TAMING STRAINED MOLECULES
Strained molecules are fascinating for many reasons. In a very simplistic way, they allow to store energy within their geometrical shape. The Wahl laboratory is devoted to exploring and understanding the reactivity of such highly energetic compounds. Our current activities in this field can be roughly divided into three areas covering enantioselective desymmetrization, nitrogen insertion, and light-enabled synthesis. Overall, we thrive to apply the potential of strained molecules to tackle unsolved chemical problems.
a) Desymmetrization as a Strategy towards Molecular Complexity.
Converting a simple precursor into a complex target is one of the key challenges in synthetic chemistry with major implications in natural product synthesis and medicinal chemistry. Strained molecules offer a unique opportunity, because they often react under particularly mild conditions and even undergo transformations that are normally not possible. A powerful strategy to build molecular complexity is by desymmetrization, which we aim to exploit for strained compounds within this research project.
b) Molecular Editing by Nitrogen Insertion.
Molecular editing describes the idea to change the core structure of an advanced molecule in a mild and selective fashion. This concept has come to the forefront of organic chemistry because of its promising impact on medicinal chemistry. However, many simple transformations that allow the precise “editing” at the late stage of a synthetic sequence have not reached maturity yet. One example is the introduction of nitrogen, which is of great interest based on the high percentage of nitrogen atoms in current drug molecules. Within this program, we envision to develop methods that allow the selective nitrogen insertion at (strained) rings.
c) Molecular Strain from Light-Enabled Reactions.
Herein, we address the question where strain energy comes from and how strained molecules can be accessed in a sustainable way. In an ideal process, the energy of sunlight can be used to forge the strained molecular entity. To develop such an “out of equilibrium” process, a suitable candidate must be found that undergoes a productive transformation after solar light excitation. Applications can range from the development of novel bioisosteres for drug discovery to molecular solar thermal (MOST) materials.
We believe that strained molecules are not only a purely academic curiosity, but that they will play an important role in solving the many challenges of the 21st century. For one they can shorten synthetic routes and act as bioisosteres, which are two essential features in contemporary drug discovery and will impact future medicine. Furthermore, strained molecules can store energy and will, besides hydrogen and batteries, offer a complimentary method to tackle the current energy crisis. Also fundamentally, advancing organic chemistry will be possible by studying strained molecules as they often reveal unusual and even unknown reaction pathways and outcomes.