The Rational Development of Organometallic Reagents through Fluorescence Microscopy Experiments

• Applicant: Dr. Kristof Jess
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2018 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405360690

The key objective of the project is to answer long-standing questions about how additives facilitate the formation of organometallic reagents. To achieve this objective, fluorescence microscopy approaches with sensitivity for the detection of single molecules of organometallic intermediates will be developed. Organometallic reagents are important for the synthesis of complex organic compounds, e.g., natural products and pharmaceuticals. A simple route to such reagents is the formation of a metal and an organohalide species. However, this simple route is often only possible using certain additives. For example, Blum's research group has recently discovered that lithium chloride helps to dissolve organozinc reagents from the zinc surface, using a highly sensitive microscopy approach. The key experiment is the visualization of small quantities of surface organometallic intermediates by fluorescence microscopy and the determination of the conditions under which these species are observed. The quantity of these intermediates is too low to be detected by traditional analytical instrumentation. Through the development of imaging agents for this approach, I aim to answer four questions: (A) Organometallic reagents of manganese and aluminum require catalytic amounts of metal salts (chlorides of titanium, indium, lead, or bismuth). However, the mechanism of action of these additives is still unclear. Five mechanistic possibilities will be considered and investigated by fluorescence microscopy.(B) An alternative route to organometallic reagents is the synthesis from so-called Rieke metals – finely divided and highly reactive metal powders. It has been shown that the synthetic route towards Rieke metals has an impact on their reactivity; the difference in reactivity is believed to be caused by by-products formed in each synthesis. Here, I want to investigate why Rieke metals from different routes have different reactivities, by determining the role of the by-products directly.(C) The origin of pronounced solvent effects in the formation of organozinc reagents will be determined.(D) Two practical applications are proposed through rational reaction design: 1) enabling the simple and safer synthesis of organotin reagents – important reagents in the Stille coupling and 2) improvement of the synthetically important Ullmann coupling.Conclusion: The intended research will help to understand the mechanistic role of additives in organometallic reagent synthesis for organic and organometallic chemistry. In the future, this understanding may enable the preparation of organometallic reagents from commercial metal powders for a significantly larger range of metals. At the same time, fluorescence microscopy will be developed as a new analytical method in inorganic chemistry.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Suzanne A. Blum, Ph.D.