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. 

A more general method for preparing carbenes often involves the a elimination of halides from carbanions.1-57 PAC can be used to examine the rates and energetics of the reverse reactions, the complexation of halides with carbenes (Fig. 5).58 Plots of A//com versus the proton affinities (PA) of the halides are linear for the two carbenes studied. Although the slopes of the plots are similar, complexation of the halides with phenylchlorocarbene is more exothermic than phenylfluorocarbene. This indicates that fluoro substitution stabilizes the carbene relative to the carbanion more than chloro substitution. The rate of complexation of carbenes with salts has also been examined by nanosecond absorption spectroscopy.59... 

Reaction of Glycosyl Halides with Organometallics and Carbanions... 

Little mechanistic work has been reported on the direct reaction of F-vinyl halides with Zn°. Jairaj and Burton have studied the mechanistic details of the reaction between Z-l-iodopentafluoropropene with Zn° and have presented mechanistic evidence consistent with the formation of a vinyl carbanion that is captured in situ by zinc halide to form the vinylzinc reagent45. Their mechanism is presented in Scheme 1. 

From oxidative cleavage of 1,2-diols and 1,2-amino alcohols Dibutyltin oxide, 95 By reaction of alkyl halides with sulfur-stabilized carbanions Methylthiomethyl p-tolyl sulfone, 192 From reduction of carboxylic acids Vilsmeier reagent, 341 From terminal alkenes by addition reactions... 

Halide complexes of this group react with carbanions to form stable alkylmetalloporphyrins.27 The thallium atom is significantly displaced (0.98 A) from the N4 plane with a large T1—N,, distance (2.29 A) in Tl(TPP)Me, formed by the reaction of H2TPP and MeTl(OCOMe)2 (Scheme 5). Monovalent thallium porphyrin complexes are also known.17 They can be prepared by treating a porphyrin with thallium(I) ethoxide in THF.29 Unlike the other Group IIIB metalloporphyrins, [Tl i Por) is easily hydrolyzed. 

Organometallic compounds which contain a carbon-metal bond are the most reactive carbon nucleophiles. In most cases they are also powerful bases and must be prepared and used under strictly anhydrous and aprotic conditions. A very common way to produce organometallic compounds is to reduce alkyl halides with active metals. Grignard reagents and organolithium compounds are routinely produced in this manner. The transformation is a two-electron reduction of the alkyl halide to a carbanion equivalent the metal is oxidized. 

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 ... 

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]. 

These are very facile processes, and here this subject is divided into reaction of halides with (i) organometallic compounds, (ii) reaction with carbonyl stabilized anions and (iii) reaction with other carbanions. 

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. 

Entry no. 19 of Table 16 introduces one of the most important and perplexing problems of organic electron-transfer chemistry, namely the reaction between alkyl halides and carbanions or other organic anions (0-, S-, metal-centered). We have already discussed three cases of halide reductions in connection with metallic redox reagents (entries nos. 20-22 of Table 16) and found them compatible with Marcus theory, provided that the transition state was described as in (102) with the C—X bond stretched to the point of almost being broken. The latter requirement is manifested in a high X value for... 

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. 

Reduction of carbon-halogen bond by metal yields carbanion. Reaction of alkyl halide with Mg in the presence of anhydrous ether as solvent generates Grignard reagent. The Grignard reagent behaves like a carbanion. Alkyllithiums are also obtained from alkyl halides and behave as carbanions. 

Steps (a) and (b) of Scheme 6 constitute the Arens mechanism. Therefore, equation (244) was simply a case of attack on Cl in which the ion-molecule (PhC=C CISC,-H,-p) was the key intermediate. Attack of acetylide on the sulphur of the sulphenyl chloride leads to the product given in equation (244). Support for this step is the well-known reaction of sulphenyl chloride with carbanions to yield sulphides . The disulphides which sometimes turn up in the haloalkyne-thiolale processes (see Table 6) are easily explained by the sulphenyl halide reacting with the thiolates. 

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... 

Amino acids can be synthesized via the coupling of Schiff bases with carbanions generated by reduction of benzyl halides [143,144]. Electrolysis of benzyl chloride at mercury in DMF containing TBABr, and in the presence of the Schiff base formed from benzylamine and benzyl pyruvate, affords or-methylphenylalanine in up to 86% yield (after hydrogenolysis over palladium-charcoal). An antihypertensive agent, or-methyl-j6-(3,4-dihydroxyphenyl)alanine, has been prepared by reductive coupling of the aforementioned Schiff base with 3,4-methylenedioxybenzyl chloride. 

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