As mentioned before, our process that involves using carbon double bonds, creates a type of chemical called an "allylic carbocation" from a catalyst called Rh-carbynoid. This carbocation then undergoes a reaction that adds fluorine atoms in a specific way. With this technique, we have successfully made 40 new fluorinated compounds in good to moderate amounts, and we also adapted this method to work with a 18F radionuclide with good success.
However, we encountered a challenge when trying to create chiral molecules, with a specific kind of shape. We could not control the shape of the molecule as we wanted, and it was eventually discovered during the investigation that it could be due to the formation of a flat allylic carbocationic species. This flat structure makes it difficult to predict how other chemicals will attach to it in a specific way.
We wondered if we could harness these transformations to make other useful substances like indenes and 1,3-dienes from a group of chemicals called vinylarenes. Indenes and 1,3-dienes are found in nature and are used in medicines, like indriline, dimetindene, and piperine. From the research on the new fluorination strategies, we developed a method that allows us to selectively create indenes and 1,3-dienes by adding just one carbon atom to the vinylarene molecules (Figure 2). This technique can be applied to make other similar compounds from various starting materials. We've successfully modified 63 different substances that are widely available to obtain the desired indenes and 1,3-dienes (regiodivergent), and we are currently preparing a manuscript to share our findings in a respected scientific journal.
Based on the challenges we faced on controlling the actual fluorinated molecule’s shape, we have been trying to understand how molecules with a certain shape interact with other chemicals. We wanted to understand why some reactions did not result in the creation of molecules with a specific shape, the so-called chirality. For example, when we were trying to make a compound called erythramine alkaloid, we found that the way molecules attached to the allylic carbocation did not depend on which side they came from. However, we made an exciting discovery by achieving a specific type of reaction where we could add a single carbon atom to a molecule in a way that retained its unique shape. This has the potential to provide new insights into how chemical reactions work. We have demonstrated this by performing the same type of reaction with other chemicals like sorbic acid and trans-3-hexene, compounds that serve as simplified models for more complex molecules. Our research suggests that a specific intermediate molecule must undergo a change before it reacts with another molecule in a unique way. This reaction generates a special molecule-pair, which is trapped in the solvent used in the experiment. This allows the second molecule to attach itself in a particular way, creating a chiral product. We're in the process of preparing a manuscript about this discovery, and we believe it will have a significant impact on our understanding of how specific enantioselective (that achieve chirality) chemical reactions occur.
