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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM063188-06
Application #
8109059
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2001-06-01
Project End
2015-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
6
Fiscal Year
2011
Total Cost
$341,614
Indirect Cost
Name
Michigan State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
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Shen, Fangyi; Tyagarajan, Sriram; Perera, Damith et al. (2016) Bismuth Acetate as a Catalyst for the Sequential Protodeboronation of Di- and Triborylated Indoles. Org Lett 18:1554-7
Smith, Kyle T; Berritt, Simon; González-Moreiras, Mariano et al. (2016) Catalytic borylation of methane. Science 351:1424-7
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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
Roosen, Philipp C; Kallepalli, Venkata A; Chattopadhyay, Buddhadeb et al. (2012) Outer-sphere direction in iridium C-H borylation. J Am Chem Soc 134:11350-3
Norberg, A Monica; Smith 3rd, Milton R; Maleczka Jr, Robert E (2011) Practical One-Pot C-H Activation/Borylation/Oxidation: Preparation of 3-Bromo-5-methylphenol on a Multigram Scale. Synthesis (Stuttg) 2011:857-859

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