Control of stereogenic oxygen in a helically chiral oxonium ion

Abstract

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.

Dynamic hyperconjugation induced bond-angle rotation isomerization mechanism and anionic conformational rigidity-dependent melting points of ionic liquids

“…for the trans-trans process and four cis-trans isomerization subpathways (1)(2)(3)(4). In pathway The shorter length of S-N bond (~1.605 Å) (Table S2 shows bond lengths and angles for selective conformations of TFSI -) also implies the presence of S-N π-bonding relative to the normal value of ~1.648 Å in sulfonamides 33,34 .…”

“…The pyramidal inversion 1, a fundamental stereochemical process, is intensively studied and well-established in tricoordinated heteroatom compounds (X = N, O + , P, S + ), which involves a planar transition state and thus sp 3 -sp 2 -sp 3 re-hybridization at the heteroatoms X (Scheme 1a) [1][2][3][4] . Many isolable phosphines 1 and sulfonium salts 4 possess high inversion energy barriers of 120-185 kJ mol −1 and 100-130 kJ mol −1 , whereas nitrogen pyramidal inversion is rapid and only takes 20-25 kJ mol −1 in a tertiary amine due to quantum tunnelling 5 .…”

“…B-O-B inversion 6 overcomes an unusually high barrier of 104 kJ mol −1 , which is still lower than that of the double-torsion pathway involving only 90° motions, in singly bonded (BF)O(BF)-quinoxalinoporphyrin, owing to the geometrical restraints from B-O-B encapsulation 6 . Although all these examples involve a linear transition state, the oxygen BAI and nitrogen BAIs are distinct in the numbers of valence electron, bonding characters with ligands, and thus re-hybridization processes of central atoms (sp 3 -sp-sp 3 (O) vs. sp 2sp-sp 2 (N)). To date, there are no progresses in identifying the isomerization mechanism for bicoordinated O or its valence isoelectronic atoms (e.g., S in disulfide 12,13 ) or ions (e.g., N -) in the systems with conjugated M1-X-M2.…”

Heteroatom Chirality

“…drug to study their properties and determine whether it is advantageous to sell the drug as a pure enantiomer or as a racemate. 7 Methods for selectively synthesising, or separating each enantiomer during the production process is therefore essential, 8 as mismanagement of chiral compounds can have detrimental effects on both human health and the environment. 9…”

“…Recently, Smith, Paton, Burton and co-workers synthesised triaryl oxo nium ions and connected the aromatic rings with linkers of various length (Figure 3, p. 56). This stabilises the scaffold and locks the configuration of the stereogenic oxygen 8 to generate a molecule with helical chirality. Quantum chemical calculations of the xanthene scaffold (Figure 3a, p. 56, left) indicated that bigger substituents at R 2 would increase both the inversion barrier and pyramidalisation around oxygen.…”