Active carboxonium

We have found several examples in which adjacent cationic charge centers are shown to activate carboxonium electrophiles. A convenient method for studying this activation is through the use of the hydroxyalkylation reaction, a commercially important, acid-catalyzed condensation of aldehydes and ketones with arenes.10 It is used for example in the synthesis of bis-phenol A from acetone and phenol (eq 6). While protonated acetone is able to react with activated arenes like phenol, it is not capable of reacting with less nucleophilic... 

In the polymerisation of compounds which polymerise through the carbonyl group, the active species is believed to be a carboxonium ion IX ... 

The linear acetals units of polymer segments can also stabilise the open chain carboxonium ion 18 (thereby accelerating its formation), and the species formed (i.e. 19) can be regarded as the effective active centre, able only to propagate and unable to participate in hydride ion transfer. For steric reasons 1,3-dioxolane cannot itself stabilise carboxonium ions in this way. 

Two types of interactions have been shown to be involved in superelectrophilic species. Superelectrophiles can be formed by the further interaction of a conventional cationic electrophile with Brpnsted or Lewis acids (eq 16).23 Such is the case with the further protonation (protosolvation) or Lewis acid coordination of suitable substitutents at the electron deficient site, as for example in carboxonium cations. The other involves further protonation or complexation formation of a second proximal onium ion site, which results in superelectrophilic activation (eq 17).24... 

As discussed in Chapter 1, Brouwer and Kiffen reported the observation that HF-BF3 promoted hydride transfer from isoalkanes to acyl cations. These results were later shown by Olah and co-workers to be due to superelectrophilic activation of the acyl cation (24, eq 13).37 Diproto-nated acetone and aldehydes were also shown to abstract hydride from isoalkanes in HF-BF3 solutions.38 Carboxonium ions (25) are generally... 

In contrast, the 1,1-diphenyl ethyl cation (92) is unreactive to benzene. This indicates that the carboxonium group (or the corresponding acyl ion) participates in the superelectrophilic activation of the adjacent carboca-tionic center. 

As mentioned, 2-oxazolines may form a ring-opened distonic superelectrophile in reactions in superacid. These carboxonium-carbenium dications are capable of reacting with benzene and moderately deactivated substrates.2 For example, the optically active oxazoline (94) reacts in CF3SO3H to generate the chiral dication (95) and this superelectrophilic species is capable of reacting with o -dichlorobenzene in fair to modest yield and diastereoselectivity (eq 35). 

The observed electrophilic reactivity is indicative of superelectrophilic activation in the dication 173. Other ammonium-carboxonium dications have also been reported in the literature, some of which have been shown to react with benzene or other weak nucleophiles (Table 4).1 42b 57-60 Besides ammonium-carboxonium dications (175-179), a variety of N-heteroaromatic systems (180-185) have been reported. Several of the dicationic species have been directly observed by low-temperature NMR, including 176, 178-180, 183, and 185. Both acidic (175, 180-185) and non-acidic carboxonium (176-177) dicationic systems have been shown to possess superelectrophilic reactivity. The quinonemethide-type dication (178) arises from the important biomolecule adrenaline upon reaction in superacid (entry 4). The failure of dication 178 to react with aromatic compounds (like benzene) suggests only a modest amount of superelectrophilic activation. An interesting study was done with aminobutyric acid... 

The activating effects of ammonium groups on carboxonium electrophiles has also been exploited in the Friedel-Crafts acylations with amides.50 For example, in comparing the superacid-catalyzed reactions of acetanilide, the monoprotonated species (198) is found to be unreac-tive towards benzene (eq 67), while the diprotonated, superelectrophilic species (199) reacts with benzene to give the acyl transfer product in reasonably good yield (eq 68). 

The upper half of Figure 9.9 demonstrates that acetone can also be transformed into acetone cyanohydrin (A) by the combined treatment with sodium cyanide and ammonium chloride. Ammonium chloride is a weak acid. Consequently, the protonation of the (nonvolatile) sodium cyanide to the (volatile) hydrocyanic acid occurs to a lesser extent than with the NaCN/H2S04 method (see above). However, ammonium chloride is not acidic enough to activate acetone as the carboxonium ion to the same extent as sulfuric acid. This changes the addition mechanism. As shown in Figure 9.9, it is the cyanide anions that react with the unactivated acetone. Only when the cyanohydrin anions have thus been formed does the ammonium chloride protonate them to yield the neutral cyanohydrin. 

The mechanistic analysis shows that the oligomerization or polymerization of aldehydes can be considered as an addition reaction of a heteroatom nucleophile to the C=0 double bond of the (activated) aldehyde (Figure 7.14). The carbonyl oxygen of the (unprotonated) aldehyde functions as the nucleophilic center. The carboxonium ion A formed in an equilibrium reaction between the aldehyde and the acidic catalyst acts as the first electrophile. 

Recently, a new effective method for electrophilic activation of carbonyl compounds was proposed in order to enable the latter to react with weak nucleophiles such as nitriles102. This method involves the conversion of aldehydes and ketones into highly active acyloxycarbenium ions 163. This new type of carboxonium ions is related to the hydroxycarbenium and alkoxycarbenium ions 105, whose high stability is well known76. 

Carbonyl compounds can react with nitriles by two alternative paths (a) by an initial electrophilic activation of the carbonyl component 283 followed by reaction of the formed carboxonium ion electrophile 284 with nitrile 286 as a covalent nucleophile, and (b) by an initial electrophilic activation of the nitrile component 286 to give the cationoid electrophile 287, which then attacks the carbonyl group of 28349 forming 288 in a reaction which resembles the O-acylation by acylium ions (equation 77). 

The reaction differs from the Ritter reaction by the two types of electrophilic activation of the reagents and by the two types of rearrangement of nitrilium 285 and carboxonium ions 288 (equation 94). Besides, this interaction proceeds at an oxidation level of two, while the Ritter reaction occurs at an oxidation level of one17. While it may be shown that A-acyliminium ions 365 can be obtained from a carbonyl compound and a nitrile via the Ritter reaction, then it is only the second step b) in a three-step process where the first step (a) is the reduction of carbonyl compound 364 to alcohol 366 and the third step (c) is an oxidative dehydrogenation of amide 369 obtained3 (equation 105). 

Even with reactions of a non-radical active centre, the generated polymer is not always inert. Carbanions react with —C=N and —COOR sub-stitutents, carboxonium ions produce less acid centres by reaction with an ether-type chain (see Chap. 4, Sect. 2.3), carbocations alkylate aromatic groups, etc. All these reactions affect propagation. Sometimes the physical effect of the generated insoluble polymer is combined with its ability to react chemically in a certain way. 

The other consequence of the presence of —O—CH2—O— group in the molecule is the possibility of unimolecular opening of tertiary oxonium ion active species to form corresponding carboxonium ion. 

The rate constants of the reaction modeling the propagation on carboxonium and oxonium active species were found equal (at the conditions given above) to ... 

Thus, the contribution of carboxonium active species to propagation is small, but not negligible. 

Both oxonium and carboxonium active species are relatively strong electrophiles (stronger than in the case of tetrahydrofuran). Thus, to avoid the termination by interaction with counterion, the stable counterions of low nucleophilicity are required. It has been shown that only the most stable complex anions SbF6 and AsF6 provide the living active species, whereas BF4, SbCl6, and even PF6 anions cause termination [98],... 

Taking advantage of the fast transacetalization (scrambling) accompanying the cationic polymerization of 1,3-dioxolane, the telechelic polymers containing two allyl ether groups were obtained in the polymerization carried out in the presence of bis(allyloxy)methane (the carboxonium active species showed in the scheme for simplicity) ... 

Silver(I) compounds are often used as promoters for substitution reactions of aliphatic halides with carbon nucleophiles. A cyclic (8-bromo ether 29 can be reacted with allyltrimethylsilane (30) imder the influence of AgBp4, yielding a mixture of ally-lated products 31 and 32 (Sch. 7) [15]. Product 31 is formed by direct substitution of the bromine atom in ether 29 by an allyl group and isomeric ether 32 arises from the carboxonium ion which is generated by debromination and subsequent [l,2]-hydrogen shift. A synthesis of optically active 4-allylazetidinone 33 (Ft = phthalimido) has also been achieved by employing the silver-promoted substitution reaction of 4-chloro-azetidinone 34 with allylsilane 30 [16]... 

Under conditions where polymer does form it is still by no means clear what is the polymerization mechanism [153], nor is it entirely understood whether cyclic, as opposed to linear, macromolecules are formed. Yamashita et al. [148] have proposed that the active centre is a linear carboxonium ion, i.e. 

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