Develops Biaryl Compounds with Stable Axial Chirality
This pathway for aromatic substitution provides a straightforward route to polyfunctionalized biaryl compounds with stable axial chirality. The rapid and controlled linking of functional groups and aromatic building blocks is a prominent pattern in developing new pharmaceuticals. In one common aromatic substitution reaction known as nucleophilic substitution, the substituent donates an electron pair to the bond. However, nucleophilic substitution fails in most aromatic compounds, which tend to reject donated electron pairs. Furthermore, when this process succeeds, it typically adds only one functional group. There is a need for further advances involving this chemistry.
Researchers at the University of Florida have identified a way to incorporate nitro groups into aromatic compounds, such as coumarin, to enable processes to substitute two functional groups, leading to chiral molecules with complex functionalities.
Application
Production of polyfunctionalized biaryls with complex architectures in a few chemical steps
Advantages
- Harnesses the complimentary electron-withdrawing and leaving group properties of the nitro group to add two functional groups to aromatic compounds, increasing their possible modifications and use cases
- Transfers the chirality of the reactants to the products, allowing the manufacturer to specify the chirality of the compound from the beginning
Technology
Adding the electron-withdrawing nitro group (—NO2) to the aromatic compound coumarin forms a polar bond, rendering the resulting nitrocoumarin electrophilic. This property unlocks processes in which a second aromatic compound containing a functional group substitutes into the nitrocoumarin. The nitro group then departs and opens space for a second functional group. The end product is a biaryl, a compound with two aromatic rings and two functional groups. Since adding functional groups builds the complexity necessary for modern applications in pharmaceutical and agricultural science, this “difunctionalization” pathway, driven by the electron-withdrawing and leaving group properties of the nitro group, represents an improvement over substitution strategies that add only one functional group.
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