American chemists have developed a general approach to generating strained bicyclic alkenes, the existence of which is prohibited by Bredt's rule. The scientists obtained a set of such alkenes in situ using syn-elimination and subjected them to various cycloaddition reactions. The study was published in Science.
At the beginning of the 20th century, the German chemist Julius Bredt attempted to synthesize several alkenes containing a double bond at the bridging carbon atom of the bicyclic camphor skeleton using various elimination reactions. No products were formed, leading Bredt to hypothesize that alkenes of this type were too unstable to be synthesized. This assertion became known as Bredt's rule. It was later discovered that some alkenes that violated this rule could be detected spectroscopically. However, scientists were unable to synthesize them and react them.
The instability of alkenes that violate Bredt's rule can be explained by the unfortunate arrangement of the p-orbitals of the carbon atoms forming the double bond. Due to the rigidity of the bicyclic structure, the overlap area of these orbitals is very small, and the π-bond between the carbon atoms is too weak.
However, as chemists led by Neil K. Garg of the University of California, Los Angeles, have shown, the π-bonds in such alkenes are strong enough to be generated in solution and used in cycloaddition reactions. The scientists first set out to obtain the simplest alkene that violates the Bredt exclusion rule—bicyclo[2.2.1]hept-1-ene. To do this, they synthesized a starting material for the elimination reaction in which a trimethylsilyl group was attached to one carbon atom and a trifluoromethanesulfonate group to the other.
The chemists mixed this starting material with anthracene and tetrabutylammonium fluoride in dimethylformamide at room temperature. An elimination reaction occurred, and the resulting strained alkene underwent a Diels-Alder reaction with anthracene in situ, producing a product in 30 percent yield. Thus, the scientists confirmed that prohibition-violating alkenes can be generated in solution.
The chemists then demonstrated that their method also works with other bicyclic starting materials. The resulting alkenes can undergo not only the Diels-Alder reaction but also 1,3-dipolar cycloaddition. Furthermore, optically pure silicon derivatives were converted into products with retention of absolute configuration.
Chemists have learned to generate highly unstable alkenes that violate Bredt's rule. Using the developed method, scientists will be able to synthesize complex polycyclic compounds.
Previously, we talked about how chemists first obtained stable crystalline nitrene.
