Grant: Discovery Grants Program - Individual

Research in fundamental organic chemistry has given us the ability to design and make materials and substances with defined properties that improve our quality of life. These range from life saving small molecules used to cure or treat a broad range of diseases to materials that harness the sun's energy and will help mitigate climate decline due to continued use of fossil fuels. Despite tremendous advances in fundamental and organic chemistry, as well as assisting technologies such as analytical chemistry, there remain considerable challenges to make materials and molecules on demand and in a sustainable and economical manner. These challenges can only be met by ongoing research that truly addresses fundamental questions. Goal. The proposed research program aims to develop new ways to make functionalized cycloheptanes, which remains an enduring challenge in the synthesis of small molecules. Decorated cycloheptanes commonly appear in naturally occurring substances that are drugs or drug leads for the treatment of serious diseases such as cancer. These molecules are notoriously challenging to make in part due to the difficulty in accessing functionalized cycloheptanes. We will help resolve this synthetic gap by exploiting a very fundamental and yet neglected aspect of pericyclic chemistry: the thermal electrocyclization of heptatrienyl anions. We have recently disclosed design principles to harness this fundamental reactivity in efficient ways that make it suitable for complex molecule synthesis and allow us to use exceptionally mild conditions. Through our research program we will develop a suite of synthetic reactions that are practical and give useful cycloheptane containing molecules, and which therefore will be readily adopted by end users. Impact. Our fundamental research will generate a suite of methods for synthesis of cycloheptane containing molecules. Due to our insights in design of these reactions, they will tolerate a wide range of functionality and therefore will be useful in challenging settings often encountered in the synthesis of small molecule drugs and drug leads. As a result, we expect that these methods will be readily adopted by synthetic chemists, particularly during the exploration of new chemical space as part of the drug discovery process. This program will also help train HQP at all levels and enhance Canada's visibility in synthetic and organic chemistry.