Bent bonds (τ) and the antiperiplanar hypothesis, and the reactivity at the anomeric center in pyranosides

Abstract

The stereoselectivity of nucleophilic addition on oxocarbenium ions derived from the bicyclic pyranoside model with or without a C-OR group can be understood through the use of the bent-bond and the antiperiplanar hypothesis in conjunction with the concept of hyperconjugation as an alternative interpretive model of structure and reactivity.

The Experimental Evidence in Support of Glycosylation Mechanisms at the SN1–SN2 Interface

“…An alternative representation of oxocarbenium ions advocated by Deslongchamps uses Pauling’s concept of two bent tau bonds between the carbon and oxygen atoms rather than the standard model of a sigma and a pi bond (Figure 2). 31 In this review we adopt the classical sigma and pi representation, referring only to the tau model in regard to the stereoselectivity of addition to oxocarbenium ions.…”

“…Nucleophilic attack then is considered to take place antiperiplanar to the lowest energy τ-bond, and consequently syn to the electron-withdrawing C-X bond, and in such a manner as to generate the product in a staggered conformation with a lone pair at oxygen antiperiplanar to the newly formed C-nucleophile bond. 31 Following studies with a number of simple bicyclic compounds, this model was used to explain the known stereoselectivity of O- and C-glycosylation of 4,6- O -benzylidene-protected gluco- and mannopyranosides. For the gluco-configuration, it is suggested that an intermediate oxocarbenium ion adopts the 4 H 3 conformation, which places the electron-withdrawing C2-O bond antiperiplanar to the τ-bond on the β-face thereby lowering its energy and directing attack to the α-face resulting overall in the axial product in a chair conformation (Scheme 19).…”

“…The requirement for antiperiplanar attack of the nucleophile on the lowest lying bond therefore results in preferential reaction of the β-face and formation of the product in an initial 1 S 5 conformation (Scheme 19). 31…”

Guidelines for O-Glycoside Formation from First Principles

“… 25 − 29 We limit ourselves to the formation of O -glycosides, believing them to be more central to glycobiology, and do not anticipate that the guidelines we offer will extrapolate directly to C -glycoside formation, which operate more closely to the S N 1 end of the mechanistic spectrum and appear to depend heavily on the conformational dynamics of the putative oxocarbenium ion. 30 − 32 The guidelines we present are general considerations for reactions conducted at the S N 1/S N 2 interface 18 without the assistance of neighboring group participation, which fall under a different kinetic regime. 19 Finally, we note that while the choice of nonparticipating groups for both glycosyl donors and acceptors can significantly influence the overall rate of a glycosylation reaction under a given set of conditions by shifting the S N 1/S N 2 interface, 25 − 27 , 29 , 33 − 35 the guidelines that we offer are general, and their application should improve reproducibility whatever the protecting group regime.…”

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. − …”