Alkyl halides with organometallics

Coupling of alkyl halides with organometallic reagents other than... 

The Reaction of Alkyl Halides with Organometallic Reagents 265 Alkyl-de-halogenation... 

The coupling of alkyl halides with organometallic compounds is the only one of these methods in which carbon-carbon bonds are formed and a new, bigger carbon skeleton is generated. 

Before we describe the applications of organometallic reagents to organic synthesis let us examine their preparation Organolithium compounds and other Group I organometal he compounds are prepared by the reaction of an alkyl halide with the appropriate metal... 

Many other kinds of organometallic compounds can be prepared in a manner similar to that of Grignard reagents. For instance, alkyllithium reagents, RLi, can be prepared by the reaction of an alkyl halide with lithium metal. Alkyllithiums are both nucleophiles and strong bases, and their chemistry is similar in many respects to that of alkylmagnesium halides. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

Metallation of alkyl or aryl halides with organometallic compounds... 

Reduction of the C—N bond 0-86 Coupling of alkyl halides (Wurtz) 0-87 Coupling of alkyl halides with or-ganometallic reagents 0-89 Reaction between organometallic reagents and alkyl sulfates or sulfonates... 

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 simplest unfunctionalised carbon nucleophiles (15 and 17) are made from alkyl halides with various metals such as Li(0) or Mg(0) or by exchange with available organometallic reagents such as butyl-lithium (BuLi) in anhydrous coordinating solvents like ether (Et20) or THF (tetrahydro-furan 16). Enolates 11 are very important and will be discussed at length in later chapters. 

The reduction of alkyl halides to organometallic compounds in aprotic solvents involves a heterogeneous reaction on the metal surface. This metal surface must be pure metal if it is to react efficiently in the desired way. If the surface of the metal has reacted with oxygen (Li, Mg, Zn) or even with nitrogen (Li), one must first remove the metal oxide or lithium nitride layer. This can be accomplished in the following ways ... 

Alkyl halides, as well as sulfonates, besides being useful for the preparation of derivatives as shown above, are widely utilized for the preparation of phosphorus derivatives such as R-PPhi Hal , precursors for the generation of Wittig reagents. Alkyl halides are also extremely important as intermediates in the preparation of the most valuable derivatives of oxidation level 0, the organometallic compounds. The required reduction step is usually carried out via direct reaction of the alkyl halides with an active metal such as lithium or magnesium. 

Hydrogenolysis of the toluene-4-sulfonate of an alcohol may be carried out with a nucleophilic hydride such as lithium aluminium hydride. There are also a series of radical methods based on the reduction of alkyl halides with tri- -butyltin hydride (BUjSnH). Finally, the source of the hydrogen may be the electrophilic proton, exemplified by the decomposition of organometallic reagents such as the Grignard reagent with water. 

Other preparative routes to aluminum alkyls include reaction of aluminum halides with organometallic reagents such as lithium alkyls (Equation (3)). 

W. J. Considine Alkylation (arylation) of metal halides with organometallics, pp. 4-11 (11). 

Organic halides serve as effective precursors of organic radicals, and the reduction of organic halides with reactive metal cathodes leads to the formation of organometallic compounds [Eq. (5)]. For example, the reduction of alkyl halides with a Pb cathode results in the formation of R4Pb [24-28]. The reduction at a Hg cathode results in the formation of R2Hg [29-32]. Sn is also effective as a reactive cathode to give R4 n [33-35]. 

The use of indium metal in organic or organometallic synthesis is at best very limited. Schumb and Crane69 reported that reaction of several alkyl halides with metallic... 

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