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

描述(申请人提供)：金属催化的C-H硼化反应：机理、范围和应用摘要C-H硼化反应是有机分子中的C-H键与B-H或B-B键反应形成B-C键的过程。这个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，这一过程是由金属催化的，使用最广泛的系统使用Ir。C-H硼化反应的区域选择性通常是对更常用的C-H官能化方法的补充，如亲电取代(EAS)或定向邻位金属化(DOM)。虽然空间相互作用可以对区域选择性有很大的影响，但有证据表明，电子效应可能在这种化学中发挥重要的作用，尽管被忽视了。在这里，我们建议推进我们对C-H硼化反应的理解，并正交开发该方法，使其能够为生物医学界所面临的合成问题提供解决方案。具体地说，我们建议(1)深入了解这些反应的机理；(2)开发反电子C-H官能化的新策略；(3)发明用于反式选择性C-H官能化的新催化剂。我们将通过一个合作的多研究人员冒险项目来追求这些目标，该项目将无机化学、有机合成和计算方法的力量应用到这个问题上。 公共卫生相关性：金属催化的C-H硼化反应：机制、范围和应用项目叙述：新的药物需要新的化学构件。同样，成本较低的药物将需要更高效、更环保的途径来获得这些关键的合成中间体。因此，我们希望发明化学，使原本难以获得的分子的制备成为可能，从而使药物的发现、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.