Breaking Bonds: How Chemists Overturned a Century-Old Rule, Redefining Textbook Chemistry
Redefining Molecular Boundaries: The Fall of Bredt’s Rule
Bredt’s Rule has been an important part of organic chemistry for more than one hundred years. It tells us where double bonds can and can’t be placed in certain organic groups. This rule says that there can’t be double bonds at the bridgehead point of a bicyclic molecule because the geometry of the molecule would make the bond unstable. A groundbreaking study by UCLA chemists, which came out in Science on November 1, 2024, however, has disproved this long-held belief. This opens up new opportunities for molecular design, especially in drug discovery.
Innovative Synthesis: The Creation of Anti-Bredt Olefins
Neil Garg, the Kenneth N. Trueblood Distinguished Professor of Chemistry and Biochemistry at UCLA, and his team have shown that anti-Bredt olefins (ABOs) can be made and kept stable. This result goes against Bredt’s rule, which has limited chemists’ ability to study and create certain synthetic molecules that are important for pharmaceutical research for a hundred years.
Garg’s group came up with a new way to do things by treating chemicals called silyl (pseudo)halides with a source of fluoride. ABOs are made when this process starts an elimination response. Because ABOs are very unstable, the team added another chemical to “trap” these unstable molecules, making stable products that can be separated. This method not only shows how ABOs can be synthesized in the real world, but also how they can be used to make complicated, three-dimensional structures that are important for pharmaceutical uses.
Implications for Pharmaceutical Research: Beyond the Rule
Making and changing ABOs is a big step forward in organic chemistry. It gives us new tools for making molecular structures that were thought to be impossible before. Garg says that the rules of chemistry should be rethought and that they should be used as guides to encourage creativity instead of getting in the way of it. “These kinds of rules shouldn’t exist, or if they do, they should always be accompanied by the phrase ‘guidelines, not rules.'” According to Garg, rules that are supposed to be impossible to break kill innovation.
Inspiring Future Innovations: The Impact of Questioning Established Norms
This discovery could lead to more research into other “impossible” molecules, which could change the way things are made in many areas, such as materials science and drug development. The study shows how important it is to question accepted beliefs and push the limits of scientific research.
UCLA scientists made anti-Bredt olefins, which is a major turning point in the history of organic chemistry. It goes against a rule that has been around for a hundred years and makes new ways for molecular design to be improved. As time goes on, this finding will probably make chemists around the world rethink other long-held rules and explore the vast, uncharted areas of chemical space with fresh eyes and renewed energy.
The study is called “A solution to the anti-Bredt olefin synthesis problem,” and it was written by Luca McDermott, Zachary Walters, Sarah French, Allison Clark, Jiaming Ding, and Andrew Kelleghan, all of whom are graduate students or postdoctoral scholars at UCLA. It was also written by Garg’s longtime collaborator, computational chemistry expert Ken Houk.
Reference
McDermott, Luca, et al. “A solution to the anti-Bredt olefin synthesis problem.” Science 386.6721 (2024): eadq3519. https://www.science.org/doi/10.1126/science.adq3519
