Microwave-assisted Clauson-Kaas synthesis of pyrroles

Abstract

The Clauson-Kaas pyrrole synthesis involving the reaction of primary amines with 2,5-dialkoxytetrahydrofurans is traditionally carried out in refluxing acetic acid (AcOH), whereas extension to less activated nitrogen nucleophiles often necessitates the use of acidic promoters. It is now reported that the preparation of N-substituted pyrroles can be effected under microwave conditions (10 min -30 min) using acetic acid or water without additional catalysts.

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

“…(i) Microwave-assisted reactions in water: In 2009, Ketcha and colleagues [ 79 ] nicely utilized the Clauson–Kaas reaction for the environmentally friendly synthesis of various N-substituted pyrroles 55 through the microwave-assisted reaction of various primary amines 54 with 2,5-dimethoxytetrahydrofuran ( 2 ). In this protocol, without the use of any additional catalyst, the products were obtained in 12–74% yields in water and 59–96% yields in acetic acid, respectively ( Scheme 26 ).…”