Ketenes [3+2] cycloadditions – KetFlo

Developing new reactivities is crucial for the progress of Organic Chemistry, in order to develop faster, selective and sustainable access to always more complex molecules, both for research and industry. In the KetFlo project, we will study the unprecedented (3+2) cycloadditions between ketenes and 1,3-dipoles for the direct synthesis of lactams, lactones and cyclopentanones. Recently, we have found that aziridines react with ketenes upon lithium iodide catalysis, directly affording functionalized lactams. Combining theoretical studies to unveil the mechanism, and flow chemistry to extend the ketenes range compatible with this trasnformation, will allow broadening the scope and complexity of the accessible lactams. Different ways to generate the ketene by flow will be studied, and other dipoles to access lactones and cyclopentanones will then be explored. The in situ generation of the dipoles from simple acyclic substrate combined with the flow generation of ketenes will generate a high degree of complexity in a very short time: this one-pot multi-steps synthesis will save efforts for intermediate separation and purification, while often increasing the overall chemical yields and safety.