A General Strategy for the Stereoselective Synthesis of Pyrrole‐Fused Chiral Skeletons: [3+2] Cycloaddition with 2‐Nitro‐2,3‐Unsaturated Glycosides

Abstract

AbstractIn this study, a two‐step methodology was developed for the synthesis of chiral pyrroles from 2‐nitroglycals via Ferrier rearrangement and Barton‐Zard reaction under mild conditions without transition metal catalysts. The Ferrier rearrangement reaction of 2‐nitro‐glycals and a series of O‐nucleophiles proceeded smoothly in the presence of N‐heterocyclic carbene (NHC) catalyst and K2CO3 which allowed the highly stereoselective synthesis of the diverse 2‐nitro‐2,3‐unsaturated glycosides in excellent yields. Subsequently, the rearrangement products were conveniently transformed into the desired chiral pyrroles by [3+2] cycloaddition (Barton‐Zard reaction) with isocyanoacetate in the presence of Cs2CO3. One‐pot strategy was also successfully demonstrated for the gram‐scale synthesis of one chiral pyrrole. This is the first report of stereoselective conversion from 2‐nitroglycals to chiral pyrrole.