Stereoselective Thioconjugation by Photoinduced Thiol‐ene Coupling Reactions of Hexo‐ and Pentopyranosyl d‐ and l‐Glycals at Low‐Temperature—Reactivity and Stereoselectivity Study

Abstract

A comprehensive optimization and mechanistic study on the photoinduced hydrothiolation of different d‐ and l‐ hexo‐ and pentoglycals with various thiols was performed, at the temperature range of RT to −120 °C. Addition of thiols onto 2‐substituted hexoglycals proceeded with complete 1,2‐cis‐α‐stereoselectivity in all cases. Hydrothiolation of 2‐substituted pentoglycals resulted in mixtures of 1,2‐cis‐α‐ and ‐β‐thioglycosides of varying ratio depending on the configuration of the reactants. Hydrothiolation of unsubstituted glycals at −80 °C proceeded with excellent yields and, except for galactal, provided the axially C2‐S‐linked isomers with high selectivity. Cooling was always beneficial to the efficacy, increased the yields and in most cases significantly raised the stereoselectivity. The suggested mechanism explains the different conformational preferences of the intermediate carbon‐centered radicals, which is a crucial factor in the stereoselectivity of the reactions.

Synthesis and photoinitiated thiol–ene reactions of exo-mannals – a new route to C-β-d-mannosyl derivatives

“…In the case of benzenethiol 7a no transformation was detected at room temperature, but at À78 C 43,44 the suldes 8aa and 8ba were isolated by column chromatography in 79 and 47% yields, respectively.…”

Synthesis of Thiodisaccharides Bearing N‐Acetylhexosamine Residues: Challenges, Achievements and Perspectives

“…Borbás and co‐workers [100–102] also made important contributions in this field. They reported the synthesis of α(1→1) and α(1→2) hexosamine‐bearing thiodisaccharides, among others, by TEC reaction, using endocyclic enoses and 2‐acetoxyglycals as starting materials.…”

“…Additionally, the reaction proceeded with very good yields, although it was not stereoselective (Scheme 37). [99] Borbás and co-workers [100][101][102] also made important contributions in this field. They reported the synthesis of α(1!1) and α(1!2) hexosamine-bearing thiodisaccharides, among others, by TEC reaction, using endocyclic enoses and 2acetoxyglycals as starting materials.…”

“…However, for trisaccharide 214, the reaction gave better results at À 40 °C (33 % and 65 % yield, respectively). [102] It should be mentioned that Borbás recently published an excellent review which collects all the latest results on the photoinitiated thiol-ene reactions involving unsaturated sugars as precursors, portraying this method as a powerful tool for the construction of thiodisaccharides. [103]…”

Addition of Heteroatom Radicals to endo-Glycals †

“…Phosphorus-centered radicals have been less intensively studied in carbohydrate chemistry, but addition products can be used for further transformations. On the other hand, the addition of sulfur-centered radicals to glycals has become very attractive for the synthesis of thio-disaccharides [68][69][70][71][72]. Photochemical initiators based on ketones have been developed for The addition of thiols by radical chain reactions to the 2-position of glycals has only one disadvantage: that the 1-position is reduced under the reaction conditions.…”