Elusive Dehydroalanine Derivatives with Enhanced Reactivity.

For the first time, a simple methodology for the chemical synthesis and utilization of highly reactive 4-methylen-oxazol-5(4H)-ones from serine is presented. These dehydroalanine derivatives, which resemble the natural 4-methylideneimidazole-5-one (MIO) cofactor present in lyases and aminomutases, undergo rapid reaction with carbon nucleophiles such as silyl enol ethers, and cycloaddition reactions with diazo compounds and reactive dienes under very mild conditions and in the absence of metal catalysts and ring-strain activation, offering potential for bioconjugation.