Ketones with organometallic reagents

The formation of chiral alcohols from carbonyl compounds has been fairly widely studied by reactions of aldehydes or ketones with organometallic reagents in the presence of chiral ligands. Mukaiyama et al. 1081 obtained excellent results (up to 94% e.e.) in at least stoichiometric addition of the chiral auxiliary to the carbonyl substrate and the organometallic reagent. 

A diazonium salt reacts with copper(I) cyanide to form a benzonitrile. Because a cyano group can be hydrolyzed to a carboxylic acid, reduced to an amine or aldehyde, or converted to a ketone with organometallic reagents, this reaction provides easy access to a wide variety of benzene derivatives using chemistry described in Section 22.18. 

FIGURE 16.63 The reaction of ketones with organometallic reagents, followed by hydrolysis, yields tertiary alcohols. 

The asymmetric alkylation additions of the prochiral aldehydes and ketones with organometallic reagents have been studied extensively during the last several decades. Alkyltitanium complexes can be obtained from metal carbanions via titanation. Introduction of chirality at the titanium center or on the ligand (or a combination of both) enables the possibility of asymmetric induction in the carbonyl addition reaction. Since the alkyllithiums and Grignard reagents are... 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

Reaction of Nitriles with Organometallic Reagents Grignard reagents add to a nitrile to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 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 organometallic reagents to yield ketones. 

Bicyclic ketones react with organometallic reagents to give the products of addition from the less hindered face of the carbonyl group. 

Only a few reports deal with the reaction of thionoesters with organometallic reagents, and carbophilic addition was observed as the usual mode. The reaction of O-ethyl thioesters with alkyllithiums afforded, after methylation, good yields of monothioacetals, which can be hydrolysed to ketones [353]. 

Three different routes to the key compounds for the sila-Peterson elimination, the a-alkoxydisilanes 157, are described in the literature, namely A, reaction of silyllithium reagents with ketones or aldehydes B, addition of carbon nucleophiles to acylsilanes C, deprotonation of the polysilylcarbinols. In addition, method D, which already starts with the reaction of 2-siloxysilenes with organometallic reagents, leads to the same products. The silenes of the Apeloig-Ishikawa-Oehme type synthesized so far are summarized in Table 4. 

R. K. Dieter, Reaction of Acyl Chlorides with Organometallic Reagents A Banquet Table of Metals for Ketone Synthesis, Tetrahedron 1999, 55, 4177 -1236. 

Enediamine 93 undergoes an easy C-alkylation with a,/ -unsaturated ketones under comparable conditions and no cyclocondensation products are observed36. Similar C-alkylations with other electrophilic olefins such as unsaturated lactones, propenonitrile, vinyl sulfoxide, sulfone and phenylphosphonium bromide have been achieved36. All the adducts 135 exist predominantly as the imine form (see Section II.A). Treatment with organometallic reagents transforms the C-alkylated products into... 

Acid chlorides and esters can be converted to ketones or 3° alcohols with organometallic reagents. The identity of the product depends on the identity of R —M and the leaving group Z. 

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