West LA Times

UCLA chemists have challenged a century-old principle in organic chemistry, known as Bredt's rule, suggesting that it is time for textbooks to be revised. This rule, established in 1924, states that double bonds cannot exist at the bridgehead position of bridged bicyclic molecules due to geometric constraints. These molecules typically do not conform to the rigid geometry of alkenes described in traditional teachings.

A recent study published in Science by UCLA researchers has demonstrated methods to synthesize molecules that defy Bredt’s rule. These compounds, termed anti-Bredt olefins (ABOs), open new avenues for chemical reactions and potential applications in drug discovery.

Neil Garg, the Kenneth N. Trueblood Distinguished Professor of Chemistry and Biochemistry at UCLA and corresponding author of the study, emphasized the need to reconsider such rules. "People aren’t exploring anti-Bredt olefins because they think they can’t," Garg noted. He argued that such constraints hinder creativity and scientific exploration.

Garg's team employed a reaction involving silyl (pseudo)halides treated with a fluoride source to form ABOs. Given their instability, another chemical was used to stabilize these compounds, allowing them to be isolated for practical use. The success of this approach suggests significant potential for developing new pharmaceuticals.

The research team included UCLA graduate students and postdoctoral scholars Luca McDermott, Zachary Walters, Sarah French, Allison Clark, Jiaming Ding, Andrew Kelleghan, and Ken Houk—a distinguished research professor specializing in computational chemistry at UCLA. Their work was supported by funding from the National Institutes of Health.

“There’s a big push in the pharmaceutical industry to develop chemical reactions that give three-dimensional structures like ours because they can be used to discover new medicines,” Garg added. This breakthrough challenges longstanding conventions and could reshape approaches within organic chemistry and pharmaceutical development.