include developing a breadth of reactivity, providing access to novel chiral blocks, and new reaction development. Bond constructions are selected to access chiral synthetic intermediates that could be used in the construction of pharmaceuticals and natural products. The results will transform the way boronate nucleophiles are utilized in enantioselective synthesis.

描述（由申请人提供）：新化学方法的开发是有机合成的一个重要目标。有机硼烷和硼酸盐的化学是持续激发化学家灵感的一个领域。硼的独特性质以及激活有机硼酸盐以提供碳亲核试剂的能力已经产生了一系列令人印象深刻的化学方法和工艺。我们将扩展有机硼烷和硼酸盐在新型缩合反应（包括化学选择性羰基缩合和多组分反应）中提供碳负离子当量的能力。通过不对称催化剂和手性硼酸酯试剂的开发以及药物和天然产物的不对称合成所证明的开发方法的实用性，这些反应将变得不对称。通过与手性二醇进行配体交换对硼酸酯活化的机理的理解已经取得了重大进展。我们将利用我们获得的机理见解来扩展动态配体交换过程催化的反应库，包括作为亲电子试剂的酰基氰化物、硼基-聚醚反应和邻醌甲基化物化学。我们对反应发现的持续兴趣导致了手性二醇酸催化剂的鉴定，该催化剂能够促进缩醛的对映选择性加成反应。我们寻求探索这种反应性并将其扩展到包括以下类型 除了氧鎓和亚胺以及硼酸杂狄尔斯-阿尔德反应之外，还包括官能化亲核试剂。该研究计划的目标包括开发广泛的反应性、提供新型手性嵌段以及新反应的开发。选择键结构来获得可用于构建药物和天然产物的手性合成中间体。这些结果将改变硼酸盐亲核试剂在对映选择性合成中的利用方式。