Beyond the Limits of Atropochirality: Design of Highly Conformationally Restrained Biaryls with Bridgehead Phosphine Oxide

In the last three decades, reacting sterically congested ortho-substituted arenes to form atropochiral biaryls is an appealing venture and a challenging subject that has garnered significant attention. Therefore, there is interest in developing methods to prepare these compounds. In this study, an efficient approach to produce a new class 2,2' disubstituted biaryls bridgehead phosphine oxides with an unusual topology and exceptional conformational stability is presented. Our methodology demonstrates that depending on the substitution pattern on the aryl moieties, the methanophosphocine backbone could be rigid enough to observe a double atropochirality, resulting in an under covered class of molecules. Notably, our studies revealed that replacing only one hydrogen at the ortho position by a fluorine atom led to sufficiently restricted rotation at temperatures below 80 & DEG;C, extending far away the limits of atropostability. Finally, our investigations, which employed variable-temperature NMR spectroscopy and DFT calculations, yielded unique insights into the isomerisation mechanism, indicating that the two biaryl motifs are fully independent in spite of their proximity.

Automated summary

In the past 30 years, researchers have shown great interest in synthesizing atropochiral biaryls with steric congestion on the ortho-substituted arenes. This study presents an efficient approach to produce a new class of 2,2' disubstituted biaryls bridgehead phosphine oxides with exceptional conformational stability. The researchers found that by replacing only one hydrogen atom at the ortho position with a fluorine atom, the rotation of the biaryl backbone can be restricted at temperatures below 80°C, significantly extending the limits of atropostability. Additionally, their investigations revealed unique insights into the isomerization mechanism of these molecules.