Ketones addition reaction with Grignard reagents

When the carbonyl carbon is substituted with a potential leaving group, the tetrahedral adduct can break down to regenerate a C=0 bond and a second addition step can occur. Esters, for example are usually converted to tertiary alcohols, rather than ketones, in reactions with Grignard reagents. 

Consequently, aldehydes and ketones undergo nucleophilic addition reactions with Grignard reagents (Section 17.3). 

The emphasis of this chapter will be on the mechanistic aspects of the ( normal ) addition reaction of Grignard reagents to the carbon-oxygen double bond, as is found for ketones. However, it will become clear that for reactions with other substrates, the general mechanistic aspects of these carbonyl addition reactions are also applicable. 

Unlike similar reactions with Grignard reagents reduction is not a serious problem.245 Organolithium reagents such as n-butyllithium easily add to hindered ketones such as di-terr-butyl ketone (215). The product is the alcohol by direct addition to the carbonyl, 216.245b Simple organolithium reagents that are commercially available can be added to carbonyl derivatives and often provide the most efficient route to substituted... 

Since this chapter was prepared, several important papers on the subject have been published. Wang et al. used a modified amino acid as a chiral ligand to synthesize a chiral MOPM with ID channels (5.12 x 2.87 A ) [108]. The chiral MOPM catalyzes the addition reaction of Grignard reagent to a,P-unsaturated ketones with... 

Interestingly, a,P-unsaturated aldehydes and ketones generally react with Grignard reagents at the carbonyl. Reactions in which the major product is derived from a process involving the double bond and the carbonyl (conjugate addition) are rare. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by 5 2 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 Grignard reagents to yield ketones. 

Methoxyallene has previously been used to prepare acetylenes via its reaction with Grignard reagents, in the presence of copper(i) halides.The use of preformed dialkylcuprates, however, gave the vinyl ethers instead. The E Z ratio varied with the substituent but it is difficult to explain why the difference is observed.Methoxyallene has also been converted into its vinyl anion and used in the synthesis of dihydrofurans and furans in an analogous way to ordinary vinyl ethers.Similarly allenic cuprates have been prepared and used in the synthesis of allenes and allenic pheromonessome examples are outlined in Scheme 58. The addition of lithium dimethylcuprate to allene phosphine oxides and allenic ketones was interpreted in terms of a 1,2- rather than a 1,4-addition process, in contrast to a/3-unsaturated... 

Addition of hydrogen cyanide to an aldose to form a cyanohydrin is the first step in the Kiliani-Fischer method for increasing the carbon chain of aldoses by one unit. Cyanohydrins react with Grignard reagents (see Grignard reaction) to give a-hydroxy ketones. 

The conversion of a nitrile R —CN into a ketone R —CO—R demonstrates that polarized multiple bonds other than C=0 also react with Grignard reagents, and that such reactions are synthetically useful. Esters 22 and acid chlorides can react subsequently with two equivalents of RMgX the initially formed tetravalent product from the first addition reaction can decompose to a ketone that is still reactive, and reacts with a second RMgX. The final product 23 then contains two substituents R, coming from the Grignard reagent ... 

The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

Alkylation of enamines Addition of amines to triple-bond compounds Addition of amines to aldehydes or ketones Reaction between Grignard reagents and formamides Reaction of phosphonates with aldehydes or ketones... 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

The synthetic application of organocopper compounds received a major impetus from the study of the catalytic effect of copper salts on reactions of Grignard reagents with y.,(i-unsaturated ketones.1 Whereas Grignard reagents normally add to conjugated enones to give the 1,2-addition product, the presence of catalytic amounts of Cu(I) results in... 

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