Synthesis of ketones and

Examples of this approach to the synthesis of ketones and carboxylic acids are presented in Scheme 1.4. In these procedures, an ester group is removed by hydrolysis and decarboxylation after the alkylation step. The malonate and acetoacetate carbanions are the synthetic equivalents of the simpler carbanions that lack the additional ester substituent. 

Organopalladium intermediates are also involved in the synthesis of ketones and other carbonyl compounds. These reactions involve acylpalladium intermediates, which can be made from acyl halides or by reaction of an organopalladium species with carbon monoxide. A second organic group, usually arising from any organometallic reagent, can then form a ketone. Alternatively, the acylpalladium intermediate may react with nucleophilic solvents such as alcohols to form esters. 

Relatively acidic carbon acids such as malonic esters and jS-keto esters were the first class of carbanions for which reliable conditions for alkylation were developed. The reason being that these carbanions are formed using easily accessible alkoxide ions. The preparation of 2-substiuted /i-kcto esters (entries 1, 4, and 8) and 2-substituted derivatives of malonic ester (entries 2 and 7) by the methods illustrated in Scheme 1.5 are useful for the synthesis of ketones and carboxylic acids, since both /1-ketoacids and malonic acids undergo facile decarboxylation ... 

Examples of this approach to the synthesis of ketones and carboxylic acids are presented in Scheme 1.6. In these procedures, an ester group is removed by hydrolysis and decarboxylation after the alkylation step. The malonate and acetoacetate carbanions are the synthetic equivalents of the simpler carbanions lacking the ester substituents. In the preparation of 2-heptanone (entries 1, Schemes 1.5 and 1.6), for example, ethyl acetoacetate functions as the synthetic equivalent of acetone. It is also possible to use the dilithium derivative of acetoacetic acid as the synthetic equivalent of acetone enolate.29 In this case, the hydrolysis step is unnecessary, and decarboxylation can be done directly on the alkylation product. 

Scheme 1.6. Synthesis of Ketones and Carboxylic Acid Derivatives via Alkylation Followed by Decarboxylation... 

Structure of the Carbonyl Group 817 18-3 Nomenclature of Ketones and Aldehydes 818 18-4 Physical Properties of Ketones and Aldehydes 820 18-5 Spectroscopy of Ketones and Aldehydes 822 18-6 Industrial Importance of Ketones and Aldehydes 828 18-7 Review of Syntheses of Ketones and Aldehydes 829 18-8 Synthesis of Ketones from Carboxylic Acids 833 18-9 Synthesis of Ketones and Aldehydes from Nitriles 833... 

Asymmetric synthesis of ketones and acids A new synthesis of chiral ketones and acids starts with the reaction of an anhydride or an acid chloride with either I-or li-ephedrin to form a chiral N,N-disubstituted amide (1) in almost quantitative yield. The amide (1) is then alkylated via the anion to give 2, which contains three asymmetric centers. Acid hydrolysis of 2 gives a carboxylic acid (3) with an optical yield of 75% (two examples). Cleavage of 2 with methyllithium gives a methyl ketone (4), in optical yields of 45-75%. 

Synthesis of ketones and aldehydes from acid chlorides (or esters) via reaction of N-methoxy-N-methylamides with a Grignard or organolithium reagent (see 1 edition). 

Heteroatom-stabilized Carbanions. Heteroatom-stabilized and allylic carbanions serve as homoenolate anions and acyl anion equivalents, e.g. a-anions of protected cyanohydrins of aldehydes and Q ,/3-unsaturated aldehydes are intermediates in general syntheses of ketones and Q ,/3-unsaturated ketones (eq 36). Allylic anions of cyanohydrin ethers may be a-alkylated (eq 37) or, if warmed to —25°C, may undergo 1,3-silyl migration to cyanoenolates which may be trapped with TMSCl. Metalated Q -aminonitriles of aldehydes are used for the synthesis of ketones and enamines (eq 38). Similarly, allylic anions from 2-morpholino-3-alkenenitriles undergo predominantly a-C-alkyl-ation to give, after hydrolysis, a,/3-unsaturated ketones (eq 39). ... 

Use of /3-hetero-snbstitnted allylic electrophiles for the synthesis of ketones and other fnnctional derivatives. 

TABLE 4. Pd-Catalyzed Synthesis of Ketones and Aldehydes Via Cyclic Carhopalladation-Carhonylative Trapping with Carhanion and Hydride Sonrces ... 

The epoxy esters formed in the Darzens condensation have been used in the synthesis of ketones and aldehydes. The acids formed by saponification of the esters... 

More recently, several papers reporting the solid phase synthesis of peptide aldehydes have been published. Dinh and Amstrong (61) outline the use of Weinreb-type amides on solid support for the synthesis of ketones and aldehydes Ede and Bray (62) report a new linker based on the oxazolidine moiety and use this method with Multipin technology Galeotti et oL (63) apply their thiazolidinyl linker to a solid support. The great interest in these aldehydic compounds has also been demonstrated by the fact that the Weinreb amide resin is now commercially available from Bachem and Novabiochem. 

Alkyldichloroboranes can be converted into a host of valuable organoborane intermediates via the hydridation-stepwise hydroboration procedure. The procedure enables a general synthesis of unsymmetrical dialkylboranes and totally mixed trialkylborane intermediates for the synthesis of ketones and tertiary alcohols, respectively. 

Reaction of tetrasubstituted tin derivatives with acid chlorides is a useful method for the synthesis of ketones, and some further variations have been described this year. The stannylethynyl ether (141, = Me, Ph) reacts with... 

Chikashita, H. Ishihara, M. Takigawa, K Itoh, K. (1991). Synthetic ap>phcation of benzothiazole ring system as an on-off type of leaving group. Synthesis of ketones and carboxylic acid derivatives from 2-(l-substituted 1-hydroxyalkyl)- and 2-(l-hydroxyalkyl)benzothiazoles. Bidl. Chem. Soc. Jpn. Vol. 64, pp. 3256-3261, ISSN. 

Rahman, O., Langstrom, B., Kihlberg, T., Llop, J. 2005. Methods for carbon isotope labeling synthesis of ketones and amines by Suzuki coupling reactions using carbon- isotope monoxide. PCT Int. Appl. 

Abe, S. Miyaura, N. Suzuki, A. 1992. The palladium-catalyzed cross-coupling reaction of enol acetates of a-bromo ketones with 1-alkenyl-, aryl-, or alkylboron compounds A facile synthesis of ketones and their enol acetates. J. Am. Chem. Soc. 65 2863-2865. 

Scheme 1.5. Synthesis of Ketones and Carboxyik Add Derivatives via Alkylation...

Synthesis of ketones and carboxylic acid derivatives via alkylation techniques... 

Dinh TQ, Armstrong RW (1996) Synthesis of ketones and aldehydes via reactions of Weimeb-type amides on solid support. Tetrahedron Lett 37 1161-1164... 

Zadel G, Breitmaier E (1992) A one-pot synthesis of ketones and aldehydes from carbon dioxide and organolithium compounds. Angew Chem Int Ed Engl 31 1035-1036... 

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