Modular Assembly of beta-Amino Acids via Donor-Acceptor Cyclopropanes

• Applicant: Dr. Sebastian Govaerts
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 529272988

The aim of this project is to develop a new method to synthesize beta-amino acids from olefins and amines. Beta-amino acids are a class of non-canonical amino acids with beneficial effects on the properties of peptides. I aim to address some of the limitations of the current methods used to prepare beta-amino acid derivatives. For this, I have created a three-step synthetic sequence with the following steps: 1) atom-transfer radical addition-ring closure to synthesize 1,1-dicyanocyclopropanes from olefins and alpha-bromomalononitrile, 2) ring-opening of electrophilic 1,1-dicyanocyclopropanes with amines to form 3-aminomalononitriles and 3) aerobic functionalisation to convert 3-aminomalononitriles to beta-amino acid derivatives with oxygen. Particular emphasis will be placed on the preparation of hindered beta-3 and beta-3,3 amino acid derivatives, as these are difficult to prepare with current methods. Each of the individual steps will provide interesting results with the possibility of many different side-projects to access other interesting compounds from olefins, such as spirocyclic amides and other nitrogen heterocycles.

• DFG Programme: WBP Position