Stereochemistry oxocarbenium ions

Figure 3.1 Stereochemistry of oxocarbenium ions. Top the methoxymethyl cation, showing overlap between an empty p orbital on carbon and a p-type lone pair of electrons on oxygen and also the two mechanisms for isomerisation. Rotation involves breaking the n bond, via a perpendicular transition state, whereas during inversion the ion remains planar and the oxygen atom undergoes a process similar to the inversion of ammonia. Centre the two permitted conformations of a xylofuranosyl cation. Bottom the four permitted conformations of a xylopyranosyl cation.

All of the three mentioned mechanisms involve oxocarbenium ion-like transition states and a pair of carboxylic acids at the active site however, they differ in several aspects. The inverting mechanism is a one-step reaction that results in the formation of a product with inverted stereochemistry at the anomeric center. The other two alternatives are retaining in stereochemistry at the anomeric center and differ from each other primarily in the nature of the intermediate in the second mechanism, this species is a covalent enzyme adduct, whereas in the third case it is believed to be a bicyclic oxazoline or oxazolinium ion. ... 

Ayala L, Lucero CG, Romero JAC, Tabacco SA, Woerpel KA (2003) Stereochemistry of nucleophilic substitution reactitms depending upon substituent evidence for electrostatic stabilization of pseudoaxial conformers of oxocarbenium ions by heteroatom substituents. J Am Chem Soc 125 15521-15528... 

Calculated energies of stabilized cations corresponding to the anchimeric assistance from the positions 3, 4, and 6 were compared with the energies of two possible conformations of the nonstabiUzed oxocarbenium cation (Scheme 5.21). Two most stable conformations of the nonstabiUzed cation, H4 and undergo a nucleophilic attack preferentially from P- and a-sides, respectively, giving products with the opposite stereochemistry [49-55]. Calculations showed that a-selective conformation of the oxocarbenium ion is by almost 3kcalmol more stable than P-selective one, that is, the a-selectivity is intrinsic to this... 

Mechanistically, the oxocarbenium ion resulting from the ionization of methyl pyranoside with trimethylsilyl tri-fluoromethanesulfonate (TMSOTf) favors the pseudoaxial orientation of the 4-methoxy group, as reported previously for the formation of 2,6-trans tetrahydropyran (Scheme 37.25). As a result, the hydride delivery presumably occurs via prefential axial attack resulting in the 2,6-cis stereochemistry. 

SCHEME 37.25. Generation of 2,6-trans relative stereochemistry in 97 via oxocarbenium ion intermediate. 

TMSBr, a 1 1.4 mixture of axial and equatorial THPs (N + M) was formed. To explain this reversal of selectivity, the authors hypothesized that SnBrs and the oxocarbenium formed a dissociated ion pair thus favoring the equatorial addition (Scheme 41). We have to point out that substituted allenes can be used and, depending on the configuration of the double bond, the stereochemistry at C5 can be controlled. 

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