Reactions with halogen electrophiles

Reaction with Halogen Electrophiles. The synthesis of l-haloa2iridines, which are prone to explosion, has been carried out using hypohahtes (290,291). l-Chloroa2iridine [10165-13-6] produced in this way reacts with l-Hthiated ethyleneimine to give l,l -dia2iridine [4388-03-8]. Perchloryla2iridine [112405-46-6] has been prepared by reaction of ethyleneimine with dichlorine heptoxide at —20° C (292). 

This realization led me to study related possible intermolecular electrophilic reactions of saturated hydrocarbons, Not only protolytic reactions but also a broad scope of reactions with varied electrophiles (alkylation, formylation, nitration, halogenation, oxygenation, etc.) were found to be feasible when using snperacidic, low-nucleophilicity reaction conditions. 

The classical Reformatsky reaction consists of the treatment of an a-halo ester 1 with zinc metal and subsequent reaction with an aldehyde or ketone 3. Nowadays the name is used generally for reactions that involve insertion of a metal into a carbon-halogen bond and subsequent reaction with an electrophile. Formally the Reformatsky reaction is similar to the Grignard reaction. 

Multiple products were produced with halogen electrophiles, while with metal electrophiles, no reaction was observed with the exception of mercury (II). 

It has been demonstrated in CHEC-II <1996GHEC-II(7)431> that halogen substituents as well as other good leaving substituents can be readily replaced by carbon nucleophiles, for example, cyanide ion or active methylene compounds. Also, direct cyanation of l-phenylpyrazolo[3,4-i/]pyrimidine was demonstrated. Since then, reactivity toward carbon nucleophiles has not received much attention. However, a few interesting reactions with carbon electrophiles have been reported in the last few years. Thus, reacting 154 with 155 affords 156 (Equation 9) <2002BML1687>. 

The three-membered ring of the cycloproparenes is opened easily by an electrophile and the attack can be at either the a or the n framework. The reactions with halogens (non-photochemical)58-59,61 and acids250 give rise to benzyl derivatives that are best accounted for by 7t capture of the electrophile (E+) at the bridge, electrocyclic opening of the cyclopropyl cation to benzyl cation (path a, Scheme 21) and capture by the nucleophile. 

Ethers do not exhibit marked nucleophilicity towards arynes but readily enter into reaction with more electrophilic halogenated analogs like (121). In the betaine derived from (121) and ethyl ether, a proton... 

With halogen electrophiles both retention and inversion of stereochemistry have been observed. In this case the addition of the electrophile may lead to the -silicon cation, or a cyclic halonium ion. Scheme 5 shows a generalized mechanism for the reaction of vinylsilanes with electrophilic reagents120. 

Replacement of the halogen by a metal atom, and further reaction with an electrophile E+ (Curtin and Harris, 1951a, b Curtin et al., 1955) also result in a formal vinylic substitution (XVI), but will not be discussed here. 

Arenols 4 and their conjugate arenolate bases are both (a) oxygen- and (b) carbon-based nucleophiles, which react with a wide range of electrophilic reagents (Figure 3). Their reactions with soft electrophiles can lead directly to cyclohexadienone derivatives this is the case, for example, with electrophilic halogenation, which effectively occurs at the electron-rich carbon centers (4 —> 5b) [29, 30]. 

Q Show how enols, enolate ions, and enamines act as nucleophiles. Predict the products of their reactions with halogens, alkyl halides, and other electrophiles. Show how they are useful in synthesis. 

Table 2. Lithium-Halogen Exchange Followed by Reaction with an Electrophile ...

From metalopyridazines by reaction with an electrophilic halogen source... 

Lithio-heterocycles have proved to be the most useful organometallic derivatives they react with the whole range of electrophiles in a manner exactly comparable to that of aryllithiums and can often be prepared by direct metallation (C-hydrogen deprotonation), as well as by halogen exchange between a halo-heterocycle and an alkyllithium. As well as reaction with carbon electrophiles, Uthiated species are often the most convenient source of heterocyclic derivatives of less electropositive metals, such as zinc, boron, silicon and tin, as will be seen in the following sections. 

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