Luis Bohé

Dissecting the mechanisms of a class of chemical glycosylation using primary 13C kinetic isotope effects

Although arguably the most important reaction in glycoscience, chemical glycosylations are among the least well understood of organic chemical reactions, resulting in an unnecessarily high degree of empiricism and a brake on rational development in this critical area. To address this problem, primary 13C kinetic isotope effects have now been determined for the formation of β- and α-manno- and glucopyranosides using a natural abundance NMR method. In contrast to the common current assumption, for three of the four cases studied the experimental and computed values are indicative of associative displacement of the intermediate covalent glycosyl trifluoromethanesulfonates. For the formation of the α-mannopyranosides, the experimentally determined KIE differs significantly from that computed for an associative displacement, which is strongly suggestive of a dissociative mechanism that approaches the intermediacy of a glycosyl oxocarbenium ion. The application of analogous experiments to other glycosylation systems should shed further light on their mechanisms and thus assist in the design of better reactions conditions with improved stereoselectivity. Chemical glycosylations are perhaps the most important reactions in glycoscience, but the mechanisms are not well understood. Here, quantum chemical calculations combined with natural-abundance NMR measurements of 13C kinetic isotope effects reveal both associative and dissociative mechanisms at the extremes of a continuum that depends on the relative stereochemistry of the substrate and the anomeric configuration of the product.

The stereospecific synthesis of a new chiral oxaziridinium salt.

Abstract A new chiral oxaziridinium salt has been prepared from (1S, 2R)-(+)-norephedrine. Enantioselective oxygen transfer to prochiral olefins and sulfides may be performed either stoichiometrically or in a catalytic cycle.

Oxygen atom transfer from a chiral oxaziridinium salt. Asymmetric epoxidation of unfunctionalized olefins

Abstract The synthesis of an optically pure oxaziridinium salt from (1S,2R)-(+)-norephedrine and the study of the asymmetric oxygen transfer reactions from this reagent to unfunctionalized olefins are described.

A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art.

An overview of recent advances in glycosylation with particular emphasis on mechanism is presented. The mounting evidence for both the existence of glycosyl oxocarbenium ions as fleeting intermediates in some reactions, and the crucial role of the associated counterion in others is discussed. The extremes of the SN1 and SN2 manifolds for the glycosylation reaction are bridged by a continuum of mechanisms in which it appears likely that most examples are located.

Cation Clock Permits Distinction Between the Mechanisms of α- and β-O- and β-C-Glycosylation in the Mannopyranose Series: Evidence for the Existence of a Mannopyranosyl Oxocarbenium Ion

The use of a cationic cyclization reaction as a probe of the glycosylation mechanism has been developed and applied to the 4,6-O-benzylidene-protected mannopyranoside system. Cyclization results in the formation of both cis- and trans-fused tricyclic systems, invoking an intermediate glycosyl oxocarbenium ion reacting through a boat conformation. Competition reactions with isopropanol and trimethyl(methallyl)silane are interpreted as indicating that β-O-mannosylation proceeds via an associative S(N)2-like mechanism, whereas α-O-mannosylation and β-C-mannosylation are dissociative and S(N)1-like. Relative rate constants for reactions going via a common intermediate can be estimated.

OXYGEN ATOM TRANSFER FROM A CHIRAL N-ALKYL OXAZIRIDINE PROMOTED BY ACID. THE ASYMMETRIC OXIDATION OF SULFIDES TO SULFOXIDES

Abstract Chiral N-alkyl oxaziridines may be used as reagents for the asymmetric oxidation of sulfides in an acid-promoted reaction leading exclusively to the corresponding sulfoxides A planar transition state geometry seems consistent with the observed stereochemistry which should result from the steric interactions in the transition state. The influence of the solvent and the acid strength on the oxygen transfer reaction are discussed.

Catalytic oxaziridinium-mediated epoxidation of olefins by Oxone®. A convenient catalyst excluding common side reactions

Abstract The nicely crystalline, easily prepared and handled, 3,3-dimethyl-3,4-dihydroisoquinolinium salt 6 , is a convenient catalyst for the oxaziridinium-mediated epoxidation of alkenes by Oxone®.

Cation Clock Reactions for the Determination of Relative Reaction Kinetics in Glycosylation Reactions: Applications to Gluco- and Mannopyranosyl Sulfoxide and Trichloroacetimidate Type Donors

The development of a cation clock method based on the intramolecular Sakurai reaction for probing the concentration dependence of the nucleophile in glycosylation reactions is described. The method is developed for the sulfoxide and trichloroacetimidate glycosylation protocols. The method reveals that O-glycosylation reactions have stronger concentration dependencies than C-glycosylation reactions consistent with a more associative, S(N)2-like character. For the 4,6-O-benzylidene-directed mannosylation reaction a significant difference in concentration dependence is found for the formation of the β- and α-anomers, suggesting a difference in mechanism and a rationale for the optimization of selectivity regardless of the type of donor employed. In the mannose series the cyclization reaction employed as clock results in the formation of cis and trans-fused oxabicyclo[4,4,0]decanes as products with the latter being strongly indicative of the involvement of a conformationally mobile transient glycosyl oxocarbenium ion. With identical protecting group arrays cyclization in the glucopyranose series is more rapid than in the mannopyranose manifold. The potential application of related clock reactions in other carbenium ion-based branches of organic synthesis is considered.

A mechanistic approach to the reaction between imines and sodium hydrogen telluride

Abstract A study of the mechanism of the action of sodium hydrogen telluride on imines is presented. It accounts for the observed reduction of the amine function to secondary amino or methylene groups depending on the structure of the substrate.

Sodium hydrogen telluride: a mechanistic chameleon

Abstract Relative rates of reduction of several α,β-unsaturated esters andstyrenes added to recently obtained results from other substrates show that sodium hydrogen telluride (NaTeH) can react according to different mechanisms: nucleophilic substitution, hydride transfer, hydrogen atom transfer and electron transfer. Relative rates of reduction by HTeNa in addition to some other known results indicate that HTeNa reacts by different pathways according to the substrate and reaction conditions.