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
; 30(12): e202303904, 2024 Feb 26.
Article
in En
| MEDLINE
| ID: mdl-38116880
ABSTRACT
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 31 P NMR analysis provides insights into the reaction mechanism. We demonstrate that, following a tandem Staudinger/aza-Wittig 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 inâ
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Chemistry
Journal subject:
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
Canada
Country of publication:
Germany