Synthesis of N-Hydroxypyrroles Using N-Selective Nucleophilicity of Oximes

Significance

Reported is the amine-catalyzed synthesis of tetrasubstituted N-hydroxypyrroles by reaction of α-carbonyloximes with α,β-unsaturated aldehydes through an iminium activation strategy. A mechanism involves an unusual N-selective nucleophilic Michael addition (K. Narasaka and co-workers Eur. J. Org. Chem 2005, 4505) followed by an intramolecular enamine aldol condensation and final aromatization. The use of diisopropylamine as catalyst affords tetrasubstituted N-hydroxypyrroles under mild conditions in moderate to good yields with several types of R^¹ groups whereas the variation of R^² is more limited. The reaction is successful with α,β-unsaturated aldehydes bearing R^³ = nonaromatic but is completely inhibited if R^³ = aromatic. When R^¹ = Ph and R^² = Me, the proportion of the undesired regioisomer was reduced to traces by using amines I and II as catalyst.