Thioarylation of 6-Amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic Acid (IminoKdo): Access to 3,6-Disubstituted Picolinates and Mechanistic Insights

Manmode, Sujit; Hussain, Nazar; Marin, Oscar Javier Gamboa; Kato, Atsushi; Veytia-Bucheli, José Ignacio; Vincent, Stéphanie P et Gauthier, Charles ORCID: https://orcid.org/0000-0002-2475-2050 (2023). Thioarylation of 6-Amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic Acid (IminoKdo): Access to 3,6-Disubstituted Picolinates and Mechanistic Insights Chemistry- A European Journal , vol. 30 , nº 12. pp. 1-7. DOI: 10.1002/chem.202303904.

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Résumé

In this work, we present a metal-free coupling protocol for the regio- and stereoselective C3-thioarylation of 6-amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic acid (iminoKdo). The developed procedure enables the coupling of electron-rich, electron-deficient, and hindered arylthiols, providing a series of C3-modified iminoKdo derivatives in moderate to good yields. Elucidation of active species through controlled experimental studies and time-lapse 31P NMR analysis provides insights into the reaction mechanism. We demonstrate that, following a tandem Staudinger/aza-Witting reaction of an azido-containing keto ester, an inseparable equimolar mixture of imine/enamine is formed. The enamine then undergoes a Stork-like nucleophilic attack with the in situ-formed disulfide reagent, resulting in the formation of the coupling products. Additionally, we describe a rarely reported acid-promoted aromatization of the C3-thioarylated iminoKdo skeleton into 3,6-disubstituted picolinates, which are reminiscent of dichotomines.

Type de document:	Article
Informations complémentaires:	document e202303904
Mots-clés libres:	3-deoxy-D-manno-oct-2-ulosonic acid; Staudinger/aza-Wittig; iminosugars; picolinates; thioarylation
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	04 janv. 2024 14:40
Dernière modification:	12 févr. 2026 16:10
URI:	https://espace.inrs.ca/id/eprint/13909

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