Organomagnesium and Organolithium Compounds

Lithium and magnesium react with alkyl halides (RX, X F) to yield alkyllithium (RLi) and alkylmagnesium (RMgX) compounds, respectively  

Mechanistically, the same kind of process is believed to be involved for both metals but here we arbitrarily choose to discuss the magnesium case. In the first step, the metal is believed to transfer a single electron to the alkyl halide, cleaving the latter into an alkyl radical and a halide ion  

A second electron then reduces the alkyl radical to the carbanion stage, that is, effectively an organometallic compound  

There is good evidence for the existence of radical intermediates in this process. Treatment of the Mg/RX reaction mixture with the stable organic radical 2,2,6,6-tetramethylpiperidinyl-l-oxy (TEMPO, see structure below) results in high yields of a TEMPO-R adduct, strongly indicating the intermediacy of alkyl radicals  

A reagent such as TEMPO that specifically reacts with radicals is called a radical trap such compounds are clearly very useful as mechanistic probes. 

Two of the most common organometallic compounds are organolithium compounds and organomagnesium compounds. Organolithium compounds are prepared by adding lithium to an alkyl halide in a nonpolar solvent such as hexane. 

Organomagnesium compounds (commonly called Grignard reagents after their 

Alkyl halides, vinylic halides, and aryl halides can all be used to form organolithium and organomagnesium compounds. Alkyl bromides are used most often, because they react more readily than alkyl chlorides and are less expensive than alkyl iodides. 

Because carbon is more electronegative than the metal to which it is attached, organolithium and organomagnesium compounds react as if they were carbanions. Thus, they are nucleophiles and bases. 

Organomagnesium and organolithium compounds are very strong bases. Therefore, they will react immediately with any acid present in the reaction mixture, even with very weak acids such as water and alcohols. When this happens, the organometallic compound is converted into an alkane. Although this is not how one would normally synthesize an alkane, it is a useful way to prepare deuterated hydrocarbons. Just use D2O instead of H2O. 

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The carbon-metal bonds of organolithium and organomagnesium compounds have appreciable carbamomc character Carbanions rank among the strongest bases that we 11 see m this text Their conjugate acids are hydrocarbons—very weak acids indeed The equilibrium constants for ionization of hydrocarbons are much smaller than the s for water and alcohols thus hydrocarbons have much larger pA s... 

Organolithium and organomagnesium compounds find their- chief use in the preparation of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first exanine the reactions of these organometallic compounds with proton donors. 

Organolithium and organomagnesium compounds are stable species when prepaied in suitable solvents such as diethyl ether. They aie strongly basic, however, and react instantly with proton donors even as weakly acidic as water and alcohols. A proton is transfened from the hydroxyl group to the negatively polaiized caibon of the organometallic compound to fomn a hydrocaibon. 

Reactions of Enamine Salts with OrganometalUc Compounds Organolithium and organomagnesium compounds react with enamine salts to give amines substituted on the ix-carbon atoms. The treatment of. -dehydroquinolizidinium perchlorate (163) with alkylmagnesium halides gives 9-alkylated quinolizidines (164) (252,256). Formation of... 

Organolithium and organomagnesium compounds are of great importance in organic synthesis. 

Addition of organometallics will not be considered in detail here we wish merely to note that additions of organolithium and organomagnesium compounds are analogous to the processes that have been considered up to this point.36 Although the detailed structure of these organometallics may vary from one compound to another, and may in some cases be unknown, they consist essentially of a strong, soft carbon Lewis base coordinated to a hard metal ion Lewis acid.37 Combination... 

Acidic protons were a major problem in several syntheses of the anticancer compounds, daunorubicin and adriamycin, which start with a nucleophilic addition to a ketone with a pair of particularly acidic protons. Organolithium and organomagnesium compounds remove these pro-... 

We possess more information on systems containing polar monomers. Organolithium and organomagnesium compounds initiate the polymerization of a number of monomers with an electron-withdrawing substituent. These polymerizations are rarely of the living type. The initiator usually reacts not only with the double bond of the monomer, but also with the polar substituent (both on the monomer and the polymer) yielding inactive products. 

Addition reactions. a,0-Unsaturated carbonyl compounds 1 and 3 undergo exclusive 1,4-addition reactions with organolithium (and organomagnesium) compounds owing to steric hindrance of the carbonyl group. The adducts 2 and 4 are converted into carboxylic acids by cleavage with potassium t-butoxide and H2O in the case of 2 see potassium r-hutoxidc, this volume) and by treatment with ethanolic... 

Ell. International Organometallic Conference, Paris, 1962. Proceedings published in Bull. Soc. Chim. Fr. 1345-1508 (1962). Many of the papers are in French and deal with the chemistry of organolithium and organomagnesium compounds. 

White phosphorus also reacts with carbon nucleophiles in ether or tetrahydrofuran to give dark red solutions believed to be complex organophosphides (Rauhut and Semsel). Hydrolysis of a mixture obtained from reactions of white phosphorus with organolithium and organomagnesium compounds gives the primary phosphine as the major product, with small amounts of secondary and tertiary phosphines being formed under some conditions. 

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