UCLA chemists challenge century-old rule in organic chemistry

Chemists at the University of California, Los Angeles (UCLA) uncovered a significant flaw in a century-old rule of organic chemistry, calling for a complete revision of educational textbooks.

Their groundbreaking research reveals that the established principles governing the structure of organic molecules are not as rigid as previously believed.

Rethinking Bredt’s rule

Organic molecules, primarily composed of carbon, are typically defined by specific atomic arrangements and shapes. Olefins, characterized by carbon-carbon double bonds, are particularly interesting due to their roles in pharmaceutical research.

A long-standing guideline, known as Bredt’s Rule, formulated in 1924, posits that carbon-carbon double bonds cannot exist at the ring junction of bridged bicyclic molecules. This rule suggests that such configurations would result in distorted geometries that deviate from the standard shapes taught in organic chemistry.

Innovative findings open new possibilities

However, a recent paper published in the journal Science challenges this notion. The UCLA researchers demonstrated the creation of molecules that contravene Bredt’s Rule, termed anti-Bredt olefins (ABOs). This discovery paves the way for chemists to explore a wider range of synthetic molecules and their potential applications in drug discovery.

Neil Garg, a distinguished professor of chemistry and biochemistry at UCLA and the study’s corresponding author, emphasized the need to rethink these conventional rules. “People aren’t exploring anti-Bredt olefins because they think they can’t,” he stated. “We should approach these guidelines with the understanding that they are not absolute, as strict rules hinder creativity in scientific exploration.”

Practical applications in pharmaceutical research

The research team successfully produced ABOs by treating silyl (pseudo)halides with a fluoride source to initiate an elimination reaction. Although these compounds are notoriously unstable, the researchers incorporated a chemical agent that could stabilize the ABOs, allowing for practical applications.

Garg noted, “There’s a significant drive within the pharmaceutical industry to develop chemical reactions that yield three-dimensional structures like ours, as they are instrumental in discovering new medicines.” The findings suggest that contrary to a century of accepted wisdom, chemists can indeed create and utilize anti-Bredt olefins to generate valuable products.

Collaborative effort from UCLA chemists

The research team includes UCLA graduate students and postdoctoral scholars – Luca McDermott, Zachary Walters, Sarah French, Allison Clark, Jiaming Ding and Andrew Kelleghan – as well as Ken Houk, a prominent research professor and computational chemistry expert at UCLA. This collaboration showcases the innovative spirit at UCLA and its commitment to pushing the boundaries of chemical research.

This pioneering study not only challenges a fundamental principle of organic chemistry but also opens new avenues for research and application in pharmaceuticals. As chemists embrace the potential of anti-Bredt olefins, the landscape of organic chemistry may undergo a profound transformation, leading to advancements in medicine and beyond.