Oxonium ions for the synthesis of strained alkynes and allenes

• Applicant: Marvin Fresia
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 542965079

This project’s aim is the development of oxonium ion precursors for functionalised strained alkynes and allenes, which are useful synthons for the rapid synthesis of complex organic molecules. Oxonium ions are excellent leaving groups and this has been leveraged in a brief investigation of the use of triaryl oxonium ions as aryne precursors by Hellwinkel and Tolstaya. More recently, Smith and Burton have reported the use of dibenzofuranyl oxonium ions as bench-stable salts that generate arynes under very mild conditions. Fujita and Okuyama demonstrated that cyclohexyne could be generated from the corresponding alkenyl iodonium salts with a variety of mild bases, and this method of cyclohexyne generation has been popularised by Carreira for use in natural product synthesis. The other popular method for cyclohexyne, 1,2-cyclohexadiene and cyclopentyne, and most recently, 1,2,3-cyclohexatriene generation has been the Kobayashi silyl triflate method reported by the Garg group. This is the current state-of-the-art in the synthesis of strained alkynes and cumulenes. Given that aryne generation from oxonium ions has only recently been explored in depth and occurs under very mild conditions, it is fitting to investigate oxonium ion precursors for the synthesis of other strained alkynes and allenes. This project starts with the synthesis of the dibenzofuranyl oxonium ion precursors of unfunctionalised cyclohexynes, cyclopentynes, 1,2-cyclohexadienes, 1,2-cyclopentadienes, and 1,2,3-cyclohexatrienes. Afterwards, the generation and trapping of these strained alkynes and allenes will be investigated. Next, the functional group tolerance of the formation of strained alkynes/allenes will be investigated. The most straightforward method for assessing the functional group tolerance will be to evaluate the compatibility of a range of substituents on the tetralone starting materials, including functional groups such as nitro, aldehyde, ketone, ester, nitrile, alcohol, amine etc. With the formation and trapping of unfunctionalized strained alkynes and allenes thoroughly explored, the strategy will be expanded to the functionalized variants. Perhaps the most interesting and potentially the most synthetically useful functionalized strained alkynes/allenes are the cyclohexynones/cyclopentynones and corresponding alpha,beta,beta,gamma-unsaturated cyclohexanones/cyclopentanones. The synthetic approach to these should be straightforward and allow the study of these unusual strained alkynes, of which little has been reported.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Jonathan Burton, Ph.D.