Reactivity exploration of alkyne-functionalized bicyclobutanes: Access to medicinally relevant multicyclic compounds

Abstract

The development of new drug molecules increasingly relies on efficient and versatile synthetic methods. As medicinal chemists aim to balance efficacy with desirable 'drug-like' properties such as solubility, metabolic stability, and absorption, bioisosteres have become a powerful tool. Bioisosteres are exchangeable chemical groups that are similar in size but remain biologically distinct. Bicyclic bioisosteres of aromatic rings are becoming increasingly popular due to their ability to enhance drug-like properties; however, accessing these structures remains synthetically challenging. This project aims to explore the metal-catalyzed functionalization of alkynyl bicyclo[1.1.0]butanes, which serve as versatile intermediates for constructing complex bicyclic bioisosteres. The research focuses on achieving efficient synthetic pathways towards a diverse set of alkynyl bicyclobutanes, including heteroatom-containing and highly functionalized variants, and evaluating their reactivity towards transition metal catalysts. The objective is to generate unique bicyclic compounds through coupling reactions. Research activities include the synthesis and purification of bicyclobutane derivatives, the design and execution of high-throughput screening experiments, and the scale-up of promising conditions.Jamie Cassels Undergraduate Research Awards (JCURA)UndergraduateReviewe