Project Title: Metal-Catalyzed C-H Borylation: Design of New Catalysts with New Selectivities Abstract C?H borylation is a synthetic methodology where C?H bonds in an organic molecule react with B?H or B?B bonds forming a B?C bond. It has been widely applied in the functionalization of sp2 C?H bonds, but examples of sp and sp3 C?H bonds have been reported. The products of these reactions are important intermediates, which leverage the remarkable versatility of B?C bonds for installation of other functional groups under mild conditions. In this renewal application, 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. Some of the specific aims build on chemistry that was developed in the previous funding cycle, while other specific aims are entirely new. Specifically, we propose to (1) the design of low- coordination number catalysts for directed sp2 and sp3 C?H borylation; (2) The design of ligand frameworks for meta and para C?H borylations; and (3) Hydrogenation of C?H borylated arenes and heterocycles to achieve formal sp3 C?H borylation. We will pursue these aims through a collaborative multi-investigator venture that bring the power of inorganic chemistry and organic synthesis to bear on the problem.

Public Health Relevance

Project Title: Metal-Catalyzed C-H Borylation: Design of New Catalysts with New Selectivities 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 #
2R01GM063188-10
Application #
9177512
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2001-06-01
Project End
2020-07-31
Budget Start
2016-09-20
Budget End
2017-07-31
Support Year
10
Fiscal Year
2016
Total Cost
$293,418
Indirect Cost
$78,418
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
Chattopadhyay, Buddhadeb; Dannatt, Jonathan E; Andujar-De Sanctis, Ivonne L et al. (2017) Ir-Catalyzed ortho-Borylation of Phenols Directed by Substrate-Ligand Electrostatic Interactions: A Combined Experimental/in Silico Strategy for Optimizing Weak Interactions. J Am Chem Soc 139:7864-7871
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
Ghaffari, Behnaz; Vanchura 2nd, Britt A; Chotana, Ghayoor A et al. (2015) Reversible Borylene Formation from Ring Opening of Pinacolborane and Other Intermediates Generated from Five-Coordinate Tris-Boryl Complexes: Implications for Catalytic C-H Borylation. Organometallics 34:4732-4740
Kallepalli, Venkata A; Gore, Kristin A; Shi, Feng et al. (2015) Harnessing C-H Borylation/Deborylation for Selective Deuteration, Synthesis of Boronate Esters, and Late Stage Functionalization. J Org Chem 80:8341-53
Ghaffari, Behnaz; Preshlock, Sean M; Plattner, Donald L et al. (2014) Silyl phosphorus and nitrogen donor chelates for homogeneous ortho borylation catalysis. J Am Chem Soc 136:14345-8
Jayasundara, Chathurika R K; Unold, Jason M; Oppenheimer, Jossian et al. (2014) A catalytic borylation/dehalogenation route to o-fluoro arylboronates. Org Lett 16:6072-5
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

Showing the most recent 10 out of 17 publications