Pd-Catalyzed Synthesis of 1-(Hetero)aryl Thioglycosides: Strategy for the Trapping of an Acyl Group of Glycosylthioesters by Coupling of Bis-Electrophilic-Nucleophilic Partners

J Org Chem. 2024 Nov 1;89(21):15777-15792. doi: 10.1021/acs.joc.4c01867. Epub 2024 Oct 15.

Abstract

Herein, we describe a stereoretentive palladium-catalyzed cross-coupling between the in situ-generated glycosyl thiolate anion and diverse (hetero)aryl iodides at room temperature for creating the library of (hetero)aryl thioglycosides. The key to success is the judicious pairing of bis-electrophilic-nucleophilic partners with a variety of thioesters in an atom-economical way in which both the glycosyl thiolate anion and the acylium cation are incorporated into the final analogue. The advantage of this method is the acyl transfer on various nucleophilic partners, including a hydroxyl, a primary or secondary amine, an amino acid, and the biologically active hSGLT1 inhibitor.