Gwyneth Perseveranda

Imagine if a century-old rule in chemistry, once trusted as fact, is now being questioned.

Scientists have uncovered a flaw in a fundamental rule in organic chemistry, opening doors to future scientific endeavors that this rule has limited for 100 years.


Chemists from University of California, Los Angeles (UCLA) have synthesized a new type of molecule, called anti-Bredt olefins (ABOs), which for about a century, were believed to be too unstable to exist.

Organic molecules, primarily composed of carbon, come in different shapes depending on how atoms are linked together.

Olefins or alkenes (double bonds between two carbon atoms), hydrocarbons often used in the reactions for drug development, have a double bond that keeps the attached atoms in a flat, single plane.

This structure is typical for alkenes and provides them a stable, flat geometry.

The rule in question, Bredt's rule, established by organic chemist Joseph Bredt in 1924, states that certain molecules cannot have double bonds at a specific part of their structure known as the bridgehead. 

This position would cause strain and instability in the molecule, preventing the double bond from forming.

Bredt’s rule has limited the creation of synthetic molecules by preventing chemists from designing certain structures, potentially hindering the innovations in drug discovery.

Since olefins are crucial in pharmaceutical research, this rule has restricted the types of molecules chemists could envision, affecting the chances of exploring new possibilities in drug development.

"People aren't exploring anti-Bredt olefins because they think they can't," said author Neil Garg, professor of chemistry and biochemistry at UCLA.

"We shouldn't have rules like this—or if we have them, they should only exist with the constant reminder that they're guidelines, not rules. It destroys creativity when we have rules that supposedly can't be overcome," Garg said.

In Garg’s laboratory, they treated molecules called silyl (pseudo)halides with a fluoride source to start a chemical reaction that synthesizes ABOs.
Given that ABOs are highly unstable, they added another chemical which “traps” the unstable ABO molecules, allowing them to isolate and study the formed products.

The yielded reaction demonstrated that ABOs can be generated and trapped to provide structures of practical value.

"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 said.

"What this study shows is that contrary to one hundred years of conventional wisdom, chemists can make and use anti-Bredt olefins to make value-added products," he said.