A General Strategy For The Stereoselective Synthesis Of Pyrrole-Fused Chiral Skeletons: [3+2] Cycloaddition With 2-Nitro-2,3-Unsaturated Glycosides

In 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.