Ketones, addition derivatives Grignard reaction

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 most conspicuous property of aliphatic amines, apart from their fishy smell, is their high basicity, which usually precludes N-alkylations under acidic reaction conditions (last reaction, Scheme 6.3). Hence, alkylation of amines with tertiary alkyl groups is not usually possible without the use of highly stabilized carbocations which can be formed under basic reaction conditions. Rare exceptions are N-alkyla-tions of amines via radicals (Scheme 4.2), copper-catalyzed propargylations (Scheme 6.3), and the addition of amines to some Michael acceptors and allyl palladium or iridium complexes. Better strategies for the preparation of tert-alkylamines include the addition of Grignard reagents to ketone-derived imines [13] or the reduction of tert-alkyl nitro compounds. 

In a similar vein, De Lucchi and co-workers [24] prepared precursors to anti-inflammatory atrolactic acid derivatives. They used l,r-binaphthalene-2,2 -diol as an auxiliary for hydroxy aldehydes [Eq. (9)]. The symmetry of the diol ensures that only one isomer can be formed. Reaction of the diol with dibromoacelophenone produced the ketone (65 % yield). Grignard addition and hydrolysis gave only the R-hydroxyaldehyde. 

Iron catalysts are very effective for the substitution of acyl chlorides [Eq. (198) 439.440] and thiol esters [Eq. (199) 376] with Grignard reagents to yield ketones. 1.4-Addition of Grignard reagents to an alkylidenemalonate derivative, as shown in Eq. (158) [182,183] was also promoted with an iron catalyst, but the degree of the asymmetric induction was inferior to that of the reaction catalyzed by nickel. 

Etiolates formed by organocopper conjugate addition may be acylated cleanly by acid chlorides to give 3-diketones. Although 0- and C-acylation are both possible, the latter is favored by the use of acid chlorides rather than anhydrides and by the use of diethyl ether as solvent, rather than DME. Good yields of 3-diketones have been obtained by acylation of the anions derived from both acyclic and cyclic unsaturated ketones with cuprates, or in copper-catalyzed Grignard reactions. Some synthetic applications are given in Scheme 54. 

Esters react with two equivalents of an organolithium reagent to yield a tertiary alcohol in which two of the alkyl groups are derived from the organolithium reagent (Following fig.). The mechanism of the reaction is the same as that described in the Grignard reaction, i.e., nucleophilic substitution to a ketone followed by nucleophilic addition. 

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