Amine-Catalyzed Cascade Reactions of Unprotected Aldoses—An Operationally Simple Access to Defined Configured Stereotetrads or Stereopentads

Abstract

An amine-catalyzed cascade reaction of unprotected carbohydrates with 1.3-diketones was elaborated. This cascade is based on a Knoevenagel reaction/intramolecular ketalization/retro-aldol reaction. By application of this operationally simple protocol, a direct access to optically active stereopentads or stereotetrads is given. Rules of configurative outcomes will be discussed.

Organocatalysis applied to carbohydrates: from roots to current developments

“…The Mahrwald group has been highly active in the field of organocatalysed modification of unprotected carbohydrates, especially by amine-catalysed Knoevenagel reactions. [62][63][64] The use of less reactive methyl ketones was then explored requiring stoichiometric amounts of proline catalyst (S)-9. 65 The different aldopentoses 183-187 were tested affording the desired furanosides in variable yields and selectivity depend-ing on the configuration of the starting carbohydrate (Scheme 27).…”

Synthesis of Carbohydrate Mimetics by Intramolecular 1,3‐Dipolar Cycloaddition of N‐(3‐Alkenyl)nitrones Derived from Unprotected d‐Aldopentoses

“…Although such protection/deprotection strategies do give access to structurally advanced derivatives, they increase the number of steps, and often make the syntheses of these glycomimetics arduous. In contrast, a relatively large group of C ‐glycosides have been synthesized from unprotected carbohydrates using reactions such as the aldol, Knoevenagel, Friedel–Crafts, and Horner–Wadsworth–Emmons reactions , . The direct use of the carbonyl group in this way seems to be a more promising approach than the traditional protection/deprotection protocol …”

Copper(I)-Catalyzed Dehydrative C-Glycosidation of Unprotected Pyranoses with Ketones

“…In this context, catalytic C–C bond-forming reactions at the anomeric position of unprotected aldoses are a representative carbon skeleton elongation method for streamlined synthesis of various C-glycoside motifs . Previously reported nucleophiles for the catalytic synthesis of C-glycosides and related molecules, however, are limited to 1,3-dicarbonyl, ketone, aryl, allyl, alkynyl, and propargyl groups . Among these nucleophiles, incorporation of ketone, alkynyl, and propargyl groups has scarcely developed.…”