Palladium-Catalyzed O-Glycosylation through π-π Interactions

Org Lett. 2024 Jun 28;26(25):5396-5401. doi: 10.1021/acs.orglett.4c02019. Epub 2024 Jun 13.

Abstract

A stereodivergent synthesis of β- and α-O-glycosides using 3-O-quinaldoyl glucals was developed by palladium catalysis at 60 and 110 °C respectively. Various alcohols, monosaccharides, and amino acid were glycosylated to form β- and α- products in good yields with high stereoselectivity. Mechanistic studies indicated no classic Pd-N (quinoline) coordination, but π-π stacking interactions promoted the anomeric stereodiversity. The practicality was demonstrated by glycosylating natural products/drugs and synthesizing a complex tetrasaccharide.