Oxo-Rhenium-Mediated Allylation of Furanoside Derivatives: A Computational Study on the Mechanism and the Stereoselectivity

Abstract

Properly substituted tetrahydrofuran (THF) rings are important building blocks in the synthesis of many natural metabolites. Having reliable procedures to control the stereoselectivity at the THF core while decorating it with different substituents is a fundamental requirement to achieve and fulfill the complexity of nature. We recently reported a new chemical approach to control the stereochemistry in the alkylation and arylation of furanoside derivatives by using a rhenium(V) complex to form an intermediate oxo-carbenium species able to react with proper soft nucleophiles. Here, we describe theoretical calculations, performed at the DFT B3LYP level, to disclose the important mechanistic features which regulate the entire catalytic cycle of the reaction of mono- and disubstituted furanosides with allyltrimethylsilane catalyzed by Re(O)Cl3(OPPh3)(Me2S). Moreover, the key factors governing the allylation step were investigated, confirming that the stereoselectivity, which is independent of the anomeric configuration of starting acetal, mainly arises from the orientation of the substituent at C-4, with only marginal contribution of the substituent at C-5. Finally, puckering Cremer–Pople parameters were used to take trace of the structural modifications throughout the catalytic cycle.