Applying the Bent Bond/Antiperiplanar Hypothesis to the Stereoselective Glycosylation of Bicyclic Furanosides

Abstract

The glycosylation stereoselectivities for a series of bicyclic furanoside models have been carried out in the presence of weak nucleophiles. These results were analyzed through the bent bond/antiperiplanar hypothesis (BBAH) orbital model to test its validity. According to the BBAH, incoming nucleophiles displace one of the two bent bonds of bicyclic oxocarbenium ion intermediates in an antiperiplanar fashion. The glycosylation stereoselectivity is then governed by the displacement of the weaker bent bond as determined by the presence of electron-withdrawing or -donating substituents at C2. Overall, the BBAH analysis expands Woerpel’s “inside/outside attack” glycosylation model by considering the stereoelectronic influence of neighboring electron-withdrawing and -donating groups on the nucleophilic addition to oxocarbenium ion intermediates.

Bent Bond/Antiperiplanar Hypothesis: Modulating the Reactivity and the Selectivity in the Glycosylation of Bicyclic Pyranoside Models

“…These results can be readily rationalized by the BBAH model, ,, considering hyperconjugation of the C 2 substituents . In the oxocarbenium intermediate, hyperconjugation between the electron-donating C 2 –H bond and its antiperiplanar τ bond (σ CH → τ* interaction) increases the electron density of that bent bond.…”

“…For instance, using the enantiomer of the C 2 –OBn donor studied by Woerpel, the transition state for the addition of deuterated triethylsilane was found to be 0.5 kcal/mol lower for the cis addition, in agreement with the experiment (66:34 cis / trans ratio). Where the work of Codée and Woerpel shows the factors leading to a selective S N 1 glycosylation through intermediate pyranosyl cations, our work aims to explain how those very reactive intermediates can be tamed through hyperconjugative effects predicated by the BBAH model. ,, In a similar fashion to the work of Jensen, the reactivities of our bicyclic glycosylation donors were studied by modifying the nature of their substituents. In this work, the donors listed in Scheme were specifically designed not to have any oxygenated substituent, other than the one at C 2 , to isolate the stereoelectronic contribution of the C 2 substituents on modulating glycosylation reactivity.…”

“…Over the last nine years, we have reported on the initial development and multiple applications of the bent bond/antiperiplanar hypothesis (BBAH), a conceptually novel orbital model for rationalizing the reactivity of various types of unsaturated systems. − In this regard, we sought to better understand the fundamental principles governing the stereoselectivity of the glycosylation reaction at the anomeric center of carbohydrates. We have previously shown that the O- and C-glycosylation of simplified bicyclic pyranoside and furanoside models under S N 1 conditions could be rationalized through the BBAH model . We wish to report an important extension of the initial study using bicyclic pyranoside model substrates bearing a wider variety of substituent types at C 2 in terms of electronic and steric properties.…”

Bent Bond/Antiperiplanar Hypothesis and the Chemical Reactivity of Annulenes

“…We previously reported that the bent bond (τ bond) model, combined with the antiperiplanar hypothesis (BBAH), constitutes a simple and highly useful orbital model for rationalizing the conformation and stereochemical reactivity of various classes of unsaturated organic molecules. − …”

“…In some sense, the BBAH model predicts that the allyl radical reacts in a higher energy and nonplanar geometry as represented by the resonance structures. The simple BBAH concepts illustrated here for the allyl radical exemplar have been applied to an ever-widening range of organic structures and reactions and accounted for reactions that previously defied a mechanistic interpretation. − …”