Acetic Acid‐Catalyzed Selective Synthesis of N‐Substituted 2‐Amino‐3‐Cyanopyrroles via a Three‐Component Reaction Between Carbohydrates, Primary Amines and Malononitrile

Abstract

AbstractDirect conversion of unprotected carbohydrates to N‐heterocycles is challenging and highly desirable. A simple three‐component synthesis of N‐substituted 2‐amino‐3‐cyanopyrrole key framework is developed from the reaction between unprotected carbohydrates, malononitrile, and primary amines. The reaction proceeded under mild reaction conditions (AcOH catalyst, EtOH, 60 °C, 2 hours), tolerated a wide substrate scope, worked smoothly on a 4 g scale, and gave the pyrroles in up to 86% yield. The pyrroles were also converted into functional intermediates to demonstrate their versatility. NMR and LC–MS experiments supported a proposed cascade reaction mechanism. The approach demonstrates a robust upcycling process for the challenging synthesis of highly functionalized N‐heterocyclic compounds from unprotected carbohydrates.