Dartmouth professor emeritus David Lemal recently discovered new pathways for cycloaddition reactions of o-fluoranil, a highly reactive and versatile electrophile. The finding, which was published last month in The Journal of Organic Chemistry, could lead to important applications in daily life.
Organic molecules called hydrocarbons are composed of chains of carbon atoms bonded to hydrogen atoms. Substitution of hydrogens with fluorines dramatically alters the physical and chemical properties of the molecules. The so-called fluorocarbons and their derivatives are the key chemicals in various products today, ranging from non-stick Teflon pans to refrigerants and oxygen carriers in artificial blood.
Diels-Alder reaction of o-fluoranil
According to Lemal, “It [o-fluoranil] has been difficult to synthesize, and as a result has received very little attention in the chemical literature. Our interest in it is twofold. We want to learn about and understand its chemical reactivity in detail, and to demonstrate its usefulness as a building block in the synthesis of more complex organic molecules.”
o-fluoranil can undergo Diels-Alder cycloaddition, a type of organic chemistry reaction in which a conjugated diene and a dienophile combine to form cyclohexene ring structure. Specifically, o-fluoranil will react with both electron-rich and electron-poor dienophiles and with preservation of stereochemistry, or spatial configuration.
Lemal and his research team found that asymmetric substitution on the dienophile does not cause loss of stereochemical control, although current scientific theory suggests that such reactions should be highly asynchronous. The research team also found that steric effects can greatly alter the course of events, sometimes resulting in reaction with an oxygen atom on o-fluoranil rather than the usual carbon.
Furthermore, the research team discovered that there is a preference for one specific orientation in the reaction. The diene and the dienophile may approach each other in two distinct orientations: the substituent on the dienophile may be directed away from the diene (exo approach) or towards it (endo approach). In o-fluoranil’s case, the endo addition configuration is preferred due to a repulsive secondary orbital interaction in the exo transition states.
“An important reason for our interest in the Diels-Alder chemistry of the quinone is its ability to serve as a synthetic building block, specifically a –(CF=CF-CF=CF)- synthon; i.e., a molecule that can build such a fragment into another molecule. We have already carried out a few reaction sequences of this type, and will flesh out this facet of our o-fluoranil research in the future,” Lemal said.
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