Synthesis of Highly Condensed Polycyclic Carbohydrates by Reaction of a Spirocyclic Enamino Sulfonate Derived from d-Xylofuranose with Bifunctional Reagents

Abstract

The appropriately substituted 5-O-tosyl derivative (1), easily prepared from 1,2-O-isopropylidene-alpha-d-xylofuranose, serves as a useful precursor for the preparation of highly condensed cyclic carbohydrates. The synthesis involves a first cyclization of the 5-O-tosyl sugar derivative 1 to a highly reactive cyclic enamine, which subsequently undergoes the nucleophilic attack of a bifunctional reagent X(CH2)nZ in a regio- and stereospecific way. Finally, a spontaneous cyclization step allows the formation of a stereochemically defined extra ring, fused to the sugar backbone. The functionalization and size of this ring can be varied by the proper choice of the bifunctional reagent. X-ray diffraction analysis and intensive NMR studies with one of these carbohydrates were performed to highlight the strained nature of these compounds.

Application of a Double Aza-Michael Reaction in a ‘Click, Click, Cy-Click’ Strategy: From Bench to Flow

“…Hetero-Michael reactions are efficient pathways that, historically, have been broadly used in synthesis, including several intramolecular examples to access a variety of heterocycles, namely, dioxolanes en route to 1,3-diols, 1 azacycles, 2 oxacycles, 3 thiacycles, 4 and bis-heterocycles. 5 Recently, double aza-Michael reactions have been utilized as efficient means to install two N–C bonds in a single operation. 6 Herein, we report a new approach termed ‘click, click, cy-click’ that utilizes two click reactions 7 and a double aza-Michael reaction for the facile synthesis of 1,2,5-thiadiazepane 1,1-dioxides.…”