Chemists at UCLA have uncovered a significant flaw in the foundational concepts of organic chemistry, challenging a key principle that has remained unexamined for a century. Their recent discoveries suggest that textbooks may need to be revised. Organic chemistry, which focuses on carbon-based molecules, includes specific guidelines about how atoms bond to form these compounds. A class of molecules known as olefins (or alkenes) features two carbon atoms connected by a double bond, resulting in a flat, two-dimensional structure.

For many years, the scientific community believed that it was impossible to create a carbon-carbon double bond in the bridging position of a bicyclic molecule. This notion, known as Bredt’s rule, has been included in textbooks since 1924. According to this rule, placing a double bond in this position would cause excessive twisting, rendering the molecule unstable. Consequently, chemists have generally steered clear of attempting to synthesize such structures, which has constrained their efforts in drug discovery.

Olefins play a crucial role in pharmaceutical research, and the insights gained from this study may facilitate the development of new medications. “The pharmaceutical industry is eager to create chemical reactions that yield three-dimensional structures like ours, as they can lead to new therapeutic discoveries,” explained Neil Garg, the UCLA professor leading this research.

The UCLA team has published their findings in the journal Science, presenting evidence that Bredt’s rule is not as inflexible as previously believed. They successfully devised a method to synthesize these so-called "impossible" molecules with a double bond in the bridging position, which they refer to as anti-Bredt olefins (ABOs). The creation of these ABOs could open new avenues for drug development and other valuable chemical products.

To achieve this, the UCLA researchers employed an innovative chemical strategy, starting with a molecule called a silyl halide, then adding a second reagent to initiate a reaction that produced the new ABO molecules. Given the inherent instability of ABOs, they introduced an additional chemical to "trap" or stabilize them, allowing for further study and application of these compounds.

Neil Garg emphasized that rules like Bredt’s can stifle creativity when viewed as immutable. Now that it’s clear these boundaries can be pushed, exciting new opportunities in chemistry arise. “We shouldn't regard rules like this as absolute, or if we do, they should be perceived more as guidelines than as unbreakable laws. Such rules can restrict creativity by implying that certain achievements are impossible when, in fact, they are not,” Garg concluded.