1,2-cis-Glycosides are frequently found in many biologically active natural products and pharmaceutical compounds. Therefore, to reveal the precise biological roles and structure-activity relationships of the glycosides, the development of efficient synthetic methods has been required. However, the stereoselective synthesis of these glycosides is still challenging task because neighboring group participation from a 2-O-acyl functionality of a glycosyl donor cannot be directly applied to the stereoselective synthesis of 1,2-cis-glycosides. In this context, we have recently developed 1,2-cis-stereoselective glycosylations using mono-ol acceptor-derived borinic ester catalysts, and regio- and 1,2-cis-stereoselective glycosylations using diol sugar acceptor-derived boronic ester catalysts. In this presentation, I wish to report the development of a novel boronic-acid-catalyzed regio- and 1,2-cis-stereoselective glycosylation of unprotected sugar acceptors via SNi-type mechanism, and the applications of our organoboron-catalyzed glycosylation methods. Initially, we selected 3,4,6-tri-O-Bn-1,2-anhydroglucose (1) and glucal (2) as the glycosyl donor and the unprotected sugar acceptor, respectively, and examined glycosylations of 1 and 2 using several boronic acid catalysts under various reaction conditions. The results showed that the glycosylation of 1 and 2 using p-nitrophenylboronic acid (3) catalyst in the presence of water proceeded effectively to give a corresponding α(1,4) glycoside in high yield with high regio- and excellent stereoselectivities. In addition, this method could be applied to several 1,2-anhydro donors and unprotected sugar acceptors. Next, the reaction mechanism of this glycosylation was analyzed by KIEs and DFT calculations. The results suggested that the present glycosylation can be regarded as a highly dissociative concerted SNi-type mechanism. Furthermore, this method was applied successfully to the direct glycosylation of natural glycosides and efficient synthesis of complex carbohydrates.

Organoboron-catalyzed regio- and 1,2-cis-stereoselective glycosylation via SNi-type mechanism

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.