Triaryl Oxonium Ions: A mild strategy to functionalised arynes.

Onium ions are ubiquitous reagents in synthetic chemistry. Iodonium salts and ylides of sulfonium and phosphonium ions are invaluable synthetic tools. However, the formation of oxonium ions and their use in synthesis is significantly more limited. Trialkyl oxonium ions were first discovered in 1937 by the reaction of an epoxide with an ether in the presence of a Lewis acid and they have been used as strong alkylating agents ever since. Triaryl oxonium ions first emerged in 1957 and exhibit enhanced stability compared with their alkyl counterparts and undergo electrophilic aromatic substitution reactions. Despite this, they have largely been forgotten - demonstrated by the fact that triaryl oxonium ions are incredibly rare in the chemical literature with fewer than 10 distinct scaffolds. Furthermore, there are no reports of them being used as aryne precursors despite aryne formation being a proposed decomposition pathway under basic conditions and other onium ions, such as iodonium salts, being used for aryne generation. Iodonium ions form arynes under strongly basic conditions or with adjacent trimethylsilyl groups that can be activated by fluoride. Fluoride activation of trimethylsilylaryltriflates is the most common method to generate o-arynes, however, sensitive functional groups are generally installed at the end as they are not compatible with the conditions require to install the reactive moieties. This incompatibility, synthetic challenges and the use of fluoride or strong bases results in arynes being rarely used in complex molecules and late stage functionalisation despite their synthetic potential for complexity generation and diverse reactivity.
We aim to develop a mild and scalable synthetic route to the desired oxonium ions. We would subsequently test their ability to generate arynes under basic conditions, optimise their reactivity and then apply it to complex systems with sensitive functional groups to expand the reach of aryne chemistry. Furthermore, the high leaving group ability of oxonium ions should allow us to generate arynes from substrates where the traditional methodology fails.
Pursuit of increasing the efficiency and scope of the aryne chemistry closely aligns with the EPSRC grand challenge of 100% efficient synthesis in the chemical sciences. It is also hoped that the methodology being developed will be utilised to aid synthetic chemists constructing complex molecules from polyaromatic hydrocarbons to drug discovery and beyond. This project falls within the EPSRC Physical Chemistry (Synthetic Organic Chemistry) research area.