Vinyl Diazonium Ions as Synthetic Intermediates

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Matthias Brewer of the University of Vermont is developing new ways to make organic molecules using compounds called vinyl diazonium ions to achieve new carbon-carbon bond connections. Vinyl diazonium ions are uncommon chemical building blocks with the potential to become important synthetic tools.

Professor Brewer and his students are testing these compounds in complex synthetic examples and systematically establishing their fundamental reactivity. Investigating innovative strategies to prepare organic molecules is an important goal as it enables advances in many other fields of research that depend on complex organic molecule synthesis such as drug discovery and materials science.

This program is being used to engage economically-disadvantaged high school students in science, technology, engineering, and mathematics (STEM) activities in collaboration with the American Chemical Society (ACS) Project SEED program. Professor Brewer is also organizing an annual retreat for University of Vermont students of color in STEM disciplines.

This retreat will help to overcome the sense of isolation that students of color in STEM fields feel by providing these students a chance to meet and build a greater sense of community at the University of Vermont.

Vinyl diazonium ions are underdeveloped synthetic intermediates with the potential to provide solutions to current synthetic challenges. Professor Brewer and his research team are investigating the reactivity of vinyl diazonium ions to provide new approaches to the synthesis of all-carbon quaternary centers, access complex structures that contain a diazo functional group, and provide a strategy towards the first total synthesis of anadensin, a fusicoccane diterpenoid with anti-cancer and anti-microbial activity.

All-carbon quaternary centers in complex organic compounds are challenging to install due to their sterically encumbered nature but are found in many biologically active molecules including natural products that have been shown to be excellent medicinal leads. Vinyl diazonium ions are being studied as electrophiles to provide new stereoselective routes to all-carbon quaternary centers that are difficult to make by traditional methods.

The diazo group is one of the most versatile functional groups in synthetic chemistry and the products formed by the addition of nucleophiles to vinyl diazonium ions are being explored as activated synthetic intermediates for subsequent complexity building reactions. Investigations towards the synthesis of anadensin are being used to test a new strategy for preparing complex dicyclopenta[a,d]cyclooctene 5-8-5 ring systems.

These activities are synergistically providing important training in synthetic chemistry for a diverse group of graduate and undergraduate students at the University of Vermont.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.