A Metal-Free Domino Process for Regioselective Synthesis of 1,2,4-Trisubstituted Pyrroles: Application toward the Formal Synthesis of Ningalin B

A new
one-pot, transition-metal, acid/base-free domino process
is developed for the regioselective synthesis of 1,2,4-trisubstituted
pyrroles. The process involves 1,3-dipolar cycloaddition of unsymmetrical
azomethine ylide resulting from the thermal C–C bond cleavage
of unactivated aziridines with β-bromo-β-nitrostyrene,
followed by a cascade of elimination and aromatization reaction sequence
to preferentially furnish 1,2,4-trisubstituted pyrroles instead of
the expected 1,2,3-trisubstituted pyrroles, in good to excellent yields.
Further, the application of the methodology for the formal synthesis
of ningalin B is delineated.