Metal-Catalyzed C-H Borylation: Mechanism, Scope, and Applications

芳香族和杂芳族单元是分子中重要且普遍的结构基元， 无论是天然的还是人工的，都显示出生物活性。含芳烃和杂芳烃 分子通常使用传统的合成方法或生物合成来制备。为 传统的，在一定程度上，生物合成原料，母结构通常是 最丰富的形式和更复杂的类比可以通过它们的直接 功能化。亲电芳香族取代(EAS)是最常被要求进行的反应 这样的功能化。在这里，是对EAS的有益补充，即 提出了SP2杂化芳烃和/或杂芳烃C？H键。在本建议书中，具体 发明的溶液是硼烷B？H和sp2C？H键的催化脱氢偶联 在密歇根州立大学的史密斯实验室。 将实现以下具体目标： 1.机械论研究。一种统一的实验和计算方法正在进行中 旨在阐明C？H-硼化反应的机理特征。调查结果将用于 优化现有催化剂，设计新的催化剂。 2.催化剂设计。部分是由特定目标1催化剂的机理研究指导的 将作出修改，以(A)改善类似群体之间的歧视 空间要求，(B)增强富电子底物的反应性，(C)歧视 当两者都存在时，在富电子环系和贫电子环系之间，以及(D) 探索立体选择性C？H硼化反应的潜力。 3.复杂体系中的硼化反应。分子结构的复杂性可以 两者都由特定的反应操作和构造，最终决定了它的 冲击作为一种合成方法。考虑到这一点，C？H硼化将应用于(A) 选定的生物活性分子的官能化，其中大部分是商业化的 可获得，(B)在通往TMC功能核心的途中精制受保护的三肽- 95a和(C)自溶霉素和()-异斜坡菌素C和D的全合成。

Aromatic and heteroaromatic units are important and pervasive structural motifs in molecules, both natural and artificial, that exhibit biological activity. Arene and heteroarene containing molecules are typically prepared using traditional synthetic approaches or biosynthesis. For traditional, and to a certain extent, biosynthetic feedstocks, the parent structures are typically the most abundant forms, and more complex analogs can be obtained through their direct functionalization. Electrophilic aromatic substitution (EAS) is most often called upon to effect such functionalizations. Herein, useful complement to EAS, namely direct functionalizations of sp2-hybridized arene and/or heteroarene C¿H bonds, are proposed. In this proposal specific solution is the catalytic dehydrogenative coupling of borane B¿H and sp2 C¿H bonds invented in the Smith laboratories at Michigan State University. The following Specific Aims will be addressed: 1. Mechanistic Studies. A unified experimental and computational approach is being designed to elucidate mechanistic features of C¿H borylation. Findings will be used to optimize existing catalysts and designing new catalysts. 2. Catalyst Design. Guided in part by the mechanistic studies in Specific Aim 1, catalyst modifications will be made to (a) improve discrimination between groups with similar steric requirements, (b) enhance reactivities of electron-rich substrates, (c) discriminate between electron-rich and electron-deficient ring systems when both are present, and (d) explore to potential for stereoselective C¿H borylation. 3. Borylations in Complex Systems. The complexity of molecular architectures that can both be operated upon and constructed by a particular reaction ultimately determines its impact as a synthetic method. With this in mind, C¿H borylation will be applied to (a) functionalization of selected biologically active molecules, most of which are commercially available, (b) elaboration of a protected tripeptide en route to a functional core of TMC- 95A, and (c) total syntheses of autolytimycin and (+)-isoplagiochin C and D.