Regioselective access to electron-deficient and highly substituted pyrroles from simple building blocks remains challenging. Here we show that O-vinylhydroxylamines enable the de novo construction of pyrroles through an aza-Michael/oxaza-Cope 3,3-sigmatropic rearrangement/aromatization cascade with activated alkynes. This one-pot transformation proceeds rapidly at room temperature using catalytic amounts of a mild organic base and furnishes dihydropyrrole hemiaminal intermediates that can be directly converted to pyrroles or selectively functionalized. The method accommodates a broad range of O-vinylhydroxylamines and activated alkyne partners and enables access to substitution patterns that previously required harsh conditions or hazardous acetylene-based methods. These results establish O-vinylhydroxylamines as versatile building blocks for the synthesis of highly functionalized pyrroles.
Randolph et al. (Sat,) studied this question.