Aryl halides with carbanions

By far one of the most important reactions through the S l mechanism is formation of a C—C bond by the reaction of aryl halides with carbanions derived from hydrocarbons, ketones, esters, amides, nitriles and even, with some limitations, from aldehydes. The reactions of cyanide ions and carbonyl complexes of Co and Fe also form a new C—C bond. 

Wu, B. Q., Zeng, F. W, Ge, M., Cheng, X., and Wu, G., A new synthetic route to a-aryl propionic acid and a quantitative study of the photo-Sr I reaction of aryl halides with carbanion from alkyl nitrile, Sci. China, 34, 111, 1991. 

The carbanions derived from A,A-disubstituted amides and lactams react with certain aromatic halides in liquid ammonia under photostimulation [85,86] to form the expected a-arylated compounds in good yields. Unsymmetrical a, a-diaryl amides can be formed by reaction of aryl halides with the anion of the oc-aryl-A,7V-dimethyl acetamides [85]. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

Scheme 6). An SknI mechanism is suggested for both this substitution and for the facile light-induced condensation of aryl halides with thiolate86 and carbanion nucleophiles.87... 

Consider an alternative mechanism (Figure 8.70) for the formation of m-tri-fluoromethylaniline by reaction of o-chlorotrifluoromethylbenzene with KNH2 in liquid ammonia in which a phenyl carbanion isomerizes prior to an SNAr reaction. Suggest experiments to determine whether such a mechanism occurs in this case or in other reactions of aryl halides with KNH2 in liquid anunonia. 

The reaction of aryl and hetaryl halides with the nitrile-stabilized carbanions (RC -CN) leads to derivatives of the type ArCH(R)CN. Sometimes, however, dimeric products of the type ArCH(R)CH(R)Ar are formed (Moon et al. 1983). As observed, 1-naphthyl, 2-pyridyl, and 2-quinolyl halides give the nitrile-substituted products, while phenyl halides, as a rule, form dimers. The reason consists of the manner of a surplus electron localization in the anion radical that arises upon replacing halogen with the nitrile-containing carban-ion. If the resultant anion radical contains an unpaired electron within LUMO covering mainly the aromatic ring, such an anion radical is stable, with no inclination to split up. It is oxidized by the initial substrate and gives the final product in the neutral form, Scheme 1-7 ... 

Carbanions occasionally react with aryl halides spontaneously, mostly under irradiation, or by supplying electrons either from dissolved metals or from a cathode. However, certain Fe+2 salts catalyse the S l reactions with carbanions. That was the case for the reaction of PhBr or Phi with acetone or pinacolone enolate ions in liquid ammonia or DMS0172a, as well as for the reaction of the enolate ion of several carbanions with several aryl and hetaryl halides in DMS0172b. Since these reactions are inhibited byp-DNB andp-cymene, and the relative reactivity of nucleophiles is similar to that determined in photo-stimulated or spontaneous reactions, it seems that FeCl2 initiates the S l process. 

The coupling takes place as if a carbanion (R ) were present and the carbanion attacked the alkyl halide to displace the halide ion. This is probably not the actual mechanism, however, because dialkylcuprates also couple with vinyl halides and aryl halides, which are incapable of undergoing SN2 substitutions. 

This topic is discussed in detail in Chapter 9 and only an outline is presented here. When simple aryl halides react with strong bases such as the amide ion, NH2 , a hydrogen atom adjacent to the C-halogen unit is abstracted by the base. The resulting carbanion acts as a nucleophile... 

A useful, although somewhat limited, method of preparing vinyl azides involves the addition of azide ion to vinyl halides with subsequent elimination of halide ion. This reaction is only possible when the halogen is located to a group which can effectively stabilize the intermediate carbanion. A number of alkyl and aryl substituted )3-chlorovinyl ketones (23) have been found to react in this way ". In many cases, however, the resulting /3-azidovinyl ketones (26) cannot... 

Reduction of an aryl halide at a cadmium-modified nickel cathode in DMF containing TBABF4 leads to a formylation reaction between aryl carbanions and the solvent [186]. Two papers [187,188] have appeared in which reduction of aryl halides gives an aryl carbanion, which, by acting as a base to deprotonate a suitable nitrile, can cause coupling of the nitrile with esters, aldehydes, and ketones. Electrochemical trimethylsilylation of aryl halides can be effected at a stainless-steel or carbon-cloth cathode in THF-HMPA containing TEABF4 and trimethylchlorosilane [189]. 

This reaction involves nucleophilic attack on the alkyl halide by the carbanion, CH(C00C2H5)2, and, as we might expect, gives highest yields with primary alkyl halides, lower yields with secondary alkyl halides, and is worthless for tertiary alkyl halides and for aryl halides. 

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