Stabilization of glucosyl dioxolenium Ions by "dual participation" of the 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) protection group for 1,2-cis-glucosylation

Remmerswaal, W.A.; Houthuijs, K.J.; Ven, R. van de; Elferink, H.; Hansen, T.; Berden, G.; ... ; Codee, J.D.C. (2022)

Article / Letter to editor

The stereoselective introduction of glycosidic bonds is of paramount importance to oligosaccharide synthesis. Among the various chemical strategies to steer stereoselectivity, participation by either neighboring or distal acyl groups is used particularly often. Recently, the use of the 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) protection group was shown to offer enhanced stereoselective steering compared to other acyl groups. Here, we investigate the origin of the stereoselectivity induced by the DMNPA group through systematic glycosylation reactions and infrared ion spectroscopy (IRIS) combined with techniques such as isotopic labeling of the anomeric center and isomer population analysis. Our study indicates that the origin of the DMNPA stereoselectivity does not lie in the direct participation of the nitro moiety but in the formation of a dioxolenium ion that is strongly stabilized by the nitro group.

• All authors: Remmerswaal, W.A.; Houthuijs, K.J.; Ven, R. van de; Elferink, H.; Hansen, T.; Berden, G.; Overkleeft, H.S.; Marel, G.A. van der; Rutjes, F.; Filippov, D.V.; Boltje, T.J.; Martens, J.; Oomens, J.; Codee, J.D.C.
• Date: 2022-06-24
• Journal: Journal of Organic Chemistry (JOC)
• Volume: 87
• Issue: 14
• Pages: 9139 - 9147
• DOI: doi:10.1021/acs.joc.2c00808
• Sponsorship: NWO
• Grant number: NWO-VICI grant VI.C.182.020