Carboxylic acids silyl enol ether

As in the Japp-Klingemann reaction, when Z is an acyl or carboxyl group (in the case of R2CH—Z), it can be cleaved. Since oximes and nitroso compounds can be reduced to primary amines, this reaction often provides a route to amino acids. As in the case of 12-4, the silyl enol ether of a ketone can be used instead of the ketone itself. Good yields of a-oximinoketones (20) can be obtained by treating ketones with fert-butyl thionitrate. ... 

Monoalkyl ethers of (R,R) 1,2-bis[3,5-bis(trifluoromethyl)phenyl]ethanediol, 24, have been examined for the enantioselective protonation of silyl enol ethers and ketene disilyl acetals in the presence of SnCU (Scheme 12.21) [25]. The corresponding ketones and carboxylic acids have been isolated in quantitative yield. High enantioselectivities have been observed for the protonation of trimethylsilyl enol ethers derived from aromatic ketones and ketene bis(trimethylsilyl)acetals derived from 2-arylalkanoic acids. 

Esters of allylic alcohols can be rearranged to y,<5-unsaturated carboxylic acids via the O-trimcthylsilyl ether of the ester enolate.161 This rearrangement takes place under much milder conditions than the ortho ester method. The reaction occurs at or slightly above room temperature. Entries 14 and 15 of Scheme 6.12 are examples. The example in entry 16 is a rearrangement of the enolate without intervention of the silyl enol ether. 

Formation of a silyl enol ether will generate an allyl vinyl ether which after rearrangement can be desilylated to give a carboxylic acid. 

Homologated (E)-unsaturated carboxylic acids The anion (2) of 1, formed with LDA in THF at — 50°, is alkylated exclusively at the /-position. The products (3) are converted into a,/S-unsaturated acids (4) on oxidation and thermolysis. This behavior contrasts with that of the anion of the corresponding silyl enol ether, CH3SCH2CH=C(CN)OSi(CH3)3, which undergoes exclusively a-alkylation.2... 

You might think that the presence of the acidic proton in a carboxylic acid would present an insuperable barrier to the formation and use of any enol derivatives. In fact, this is not a problem with either the lithium enolates or the silyl enol ethers. Addition of BuLi or LDA to a carboxylic acid... 

Sometimes it is better to convert the lithium enolate into the silyl enol ether before heating to accomplish the [3,3]-sigmatropic rearrangement. In any case, both products give the unsaturated carboxylic acid on work-up. 

Most frequently the reactions are performed by treating the crude silyl enol ether with MCPBA at 0-25 C in dichloromethane. Solvent effects have been observed. Thus treatment of enol ether (53) with MCPBA in ether resulted in isolation of the benzoate (54). This was considered to arise as a result of the increased nucleophilicity of the residual carboxylic acid in ether over that in dichloromethane. Isolation of the silyloxy epoxide by an analogous ethereal oxidation suggests perhaps that the 1,4-silyl migration is intrinsically less facile in this solvent. Generally however the process is efficient and simple substrates are readily oxygenated (Scheme 11). 

BINOL-Me, and stoichiometric amounts of 2,6-dimethylphenol as an achiral proton source, protonation of the ketene bisftrime-thylsilyl)acetal derived from 2-phenylpropanoic acid proceeds at —80°C to give the (5)-carboxylic acid with 94% ee. (/ )-BINOL-Me is far superior to (/ )-BINOL as a chiral proton source during the catalytic protonation, and 2,6-dimethylphenol is the most effective achiral proton source. In addition, it is very important that the molar quantity of SnCU should be less than that of (/ )-BINOL-Me to achieve a high enantioselectivity. For the reaction of 2-phenylcyclohexanone, however, the use of tin tetrachloride in molar quantities lower than BINOL-Me remarkably lowers the reactivity of the chiral LBA (eq 3). Excess SnCLt per chiral proton source, in contrast, promotes this protonation. In the protonation of silyl enol ethers less reactive than ketene bis(trialkylsilyl) acetals, chelation between excess tin tetrachloride and 2,6-dimethylphenol prevents the deactivation of the chiral LBA. 

Silyl enol ethers, which are readily generated regiospecifically from ketones, can also be reduced to al-kenes, particularly by hydroboration. " Hydroboration of silyl enol ethers results in the addition of boron to the 3-c on of the double bond to afford fra/is-3-trimethylsilyloxy organoboranes, which in cyclic systems undergo anti elimination in the presence of acid to give the alkenic product (Scheme 42). A number of acids have been tested successfully, including carboxylic acids, BF3-Et20 and... 

Silyl enol ethers with a chiral auxiliary appendage react with achiral aldehydes to produce, after cleavage of the auxiliary group, enantiomerically enriched [3-hydroxy carboxylic acids. 

Acylsilanes are versatile intermediates for carbon-carbon bond formation reactions, and may serve as precursors for the synthesis of silyl enol ethers, aldehydes, or carboxylic acids. In the presence of a base or certain nucleophiles, they undergo the Brook rearrangement, where the silyl moiety migrates from carbon to oxygen (see below in this section). 

Alkylation or acylation of ketones, sulfides, and amines. This reagent generally reacts with alcohols or carboxylic acids to form 2,2,2-trifluoroethyl ethers or esters in satisfactory yields, except in the case of alcohols prone to dehydration. The reaction of these ethers provides a simple synthesis of unsymmetrical sulfides (equation I). A similar reaction can be used for preparation of secondary amines or amides (equation II). Enolate anions (generated from silyl enol ethers with KF) can be alkylated or acylated with a or b (equation III). Use of Grignard reagents in this type of coupling results in mediocre yields. 

Shortly after, the same group published a study where readily available carboxylic acids, diacids, and N-protected amino acids were screened as proton sources [6]. The same substrates were used in the presence of citric acid instead of HF. This catalytic system displayed somewhat lower selectivity. For example, by using similar experimental conditions in the presence of citric acid at —10 °C, the enantioseiective protonation of silyl enol ether 5c afforded the corresponding ketone 7c in excellent yield but lower enantioselectivity (up to 75% ee, Scheme 7.4, to be compared with entry 3, Table 7.1). However, upon further optimization, this process seems appealing in terms of simplicity, practicability, environmental concerns, and cost therefore, adjustable for industrial use. 

The carbenoid reaction between alkyl diazoacetates and enol ethers, enol acetates and silyl enol ethers furnishes P-oxycyclopropane carboxylates (see Tables 2, 4, 5, 6, 7 and Scheme 5). The recently recognized synthetic versatility of these donor/acceptor-substituted cyclopropanes i 2,io3) (precursors of 1,4-dicarbonyl and P, 7-unsaturated carbonyl compounds, 4-oxocarboxylic acids and esters, among others) gave rise to the synthesis of a large number of such systems with a broad variation of substituents p-acetoxycyclopropanecarboxylates , p-alkoxy- or p-aryloxysubstituted cyclopropanecarboxylates 2-alkoxy-1-methyl-1-cy-... 

Silyl enol ethers of carboxylic acid esters can be alkylated by means of (CH3)3CC1 in the presence of ZnCl2 to give a-butylated products.The... 

Lithium enolates of carboxylic acids Enamines and silyl enol ethers Reactions with Other Electrophiles... 

Asymmetric Mannich-type reactions provide useful routes for the synthesis of enantiomerically enriched P-amino ketones or esters [48a, 48b]. For the most part, these methods involve the use of chirally modified enolates or imines. Only a handful of examples has been reported on the reaction of imines with enolates of carboxylic acid derivatives or silyl ketene acetals in the presence of a stoichiometric amount of a chiral controller [49a, 49b, 49c]. Reports describing the use of a substoichiometric amount of the chiral agent are even more scarce. This section contains some of the most recent advances in the field of catalytic enantioselective additions of lithium enolates and silyl enol ethers of esters and ketones to imines. 

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