Synthesis of Polysubstituted 2-Aminopyrroles via a Multicomponent Reaction

Significance

Reported is the synthesis of tetra- and pentasubstituted 2-aminopyrroles 5 and 6 by a one-pot three-component reaction of N-(aryl, heteroaryl or alkylsulfonamido)acetophenones 1, diverse aldehydes 2 and cyanoacetic acid derivatives 3, respectively. Based on a previous report (I. V. Magedov et al. Bioorg. Med. Chem. Lett. 2008, 18, 1392), this reaction leads to multisubstituted cis- and trans-pyrrolines which are oxidized in the presence of DDQ to afford multisubstituted pyrroles. The process works well for the synthesis of 5, incorporating a variety of aliphatic, aromatic (including sterically hindered or heteroaromatic) ­aldehydes and malonitrile, cyanoacetamide or ethylcyanoacetate. Base-promoted dehydro­sulfinylation afforded the NH-pyrroles 6.