UCLA chemists have discovered a big issue with Bredt's rule, a fundamental rule of organic chemistry that has been used since 1924.
Bredt's rule states that molecules cannot have a carbon-carbon double bond at the bridgehead. A double bond on these structures would cause the geometrical shapes to twist and distort from the rigid geometry of alkenes commonly taught in chemistry textbooks.
Olefins, which contain alkenes, are of great interest to the pharmaceutical industry. Still, Bredt's rule has limited the molecules scientists can make with them, potentially hampering their use in drug discovery.
In the research, published in the journal Science, UCLA researchers have invalidated Bredt's rule including creating several anti-Bredt olefins, or ABOs, which violate the hundred-year-old organic chemistry principle.
"People aren't exploring anti-Bredt olefins because they think they can't," said 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."
By treating silyl (pseudo)halides with a fluoride source, the researchers could induce a reaction that form ABOs. While ABOs are highly unstable, the team discovered that another chemical could be added to “trap” the unstable ABO resulting in a product that can be isolated.
"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."