Ionic reactions carbocations

The synthesis of C-glycosyl compounds, commonly known as C-glycosides, in ionic reactions relies on the electrophilicity of the anomeric center and, therefore, involves the attack of an appropriate C-nucleophile. An umpolung method has been developed, and is described in the previous chapter. But instead of going from a carbocation to a carbanion, one can also consider homolytic or radical reactions to reverse the philicity (Scheme 1). 

If Xs and the carbocation, R , stay in close proximity, as is likely to be the case in a solvent that does not promote ionic dissociation, then a more or less tight ion pair is formed, R Xs. Such ion pairs often play an important role in ionic reactions in solvents of low dielectric constant (Section 8-7F). 

Note that both mechanisms for the addition of HBr to an alkene (with and without peroxides) follow our extended statement of Markovnikov s rule In both cases, the electrophile adds to the less substituted end of the double bond to give the more stable intermediate, either a carbocation or a free radical. In the ionic reaction, the electrophile is H+. In the peroxide-catalyzed free-radical reaction, Br is the electrophile. 

Carbocations are electrophiles and carbanions are nucleophiles. Reactions of these intermediates involving, at some stage, the bonding of a nucleophile to an electrophile are sometimes called ionic reactions. 

Even more important is the fact that the formation of the triol carbocations (PAHTC) has not been correctly calculated. Any treatment based on a simple Hiickel-MO or PMO calculations for odd AH ions neglect the effect of the differently charged carbon atoms and hence, must be in error. The ionic charge distributed over the aromatic system affects the electronegativity of carbon atoms in specific ways and this has a profound effect on the 7i-energy. Breakdowns of both the PMO and HMO approximations with ionic reaction intermediates are documented in the work of Dewar and Thompson [36,70], Streitwieser et al [35,71] and Szentpaly [39]. The reactivity patterns with radical and ionic reaction intermediates of PAH are different [34-39]. It has been pointed out by Dewar [36] that the PMO method works better for radical than ions, and adequate modifications of the PMO method have been developed for ionic intermediates [16,38,39]. 

Chemical reactions have been presented in a very general sense, but the issue of why two molecules should react with each other has not been addressed. A reactive center is the atom in a molecule that reacts with another atom. Most of the reactions to be discussed not all) involve ionic reactions, where one or both reactants have a formal charge (positive or negative carbocations or carbanions) or are polarized (6- or 6+). If the simplifying assumption is made that most reactions occur when polarized bonds or ionic reactants are present, certain trends in chemical reactivity are apparent. 

As depicted in Scheme 10.2, the mechanism of the reaction presumably involves protonation of 1-hexene to afford the secondary carbocation 43. Attack of bromide ion on this ion then leads to 2-bromohexane (41). The carbocation may also rearrange by way of a hydride shift (Sec. 10.3) to provide a different secondary carbocation, 44, which would provide 3-bromohexane (45) upon reaction with bromide ion. Alternatively, it may deprotonate to form 2-hexene (46), addition of H-Br to which could afford both 41 and 45. In this experiment, you will determine the regiochem-istry of the addition of H-Br to the unsymmetrical alkene 1-hexene (40) and thereby assess whether this ionic reaction proceeds according to Markovnikov s rule. 

Under radical initiation conditions, typically peroxides, hypervalent iodine reagents can be homolytically cleaved to iodine-centered radicals. These iodine centered radicals abstract a hydrogen atom from a labile benzylic C—H bond to yield a resonance-stabilized benzylic radical. At this point in the mechanism, researchers seem divided on the next step. Some propose a second single electron transfer (SET) to form a benzylic carbocation, ° which undergoes ionic reactions to form product. Others suggest radical combination to form an alkyl halide or organic peroxide which reacts further under the reaction conditions to form product. 

When double bonds are reduced by lithium in ammonia or amines, the mechanism is similar to that of the Birch reduction (15-14). ° The reduction with trifluoro-acetic acid and EtsSiH has an ionic mechanism, with H coming in from the acid and H from the silane. In accord with this mechanism, the reaction can be applied only to those alkenes that when protonated can form a tertiary carbocation or one stabilized in some other way (e.g., by a OR substitution). It has been shown, by the detection of CIDNP, that reduction of a-methylstyrene by hydridopenta-carbonylmanganese(I) HMn(CO)5 involves free-radical addition. ... 

In both mechanisms, the regiochemistry is determined by a preference for forming the most stable intermediate possible. For example, in the ionic mechanism, adds to produce a tertiary carbocation, rather than a secondary carbocation. Similarly, in the radical mechanism, Br adds to produce a tertiary radical, rather than a secondary radical, hi this respect, the two reactions are very similar. But take special notice of the fundamental difference. In the ionic mechanism, the proton comes on first. However, in the radical mechanism, the bromine comes on first. This critical difference explains why an ionic mechanism gives a Markovnikov addition while a radical mechanism gives an anti-Markovnikov addition. 

In the course of the salt synthesis, it was found that a hydrocarbon [3-2], which was formed by an unfavourable cation-anion combination reaction, dissociates into the original carbocation and carbanion in a polar aprotic solvent (Okamoto et ai, 1985) (1). This was the first example of ionic dissociation of the carbon-carbon a bond in genuine hydrocarbons, although a few cases of heterolytic dissociation of carbon-carbon tr bonds had been reported by Arnett (Arnett et al., 1983 Troughton et al., 1984 Arnett and Molter, 1985) for compounds bearing cyano and nitro groups, e.g. [4-6] and [5-6] as in (2). 

Carbocation-carbanion zwitterionic intermediates were proposed for the thermal cleavage of several cyclic compounds. In most of these reactions the ionically dissociating bond belongs to one of four strained ring systems, i.e. cyclopropane (13), cyclobutane (14), cyclobutene (15) or norbornadiene (16). The mechanism is distinguished from the formation of a diradical intermediate through homolysis in terms of solvent and substituent effects... 

In view of the observations of the ionic dissociation of nitro-cyano compounds, it is hardly surprising that even a hydrocarbon could dissociate ionically into a stable carbocation and carbanion, provided that the medium is polar enough to prevent the recombination reaction and to ensure equilibration. 

As the cation becomes progressively more reluctant to be reduced than [53 ], covalent bond formation is observed instead of electron transfer. Further stabilization of the cation causes formation of an ionic bond, i.e. salt formation. Thus, the course of the reaction is controlled by the electron affinity of the carbocation. However, the change from single-electron transfer to salt formation is not straightforward. As has been discussed in previous sections, steric effects are another important factor in controlling the formation of hydrocarbon salts. The significant difference in the reduction potential at which a covalent bond is switched to an ionic one -around -0.8 V for tropylium ion series and —1.6 V in the case of l-aryl-2,3-dicyclopropylcyclopropenylium ion series - may be attributed to steric factors. 

As the understanding of the ionic intermediates has progressed, advantage has been taken of the fact that bromination, like SN1 heterolysis, is a carbocation-forming reaction. Kinetic data on this addition have therefore been used to examine in detail how the basic concepts of physical organic chemistry work as regards transition-state shifts with reactivity (Ruasse et al, 1984). Bromination lends itself particularly well to the quantitative application of the BEMA HAPOTHLE (acronym for Bell, Marcus, Hammond, Polanyi, Thornton and Leffler Jencks, 1985). In particular, it has been possible to evaluate the transition-state dependence on the solvent and substituents. The major disadvantage that bromination shares with many... 

Bromination can exhibit stereo-, regio- and chemo-selectivity when the reaction is carried out in the presence of nucleophiles (solvent or added salt). When the ionic intermediate is a bromonium ion, a stereospecific but non-regioselective reaction is expected. In contrast, for an open bromo-carbocation, the products should be formed regioselectively but not stereo-specifically. These considerations were understood very early since, in fact, Roberts and Kimball (1937) suggested bridged ions as bromination inter-... 

Now, just the same sort of rationalization can be applied to the radical addition, in that the more favourable secondary radical is predominantly produced. This, in turn, leads to addition of HBr in what is the anti-Markovnikov orientation. The apparent difference is because the electrophile in the ionic mechanism is a proton, and bromide then quenches the resultant cation. In the radical reaction, the attacking species is a bromine atom, and a hydrogen atom is then used to quench the radical. This is effectively a reverse sequence for the addition process but, nevertheless, the stability of the intermediate carbocation or radical is the defining feature. The terminologies Markovnikov or anti-Markovnikov orientation may be confusing and difficult to remember consider the mechanism and it all makes sense. 

In this first reaction, unless the process is occurring at very high temperatures, solvation of the ionic products is needed to provide the energy needed in the bondbreaking step. Because the carbocation has planar sp hybridization, the second reaction can occur on either face. This second step may just as well be written in either of the following ways ... 

Since the required activation energy for ionic polymerization is small, these reactions may occur at very low temperatures. The carbocations, including the macrocarbocations, repel one another hence, chain termination does not occur by combination but is usually the result of reaction with impurities. 

In organo-fluorine chemistry many reactions are known where more or less stable ionic or radical intermediates are formed, for example, carbocations, carbanions. and partially fluorinated and perfluorinated radicals and carbenes. While some of these species are short lived, others are surprisingly stable and isolable. In the latter case electronic and steric arrangements often kinetically stabilize the intermediate. 

Silver ion makes possible in the second reaction an isnmeri/ation-free hydrolysis of the S,0 acetal to ketone 32. Generation of the cnol triflate 33 is accomplished in the third step with the Hendrickson-Me M it rry reagent (Tf2NPh).10 Addition of an alcohol produces the potassium aikoxide, which because of its lower basicity permits isomerization to the thermodynamically favored enolate. Chemose-lective reaction to bromohydnn 9 is achieved in the last step with NBS as brominating agent in aqueous THF. NBS acts here as a source of cationic bromine in an ionic mechanism. The intermediate bromonium ion forms preferentially at a) electron-rich double bonds and h) the sterieally least hindered double bond. It also opens in such a way as to provide the most stable carbocation. 

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