Organometallic reagents reactions with ketones

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. 

In a number of reactions, such as those leading to amidines and the formation of ketones by reaction with organometallic reagents, the cyanopyridines behave normally, and these call for no comment. The simultaneous attack of propyl magnesium bromide on the cyano group and C(4) in nicotinonitrile has been mentioned (p. 200). 

The oxidation of alcohols to aldehydes and ketones by chromium(VI) reagents opens up important synthetic possibilities based on further reactions with organometallic reagents. 

Diphenylphosphinic mixed anhydrides have been utilized to form peptide bonds. Peptides are easier to isolate by this method than by employing 1,3-Dicyclohexylcarbodiimide. These anhydrides are the method of choice for the formation of amides of 2-alkenoic acids (eq 1 ). Carbodiimide and acyl carbonate methods proved to be inferior. Primary amines result in better yields than secondary amines. This activation protocol can be employed to form thiol esters (eq 2) p-Amino acids are readily converted to p-lactams with chlorodiphenylphosphine oxide (eq 3). Secondary amines work best. This activation protocol has been utilized to convert acids to amines via a Curtius rearrangement. Phenols have been generated from diene acids, presumably via base-induced elimination of diphenylphosphinic acid from the mixed anhydrides to form ketenes which spontaneously cyclize. Acids have been converted to ketones via activation followed by reaction with organometallic reagents (eq 4)."... 

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. 

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. 

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. 

With the usual reaction of organometallic reagents with acid derivatives (ester or acid chloride), the starting materials can add two equivalents of organometallic compound. The ketone generated after the first addition is quite reactive, and there is quite no selectivity between it and the starting acid derivative ... 

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

Reaction of organometallic reagents with aldehydes and ketones... 

Reaction of Organometallic Reagents with Aldehydes and Ketones... 

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. 

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