Carbocations carbocationic rearrangement

The Friedel-Crafts acylation of alkanes requires hydride abstraction, which can be induced by the acylium ion itself, to form the corresponding carbocation. This may undergo carbocationic rearrangements prior to a proton loss to form an alkene, which then reacts with the acylating agent. Similar to the acylation of alkenes, the product is an unsaturated ketone. The reaction is limited to alkanes that are prone to undergo hydride transfer. 

Stereospecific 2,3-epoxidation of squalene, followed by a nonconcerted carbocationic cyclization and a series of carbocationic rearrangements, forms lanosterol [79-65-0] (77) in the first steps dedicated solely toward steroid synthesis (109,110). Several biomimetic, cationic cydizations to form steroids or steroidlike nuclei have been observed in the laboratory (111), and the total synthesis of lanosterol has been accomplished by a carbocation—olefin cydization route (112). Through a complex series of enzyme-catalyzed reactions, lanosterol is converted to cholesterol (2). Cholesterol is the principal starting material for steroid hormone biosynthesis in animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to be normal constituents, in trace amounts, in tissues that are actively synthesizing cholesterol. 

The major mechanisms for carbocationic rearrangements are 1,2-hydride shifts and 1,2-alkyl shifts. Both of these occur in the rearrangement of the cyclo-hexylium ion (a 2° carbocation) to the 1-methylcyclopentylium ion (a 3° carbocation). A 1,2-alkyl shift of the C3-C2 bond of cyclohexylium from C2 to Cl gives a cyclopentylmethylium ion (a 1° carbocation). This reaction is uphill in energy. However, a 1,2-hydride shift of the Cl-H bond from Cl to C2 gives a much more stable product. 

Carbocationic rearrangements usually occur to equal or more stable carbocations. Carbocation rearrangements are favored by acidic media and poor nucleophiles, so that carbocation has time to rearrange. A rearrangement spectrum exists similar to the Sm2/Sn1 spectrum. Certain systems are more prone to rearrangement... 

The first step in the oxymercuration reaction is the formation of a cyclic mer-curinium ion (Fig. 10.22). Open carbocations are unlikely intermediates, as they would surely undergo carbocationic rearrangements, and these are not seen even in systems normally prone to rearrangement. 

The reason for this is simple. Since we are forming a complex with carbocationic character, it is possible for a carbocation rearrangement to occur. It is not possible for a methyl carbocation to rearrange. Similarly, an ethyl carbocation cannot rearrange to become any more stable. But a propyl carbocation CAN rearrange (via a hydride shift) ... 

Carbocations derived from the alcohol are probably the reactive species, but data concerning by-products expected with carbocationic intermediates are lacking. Rearrangement of 2-alkylaminothiazoles to 2-amino-5-alkylthiazoles may also explain the observed products 2-aminothiazole with benzyl chloride yields first 2-benz Iaminothiazole (206). which then rearranges to 2-amino-5-benzvlthiazole (207) (Scheme 130) (163. 165. 198). 

Thus in the above case the elimination product is found to contain 82 % of (7). Unexpected alkenes may arise, however, from rearrangement of the initial carbocationic intermediate before loss of proton. El elimination reactions have been shown as involving a dissociated carbocation they may in fact often involve ion pairs, of varying degrees of intimacy depending on the nature of the solvent (cf. SN1, p. 90). 

Catalytic reforming92-94 of naphthas occurs by way of carbocationic processes that permit skeletal rearrangement of alkanes and cycloalkanes, a conversion not possible in thermal reforming, which takes place via free radicals. Furthermore, dehydrocyclization of alkanes to aromatic hydrocarbons, the most important transformation in catalytic reforming, also involves carbocations and does not occur thermally. In addition to octane enhancement, catalytic reforming is an important source of aromatics (see BTX processing in Section 2.5.2) and hydrogen. It can also yield isobutane to be used in alkylation. 

The addition of HX to double bonds in the dark and in the absence of free-radical initiators is closely related to hydration The orientation of the elements of HX in the adduct always rnrrrsponds to Markownikoff addition 16 no deuterium exchange wish solvent is found in unreacted olefins recovered after partial reaction, nor is recovered starting material isomerized after partial reaction.17 However. the addition of HX apparently can proceed by a number of different mechanisms depending on the nature Ol the substrate and on the reaction conditions. Thus when HC1 is added to f-butylethylene in acetic acid, the rate is first-order in each reactant and the products are those shown in Equation 7.5.le Since 4 and 6 were demonstrated to be stable to the reaction conditions, the rearranged product (5) can be formed only if a carbocationic intermediate is formed during reaction. However, the carbocation exists almost solely in an intimate ion pair, and the rate of collapse of the ion pair to products must be faster than, or comparable to, the rate of diffusion of Cl- away from the carbocation. This must be so because the ratio of chloride to acetate products is unaffected by... 

The addition of HN3 to alkenes in the presence of Lewis acids also involves carbocationic intermediates. This is nicely illustrated by the boron trifluoride-catalyzed addition of HN3 to a- or (J-pinene in which carbocation rearrangements are observed (equation 182).263... 

Reaction of (284) with an aldehyde, ketone, or enol ether in the presence of acid results in an electrophilic substitution that produces a -ferrocenylalkyl carbocations that may be trapped by nucleophiles (azides, amines, thiols). This chemistry may be used to prepare enantiomerically pure ferrocene derivatives in a maimer that avoids resolution procedures (Scheme 86)." For example, the enol ether from (-)-menthone affords a kinetic carbocation (302) that may be trapped or allowed to rearrange to the more thermodynamically stable cation (303) and then trapped, thus offering a means of controlling the configuration of the stereocenter adjacent to the ferrocene unit. Use of an enantiomerically pure aldehyde derived from Q -pinene (304) affords a 1 1 carbocationic mixture that similarly isomerizes to a single cation. 

Organozirconates. Zwitterionic zirconocene-ate see Ate Complexes) intermediates have been evoked to explain some reaction mechanisms (see Section 2.3.3). In fact, electron transfer from an organic ligand to 16-electron metal center permits the generation of a carbocationic center which can, then, undergoes isomerization and rearrangement characteristic of carbocations. It is now possible to isolate and characterize stable zwitterionic phosphonium zirconate complexes (eqnation 18). ... 

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

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