Carboxylic acids metal enolates

Several syntheses of chiral camphor derivatives make use of the CH acidity of the methylene group attached in a-position to the carbonyl function (C-3). Thus, isoamyl nitrite converts camphor to 3-isonitrosocamphor which readily undergoes hydrolysis to the yellow camphorquinone. Bromination leads to 3-bromocamphor which is sulfonated to 3-bromocamphor-3-sulfonic acid with concentrated sulfuric acid. 3-Lithiated camphor obtained with phenyllithium is carboxylated to endo- and exo-isomers of camphor carboxylic acid. The Claisen condensation of camphor with esters of carboxylic acids provides enolized chiral 1,3-diketones, converting metal cations to chiral metal chelates. 

The chemical properties of heterometallic alkoxides are in general similar to their homometal counterparts (i) hydrolysis, (ii) alcoholysis, (iii) trans-esterification reactions, (iv) reactivity with carboxylic acids and enolic forms of chelating ligands such as /3-diketones/j6-ketoesters. The hydrolytic reactions are now widely employed for the preparation of homogeneous mixed metal-oxide ceramic materials and the rest have found wide applications for the synthesis of a variety of novel metallo-organic derivatives (sometimes unique), which are not often available through any other synthetic route. ... 

One of the standard methods for preparing enantiomerically pure compounds is the enantioselective hydrogenation of olefins, a,/3-unsaturated amino acids (esters, amides), a,/3-unsaturated carboxylic acid esters, enol esters, enamides, /3- and y-keto esters etc. catalyzed by chiral cationic rhodium, ruthenium and iridium complexes ". In isotope chemistry, it has only been exploited for the synthesis of e.p. natural and nonnatural H-, C-, C-, and F-labeled a-amino acids and small peptides from TV-protected a-(acylamino)acrylates or cinnamates and unsaturated peptides, respectively (Figure 11.9). This methodology has seen only hmited use, perhaps because of perceived radiation safety issues with the use of hydrogenation procedures on radioactive substrates. Also, versatile alternatives are available, including enantioselective metal hydride/tritide reductions, chiral auxiliary-controlled and biochemical procedures (see this chapter. Sections 11.2.2 and 11.3 and Chapter 12). 

In another approach, a glucose-derived titanium enolate is used in order to accomplish stereoselective aldol additions. Again the chiral information lies in the metallic portion of the enolate. Thus, the lithiated /m-butyl acetate is transmetalated with chloro(cyclopentadienyl)bis(l,2 5,6-di-0-isopropylidene- -D-glucofuranos-3-0-yl)titanium (see Section I.3.4.2.2.I. and 1.3.4.2.2.2.). The titanium enolate 5 is reacted in situ with aldehydes to provide, after hydrolysis, /i-hydroxy-carboxylic acids with 90 95% ee and the chiral auxiliary reagent can be recovered76. 

Methyl 2 hexynoate has been prepared by the esterification of 2-hexynoic acid, which wras prepared by the carboxylation of sodium hexynylide.4 a,/5-Alkynoic acids have generally been obtained by either carboxylation of metal alkynylides or by eliminationreactions.5In particular, they have been prepared by the elimination of enol brosylatcs and... 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

A method for enantioselective synthesis of carboxylic acid derivatives is based on alkylation of the enolates of /V-acyl oxazolidinones.59 The lithium enolates have the structures shown because of the tendency for the metal cation to form a chelate. 

Highly stereoselective aldol reactions of lithium ester enolates (LiCR1 R2CC>2R3) with (/0-2-(/ -tolylsulfiny I (cyclohexanone have been attributed to intermediacy of tricoordinate lithium species which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates.43 The O-metallated /<-hydroxyalkanoatcs formed by aldol-type reaction of carbonyl compounds with enolates derived from esters of alkanoic acids undergo spontaneous intramolecular cyclization to /1-lactones if phenyl rather than alkyl esters are used the reaction has also been found to occur with other activated derivatives of carboxylic acids.44... 

In contrast, some rr- allyl ruthenium complexes containing a chelating diphosphine ligand were the first metal complexes which favoured the anti-Markovnikov addition of carboxylic acids to terminal alkynes to form (Z)-enol and (E)-enol esters with high regioselectivity and stereoselectivity [17-19] according to Eq. (1). 

The procedure described here involves the metallation of dihydrofuran and subsequent alkylation with an alkyl iodide (bromides are much less reactive).5 The resulting substituted dihydrofuran, the intermediate postulated in the Larson procedure, is then treated with chromic acid to hydrolyze the enol ether and oxidize the resulting primary alcohol to the corresponding carboxylic acid as in the Larson procedure. The isolated oxidation product is of suitable purity for subsequent reactions, but if necessary, recrystallization from hexanes is readily accomplished. ... 

Selective activation of carboxylic acids. Carboxylic acids add exclusively to the triple bond of 1 to form an adduct (a) that rearranges to the (Z)-enol ester 2. Hydroxyl, phenolic, amino, and mercapto groups do not react with 1 under the same conditions. The esters (2) react with alkali metal salts of thiols and of selenophenol in THF at 0° to form thiol and selenol esters (3). 

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