The control of tetrahedral carbon stereocentres remains a focus of modern synthetic chemistry and is enabled by their configurational stability. By contrast, trisubstituted nitrogen1, phosphorus2 and sulfur compounds3 undergo pyramidal inversion, a fundamental and well-recognized stereochemical phenomenon that is widely exploited4. However, the stereochemistry of oxonium ions—compounds bearing three substituents on a positively charged oxygen atom—is poorly developed and there are few applications of oxonium ions in synthesis beyond their existence as reactive intermediates5,6. There are no examples of configurationally stable oxonium ions in which the oxygen atom is the sole stereogenic centre, probably owing to the low barrier to oxygen pyramidal inversion7 and the perception that all oxonium ions are highly reactive. Here we describe the design, synthesis and characterization of a helically chiral triaryloxonium ion in which inversion of the oxygen lone pair is prevented through geometric restriction to enable it to function as a determinant of configuration. A combined synthesis and quantum calculation approach delineates design principles that enable configurationally stable and room-temperature isolable salts to be generated. We show that the barrier to inversion is greater than 110 kJ mol−1 and outline processes for resolution. This constitutes, to our knowledge, the only example of a chiral non-racemic and configurationally stable molecule in which the oxygen atom is the sole stereogenic centre.
The pyramidal inversion of trisubstituted nitrogen, phosphorus and sulfur compounds and its impact on configurational stability is a fundamental and well-recognized stereochemical phenomenon that is widely exploited. In contrast, the chemistry of oxonium ions – compounds bearing three substituents on a positively charged oxygen atom – is poorly developed and there are few applications in synthesis beyond their existence as reactive intermediates. There are no examples of configurationally stable oxonium ions in which the oxygen atom is the sole stereogenic centre, likely due to the low barrier to oxygen pyramidal inversion, and the perception that all oxonium ions are highly reactive. Here we describe the design, synthesis and characterization of a helically chiral triaryloxonium ion in which inversion of the oxygen lone pair is prevented through geometric restriction to enable it to function as a determinant of configuration. A combined synthesis and quantum calculation approach delineate design principles that enable configurationally stable and room-temperature isolable salts to be generated. We show that the barrier to inversion is >110 kJ mol-1 and outline a process for resolution. This constitutes the only example of a chiral non-racemic and configurationally stable molecule in which the oxygen atom is the sole stereogenic centre.
Arynes are highly reactive and versatile intermediates for the functionalization of aromatic rings that are often generated using strong bases or fluoride sources, which in some cases can limit functional group tolerance. Here we demonstrate that triaryl oxonium ions can be transformed into arynes through treatment with solid potassium phosphate at room temperature. A substantial range of functional group-bearing arynes including 4,5-pyrimidynes may be generated and trapped by cycloaddition reactions in high yields. Other arynophiles including nitrones, alkenes, and azides are compatible with these conditions. Quantum computation in conjunction with an intramolecular kinetic isotope study is consistent with an E1cB-like mechanism of elimination to form the aryne. These investigations demonstrate that the oxonium ion is a powerful electron-withdrawing group and a particularly effective leaving group. We anticipate this study will stimulate further investigations into the synthetic utility of aryl oxonium ions.
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