Skipping Steps To Skipped Polyenes

A strategy for creating skipped polyenes—1,4-dienes and their higher homologs—could lead to more efficient synthetic routes to polyunsaturated fatty acids, antibiotic and antifungal drugs, and other compounds that include this common structural motif (Nat. Chem., DOI: 10.1038/nchem.665). A general route to skipped polyenes with varied stereochemistries and substitution patterns has been lacking. But Todd K. Macklin and Glenn C. Micalizio at Scripps Florida have now developed a C–C bond-forming reaction that provides access to a wide range of the structures. The reaction (shown) is a metal-promoted reductive cross-coupling between vinylcyclopropanes and either alkynes or vinylsilanes. The vinylcyclopropane substrates are available in a few steps from allylic diazoacetates by an established synthetic route. Macklin and Micalizio demonstrated their skipped polyene reaction by using it to prepare novel polyunsaturated fatty acids more efficiently than has been possible in the past. “This new reaction provides a convenient means to explore the medicinal potential of molecules bearing complex skipped polyenes—something that we simply haven’t been able to do until now,” Micalizio says.