Remarkable Oxidation Stability of Glycals: Excellent Substrates for Cerium(IV)-Mediated Radical Reactions

Abstract

Abstract:The remarkable stability of glycals under oxidative conditions becomes apparent by their redox data in solution, computed HOMO energies, and behavior on the addition of electrophilic radicals generated in the presence of cerium(IV) ammonium nitrate. Oxidation potentials up to 2.03 V vs ferrocene were obtained, which are exceptionally high for cyclic enol ethers but correlate nicely with the reaction times of the radical reactions. Protecting groups have a strong influence on the oxidation stability and HOMO energies of glycals as E ox is shifted from O-silyl over O-benzyl to O-acetyl by more than 500 mV. Interestingly, this effect must be transmitted through σ-bonds, even up to the para-position of a benzoate group, as verified by a wide variation of remote substituents in the carbohydrate. Favorable interactions of the σ*-orbital of the adjacent C-O bond with the HOMO of the double bond are proposed as a mechanistic rationale, which might be important for the redox behavior of other allylic systems. Finally, donors and acceptors in the 1-position exert the strongest influence on the oxidation stability, shifting the potentials by almost 1 V and resulting in different follow-up reactions of the cerium(IV)-mediated additions of malonates. It is the remarkable oxidation stability of glycals that makes them valuable building blocks in carbohydrate chemistry.

α‐Selective Organocatalytic Synthesis of 2‐Deoxygalactosides

“…Modification of Schreiners reaction for use in stereoselective glycosylations was not a trivial task, as the physical properties and solubilities of our substrates were not amenable to the methods described. [13] We optimized the reaction of protected galactal 2 a [15] (1.2 equiv.) with model acceptor 3 a and found that 1 mol % of catalyst 1, in a solution of CH 2 Cl 2 heated to reflux, gave excellent results.…”

Recent advances in CAN mediated reactions in organic synthesis

“…48-50 The remarkable stability of glycals under oxidative conditions was justified by their redox data in solution. 51 The [3þ2] cycloaddition of 2-hydroxy-1,4-naphthoquinone 17 to alkenes mediated by CAN resulted in the formation of furo-p-quinones as well as o-quinone derivatives. 52 This was further utilized for the synthesis of phenalenofuranones, 53 furopyranones, furoquinolinones, 54 and dihydrofuropyrimidinediones.…”

Simple Synthesis of Conformationally Fixed Glycosamine Analogues by Beckmann Rearrangement at the Carbohydrate Ring

“…All additions are orbital-controlled and give exclusively one regioisomer, in agreement with the HOMO energies and coefficients of all glycals 6, which we previously determined by cyclic voltammetry and calculation. [17] The excellent stereoselectivities of the reactions are due to steric interactions with the O-acetyl groups, in accordance to radical additions to glycals.…”