Enantioselective Catalytic Boronate Reactions

描述(申请人提供)：开发新的化学方法是有机合成的一个重要目标。一个继续激励化学家的领域是有机硼烷和硼酸盐的化学。硼的独特性质和激活有机硼酸盐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过程。我们将扩大有机硼烷和硼酸盐在新型缩合反应中提供碳负离子当量的能力，包括化学选择性的羰基缩合反应和多组分反应。通过开发不对称催化剂和手性硼酸酯试剂，以及通过药物和天然产物的不对称合成所展示的方法的应用，这些反应将变得不对称。通过与手性二醇的配体交换来理解硼酸盐活化的机理已经取得了重大进展。我们将使用我们获得的机理洞察力来扩展动态配体交换过程催化的反应体系，包括作为亲电体的酰基氰化物、硼-彼塔什反应和邻苯二酚甲基化学。我们对反应发现的持续兴趣导致了能够促进缩醛的对映选择性加成反应的手性二醇酸催化剂的鉴定。我们试图探索这种反应性，并将其扩展到包括以下类型 除了氧和亚胺以及硼酸盐的杂-Diels-Alder反应外，还有官能化的亲核试剂。该研究计划的目标包括开发广泛的反应性，提供获得新手性嵌段的途径，以及新的反应开发。选择键结构来获得手性合成中间体，这些中间体可用于构建药物和天然产品。这一结果将改变硼酸盐亲核剂在对映选择性合成中的应用方式。

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.