Ellen Phiddian
Cosmos science journalist
Chemistry is littered with rules that, on closer inspection, are alarmingly brittle.
Researchers are calling for a 100-year-old rule to be thrown out, after they’ve made molecules that defy it.
They’ve published their finding in Science.
“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,” says corresponding author Professor Neil Garg, a chemist at the University of California – Los Angeles, USA.
“It destroys creativity when we have rules that supposedly can’t be overcome.”
The rule, called Bredt’s Rule, relates to a class of molecules called olefins. These are carbon-based (organic) molecules, that contain a double bond where 2 carbon atoms share 2 pairs of electrons.
Carbon-carbon double bonds are common in nature, but they are particularly coveted by the pharmaceutical industry and other synthetic chemistry fields.
This is because they’re valuable building blocks: the double bond can be manipulated much more easily in chemical reactions than single-bonded carbon atoms, allowing for a wider range of products to form.
In 1924, German chemist Julius Bredt published a rule about certain types of olefins, called “bridged bicyclic” molecules.
These molecules are shaped like rings, with a “bridge” branching over their top. Bredt stated that a double bond couldn’t form at a specific location in the molecule, called the “bridgehead” position.
Such a bond, ruled Bredt, would be too strained to exist – atoms tend to sit in certain, neat geometries, determined by physics. While these shapes can be bent, they can only bend so far before the molecule won’t form.
Bredt’s rule has since become a staple of organic chemistry textbooks and is recognised by the global authority on chemists: the International Union of Pure and Applied Chemistry.
Researchers have previously been able to make “anti-Bredt olefins”. But these were usually highly unstable and didn’t exist for long. Investigations into them have been sparse in the last century.
“People aren’t exploring anti-Bredt olefins because they think they can’t,” says Garg.
But his team made several of them, with double bonds sitting – well, not comfortably, but at least stably – at the bridgehead position.
They made their molecules out of compounds called silyl (pseudo)halides. These materials have silicon atoms in them, as well as atoms from the halogen class of elements which includes fluorine and chlorine.
When treated with fluoride-based compounds, the molecules formed into anti-Bredt olefins. The team used a “trapping agent” to stabilise the molecules as they formed, allowing them to be isolated and analysed.
“There’s a big push in the pharmaceutical industry to develop chemical reactions that give 3-dimensional structures like ours because they can be used to discover new medicines,” says Garg.
“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.”
