Exploring oxonium ion chemistry in natural product synthesis Harry B Hicks, Jonathan W Burton Chemistry Research Laboratory, University of Oxford, UK Oxonium ions frequently find themselves proposed as reactive intermediates in the biosynthesis of numerous Laurencia natural products. 1-9 Our group has a keen interest in synthesising L. natural products, with a particular focus on studying and characterising the proposed biomimetic oxonium ions. 3,5,10-12 The current project centres on a novel biosynthesis proposal, which utilises a complex trialkyl allyl oxonium ion to control site reactivity at C-13 to yield 5 natural products (scheme 1A). To support our initial hypothesis, a model allyl oxonium ion was synthesised and characterised by low temperature NMR (Scheme 1B). 13 Crucially, this allyl oxonium ion was shown to react at C-13, in direct contrast to structurally similar non-allyl oxonium ions. 3 To further support the hypothesis, the configuration of 5 novel L. natural products was determined by total synthesis, with the configurations found to be in keeping with the proposed biosynthesis (Scheme 1C). 12,13 Very recently, the proposed biomimetic allyl oxonium ion (Scheme 1A) was synthesised and the major product upon quenching with bromide is indeed the hypothesised C-13 allyl dibromide, heavily suggesting the role of allyl oxonium ions in the synthesis of dioxabicycloheptane containing L. natural products.
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10. Chem. Eur. J. 2013 , 19 , 12644-12648. 11. Chem. Sci. 2020 , 11 , 11592-11600. 12. Org. Lett. 2022 , 24, 50, 9174-9178 13. Burton group, manuscript in preparation.
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