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.
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.
|Preshlock, Sean M; Plattner, Donald L; Maligres, Peter E et al. (2013) A traceless directing group for C-H borylation. Angew Chem Int Ed Engl 52:12915-9|
|Holmes, Daniel; Chotana, Ghayoor A; Maleczka Jr, Robert E et al. (2006) One-pot borylation/amination reactions: syntheses of arylamine boronate esters from halogenated arenes. Org Lett 8:1407-10|
|Chotana, Ghayoor A; Rak, Michael A; Smith 3rd, Milton R (2005) Sterically directed functionalization of aromatic C-H bonds: selective borylation ortho to cyano groups in arenes and heterocycles. J Am Chem Soc 127:10539-44|
|Cho, Jian-Yang; Tse, Man Kin; Holmes, Daniel et al. (2002) Remarkably selective iridium catalysts for the elaboration of aromatic C-H bonds. Science 295:305-8|
|Tse, M K; Cho, J Y; Smith 3rd, M R (2001) Regioselective aromatic borylation in an inert solvent. Org Lett 3:2831-3|