Carbocations deprotonation

The quantitation of products that form in low yields requires special care with HPLC analyses. In cases where the product yield is <1%, it is generally not feasible to obtain sufficient material for a detailed physical characterization of the product. Therefore, the product identification is restricted to a comparison of the UV-vis spectrum and HPLC retention time with those for an authentic standard. However, if a minor reaction product forms with a UV spectrum and HPLC chromatographic properties similar to those for the putative substitution or elimination reaction, this may lead to errors in structural assignments. Our practice is to treat rate constant ratios determined from very low product yields as limits, until additional evidence can be obtained that our experimental value for this ratio provides a chemically reasonable description of the partitioning of the carbocation intermediate. For example, verification of the structure of an alkene that is proposed to form in low yields by deprotonation of the carbocation by solvent can be obtained from a detailed analysis of the increase in the yield of this product due to general base catalysis of carbocation deprotonation.14,16... 

The incorporation of the alkene product of carbocation deprotonation into an aromatic system results in the expected changes in the absolute rate constant kp and the product rate constant ratio kjkp for reaction of the carbocation. 

Acid protonates a double bond, and the electrons of a second double bond attack the carbocation. Deprotonation yields p-ionone. 

In accord with the high level of sequence similarity between d-selinene synthase and y-humulene synthase, all carbocation deprotonations result by abstraction from a hmited number of common carbon atoms (Scheme 12 and 13). It is Hkely that a single active site base can mediate deprotonations from spatially adjacent carbon atoms of these carbocationic intermediates. In the case of... 

Hastings CJ, Backlund MP, Bergman RG, Raymond KN (2011) Enzyme-like control of carbocation deprotonation regioselectivity in supramolecular catalysis of the nazarov cyclization. Angew Chem Int Ed 50(45) 10570-10573... 

Finding snch acids (called snperacids ) turned out to be the key to obtaining stable, long-lived alkyl cations and, in general, carbocations. If any deprotonation were still to take place, the formed alkyl cation (a strong Lewis acid) would immediately react with the formed olefin (a good TT-base), leading to the mentioned complex reactions. 

Write a structural formula for the carbocation intermediate formed in the dehydration of each of the alcohols in Problem 5 14 (Section 5 10) Using curved arrows show how each carbocation is deprotonated by water to give a mixture of alkenes... 

A mechanism for the formation of these three alkenes is shown m Figure 5 9 Dissociation of the primary alkyloxonmm ion is accompanied by a shift of hydride from C 2 to C 1 This avoids the formation of a primary carbocation leading instead to a sec ondary carbocation m which the positive charge is at C 2 Deprotonation of this carbo cation yields the observed products (Some 1 butene may also arise directly from the pri mary alkyloxonium ion)... 

Step (2) Ethanol acts as a base to remove a proton from the carbocation to give the alkene products (Deprotonation step)... 

Section 5 17 In the absence of a strong base alkyl halides eliminate by an El mech anism Rate determining ionization of the alkyl halide to a carbocation is followed by deprotonation of the carbocation... 

Geranyl pyrophosphate is an allylic pyrophosphate and like dimethylallyl pyrophosphate can act as an alkylating agent toward a molecule of isopentenyl pyrophosphate A 15 carbon carbocation is formed which on deprotonation gives/ar nesyl pyrophosphate... 

All these kinetic results can be accommodated by a general mechanism that incorporates the following fundamental components (1) complexation of the alkylating agent and the Lewis acid (2) electrophilic attack on the aromatic substrate to form the a-complex and (3) deprotonation. In many systems, there m be an ionization of the complex to yield a discrete carbocation. This step accounts for the fact that rearrangement of the alkyl group is frequently observed during Friedel-Crafts alkylation. 

The isomerization of isopentenyl diphosphate to dimethylally diphos phate is catalyzed by JPP isomerase and occurs through a carbocation pathway Protonation of the IPP double bond by a hydrogen-bonded cysteine residue ir the enzyme gives a tertiary carbocation intermediate, which is deprotonated b a glutamate residue as base to yield DMAPP. X-ray structural studies on the enzyme show that it holds the substrate in an unusually deep, well-protectec pocket to shield the highly reactive carbocation from reaction with solvent 01 other external substances. 

Cl—Al Cly) intermediate or a carbocation C AICI4 This intermediate electrophilically attacks the benzene ring to generate a benzenonium ion intermediate which gives alkylated benzene through deprotonation by aluminum tetrachloride anion. Finally the hydrogen aluminum tetrachloride complex affords aluminum chloride and hydrogen chloride gas. This aluminum chloride is recycled in the catalytic cycle of alkylation. 

In each mechanism above, the first step involves protonation of the alkene to form a carbocation. Then, in both cases, a nucleophile (either X or H2O) attacks the car-bocation to give a product. The difference between these two reactions is in the nature of the product. The first reaction above (hydrohalogenation) gives a product that is neutral (no charge). However, the second reaction above (hydration) produced a charged species. Therefore, one more step is necessary at the end of the hydration reaction— we must get rid of the positive charge. To do this, we simply deprotonate ... 

The mechanism of the reaction will have three steps (1) protonate the alkene to form a carbocation, (2) water attacks the carbocation, and (3) deprotonate to form the product ... 

Sulfonium ylides can also be generated by in situ alkylation with diazo compounds. The alkylation can be carried out by reaction of a diazo compound with HBF4 and DBU.281 The reagents are added alternately in small portions and the reaction presumably proceeds by trapping of the carbocation generated by dediazonization and deprotonation. 

As the intermediate formed in a polyene cyclization is a carbocation, the isolated product is often found to be a mixture of closely related compounds resulting from competing modes of reaction. The products result from capture of the carbocation by solvent or other nucleophile or by deprotonation to form an alkene. Polyene cyclizations can be carried out on reactants that have structural features that facilitate transformation of the carbocation to a stable product. Allylic silanes, for example, are stabilized by desilylation.12... 

An alkene can accept a proton to generate a carbocation in a process that is essentially the reverse of the deprotonation step in the El mechanism for dehydration of an alcohol. 

A different P-hydrogen can be removed from the carbocation, so as to form a more highly substituted alkene than the initial alkene. This deprotonation step is the same as the usual completion of an El elimination. (This carbocation could experience other fates, such as further rearrangement before elimination or substitution by an S l process.)... 

How Does Structure Determine Organic Reactivity Partitioning of Carbocations between Addition of Nucleophiles and Deprotonation... 

Table 1 Rate and equilibrium constants for partitioning of substituted a-methyl carbocations R (R2)CCH3+ between nucleophilic addition of solvent (ks) and deprotonation (kp) (Scheme 7)°... 

Kinetic studies of stepwise hydration reactions of aikenes. This work has shown that carbocations with labile jff-CH bond(s) that are stabilized by an a-amino group,35-37 or by two a-thiol groups38 0 undergo preferential deprotonation to form the products of an elimination reaction (kp > ks, Scheme 1). 

Fig. 1 Free energy reaction coordinate profiles for hydration and isomerization of the alkene [2] through the simple tertiary carbocation [1+], The rate constants for partitioning of [1 ] to form [l]-OSolv and [3] are limited by solvent reorganization (ks = kteorg) and proton transfer (kp), respectively. For simplicity, the solvent reorganization step is not shown for the conversion of [1+] to [3], but the barrier for this step is smaller than the chemical barrier to deprotonation of [1 ] (kTtOTg > kp).

It is often difficult to understand at an intuitive level the explanation for the effect of changing substituents on the rate constant ratio kjkp for partitioning of carbocations between nucleophilic addition of solvent and deprotonation. In these cases, insight into the origins of the changes in this rate constant ratio requires a systematic evaluation of substituent effects on the following ... 

Fig. 4 Free energy reaction coordinate profiles that illustrate a change in the relative kinetic barriers for partitioning of carbocations between nucleophilic addition of solvent and deprotonation resulting from a change in the curvature of the potential energy surface for the nucleophile addition reaction. This would correspond to an increase in the intrinsic barrier for the thermoneutral carbocation-nucleophile addition reaction.

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