Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Department of Chemistry, Colorado State University, Ft. Collins, CO, USA.
Nature. 2023 Mar;615(7952):430-435. doi: 10.1038/s41586-023-05719-z. Epub 2023 Mar 15.
The control of tetrahedral carbon stereocentres remains a focus of modern synthetic chemistry and is enabled by their configurational stability. By contrast, trisubstituted nitrogen, phosphorus and sulfur compounds undergo pyramidal inversion, a fundamental and well-recognized stereochemical phenomenon that is widely exploited. 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 intermediates. 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 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 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 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.
四面体碳立体中心的控制仍然是现代合成化学的焦点，这是通过它们的构型稳定性实现的。相比之下，三取代的氮、磷和硫化合物经历三角锥形翻转，这是一种广泛利用的基本且公认的立体化学现象。然而，氧鎓离子——在带正电荷的氧原子上有三个取代基的化合物——的立体化学发展较差，除了作为反应中间体存在之外，在合成中很少有应用。没有构型稳定的氧鎓离子的例子，其中氧原子是唯一的立体中心，这可能是由于氧三角锥形翻转的低能垒以及所有氧鎓离子都具有高反应性的看法。在这里，我们描述了一种手性三芳基氧鎓离子的设计、合成和表征，其中通过几何限制防止氧孤对的反转，使其能够作为构型决定因素发挥作用。综合合成和量子计算方法描绘了能够生成构型稳定和室温下可分离盐的设计原则。我们表明，反转的势垒大于 110kJ/mol，并概述了拆分过程。这是我们所知的唯一一个氧原子是唯一的立体中心的手性非外消旋和构型稳定的分子的例子。
