Electrophilic salts

As discussed in Chapter 1, many electrophiles are stable in solvents and the presence of substances of moderate Lewis basicity. Even relatively strong electrophiles can be generated and handled under appropriate conditions.1 A wide variety of electrophilic carbocationic and onium ion salts have been prepared and characterized by spectroscopic methods, X-ray crystallography, kinetic studies, and other techniques. Several types of these electrophilic salts are even available commercially (such as varied onium, iminium, and carbocationic salts, etc.). Electrophiles are generally generated by the reactions of suitable precursors with Brpnsted or Lewis acids. They can be sometimes isolated, but for synthetic conversions they are more often generated in situ and reacted directly with nucleophilic reagents. 

In contrast to classical Meerwein arylations, non-activated alkenes are well suited for this reaction type for two reasons. First, due to the relatively slow formation of azo compounds by addition of aryl radical 49 to 48, this undesired pathway cannot compete successfully with the attack of 49 on the alkene to give radical adduct 50. Second, a nucleophilic alkyl radical 50 arises from the addition step, which is effectively trapped by electrophilic salt 48 to give azo compound 51. As a result of several improvements, the methodology is now applicable for a wide range of polar to non-polar alkenes with almost no restrictions on the substitution pattern of the diazonium salt [101, 102]. Moderate diastereoselectivities have been obtained in first attempts with chiral auxiliaries [103]. The azo compounds accessible, such as 51, can be converted to carboamination products 52 by hydrogenation and to various other heterocycles. 

HF amine complexes are also employed for nucleophilic displacement of halogens and hydroxyls. Olah and coworkers used the reaction with and without the help of NCVBF for preparing fluoroadamantanes and fluorodiadamantanes28. They also found that an electrophilic salt would extract an hydride a to a C—Br moiety, followed by F attack on the resulting carbocation to form vicinal fluorobromo alkanes (equation 15)29. 

The electrophilic salt can now add to the enol (we are in acid solution) of the ketone to give the product of the reaction, an amine sometimes called a Mannich base. 

So far electrophilic substitution reactions at the silicon atoms of the silaborane clusters were unsuccessful. Adduct formation as the initial step and further treatment of this anion with the electrophilic salt [Ph3C][BF4] resulted in the isolation of methyl-phenyl-o-silaborane.1 01... 

The reaction of an electrophilic salt derived from oxalic acid, e.g. chloro(ethoxycar-bonyl)methyleneiminium chloride, with benzene-1,2-diamine under acidic reaction conditions affords 3-methylaminoqiiinoxalin-2(lf/)-one (21, mp 238°C). 

The hydrolysis of benzyl chloride is catalyzed by the presence of Hg" salts. The electrophilic salts are here behaving as acids and react with the organic halide to form a carbonium ion ... 

In the uncatalysed reaction the fact that added nitrate strongly accelerates the rate to the same extent as other salts makes it improbable that the nitronium ion is the effective electrophile. The authors of the work conclude that covalent dinitrogen pentoxide is the electrophilic... 

It has been necessary to comment upon these various studies because Olah and his co-workers have suggested that whilst nitrations, like those with nitronium salts, which give a relative rate of reaction of toluene with respect to benzene not much greater than unity involve the nitronium ion as the electrophile, this is not so in other cases. It is important to consider these opinions closely. In the earlier of the two relevant papers it is agreed that since nitrations of toluene with nitronium tetrafluoroborate in sulpholan show no abnormal o -ratio there... 

The nitronium ion is the electrophile in nitrations with nitronium salts in organic solvents. 

In other systems electrophiles other than the nitronium ion are involved with activated substrates (in these cases intermolecular selectivity is high, whereas with nitronium salts it is low). 

Of course, these schemes indicate only that the overall reactions may be classified as nucleophilic 1,3-substitutions and, in the last case, as electrophilic 1,3-substitut ions. The reactions often proceed only in the presence of catalytic or stoichiometric amounts of transition metal salts, while in their absence 1,1--substitutions or other processes are observed. The 1,1-substitutions are also catalyzed by salts of transition metals, and it is not yet well understood, which factors influence the 1,1 to 1,3-ratio. In a number of 1,3-Substitutions there is... 

Addition of arylhydroxylamines to electrophilic allenes such as methyl propadienoate or l-methancsulfonyl-l,2-propadiene is another route to 0-vinyl derivatives[2]. The addition step is carried out by forming the salt of the hydroxylamine using NaH and the addition is catalysed with LiO CCFj. The intermediate adducts are cyclized by warming in formic acid. Yields are typically 80% or better. 

Because Pd(II) salts, like Hgtll) salts, can effect electrophilic metallation of the indole ring at C3, it is also possible to carry out vinylation on indoles without 3-substituents. These reactions usually require the use of an equiv. of the Pd(ll) salt and also a Cu(If) or Ag(I) salt to effect reoxidation of the Pd. As in the standard Heck conditions, an EW substitution on the indole nitrogen is usually necessary. Entry 8 of Table 11.3 is an interesting example. The oxidative vinylation was achieved in 87% yield by using one equiv. of PdfOAcfj and one equiv. of chloranil as a co-oxidant. This example is also noteworthy in that the 4-broino substituent was unreactive under these conditions. Part B of Table 11.3 lists some other representative procedures. 

Diazo coupling involves the N exocyclic atom of the diazonium salt, which acts as an electrophilic center. The diazonium salts of thiazoles couple with a-naphthol (605). 2-nitroresorcinol (606), pyrocatechol (607-609), 2.6-dihydroxy 4-methyl-5-cyanopyridine (610). and other heteroaromatic compounds (404. 611) (Scheme 188). The rates of coupling between 2-diazothicizolium salts and 2-naphthol-3.6-disulfonic acid were measured spectrophotometrically and found to be slower than that of 2-diazopyridinium salts but faster than that of benzene diazonium salts (561 i. The bis-diazonium salt of bis(2-amino-4-methylthiazole) couples with /3-naphthol to give 333 (Scheme 189) (612). The products obtained from the diazo coupling are usuallv highly colored (234. 338. 339. 613-616). 

Acrylonitrile reacts with the sodium salt of 4.5-dimethvl-A-4-thiazoline-2-thione (73J (R4 = R5 = Me) to yield 3-(2-cyanoethyl)-4.5-dimethyl-A-4-thiazoline-2-thione (74) (R4 = R, = Me) (Scheme 35 (160). Humphlett s studies of this reaction showed that the size of the R4 substituent is a determinant factor for the S versus N ratio (161. 162). If R4 == H, 100% of the N-substituted product (74) is obtained this drops to 50% when R4 = methyl, and only the S-substituted product (75) is obtained when R4 = phenyl. The same trend is observed with various CH2 = CH-X (X = C00CH3. COCH3) reagents (149). The S/N ratio also depends on the electrophilic center for CH2 = CH-X systems thus S-reaction occurs predominantly with acrylonitrile, whereas N-substitution predominates with methvlvinvlketone (149). 

Few examples of reactivity involving the electrophilic character of the Cn atom are reported. In some cases, a catalyst or reagent convens the neutral thione into a quaternary- salt (Scheme 40), the Ct of which is clearly electrophilic (205. 206), The mechanism of Raney Ni desul-... 

It is noteworthy that some catalysts convert thioethers to quaternary salts where the reactive electrophilic center is no longer one of the two C centers but the C sp center of the thiazolium salt (284. 285). Thus... 

The high reactivity of the 5-position in 1.3-selenazoles toward electrophilic substitution was also observed on azocoupling. By reacting molar quantities of an aqueous solution of a diazonium salt with an ethanolic solution of a 2-arylamino selenazole. for example, the corresponding 2-arylamino-5 azoselenazoles are formed in a smooth reaction (100). They deposit from the deeply colored solution and form intenselv red-colored compounds after their recrystallization from a suitable solvent (Scheme 36l. 

Bulka et al. (43) have demonstrated the electrophilic reactivity of selenazoles possessing an hydrazonc in the 2-position and nonsubstituted in the 5-position toward diazonium salt to give 5-phenylazo derivatives preferentially. For example, the main product of the coupling of 2-benzylidene hydrazino-4-phenylselenazole with diazo-o-phenetidine is the 5-(o-ethoxyphenylazo)-selenazole (Scheme 371 ruby red prisms, m.p. 206°C. yield 67"o). A formazan is obtained as by-product. (See Section III.6) (43). 

Quaternarj salts are obtained by alkylation of selenazole bases, the heterocyclic nitrogen atom playing the role of nucleophile with regard to the electrophilic carbon of the alkylating, agent. 

The (thermal) decomposition of thiazol-2-yldiazonium salts in a variety of solvents at 0 C in presence of alkali generates thiazol-2-yl radicals (413). The same radicals result from the photolysis in the same solvents of 2-iodothiazole (414). Their electrophilic character is shown by their ability to attack preferentially positions of high rr-electron density of aromatic substrates in which they are generated (Fig. 1-21). The major... 

Although It IS possible to prepare aryl chlorides and aryl bromides by electrophilic aromatic substitution it is often necessary to prepare these compounds from an aromatic amine The amine is converted to the corresponding diazonmm salt and then treated with copper(I) chloride or copper(I) bromide as appropriate... 

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