Grignard reagents nucleophilic addition reactions

Reactions of highly electron-rich organometalate salts (organocuprates, orga-noborates, Grignard reagents, etc.) and metal hydrides (trialkyltin hydride, triethylsilane, borohydrides, etc.) with cyano-substituted olefins, enones, ketones, carbocations, pyridinium cations, etc. are conventionally formulated as nucleophilic addition reactions. We illustrate the utility of donor/acceptor association and electron-transfer below. 

The formation of this product need not concern us, hut its nature is important, in that it contains the equivalent of R or Ar , i.e. the alkyl or aryl group has been transformed into its carbanion. Addition of an aldehyde or ketone to the solution of the Grignard reagent allows a nucleophilic addition reaction to occur. The reaction resembles that of... 

Organolithium reagents reacts just like Grignard reagents. For example, reaction with aldehydes and ketones proceeds by nucleophilic addition to yield secondary and tertiary alcohols respectively. 

An alternative stereoselective synthesis of chiral heterocycles based on carbohydrate-induced stereodifferentiation includes nucleophilic addition reactions on heterocyclic systems already bound to the carbohydrate auxiliary. An example of this strategy has been shown by stereoselective addition of Grignard reagents to carbohydrate-linked 4-pyridones [61]. For this purpose, trimethylsiloxypyridine was glycosylated regioselectively using pivaloyl-protected glycosyl fluorides. 

Nickel-Catalyzed Addition of Grignard Reagents Ring-Opening Reactions with Nucleophiles... 

Just as addition of a Grignard reagent to an aldehyde or ketone yields an alcohol, so does addition of hydride ion, H (Section 17.4). Although the details of carbonyl-group reductions arc complex, LiAll-14 and N aBH4 act as if they were donors of hydride ion in a nucleophilic addition reaction (Figure 19.7).. Addition of water or aqueous acid after the hydride addition step protonates the tetrahedral alkoxide intermediate and gives the alcohol product. 

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. 

Nucleophilic addition to carbonyl functionalities undoubtedly represents one of the most important reactions of Grignard reagents. One such reaction is the alkylation of carbon dioxide to give carboxylic acid derivatives. Analogous reactivity is also observed between [TpBu jMgCH3 and CO2. which gives the acetate derivative [Tp ]Mg(f/ -02CCH3) [Eq (6)]. 

This chapter will focus on the nucleophilic addition reactions of transiton metal carbene and carbyne complexes with Grignard reagents. The synthesis and some general reactions of these carbene and carbyne complexes will be presented. A more detailed description of the chemistry of these complexes can be found in the literature [1]. This chapter, although not exhaustive, is descriptive of the prototypical nucleophilic addition reactions of metal-carbon (M-C) multiple bonds with Grignard reagents. 

Nucleophilic addition reactions (see also Kcaclton ot Grignard reagents)... 

In general, nucleophilic addition reactions using Grignard or organolithium reagents to -chiral or other remotely chiral ketones usually yield mixtures of stereoisomers which are not synthetically use-fiil.9,12-27 However, some specific examples of stereoselective organolithium and Grignard additions to these remotely chiral carbonyl compounds have been reported. 

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