Ketone synthesis from acid halides

No overaddition of the organometallic reagent, a side reaction that is typical for ketone synthesis from acid halides, was observed. 

D. A. Shirley, The Synthesis of Ketones from Acid Halides and Organometallic Compounds of Magnesium, Zinc and Cadmium, Organic Reactions 8, 28 (1954). 

D. A. Shirley, The synthesis of ketones from acid halides and organometallic compounds of magnesium, zinc, and cadmium, Org. React. 1954, 8, 28-58. 

Friedel-Crafts acylation of alkenes (Daizens-Nenitzescu reaction ) with unsaturated acylium ions generated from acid halides and Lewis acids constitutes a general synthesis of divinyl ketones. 

The synthesis of ketones from acid halides and organometallic compounds of magnesium, zinc and cadmium... 

The selective one-pot synthesis of ketones from acid halides and functionalized alkynes based on a hydrozirconation-copper(I)-catalyzed addition reaction has also been reported as a very efficient transformation even in the presence of very labile functionality (Scheme 12.12) [14]. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

For the ketone synthesis via the present protocol, acid chlorides are useful precursors, in deed. Nevertheless, carbonylative cross coupling with organic halides is strategically the most simple and direct way to this purpose. The palladium-catalyzed carbonylative cross-coupling reaction with various organic halides has been extensively investigated, because of its merits from synthetic as well as phenomenal point of view. Acid chlorides are not always readily available, and their preparation is not always compatible with many sensitive functionalities. Therefore the development of this type of reaction widens the scope of the ketone synthesis in the present protocol because of the ready availability and storability of organic halides and pseudohalides. 

The acyliron(0) complex (102) has been isolated and subjected to the same nucleophilic displacement (or equivalently oxidative addition) with excellent correlation (Scheme 39). The same species is also readily available from acid chlorides (i.e. formation of 103), but the overall process has not been widely used in the synthesis of ketones (Scheme 40). The final step of the process, a reductive elimination of acyliron(II) complex (104) or (105), is quite rapid and it has not been possible to isolate and identify the presumed intermediates in this case (Scheme 41). Since the oxidative addition of the acyliron complex with the alkyl halide is extremely mild, the corresponding ketone formed in the reaction is not subject to attack by organometallic reagents and no tertiary tdcohol is formed. 

The alkylation of protected cyanohydrin anions constitutes an excellent method for ketone synthesis. Generally the anions are generated from aliphatic or aromatic aldehyde protected cyanohyd with LDA under nitrogen at -78 C. The addition of an alkyl halide produces the protected ketone cyanohydrin. The carbonyl group is then liberated by successive treatment with dilute acid and dilute aqueous base. This method is applicable for the synthesis of buflomedil. ... 

Conductivity measurements have revealed that DMF and carboxylic acid chlorides form salt-like adducts (22) in an equilibrium reaction (equation 12). Such adducts can be prepared either from DMF and acid halides (chlorides and bromides) or from chloromethyleneiminium salts and salts of carboxylic acids. Acyloxyiminium salts (23) can be prepared in the pure state by reacting acid amides with carboxylic acid chlorides in the presence of silver trifluoromethanesulfonate (equation 13). Salts of type (24 equation 14) are regarded as being intermediates in the synthesis of ketones from carboxylic acids and Grignard reagents in the presence of a-chloroenamines as well as in the preparation of acyl halides (F, Cl, Br, I) by action of a-haloenamines on carboxylic acids. ... 

Tt-Allylnickel halides. Billington has reviewed the preparation of these complexes from allylic halides using Ni(CO)4 or Ni(COD)2, and their use in synthesis, mainly of natural products (54 references). These complexes react with a wide range of both aliphatic and aryl bromides or iodides as well as aldehydes, ketones, epoxides, and quinones. One advantage is that both allyl ligands react. They do not react with acid chlorides, esters, ethers, nitriles, or acetals. 

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