American chemists have developed a general approach to generating strained bicyclic alkenes, the existence of which is prohibited by the Bredt rule. The scientists obtained a set of such alkenes in situ using syn-elimination and introduced them into various cycloaddition reactions. The study was published in Science.
At the beginning of the 20th century, the German chemist Julius Bredt attempted to obtain several alkenes containing a double bond at the bridging carbon atom of the bicyclic camphor skeleton using various elimination reactions. No products were formed, and Bredt suggested that alkenes of this type were too unstable to be obtained. This statement became known as Bredt's rule. It was later found that some alkenes that violated this prohibition could be detected spectroscopically. But scientists were unable to obtain them and introduce them into the reaction.
The instability of alkenes that violate Bredt's rule can be explained by the unfortunate arrangement of the p-orbitals of the carbon atoms that form the double bond. Because of the rigidity of the bicyclic structure, the area of overlap of these orbitals is very small, and the π-bond between the carbon atoms is too weak.
But 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 order: 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 was attached to the other.
The chemists mixed this source with anthracene and tetrabutylammonium fluoride in dimethylformamide at room temperature. An elimination reaction occurred, and the strained alkene formed in situ entered into a Diels-Alder reaction with anthracene - the product was formed with a yield of 30 percent. Thus, the scientists confirmed that alkenes that violate the ban can be generated in solution.
The chemists then showed that their method works with other bicyclic starting materials. And the resulting alkenes can enter not only into the Diels-Alder reaction, but also into 1,3-dipolar cycloaddition. In addition, optically pure silicon derivatives were converted into products with retention of absolute configuration.
Thus, chemists have learned to generate extremely unstable alkenes that violate Bredt's rule. Using the developed method, scientists will be able to synthesize complex polycyclic compounds.
Earlier we talked about how chemists first obtained stable crystalline nitrene.