Carbanions from alkyl halides

Eiectrogenerated Reactive Species, Fig. 8 Trapping of eiectrogenerated carbanions from alkyl halides... 

Organometallic compounds or carbanions undergo a number of reactions in which the carbanion or carbanion-like moiety of the organometallic compound acts as a nucleophilic displacing agent. Examples are the formation of hydrocarbons from alkyl halides, alkyl halides from halogens, and ketones from acid chlorides or esters. The latter two reactions are closely related to the base-catalyzed condensations and are perhaps additions as well as displacement reactions. Related addition reactions are the carbonation of organometallic compounds and the addition to ketones or aldehydes. 

Scheme 11 Carbanion formation from alkyl halides and cobalt (III) species.

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. 

The formation of organometallic compounds from alkyl halides and their role as carbanions, thus reversing the reactive character of the carbon atom of the alkyl halide... 

The ability to trap alkyl radicals during the alkylation step is suggestive of a strong balance between electron transfer and substitution reaction. Historically, naphthalene anion, in fact, has been used explicitly to generate alkyl radicals from alkyl halides (16). The presence of alkyl radicals in the alkylation of coal can be expected to complicate interpretation of reaction pathways. The observation of alkylated but unreduced aromatic products led Stock to postulate the presence of alkyl radicals during alkylation (13), although aromatic carbanions could provide similar products through nonradical pathways (1). 

One of the first papers was published by Corey on the use of bis(methylthio)allyllithium (1 Scheme 14) for the synthesis of a,p-unsaturated aldehydes from alkyl halides. The generation of the carbanion as the lithio derivative was readily accomplished by a simple three-step sequence from epichlorohydrin. 

We may describe these species as o-complexes of carbanions with metals but they are not carbanions. As normally prepared from alkyl halides and Mg(0) or Li(0) in ether solvents (Et20 or THF), they are soluble in organic solvents as tetrahedral complexes and are not salts. Chemists are happy to draw the monomeric species RLi or RMgX and it is likely these are the reactive entities in many reactions. 

Disconnections (a), (b), and (d) in Table 10.1 all require reagents for the carbanion synthon R. Simple carbanions are almost never formed in reactions so we shall need reagents in which carbon is joined to a more electropositive atom such as a metal. The most popular are Li and Mg. Bnty lithium (BuLi) is commercially available and other alkyl lithiums can be made from it by exchange (i). Otignard reagents (2) arc usually made directly from alkyl halides and magnesium metal (iii)—a method also available for RIJ (ii). These methods are available for aryl compounds too. Transformation of RHal into RIa or RNfgBr involves a formal inversion of polarity. 

Carbanions can also be formed from alkyl halides with metals or organometallic compounds. 

This chapter will discuss carbanion-like reactions that utilize enolate anions. The acid-base reactions used to form enolate anions will be discussed. Formation of enolate anions from aldehyde, ketones, and esters will lead to substitution reactions, acyl addition reactions, and acyl substitution reactions. Several classical named reactions that arise from these three fundamental reactions of enolate anions are presented. In addition, phosphonium salts wiU be prepared from alkyl halides and converted to ylids, which react with aldehydes or ketones to form alkenes. These ylids are treated as phosphorus-stabilized car-banions in terms of their reactivity. 

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 reactivities of the substrate and the nucleophilic reagent change vyhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides S l and mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further (see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process (see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods (see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

Alkylation of carbanions derived from allyl aryl sulfones 236 with alkyl halides is known... 

The procedure involves C-alkylation of an a-sulfonyl carbanion derived from 245 with alkyl halides or carbonyl compounds, followed by cleavage of the cyclopropanols 247 produced by deprotection of the hydroxy group of 246 to give (E)-substituted aldehydes141. 

Alkyl aluminium halides are used in many ways as coinitiators for the cationic polymerization. Due to presence of alkyl groups, which have the characteristics of potential carbanions, the alkyl aluminium halides and the counterions formed from them cause the following irreversible competing reactions whereby hydrocarbons are released — Termination by interaction of the cation with the alkyl group of the counterion, e-g-... 

The mechanism of these reactions is usually Sn2 with inversion taking place at a chiral RX, though there is strong evidence that an SET mechanism is involved in certain cases, ° especially where the nucleophile is an a-nitro carbanion and/or the substrate contains a nitro or cyano group. Tertiary alkyl groups can be introduced by an SnI mechanism if the ZCH2Z compound (not the enolate ion) is treated with a tertiary carbocation generated in situ from an alcohol or alkyl halide and BF3 or AlCla, or with a tertiary alkyl perchlorate. ... 

An allylic sulfenate, like 199, is known to be in equilibrium with allylic sulfoxide, like 196, although its concentration is usually low . Various allylic sulfoxides can be prepared by treatment of allylic alcohols with arenesulfenyl chlorides . Evans and coworkers prepared various allylic alcohols by treating the corresponding allylic sulfoxides with trimethyl phosphite. For example, the carbanion from a cycloalkenyl sulfoxide 201 was readily alkylated at the a-position by treatment with alkyl halide. The resulting alkylated derivative 202 was then treated with trimethyl phosphite and 3-substituted cycloalkenol was obtained. Alkylation of acyclic allylic sulfoxide 204 gave... 

Where a reagent is starred, the star indicates the atom that accepts electrons from, or donates electrons to, the substrate as the case may be. No clear distinction can necessarily be made between what constitutes a reagent and what a substrate, for though N02, OH, etc., are normally thought of as reagents, the carbanion (41) could, at will, be either reagent or substrate, when reacted with, for example, an alkyl halide. The reaction of the former on the latter is a nucleophilic attack, while that of the latter on the former would be looked upon as an electrophilic attack but no matter from which reactant s standpoint a reaction is viewed, its essential nature is not for a moment in doubt. 

This is an extremely useful reaction for the synthesis of alkenes. It involves the addition of a phosphonium ylid, e.g. (136), also known as a phosphorane, to the carbonyl group of an aldehyde or ketone the ylid is indeed a carbanion having an adjacent hetero atom. Such species are generated by the reaction of an alkyl halide, RR CHX (137), on a trialkyl- or triaryl-phosphine (138)—very often Ph3P—to yield a phosphonium salt (139), followed by abstraction of a proton from it by a very strong base, e.g. PhLi ... 

Tlte reduction potential for an alkyl or benzyl radical, relative to that of the carbon-halogen bond from which it is derived, is important in determining the isolated products. Products are derived either by radical or by carbanion chemistry. The half-wave potential for the second polarographic wave of alkyl halides is connected with reduction of the radical. Sophisticated methods have been devised for deducing radical reduction potentials in cases where (his second wave is not seen. Values are collected in Table 4.4. 

---