ADDITION REACTIONS OF ORGANOMAGNESIUM COMPOUNDS

A number of reactions of organomagnesium compounds, giving rise to new organomagnesium compounds, are covered in other chapters. They include addition to carbon-carbon multiple bonds (see Chapter 4), addition to isonitriles (see Section 5.4), addition to carbon monoxide (see Section 6.5), thiophilic addition to carbon-sulfur double bonds (see Chapter 7) and addition to carbenes (see Section 9.1). 

Early investigations of reactions of organomagnesium compounds with nitro compounds led to mixtures of products, and gave little indication that they might be useful [5]. However, it has now been established that with two equivalents of an alkylmagnesium halide in THF, nucleophilic addition to the ring of a variety of nitroaromatic compounds occurs, as summarized in Table 4.1. The product of the addition is a nitronate anion, which may be converted into various products, as illustrated by the example of 2-nitronaphthalene. 

Reactions of organomagnesium compounds with a,[3-unsaturated esters show a somewhat greater tendency to conjugate addition than reactions with a,(3-unsaturated ketones (see p. 124). However, copper(i) catalysis may be beneficial even in cases where conjugate addition is the main uncatalysed reaction [30] ... 

Reactions of organomagnesium compounds with a,(3-unsaturated dithioesters are somewhat unpredictable, 1,2-, 1,4-carbophilic and thiophilic addition having been observed [6], With a,(3-unsaturated thioamides [7] and imidothioesters [6], however, 1,4-carbophilic addition appears to predominate. 

Reactions of organomagnesium compounds with nitroso or nitro compounds are often complicated, and not useful in synthesis, or only represented by isolated examples. One exception to this generalization involves conjugate addition to a,[3-unsaturated and aromatic nitro compounds (see Section 4.2), and two others lead to the formation of carbon-nitrogen bonds. 

Addition of an organomagnesium bond to an alkene, alkyne, or a benzenoid ring generates a new organomagnesium compound. With simple alkenes, addition occurs only under strenuous conditions. This reaction will be discussed later, with appropriate examples, as a reaction of organomagnesium compounds in the Section on Amides and Lactans.. 

A striking exaple of the influence of the Schlenk equilibrium on the progress of reactions of organomagnesium compounds was observed in, what was named, a ligand-assisted nucleophilic addition reaction (LANA), in which the substrate was a lithium quinol alkoxide [29]. In a typical LANA reaction (Scheme 14) the lithium quinol alkoxide is first prepared in situ, after which follows the sequential addition of l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidone (DPMU) and a Grignard reagent. 

Uncatalyzed addition reactions of Grignard reagents with nonconjugated alkenes and aUcynes are of limited use in synthesis. However, carbon-carbon double bonds substituted by a leaving group, such as an acetate, are susceptible to be displaced by organomagnesium compounds presumably by an addition-elimination pathway. A few examples have been reported (equation 64). 

Similar acryloyl imidazolidinones have been used in the asymmetric 1,4-addition of organomagnesium compounds in the presence of a Lewis acid. The diastereoselectivity is variable and was found to be highly depending on the nature of all the reaction participants.227 A symmetric fumaramide, obtained from the camphor-derived Oppolzer sultam, adds Grignard reagents, yielding after hydrolysis monosubstituted succinic acids with up to 90% ee (Scheme 73).228... 

Reactions of organomagnesium and organolithium compounds with nitriles normally proceed via initial addition to the carbon-nitrogen triple bond or via initial a-deprotonation ... 

Both 1,2- and 1,4-addition of organomagnesium compounds to a,[3-unsaturated nitriles are known [A, 14]. Two examples of the latter reaction are shown here. 

The addition of organomagnesium compounds to the carbonyl group of aldehydes and ketones has a long history, and remains one of the most important reactions for carbon-carbon bond formation. While the overall reaction is simple, it is susceptible to a number of side-reactions, and its... 

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