Synthesis of 2,5-Disubstituted Pyrroles by Nitro-Mannich/Hydroamination Cascades

Significance

Reported is the synthesis of 2,5-disubstituted pyrroles 3 from imines 1 and alkynes 2 via a nitro-Mannich/hydroamination cascade ­under base and gold catalysis. Both the nitro-Mannich and cyclization reactions were optimized independently, followed by further optimization of the one-pot process. The reaction tolerates both EDGs and EWGs at the ortho-, meta-, and para-positions on the aromatic imine. Terminal alkynes are preferred, giving the desired 2-methylpyrroles in moderate to good yields (55-86%). One example of an internal alkyne (R^² = Me) gave the 2-ethyl-pyrrole in only 21% yield using Au(PPh₃)Cl/AgOTf (5 mol%) as catalyst.