Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates

The 3D shape of glycosyl oxocarbenium ions determines their stability and reactivity and the stereochemical course of SN1-reactions taking place on these reactive intermediates is dictated by the conformation of these species. The nature and configuration of functional groups on the carbohydrate ring effect the stability of glycosyl oxocarbenium ions and they control the overall shape of the cations. We here map the stereoelectronic substituent effects of the C2-azide, C2-fluoride and C4-carboxylic acid ester on the stability and reactivity of the complete suite of diastereoisomeric furanoses using a combined computational and experimental approach. Surprisingly all furanosyl donors studied react in a highly stereoselective manner to provide the 1,2-cis products, except for the reactions in the xylose series. The 1,2-cis selectivity in the ribo-, arabino- and lyxo-configured furanosides can be traced back to the lowest energy 3E or E3-conformers of the intermediate oxocarbenium ions. The lack of selectivity of the xylosyl donors is related to the occurrence of oxocarbenium ions, adopting other conformations.