Team Enhances Catalytic System to Perform Grignard Reaction on Carbon-Fluorine Bonds
Outline of the Kambe Group's Research. Credit: Osaka University
Making complicated organic molecules is like solving a Rubik’s cube. Organic chemists need to design sequences of reactions to carefully build up parts of a molecule, while maintaining the structure at other sites. Although chemists have developed many ingenious ways of performing chemical transformations, some chemical reactions remain out of reach.
At Osaka University, a team of organic chemists has now developed and enhanced a chemical reaction that allows controlled transformations of one of the toughest chemical bonds.
“We previously developed a cobalt catalyzed Grignard reaction for making hindered quaternary carbon centers. But that reaction also showed potential for modifying carbon-fluorine bonds. We tried many different additives and eventually found one that let us selectively build the same quaternary carbon-carbon bonds at carbon-fluorine sites,” says first author Takanori Iwasaki.
The Grignard reaction is a classic reaction in organic chemistry, useful for building the carbon skeleton of molecules by transforming carbon-halogen bonds into carbon-carbon bonds. Fluorine is also considered to be a halogen but the carbon-fluorine bond is among the strongest known and is usually unreactive to Grignard chemistry. Performing any kind of chemical reaction at carbon-fluorine bonds is difficult without affecting the rest of the molecule.
The Osaka team enhanced their catalytic system for performing difficult Grignard chemistry at very crowded, so-called quaternary carbon atoms. By adding a carefully selected additive to this catalytic system, they boosted its ability to work selectively on carbon-fluorine bonds.
“We have shown that this reaction is a very useful tool for sequentially changing parts of a molecule with great control,” says Group leader, Nobuaki Kambe. “Our control over the chemistry of carbon-fluorine bonds should enable much more synthetic freedom for building complex carbon structures.”
Co-catalyzed cross-coupling of alkyl fluorides with alkyl Grignard reagents. (Osaka University)
Iterative coupling reaction using the present catalytic system. (Osaka University)
To learn more about this research, please view the full research report entitled "Co-Catalyzed Cross-Coupling Reaction of Alkyl Fluorides with Alkyl Grignard Reagents" at this page of Organic Letters.
This article has been republished from materials provided by Osaka University. Note: material may have been edited for length and content. For further information, please contact the cited source.
Protein Target Identified That Could Prevent StrokesNews
Scientists have identified a protein, called GPR68, that senses blood flow and tells small blood vessels called arterioles when to dilate. The researchers believe medications that activate GPR68 could one day be useful to treat medical conditions, including ischemic stroke.READ MORE
How Environmental Pollutants and Genetics Work Together in Rheumatoid ArthritisNews
It is well known that individuals with a particular version of human leukocyte antigen have an increased risk for rheumatoid arthritis, but there has been growing interest in the role of environmental pollutants. In a new mouse study, researchers probed the relationship between the two.READ MORE
Neuropeptide Y Y1 Receptor Structure Solved, Offers New Opportunities for Anti-obesity Drug DiscoveryNews
Scientists solve the crystal structure of Neuropeptide Y Y1 Receptor, offering new opportunities for anti-obesity drug discovery.READ MORE