Enol esters with carboxylic acids

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

The chiral alcohols are mainly employed as esters or enol ethers. Esters with carboxylic acids can be obtained by any convenient esterification technique. Dienol ethers were obtained by transetherification with the ethyl enol ether of a 1,3-diketone, followed by Wittig reaction8 silyldienol ethers were obtained by the method of Danishefsky11-12 and simple enol ethers by mercury-catalyzed transetherification13. Esters and enol ethers have been used as chiral dienophiles or dienes in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.). (R)-l-Phenylethanol [(R)-4] has been used for enantioselective protonation (Section C.) and the (S)-enantiomer as chiral leaving group in phenol ethers for the synthesis of binaphthols (Section B.2.) the phenol ethers are prepared as described for menthol in the preceding section. (S)-2-Octanol [(S)-2] has found applications in the synthesis of chiral allenes (Section B.I.). 

For acyclic systems, the anti diastereoselectivity of the (i )-enolates is lower than the syn diastereoselectivity of comparable (Z)-enolates. For example, carboxylic acid esters, which form predominantly ( )-enolates, react with aldehydes with high anti selectivity only in those cases where bulky aromatic substituents are in the alcoholic part of the ester22 25. 

Triple bonds can give enol esters or acylals when treated with carboxylic acids. Mercuric salts are usually catalysts, and vinylic mercury compounds... 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Fig. 13.65. Acylation of various malonic diester or malonic half-ester enolates with carboxylic acid chlorides. Spontaneous decarboxylation of the acylation products to furnish /3-ketoesters (see variants 1 and 2) and transformation of the acylation products into /3-ketoesters by way of alcoholysis/decarboxylation (see variant 3).

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 sulfmylation of esters, - lactones, carboxylic acids, > amides and lactams may be effected by reacticm of the corresptHiding lithium enolates in THF at -78 to 0 C with dimethyl or difdie-nyl disulfides, or, less conunmily, with methyl or fdienyl sulfmyl halides. The enolates of ketones, however, are insufficioitly nucleq diilic to react with dialkyl sulfides unless HMPA is added to the re-acticm mixture, although they do react smoothly with diaryl sulfides. This difference allows the selective sulfenylation of esters in the presence of ketones (entry 5, Table 3). ... 

Acylation of a-lithio-a-phosphonylalkyl sulfides (440) with carboxylic acid esters was utilized as a facile route to a-alkylsulfenyl substituted p-ketophos-phonates (441). Keto-enol tautomerism of these new compounds in different solvents as well as regiochemistry of alkylation and acylation reactions and usefulness for HWE olefination reactions were studied (Scheme 104). ... 

Esters of carboxylic acids undergo oxidative coupling in the a positions with respect to ester groups when treated in the enolate form with ferric chloride. Thus ethyl acetate stirred with lithium diisopropylamide in tet-rahydrofuran at -78 °C for 10 min and subsequently with anhydrous ferric chloride in dimethylformamide yields 69% of diethyl succinate [911]. 

Condensation of alkynes with carboxylic acids. Addition of RC(X)H to alky-nes forms enol carboxylates. On the other hand, heterocyclization occurs with acetylenedicarboxylic esters. ... 

By the reaction of theenolatc of camphor with carboxylic acid esters or chlorides, 1,3-diketones [better formulated as enols. such as (hydroxymethylene)camphor] are obtained. When trifluo-roacetic acid or heptafluorobutanoic acid are used, the corresponding diketones (abbreviated as tfc or hfc, respectively) have been successfully used as ligands for lanthanides and these are used as chiral shift reagents in NMR spectroscopy12. The complex Eu(hfc)3 [derived from ( + )-camphor)] 3 was used as a chiral catalyst for enantioselective Diels-Alder-type cycloadditions of aldehydes to dienes (Section D.l.6.1.1.1.2.4.). 

Camphorsulfonyl chlorides 45 readily form amides by reaction with amines. On reduction of the carbonyl group, alcohols, e.g., 46 and 47, are obtained which are extremely useful auxiliaries for many purposes. Thus, esters are formed with carboxylic acids which may then undergo enolate reactions (SectionsD.1.1.1.3.2., D.l.5.2.1., D.3. and D.7.1.) or act as dienophiles and dipolar-ophiles (Sections D.l.6.1.1.1.2.2.1. and D.l.6.1.2.1.). Enol ethers of these auxiliaries give [2 + 2] cycloadditions with dichloroketene (Section D.l.6.1.3.), while carbamate derivatives have been used in acyliminium reactions (Section D.l.4.5.). Generally, steric hindrance in the sulfonamide group improves the stereoselectivity of the reactions and, therefore, the amides with diisopropylamine and dicyclohexylamine are used as auxiliaries both enantiomers of the dicyclohexyl derivative are commercially available. 

Phosphoramidites (89), derived from enamines, react with carboxylic acids in an irreversible manner because of the low basicity of the eliminated enamine. The anhydrides (90) may also conveniently be obtained from enol phosphites. Reactions of (89) with phenol were also studied and the kinetics found to be characteristic for bimolecular processes . In contrast to other carboxylic acid halides, acyl fluorides give tervalent phosphorus fluorides with tervalent esters (Scheme 7). ... 

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. 

Alpha halogenation, as described in the previous section, occurs readily with ketones and aldehydes, but not with carboxylic acids, esters, or amides. This is likely due to the fact that these functional groups are not readily converted to their corresponding enols. Nevertheless, carboxylic acids do undergo alpha halogenation when treated with bromine in the presence of PBt3. 

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