Yb(OTf)3 mediated MCR: a new and regioselective approach towards polysubstituted pyrroles of pharmacological interest

Abstract

A regioselective synthesis of 1,2,3,4-tetrasubstituted pyrroles has been achieved via Yb(OTf)₃-mediated 3-component reaction of amines, a 1,3-diketone and phenacyl bromide in a single pot. Yb(OTf)₃ was identified as a reusable catalyst and a number of pyrrole derivatives were prepared by using this strategy. Single crystal X-ray diffraction study of a representative compound confirmed the substitution pattern on the central pyrrole ring. The crystal structure analysis of the same compound indicated the presence of a sheet-like molecular arrangement along the bc-plane present in the molecule. A possible mechanism for the regioselective formation of 1,2,3,4-tetrasubstituted pyrrole rings is discussed. A number of compounds synthesized showed PDE4 inhibitory properties when tested in vitro and two of them were identified as inhibitors of further interest.