Oxocarbenium ion-formation

In the depurination of RNA catalyzed by ricin toxin A-chain (RTA), the reaction mechanism involved formation of equihbrium population of an oxocarbenium ion intermediate followed by an isotopicaUy insensitive irreversible step (Fig. 7)." The experimental KlEs were most consistent with the calculated ElEs for oxocarbenium ion formation. This is what would be expected for a mechanism involving freely reversible oxocarbenium ion formation followed by an isotopicaUy insensitive step. 

The oxonia-Cope rearrangement is also a key aspect of the Mukaiyama-Michael cascade reaction developed by Rychnovsky, which results in the formation of tetrahydropyran rings with high levels of stereoselectivity. As demonstrated in the example below, the Lewis acid promoted conjugate addition of enol ether 190 results in an intermediate oxocarbenium ion, formation of which is followed by Cope rearrangement. 

Yadav et al. utilized a Prins reaction in the context of a macrocyclization strategy toward leucascandrolide A (Scheme 37) [77]. Lewis acid activation of aldehyde 140 leads to oxocarbenium ion formation and Prins cyclization with nucleophilic acetate trapping. Direct base hydrolysis afforded macrocyclic fragment 141 as a single diastereomer in good yield (79 % over two steps). 

The two 2,6-cis THP rings present in the monomeric unit of the dimeric diolide (-t)-SCH 351448 offered Backes and Koert an opportunity to exploit stereoselective lactol reductiOTi (Scheme 70) [128]. Lewis acid activation of ketones 266 and 268 with BF3-OEt2, followed by closure with the pendant silyl ether, provides lactol intermediates. Subsequent oxocarbenium ion formation and hydride delivery by triethylsilane afforded the 2,6-cis THP rings 267 and 269 in high yields (98 % and 93 %, respectively) as single diastereomers. 

A case similar to the slow, practically irreversible inhibition of jack bean a-D-mannosidase by swainsonine is represented by the interaction of castanospermine with isomaltase and rat-intestinal sucrase. Whereas the association constants for the formation of the enzyme-inhibitor complex were similar to those of other slow-binding glycosidase inhibitors (6.5 10 and 0.3 10 M s for sucrase and isomaltase, respectively), the dissociation constant of the enzyme-inhibitor complex was extremely low (3.6 10 s for sucrase) or could not be measured at all (isomaltase), resulting in a virtually irreversible inhibition. Danzin and Ehrhard discussed the strong binding of castanospermine in terms of the similarity of the protonated inhibitor to a D-glucosyl oxocarbenium ion transition-state, but were unable to give an explanation for the extremely slow dissociation of the enzyme-inhibitor complex. 

However, there are several experimental observations which are against an interpretation of the reaction as being a one-step C—C cleavage process which would give rise to the formation of the relatively unstable a-oxocarbenium ion 28. 

Ketoses should react under a similar scheme. Indeed they do but an important problem in the chemistry of ketoses consists on the lack of selectivity due to (1) the complexity of their tautomeric equilibria and (2) their tendency to form tertiary oxocarbenium ions under acidic conditions. Thus, mixtures of open-chain, cyclic and dehydrated products are frequently obtained.7 The discussion about OZT structures obtained from D-fructose as proposed by Zemplen, Wickstrom and more recently by Grouiller et al. continues today. In fact, the first authors claimed the fusion of OZT on a pyran form of D-fructose, while Grouiller suggested the formation of a mixture of fused OZTs with /1-pyran (major) and p-furan (minor) forms (Scheme 22).18... 

Alkoxycarbenium ions are important reactive intermediates in modem organic synthesis.28 It should be noted that other names such as oxonium ions, oxocarbenium ions, and carboxonium ions have also been used for carbocations stabilized by an adjacent oxygen atom and that we often draw structures having a carbon-oxygen double bond for this type of cations.2 Alkoxycarbenium ions are often generated from the corresponding acetals by treatment with Lewis acids in the presence of carbon nucleophiles. This type of reaction serves as efficient methods for carbon-carbon bond formation. 

The formation of the products could be explained by hemiacetal formation followed by Prins cyclization and subsequent Ritter amidation. A tentative reaction mechanism to realize the cis selectivity is given in Fig. 20 and could be explained by assuming the formation of an (L )-oxocarbenium ion via a chair-like transition state, which has an increased stability relative to the open oxocarbenium ion owing to electron delocalization. The optimal geometry for this delocalization places the hydrogen atom at C4 in a pseudoaxial position, which favors equatorial attack of the nucleophiles. 

The addition of CF3TMS on a lactone group in position 1 allows introduction of CF3 on the anomeric position. Due to its electron-withdrawing effect, the CF3 group inhibits the possible formation of the oxocarbenium ion intermediate of the anomeric substitution. Consequently, the substiment introduced on the anomeric position (OAc,... 

The formation and the hydrolysis of acyclic and cyclic acetals have been studied in rather great detail [91]. Several reviews on this topic are available [92] and some comments have been made [13] concerning the carbohydrate series. We have shown in Schemes 1,2, and 3 that a common feature of this reaction seems to be the intermediacy of an oxocarbenium ion. However, the cyclization of such an intermediate has been questioned more recently [93] in the light of the Baldwin s rules for ring closure [94]. At least for the five-membered ring, an SN2-type displacement mechanism far the protonated form (B) of die hemiacetal (A) (favorable 5-exo-tet cyclization) has been proposed rather than the unfavorable 5-endo-trig cyclization of the oxocarbenium ion (C) (Scheme 5). Except when the formation of the enol ether (D) is structurally impossible, the intermediacy of such a compound remains feasible. 

Therefore, it seems most plausible that the stereospecific generation of the p-aceto-nitrilium ion (d) of Neu5Ac from the oxocarbenium ion (c) holds the key of the re-preponderant formation of sialyl glycosides in acetonitrile. Thus, the reactive nucleophiles, such as OH-6 of 17 have a chance to attack on other intermediates (a) (c) before the complete... 

From a strictly chemical point of view, the synthesis of glycosides still presents a formidable challenge to synthetic chemists in spite of major advances in the area [1], Unlike peptidic bonds, the formation of the glycosidic linkage is subject to various factors that include, among others, electronic, stereoelectronic, conformational, substituent, and reactivity effects generally associated with incipient oxocarbenium ions derived from carbohydrates. 

Quantum mechanical calculations show that the silyl cation (19) has a twisted structure, and that the a-C02 group provides substantial electrostatic stabilization.58 Isotope effects for its formation reaction are also reported.58 Evidence is provided for the stabilization of incipient oxocarbenium ions by axial electronegative substituents, as in (20) the presence of the most electronegative substituent results in the fastest reaction.59 Lewis acid-promoted cleavage of spirocyclic dioxanes such as (21) involves oxonium ions, and high axial vs equatorial product selectivities are possible with the correct choice of Lewis acid and nucleophile.60 Reactions which lead to 1,3-dioxenium salts have been reviewed.61... 

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