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

摘要C-H硼化是有机分子中C-H键与B-H键或B-B键反应形成B-C键的过程。这个过程的副产物是B-H试剂的二氢或B-B试剂的硼烷。在大多数情况下，这个过程是金属催化的，最广泛使用的系统使用铱。碳氢键硼化的区域选择性通常是对亲电芳取代（EAS）或定向邻金属化（DoM）等更常用的碳氢键功能化方法的补充。尽管空间相互作用对区域选择性有很强的影响，但有证据表明，电子效应可能在这种化学中起着重要的作用，尽管尚未得到充分认识。在此，我们建议提高我们对碳氢键硼化的理解，并正交发展方法，以便它可以为生物医学界面临的合成问题提供解决方案。具体来说，我们建议：(1)深入了解这些反应的机械性质；(2)制定反电子碳氢功能化的新策略；(3)发明新的碳-氢选择性官能化催化剂。我们将通过多方研究者的合作来追求这些目标，将无机化学、有机合成和计算方法的力量带到这个问题上。

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.