Carbocations ether formation

As mentioned in Section 8.1, carbenes easily undergo insertion into O-H bonds. At an early date, Kerr et al. (1967) found that in the photolysis of diazomethane- er butanol mixtures insertion is eleven times faster at O - H than at C - H bonds. The relative rates of ether formation for methanol, ethanol, 2-propanol, and tert-butanol are 2.01 1.95 1.37 1.00. Before that investigation, Kirmse (1963) postulated that diphenylcarbene is protonated to form the diphenylmethyl carbocation, which, as a strong electrophile, adds to the alcoholate anion (or to the alcohol followed by deprotonation) forming the ether (8-26 a). Bethell et al. (1969, 1971), however, favored an electrophilic attack of diphenylcarbene at the O-atom, i. e., an ylide intermediate on the basis of isotope effects (8-26 b). Finally, a concerted process via the transition state 8.39 may be feasible (8-26 c). 

A potentially important side reaction that might occur is dissociation of the dia-zonium salt 23 to a carbocation and molecular nitrogen. The carbocation could then react with ethanol to give an aryl ethyl ether as a by-product (Eq. 21.19). Fortunately, ether formation is a minor process in the present reaction, and any ether that is produced is removed by recrystallization of the product. 

What happens next depends on the solvent in which the reaction is performed, if the reaction takes place in ether, HCl is not dissociated, so there is no free chloride ion to act as a nucleophile. We are dependent on a much slower process, the collapse of the chlorosulfite ester to give a carbocation, and the chlorosulfite anion, which rapidly collapses to SO2 transferring chloride to the nearest face of the carbocation (the formation of this molecule of gas, with its associated entropy, is the driving force for this whole process). Overall, the process gives an unusual retention of stereochemistry— the cation has no opportunity to rotate before it is attacked (Figure 9.37). This is the SNj mechanism. 

The key initiation step in cationic polymerization of alkenes is the formation of a carbocationic intermediate, which can then interact with excess monomer to start propagation. We studied in some detail the initiation of cationic polymerization under superacidic, stable ion conditions. Carbocations also play a key role, as I found not only in the acid-catalyzed polymerization of alkenes but also in the polycondensation of arenes as well as in the ring opening polymerization of cyclic ethers, sulfides, and nitrogen compounds. Superacidic oxidative condensation of alkanes can even be achieved, including that of methane, as can the co-condensation of alkanes and alkenes. 

Scheme 10. Mechanislic possibililies for PF condensalion. Mechanism a involves an SN2-like attack of a phenolic ring on a methylol. This attack would be face-on. Such a mechanism is necessarily second-order. Mechanism b involves formation of a quinone methide intermediate and should be Hrst-order. The quinone methide should react with any nucleophile and should show ethers through both the phenolic and hydroxymethyl oxygens. Reaction c would not be likely in an alkaline solution and is probably illustrative of the mechanism for novolac condensation. The slow step should be formation of the benzyl carbocation. Therefore, this should be a first-order reaction also. Though carbocation formation responds to proton concentration, the effects of acidity will not usually be seen in the reaction kinetics in a given experiment because proton concentration will not vary.

The use of trichloroimidates for the preparation of ethers is an effective method for O-alkylation of alcohols [27]. This method has found widespread use in the protection of alcohols as benzyl ethers since the corresponding trichlorobenzylimi-date is inexpensive and commercially available. The mechanism involves activation of the imidate with a catalytic amount of a strong acid (typically TfOH) which leads to ionization of the electrophile and the formation of carbocation which is rapidly trapped by an alcohol. For the preparation of sec-sec ethers, this protocol has been limited to glycosidation reactions, due to the SN1 nature of the reaction which often leads to diastereomeric mixtures of products [26],... 

Another attractive domino approach starts with an aldol reaction of preformed enol ethers and carbonyl compounds as the first step. Rychnovsky and coworkers have found that unsaturated enol ethers such as 2-237 react with different aldehydes 2-238 in the presence of TiBr4. The process consists of an aldol and a Prins-type reaction to give 4-bromotetrahydropyrans 2-239 in good yields, and allows the formation of two new C-C-bonds, one ring and three new stereogenic centers (Scheme 2.56) [131]. In the reaction, only two diastereomers out of eight possible isomers were formed whereby the intermediate carbocation is quenched with a bromide. 

Examples of the behavior of other substituted vinyl substrates upon exposure to the action of trifluoroacetic acid and triethylsilane are known. For example, -butyl vinyl ether, when reacted at 50° for 10 hours, gives -butyl ethyl ether in 80% yield (Eq. 65).234 In contrast, -butyl vinyl thioether gives only a 5% yield of n-butyl ethyl sulfide product after 2 hours and 15% after 20 horns of reaction.234 It is suggested that this low reactvity is the result of the formation of a very stable sulfur-bridged carbocation intermediate that resists attack by the organosilicon hydride (Eq. 66). 

Alkenes are scavengers that are able to differentiate between carbenes (cycloaddition) and carbocations (electrophilic addition). The reactions of phenyl-carbene (117) with equimolar mixtures of methanol and alkenes afforded phenylcyclopropanes (120) and benzyl methyl ether (121) as the major products (Scheme 24).51 Electrophilic addition of the benzyl cation (118) to alkenes, leading to 122 and 123 by way of 119, was a minor route (ca. 6%). Isobutene and enol ethers gave similar results. The overall contribution of 118 must be more than 6% as (part of) the ether 121 also originates from 118. Alcohols and enol ethers react with diarylcarbenium ions at about the same rates (ca. 109 M-1 s-1), somewhat faster than alkenes (ca. 108 M-1 s-1).52 By extrapolation, diffusion-controlled rates and indiscriminate reactions are expected for the free (solvated) benzyl cation (118). In support of this notion, the product distributions in Scheme 24 only respond slightly to the nature of the n bond (alkene vs. enol ether). The formation of free benzyl cations from phenylcarbene and methanol is thus estimated to be in the range of 10-15%. However, the major route to the benzyl ether 121, whether by ion-pair collapse or by way of an ylide, cannot be identified. 

Allenylsilanes react with acetals to afford homopropargylic ethers (Table 9.37) [61]. These reactions are promoted by silyl and carbocation species. A variation of this conversion involves in situ formation of the acetal from an aldehyde and Me3SiOMe (Eq. 9.55). The success of this method indicates that conversion of the aldehyde to the acetal and its subsequent reaction with the silane must be faster than direct reaction of the aldehyde with the silane. 

Electrochemical fluorination in anhydrous hydrogen fluoride (Simons process) involves electrolysis of organic compounds (ahphatic hydrocarbons, haloalkanes, acid halides, esters, ethers, amines) at nickel electrodes. It leads mostly to perfluori-nated compounds, but is accompanied to a high extent by cleavage and rearrangement reactions. The mechanism of the formation of carbocations according to Eq. (1) and Scheme 1 is assumed... 

Diels-alder adducts at 0°C. This cation radical-vinylcyclobutane rearrangement is non-stereospecific, thus accounting for the formation of a cis-trans mixture of Diels-Alder adducts. Kinetic studies revealed (Scheme 8) that the ionization of these ethers involves an inner-sphere electron-transfer mechanism involving strong covalent (electrophilic) attachment to the substrate via oxygen (oxonium ion) or carbon (carbocation). 

A new mechanism, called the methane-formaldehyde mechanism, has been put forward for the transformation of the equilibrium mixture of methanol and dimethyl ether, that is, for the formation of the first C-C bond.643 This, actually, is a modification of the carbocation mechanism that suggested the formation of ethanol by methanol attaching to the incipient carbocation CH3+ from surface methoxy.460,462 This mechanism (Scheme 3.3) is consistent with experimental observations and indicates that methane is not a byproduct and ethanol is the initial product in the first C-C bond formation. Trimethyloxonium ion, proposed to be an intermediate in the formation of ethyl methyl ether,447 was proposed to be excluded as an intermediate for the C-C bond formation.641 The suggested role of impurities in methanol as the reason for ethylene formation is highly speculative and unsubstantiated. 

Those olefins having double bonds sufficiently electron rich to react significantly with these salts include the common monomers, alkyl vinyl ethers (28,79-81), N-vinylcarbazole (82-84) p-methoxystyrene (21,67), indene (34,74,85), cyclopen tadiene (85,86), and vinylnaphthalenes (87). Styrene itself (60,76,77,88-91), cr-divinylbenzene (92), a-methylstyrene (88), linear conjugated dienes (93) and a-olefins are much less reactive (i.e. formation of their corresponding carbocations is energetically unfavourable), and undo- normal conditions give at best slow reactions and low yields of polymer. 

The formation of ether has not been proved in this case, but the authors have proposed a decomposition mechanism including the heterolytic cleavage of an O-R bond and a subsequent attack of the carbocation formed on the oxygen atom of the neighboring OR-group [205]. 

These methods are not always applicable or convenient. A more general method used by Richard and Jencks utilizes HPLC analysis of carbocation formation in alcohol-water mixtures.22 As shown in Scheme 2 for an a-aryl ethyl cation, formation of the ether product from reaction of the carbocation with the alcohol depends on the rate constant for carbocation formation kll and the partition ratio between product formation and the back reaction to form the alcohol kROiiAii2o- This ratio may be determined from the ratio of products formed from reaction of the carbocation generated from a suitable solvolytic precursor such as an alkyl halide. 

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