Organic Chemistry

Control of stereogenic oxygen in a helically chiral oxonium ion



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.


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Supplementary material

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supplementary information
All data (experimental procedures, characterization data and cartesian coordinates for all DFT calculations) supporting the findings of this study are available within the article and its supplementary information. Crystallographic data for compounds 10, rac-16 and P-(R)O-16 (3 datasets) have been deposited with the Cambridge Crystallographic Data Centre under deposition numbers CCDC 2124020, CCDC 2124019 and CCDC 21911038-2191040.