Investigations into a Stoichiometrically Equivalent Intermolecular Oxidopyrylium [5+2] Cycloaddition Reaction Leveraging 3-Hydroxy-4-pyrone-Based Oxidopyrylium Dimers

Oxidopyrylium [5 + 2] cycloaddition reactions are powerful strategies for constructing complex bicyclic architectures. However, intermolecular cycloadditions of oxidopyrylium ylides are limited due to competing dimerization processes; consequently, high equivalents of dipolarophiles are often used to help intercept the ylide prior to dimerization. Recent studies by our lab have revealed that oxidopyrylium dimers derived from 3-hydroxy-4-pyrones are capable of reverting back to ylides in situ and as a result can be used as clean oxidopyrylium ylide sources. The following manuscript investigates intermolecular cycloaddition reactions between 3-hydroxy-4-pyronederived oxidopyrylium dimers and stoichiometrically equivalent ratios of alkyne dipolarophiles under thermal conditions. With certain reactive alkynes, pure cycloadducts can be obtained following a simple evaporation of the solvent, which is a benefit of the completely atom-economical reaction conditions. However, when less reactive alkynes are used the yields suffer due to a competing dimer rearrangement. Finally, when reactive-yet-volatile alkynes are used, such as methyl propiolate, competing 2:1 ylide/alkyne cycloadducts are observed. Intriguingly, these complex cycloadducts, which can be obtained in good yields from the pure cycloadducts, form with high regio- and stereoselectivities; however, both the regio-and stereoselectivities differ remarkably based on the source of the oxidopyrylium ylide.

Automated summary

Oxidopyrylium [5 + 2] cycloaddition reactions are powerful strategies for constructing complex bicyclic architectures, but are often limited by competing dimerization processes. Recent studies have shown that oxidopyrylium dimers derived from 3-hydroxy-4-pyrones can revert back to ylides in situ, serving as clean ylide sources. The reaction between these dimers and stoichiometrically equivalent ratios of alkyne dipolarophiles under thermal conditions resulted in pure cycloadducts with specific alkynes, while less reactive alkynes led to lower yields due to dimer rearrangement and volatile alkynes produced competing ylide/alkyne cycloadducts with high regio- and stereoselectivities based on the source of the oxidopyrylium ylide.