In organic chemistry, an oxocarbenium ion (alternatively spelled oxacarbenium) is a chemical species characterized by a central sp2-hybridized atom of carbon, a substituent atom of oxygen, and an overall positive charge that is delocalized between the central carbon and oxygen atoms (R2[CO]+R). An oxocarbenium ion is represented by two limiting resonance structures, one in the form of a carbenium ion with the positive charge on carbon (>C+−O−) and the other in the form of an oxonium species with the formal charge on oxygen (>C=O+−). As a resonance hybrid, the true structure falls between the two. Compared to neutral carbonyl (C=O) compounds like ketones (>C=O) or esters, the carbenium ion form is a larger contributor to the structure. They are common reactive intermediates in the hydrolysis of glycosidic bonds, and are a commonly used strategy for chemical glycosylation. These ions have since been proposed as reactive intermediates in a wide range of chemical transformations, and have been utilized in the total synthesis of several natural products. In addition, they commonly appear in mechanisms of enzyme-catalyzed biosynthesis and hydrolysis of carbohydrates in nature. Anthocyanins are natural flavylium dyes, which are stabilized oxocarbenium compounds. Anthocyanins are responsible for the colors of a wide variety of common flowers such as pansies and edible plants such as eggplant and blueberry.
Electron distribution and reactivity The best Lewis structure for an oxocarbenium ion contains an oxygen–carbon double bond, with the oxygen atom attached to an additional group and consequently taking on a formal positive charge. In the language of canonical structures (or "resonance"), the polarization of the π bond is described by a secondary carbocationic resonance form, with a formal positive charge on carbon (see above). In terms of frontier molecular orbital theory, the Lowest Unoccupied Molecular Orbital (LUMO) of the oxocarbenium ion is a π* orbital that has the large lobe on the carbon atom; the more electronegative oxygen contributes less to the LUMO. Consequently, in an event of a nucleophilic attack, the carbon is the electrophilic site. Compared to a ketone, the polarization of an oxocarbenium ion is accentuated: they more strongly resemble a "true" carbocation, and they are more reactive toward nucleophiles. In organic reactions, ketones are commonly activated by the coordination of a Lewis acid or Brønsted acid to the oxygen to generate an oxocarbenium ion as an intermediate. Numerically, a typical partial charge (derived from Hartree-Fock computations) for the carbonyl carbon of a ketone R2C=O (like acetone) is δ+ = 0.51. With the addition of an acidic hydrogen to the oxygen atom to produce [R2C=OH]+, the partial charge increases to δ+ = 0.61. In comparison, the nitrogen analogues of ketones and oxocarbenium ions, imines (R2C=NR) and iminium ions ([R2C=NRH]+), respectively, have partial charges of δ+ = 0.33 and δ+ = 0.54, respectively. The order of partial positive charge on the carbonyl carbon is therefore imine < ketone < iminium < oxocarbenium.
This is also the order of electrophilicity for species containing C=X (X = O, NR) bonds. This order is synthetically significant and explains, for example, why reductive aminations are often best carried out at pH = 5 to 6 using sodium cyanoborohydride (Na+[H3B(CN)]−) or sodium triacetoxyborohydride (Na+[HB(OAc)3]−) as a reagent. Bearing an electron-withdrawing group, sodium cyanoborohydride and sodium triacetoxyborohydride are poorer reducing agents than sodium borohydride, and their direct reaction with ketones is generally a slow and inefficient process. However, the iminium ion (but not the imine itself) formed in situ during a reductive amination reaction is a stronger electrophile than the ketone starting material and will react with the hydride source at a synthetically useful rate. Importantly, the reaction is conducted under mildly acidic conditions that protonate the imine intermediate to a significant extent, forming the iminium ion, while not being strongly acidic enough to protonate the ketone, which would form the even more electrophilic oxocarbenium ion. Thus, the reaction conditions and reagent ensure that amine is formed selectively from iminium reduction, instead of direct reduction of the carbonyl group (or its protonated form) to form an alcohol.
Formation Formation of oxocarbenium ions can proceed through several different pathways. Most commonly, the oxygen of a ketone will bind to a Lewis Acid, which activates the ketone, making it a more effective electrophile. The Lewis acid can be a wide range of molecules, from a simple hydrogen atom to metal complexes. The remainder of this article will focus on alkyl oxocarbenium ions, however, where the atom added to the oxygen is a carbon. One way that this sort of ion will form is the elimination of a leaving group. In carbohydrate chemistry, this leaving group is often an ether or ester. An alternative to elimination is direct deprotonation of the molecule to form the ion, however, this can be difficult and require strong bases to achieve.
Applications to synthesis
5-membered rings
The stereochemistry involved in the reactions of five-membered rings can be predicted by an envelope transition state model. Nucleophiles favor addition from the "inside" of the envelope, or from the top of the figure on the right. The "inside" addition produces a results in a staggered conformation, rather than the eclipsed conformation that results from the "outside" addition.
6-membered rings
… excerpt ends here. Continue reading the full article.
