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

Abstract

Glycosylation reactions were performed on a series of bicyclic C2-substituted pyranoside models to isolate and analyze factors that control the glycosylation stereoselectivities observed in carbohydrates. The bent bond/antiperiplanar hypothesis (BBAH) orbital model rationalizes all of these results by considering hyperconjugation interactions between groups at C2 and the two τ bonds (bent bonds) of oxocarbenium ion intermediates formed under the glycosylation conditions. According to the BBAH, nucleophiles add to oxocarbenium intermediates by SN2-like antiperiplanar displacement of the weaker of their two τ bonds.

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. − …”

Synthesis of Sialyl LewisX Mimetics with E- and P-Selectin Binding Properties and Immunosuppressive Activity

“…25 An alternative pathway that has been proposed to rationalize the selectivity for axial cyanation in similar bicyclic systems The Journal of Organic Chemistry involves the addition of MeCN at the anomeric position to form α,β-acetonitrilium reaction intermediates. 26 These intermediates could equilibrate to the preferred equatorial orientation and undergo S N 2-like displacement, leading to the axial selectivity. 26 The equatorial preference for acetonitrilium has been rationalized by invoking the debated reverse anomeric effect, 27,28 where a positively charged anomeric substituent could be electrostatically better stabilized by having two gauche interactions with the two lone pairs of the ring oxygen.…”

“…An alternative pathway that has been proposed to rationalize the selectivity for axial cyanation in similar bicyclic systems involves the addition of MeCN at the anomeric position to form α,β-acetonitrilium reaction intermediates . These intermediates could equilibrate to the preferred equatorial orientation and undergo S N 2-like displacement, leading to the axial selectivity .…”

“…26 These intermediates could equilibrate to the preferred equatorial orientation and undergo S N 2-like displacement, leading to the axial selectivity. 26 The equatorial preference for acetonitrilium has been rationalized by invoking the debated reverse anomeric effect, 27,28 where a positively charged anomeric substituent could be electrostatically better stabilized by having two gauche interactions with the two lone pairs of the ring oxygen. 29 However, the selectivity (15:1 dr) obtained in MeNO 2 (entry 10, Table 1), a solvent that is not likely to form these stabilized intermediates, leads us to attribute the observed stereocontrol in MeCN to a difference in the proposed transition states A and B (Scheme 3).…”