Hexafluoroisopropanol (HFIP)-mediated catalyst-free microwave-assisted novel multicomponent method to access 3-acyl 1,4-diaryl/alkyl pyrroles

It is becoming increasingly common for synthetic chemists to engage in a variety of synthetic transformations using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), a strong hydrogen bonding-donating, redox-stable polar solvent. Herein, we describe an HFIP-mediated green protocol for the synthesis of novel pyrroles under catalyst-free microwave-assisted conditions. The substituted pyrroles are formed in good to excellent yields (52–99 %) in 1 h from a novel multicomponent reaction of 1-aryl/heteroaryl/alkyl/cycloalkyl substituted 3-(dimethylamino)propenones, aryl/heteroaryl/alkyl/cycloalkyl amines and α-bromo ketones. Furthermore, the structures of products were confirmed by their physical properties, ¹H & ¹³C NMR and mass spectral data, and validated by single crystal X-ray diffraction analysis of 4aq and 4aw. For the current method, HFIP is recycled and reused. This protocol features catalyst-free conditions, easy recyclability and efficient reusability of HFIP, application of microwaves, ease of handling, short reaction times, high yields of products with vast substrate scope, and preparation of novel pyrroles. This protocol has also been applied for the construction of anticancer agent, 3-aroyl-1,4-diarylpyrrole (ARDAP) (5) [with about 8-fold increase of yield and 6.5-fold decrease of time], and a steroid-based complex pyrrole 4bp.