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

金属催化的C-H硼基化：机理、范围和应用摘要C-H硼基化是有机分子中的C-H键与B-H或B-B键反应形成B-C键的过程。该过程的副产物是来自B-H试剂的二氢或来自B-B试剂的硼烷。在大多数情况下，该过程是金属催化的，并且最广泛使用的系统使用铱。C-H硼基化的区域选择性通常补充更常用的C-H官能化方法如亲电芳族取代（EAS）或定向邻位金属化（DoM）的区域选择性。虽然空间相互作用对区域选择性有很大的影响，但有证据表明电子效应在这种化学中可能发挥重要作用，尽管未得到充分重视。在此，我们建议提高我们的理解C-H硼化和正交开发的方法，使它可以提供解决方案，生物医学界面临的合成问题。具体而言，我们建议（1）深入了解这些反应的机理性质;（2）开发新的反电子C-H官能化策略;（3）发明新的催化剂用于atroposelective C-H官能化。我们将通过一个多研究者合作的项目来追求这些目标，这个项目将无机化学、有机合成和计算方法的力量带到这个问题上。 公共卫生相关性：金属催化的C-H硼化反应：机理、范围和应用项目叙述：新药需要新的化学结构单元。同样，成本较低的药物将需要更有效和环保的路线来获得这些关键合成中间体。因此，我们希望发明化学，以允许制备否则无法获得的分子，从而使药物发现，开发和生产成为可能。

DESCRIPTION (provided by applicant): Metal-Catalyzed C-H Borylation: Mechanism, Scope, and Applications Abstract C-H borylation is a process where C-H bonds in an organic molecule react with B-H or B-B bonds forming a B-C bond. The byproducts of this process are dihydrogen from B-H reagents or a borane from B-B reagents. In most instances, this process is metal-catalyzed, and the most widely utilized systems employ iridium. The regioselectivities for C-H borylations often complement those of more commonly employed C-H functionalization methods like electrophilic aromatic substitution (EAS) or directed ortho-metalation (DoM). Although steric interactions can have a strong influence on regioselectivity, there is evidence that electronic effects may play an important, though underappreciated, role in this chemistry. Herein we propose to advance our understanding of C-H borylations and to orthogonally develop the methodology such that it can offer solutions to synthetic problems faced by the biomedical community. Specifically, we propose to (1) gain insight into the mechanistic nature of these reactions; (2) Develop new strategies for contra electronic C-H functionalizations; and (3) Invent new catalysts for atroposelective C-H functionalization. We will pursue these aims through a collaborative multi- investigator venture that bring the power of inorganic chemistry, organic synthesis, and computational methods to bear on the problem. PUBLIC HEALTH RELEVANCE: Metal-Catalyzed C-H Borylation: Mechanism, Scope, and Applications Project Narrative: New pharmaceuticals call for new chemical building blocks. Similarly, lower cost drugs will require more efficient and environmentally friendly routes to these key synthetic intermediates. Thus we looked to invent chemistry that will allow for the preparation of otherwise inaccessible molecule that may enable drug discovery, development, and production.