Enol esters reaction with carboxylic acids

Dixneuf reported using the ruthenium catalyst 25 in the synthesis of enol ethersfrom alkynes and carboxylic acids. Both formation of enol esters by Markovnikov addition of a carboxylic acid to a terminal alkyne (Eq. 9) and formation of dioxolanones (Eq. 10) was successful. In both cases the reactions were carried out homogeneously at 100 °C and the catalyst was recovered by cooling. Filtration led to recovery of the catalyst which was successfully recycled multiple times, as shown by experiments where a single 0.1 mmol sample of catalyst was used to prepare over 50 mmol of a mixture of enol esters using different carboxylic acids and different alkynes in a series of sequential reactions with different substrates and the same catalyst sample. 

Thioesters and Related Compounds.—A new general route to thio- and seleno-esters employs the versatile push-pull acetylene (157) as an acyl group transfer reagent. Reaction with carboxylic acids (which may contain unprotected OH, NH2, or SH groups) affords enol esters (158) which give thio- or seleno-esters on... 

Carboranyl acid halides can be very easy prepared. We have studied the acylation of malononitrile and acetoacetic ester by methylcarboranyl carboxylic acid chloride (15). The reaction with malononitrile leads to the compound 17a, which exists also as a enol form, similar to compound 13. Compound 17a can be methylated to give compound 17b, a novel synthon for the preparation of wide range of heterocyclic compounds (Scheme 7). 

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). ... 

A relatively general procedure for the preparation of dialkyl 2-oxoalkylphosphonates by direct acylation of dialkyl 1-lithioalkylphosphonates has been introduced by Corey and Kwiatkowski in 1966. The use of phosphonate carbanions as nucleophiles in reaction with carboxylic esters avoids the problems associated with the Michaelis-Arbuzov reaction. The reaction sequence is initiated by the addition at low temperature of dimethyl 1-lithiomethylphosphonate (2 eq and frequently more) to a carboxylic ester (1 eq) to give the transient lithium phosphonoenolate. The dimethyl methylphosphonate, being readily available and easy to eliminate, is the most frequently used phosphonate, but other phosphonates such as diethyl and diisopropyl methylphosphonates can be used. When the resulting enolate is treated with acid, dimethyl 2-oxoalkylphosphonate is produced in moderate to good yields (45-95%, Scheme 7.20). The reaction has been achieved with... 

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. 

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.). 

The very acidic (in the region of pK 10) 1,3-dicarbonyl compounds (—CO—CH— CO—), diketones, and ketoesters are readily converted into the enolates by reaction with alkali hydrides in polar as well as in apolar solvents [1]. Also some acidic mono-ketones, e.g., PhCH2COCH3, react smoothly with sodium hydride [4], Potassium hydride has been used to convert aldehydes into the enolates [2, compare 3]. A serious drawback of this method is the handling of the commercially available potassium hydride, which inter alia involves removal of the protecting mineral oil. Reaction of kinetically less acidic ketones and carboxylic esters with alkali hydrides, in general, gives rise to extensive formation of self-condensation products [3,6],... 

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). ... 

Therefore, diethyl malonate is deprotonated but not ethyl acetate. Moreover, the ethoxide ion is strong enough to deprotonate the diethyl malonate quantitatively such that all the diethyl malonate is converted to the enolate ion. This avoids the possibility of any competing Claisen reaction since that reaction needs the presence of unaltered ester. Diethyl malonate can be converted quantitatively to its enolate with ethoxide ion, alkylated with an alkyl halide, treated with another equivalent of base, then alkylated with a second different alkyl halide (Fig.R). Subsequent hydrolysis and decarboxylation of the diethyl ester yields the carboxylic acid. The decarboxylation mechanism (Fig.S) is dependent on the presence of the other carbonyl group at the P-position. 

An alternative reagent, trimethylsilyldiazomethane in hexane, is commercially available and appears useful for preparation of bile acid methyl esters [62], Like carboxylic acid groups, hydroxyl groups also require protection prior to GC-MS analysis. A common and mild method to prepare trimethylsilyl (TMS) ethers is to react the sample with a mixture of dry pyridine, hexamethyldisilazane (HMDS), and trimethylchlorosilane (TMCS), 3 2 1 or 9 3 1 (by volume) with, or without heating [32], However, if 0X0 groups are present in the bile acid, this reaction can yield enol-TMS ethers and multiple products. This artifact can be avoided by converting the 0X0 group into an oxime, usually a methyloxime (MO). To do this, the sample is dissolved in 50 pL pyridine with 5 mg methoxyammonium chloride and heated for 30 min at 60°C [32]. 

Analogs of the ester enolate derived from higher carboxylic acids can also be prepared by the addition of an organometal-lic agent to methyl 2-trimethylsilylacrylate (2). The resultant ester enolate from the Michael addition can be used for a subsequent Peterson alkenation reaction when reacted with a carbonyl compound (eq 4). ... 

Peptide Coupling Reagent. Woodward s reagent K reacts with an / -protected amino acid, under mild conditions, in the presence of a tertiary amine to form an enol ester intermediate, e.g. (1). This enol ester acylates an amino acid ester or peptide to afford the elongated peptide derivative (eq 1). The isoxazolium salt is not soluble in organic solvents, but as it reacts with a carboxyl group in the presence of a tertiary amine the reaction mixture clears. 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

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