Carbocations selectivity

Alkyl halides and sulfonates are the most frequently used alkylating acceptor synthons. The carbonyl group is used as the classical a -synthon. O-Silylated hemithioacetals (T.H. Chan, 1976) and fomic acid orthoesters are examples for less common a -synthons. In most synthetic reactions carbon atoms with a partial positive charge (= positively polarized carbon) are involved. More reactive, "free carbocations as occurring in Friedel-Crafts type alkylations and acylations are of comparably limited synthetic value, because they tend to react non-selectively. 

Carbocations generated from alkanes using superacids react with carbon monoxide under mild conditions to form carboxyUc acid (188). In this process isomeric carboxyUc acids are produced as a mixture. However, when the reaction is mn with catalytic amounts of bromine (0.3 mmol eq) in HF-SbF solution, regio-selective carboxylation is obtained. / -Propane was converted almost exclusively to isobutyric acid under these conditions. 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

Toluene/benzene selectivity decreases in the order X = CH3 > H Cl > NO2, in agreement with the expectation that the least stable (and most reactive) carbocation would be least selective. The reactions also show low position selectivity. 

Assuming selective formation of the most stable carbocation, which product(s) would be obtained from HCl addition to isoprene Would this outcome be different from the one predicted on the basis of thermodynamic control ... 

Protonation and subsequent loss of water should generate a earbocation. Examine all of the carbocations derived from protonation of (3-D-glueose. Identify the most stable carboeation (this is the one that will form most readily), and draw whatever resonance eontributors are needed to describe the geometry, energy, and atomie charges in this cation. Can you explain why substitution oeeurs selectively at Ci ... 

In the case of NH2OH with a sharp difference in the nucleophilicity of the two functions, the primary amino group reacts with the carbocation C-1 center. For example, the reaction of l-alkylaminoalk-l-en-3-ynes with hydroxylamine leads to selective synthesis of alkylisoxazoles (69ZOR1179). A preparative value of this method is evident because the use of dicarbonyl compounds as starting materials for the synthesis of alkylisoxazoles results in a mixture of isomers. 

Fig. 6. Comparison of relative experimental heats of formation with those calculated by means of MINDO/3 AAH°, w and AAH calc (kJ mol-1) for some selected carbocations...

Non-Kolbe electrolysis of carboxylic acids can be directed towards a selective fragmentation, when the initially formed carbocation is better stabilized in the y-position by a hydroxy or trimethylsilyl group. In this way the reaction can be used for a three-carbon (Eq. 36) [335] (Table 14, No. 1) or four-carbon ring extension (Eq. 37) [27] (Table 14, Nos. 2-4). Furthermore it can be employed for the stereo-... 

Most of these results have been obtained in methanol but some of them can be extrapolated to other solvents, if the following solvent effects are considered. Bromine bridging has been shown to be hardly solvent-dependent.2 Therefore, the selectivities related to this feature of bromination intermediates do not significantly depend on the solvent. When the intermediates are carbocations, the stereoselectivity can vary (ref. 23) widely with the solvent (ref. 24), insofar as the conformational equilibrium of these cations is solvent-dependent. Nevertheless, this equilibration can be locked in a nucleophilic solvent when it nucleophilically assists the formation of the intermediate. Therefore, as exemplified in methylstyrene bromination, a carbocation can react 100 % stereoselectivity. 

Sufficient stability of the hydrocarbon ions, as the salt or in the solution, is an obvious prerequisite for these procedures, and, in practice, selecting or designing the stable ions and choosing a proper solvent are tasks of primary importance. As an ordinary stability index for the ions, thermodynamic scales referred to the water molecule, i.e. p CR+ and pKa values, are chosen for the carbocation and carbanion, respectively. 

Figure 1. Isomerization selectivity on Pt/WOx-Zr02 (0.3% wt. Pt, 12.7% wt. W, H-atoms formed from H2 or adamantane on Pt, 073 calcination) and Pt/SOx-ZrOj sites are involved in carbocation hydrogen (0.4% wt. Pt, 4.5% wt. S, 723 K...

Carbocation intermediates are involved and the structure and stereochemistry of the product are determined by the factors that govern substituent migration in the carbocation. Clean, high-yield reactions can be expected only where structural or conformational factors promote a selective rearrangement. Boron trifluoride is frequently used... 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

In this chapter we review published results of studies of the kinetics and products of stepwise nucleophilic substitution and elimination reactions of alkyl derivatives, and we present a small amount of unpublished data from our laboratory. Our review of the literature is selective rather than comprehensive, and focuses on work that provides interesting insight into the factors that control the rate constant ratio ks/kp for partitioning of carbocations, and that provides an understanding of how the absolute rate constants ks and kp that constitute this ratio change with changing carbocation structure. 

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