Fragmentation reactions carbocations

In this section, the emphasis is on carbocation reactions that modify the carbon skeleton, including carbon-carbon bond formation, rearrangements, and fragmentation reactions. The fundamental structural and reactivity characteristics of carbocations toward nucleophilic substitution were explored in Chapter 4 of Part A. 

A fragmentation reaction occurs if one of the oxime substituents can give rise to a relatively stable carbocation. Fragmentation is very likely to occur if a nitrogen, oxygen, or sulfur atom is present a to the oximino group. 

The combination of an amine and an aldehyde under weakly acidic conditions almost always gives an iminium ion very rapidly. Such a reaction forms the N1-C8 bond. Nucleophilic C7 can then attack this iminium ion to give a carbocation. Fragmentation of the C5-Si6 bond gives the product. 

After discussing the dehydration of methanol and formation of DME, we are able to illustrate a number of key theoretical concepts. The first is that carbocation fragments are found in transition states, rather than as stable intermediates. Furthermore, the nature of these species is different from what is predicted from gas-phase studies, experimental or theoretical. The cluster, i.e., the zeolite, controls the stabilization of this carbocationic fragment. Second, we see that each different reaction requires a different transition state, rather than formation of a transition state that can be converted in a number of possible reactions. (This latter view received some support as a result of different processes possessing very similar activation barriers.)... 

Ring-protonated alkylcyclopropanes, well-known in solution , were suggested to explain the most unusual behaviour of heptyl ions. Extensive C- and D-labelling as well as a computer simulation and the analysis of CA data indicate that the major fragmentation reactions of CvHj s ions, generated via loss of I from 1-heptyl iodide, are preceded by extensive skeletal reorganization which via cyclopropane-like structures (140, 142, 144) eventually isomerize to tertiary carbocations (145 and 146, Scheme 23 where only the carbon skeleton is shown). The latter serve as actual precursors for the loss of CsH. ... 

The diketone first tautomerizes to the keto-enol. Protonation of the ketone gives a very stable carbocation, to which EtOH adds. Deprotonation of the nucleophile, protonation of the OH leaving group, and loss of H20 gives a new carbocation, which undergoes a fragmentation reaction with loss of H+ to give the enol ether product. 

Unlike radical addition and fragmentation reactions, atom abstraction has no common counterpart in carbocation chemistry. 

There are three potential options for the mechanism of Grob fragmentation reactions, one concerted and two stepwise. The stepwise reactions, which result from initial loss of either the nucleofuge or electrofuge, are less useful in synthesis since they often promote side reactions. However, one highly efficient stepwise transformation was reported by Kato. Treatment of diol 6 with pyridinium chloride results in formation of benzyl carbocation 8. Cleavage of this alcohol yields monocycle 9 and, ultimately, the ketone product 10. ... 

Reactions of aryl aldehydes with styrenes presumably proceed through coordination of the carbonyl group to the boron trihalide followed by addition of the carbonyl carbon to the alkene to form a carbocation, which then adds halide to generate the final product (Scheme 23.18). A statistical distribution of the diastereoisomers (syn/anti 50 50) indicates that the reaction involves a cation intermediate. A similar intermediate has been observed in the AlClj-catalyzed ene reactions of aldehydes with aliphatic alkenes and in the fragmentation reaction of P-aryl-P-hydeoxyketones by boron trifluoride . Another piece of supporting evidence for this mechanism is the isolation of anti-3-halo-l,3-diarylpropanols when the reactions are quenched with water prior to completion. 

In this section, we will discuss reactions which involve carbocation intermediates. These include carbon-carbon bond-forming reactions and also rearrangements and fragmentation reactions. The discussion will also include processes which are closely related in reactivity pattern but which avoid free carbocation intermediates. 

Kolbe electrolysis is a powerful method of generating radicals for synthetic applications. These radicals can combine to symmetrical dimers (chap 4), to unsymmetrical coupling products (chap 5), or can be added to double bonds (chap 6) (Eq. 1, path a). The reaction is performed in the laboratory and in the technical scale. Depending on the reaction conditions (electrode material, pH of the electrolyte, current density, additives) and structural parameters of the carboxylates, the intermediate radical can be further oxidized to a carbocation (Eq. 1, path b). The cation can rearrange, undergo fragmentation and subsequently solvolyse or eliminate to products. This path is frequently called non-Kolbe electrolysis. In this way radical and carbenium-ion derived products can be obtained from a wide variety of carboxylic acids. 

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-... 

The mechanism of these reactions is often El. However, in at least some cases, an E2 mechanism operates.It has been shown that stereoisomers of cyclic y-amino halides and tosylates in which the two leaving groups can assume an anti-periplanar conformation react by the E2 mechanism, while those isomers in which the groups cannot assume such a conformation either fragment by the El mechanism or do not undergo fragmentation at all, but in either case give rise to side products characteristic of carbocations. " ... 

The reaction that normally occurs on treatment of a ketoxime with a Lewis or proton acid is the Beckmann rearrangement (18-17) fragmentations are considered side reactions, often called abnormal or second-order Beckmann rearrangements. Obviously, the substrates mentioned are much more susceptible to fragmentation than are ordinary ketoximes, since in each case an unshared pair is available to assist in removal of the group cleaving from the carbon. However, fragmentation is a side reaction even with ordinary ketoximes and, in cases where a particularly stable carbocation can be cleaved, may be the main reaction. ... 

The focus of the next four chapters (Chapters 14-17) is mainly on the theoretical/computational aspects. Chapter 14 by T. S. Sorensen and E. C. F. Yang examines the involvement of p-hydrido cation intermediates in the context of the industrially important heptane to toluene dehydrocyclization process. Chapter 15 by P. M. Esteves et al. is devoted to theoretical studies of carbonium ions. Chapter 16 by G. L. Borosky and K. K. Laali presents a computational study on aza-PAH carbocations as models for the oxidized metabolites of Aza-PAHs. Chapter 17 by S. C. Ammal and H. Yamataka examines the borderline Beckmann rearrangement-fragmentation mechanism and explores the influence of carbocation stability on the reaction mechanism. 

Note This reaction involves a polar acidic mechanism, not a free-radical mechanism It is a Friedel-Crafts alkylation, with the slight variation that the requisite carbocation is made by protonation of an alkene instead of ionization of an alkyl halide. Protonation of C4 gives a C3 carbocation. Addition to Cl and fragmentation gives the product. 

By analogy with their behavior in mass spectrometry, branched hydrocarbons are cleaved when oxidized in CH3 CN/TEABF4 at —45 °C. The resulting acetamides of the fragments (Table 6) are formed by cleavage of the initial radical cation at the C,C bond between the secondary and tertiary C atom, to afford after a second electron transfer, carbocations, which react in a Ritter reaction with acetonitrile [29]. 

Oxidative S—C bond cleavage, followed by the attack of a nucleophile on the carbocation formed, is a classical anodic substitution reaction. In this way, OH [60], AcNH [61], AcCH2 [62], and CH2=CHCH2 [63] groups were introduced to replace the RS fragment. 

---