Enol esters, synthesis

Employing a resin-bound catalyst 92 for enol ester synthesis is an important extension of this strategy [48]. It is noteworthy that the solid-supported catalyst 92 displays the same activity as its homogeneous analog 107 and is amenable for recycling. 

Scheme 25 Enol ester synthesis catalyzed by Ti/Ru heteropolymetallic complexes...

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... 

Acetoacetic ester synthesis (Section 21 6) A synthetic method for the preparation of ketones in which alkylation of the enolate of ethyl acetoacetate... 

The smooth conversion of the enol acetate (151) into an A -acyl derivative (152) under extremely mild conditions points to the high acylating capacity of these esters. This cleavage of isoxazolium salts is also caused by other anions of carboxylic acids, and thus they can be readily converted to reactive enol esters. A very convenient and specific synthesis of peptides due to Woodward et is based on... 

Both the malonic ester synthesis and the acetoacetic ester synthesis are easy to cany out because they involve unusually acidic dicarbonyi compounds. As a result, relatively mild bases such as sodium ethoxide in ethanol as solvent can be used to prepare the necessary enolate ions. Alternatively, however, it s also possible in many cases to directly alkylate the a position of monocarbonyl compounds. A strong, stericaliy hindered base such as LDA is needed so that complete conversion to the enolate ion takes place rather than a nucleophilic addition, and a nonprotic solvent must be used. 

Alpha hydrogen atoms of carbonyl compounds are weakly acidic and can be removed by strong bases, such as lithium diisopropylamide (LDA), to yield nucleophilic enolate ions. The most important reaction of enolate ions is their Sn2 alkylation with alkyl halides. The malonic ester synthesis converts an alkyl halide into a carboxylic acid with the addition of two carbon atoms. Similarly, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone. In addition, many carbonyl compounds, including ketones, esters, and nitriles, can be directly alkylated by treatment with LDA and an alkyl halide. 

Dimethyldioxirane DMDO discovered by Murray and coworkers, is a superior choice for the epoxidation of most olefins, giving comparable or higher yields than m-CPBA-based epoxidation [21]. Proceeding rapidly under neutral and mild conditions, it is especially well suited for the synthesis of sensitive epoxides of enol esters, enol lactones [22], and enol ethers [23]. The reaction is stereospecific, gen-... 

This novel resin-bound CHD derivative was then utilized in the preparation of an amide library under microwave irradiation. Reaction of the starting resin-bound CHD with an acyl or aroyl chloride yields an enol ester, which, upon treatment with amines, leads to the corresponding amide, thus regenerating the CHD. This demonstrates the feasibility of using the CHD resin as a capture and release reagent for the synthesis of amides. The resin capture/release methodology [126] aids in the removal of impurities and facilitates product purification. 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

Solutions of acetyl nitrate have also been used for the synthesis of a-nitroketones from enol esters and ethers. ° ... 

Optimization of biological properties in a series of miticidal and mite ovicidal 2-aryl-l,3-cycloalkanediones, Ia,b, and enol esters, II, was achieved through analog synthesis and testing supported by the development of quantitative structure/ activity trends during the course of the project. QSAR equations developed during an initial phase provided the basis for both... 

In the early 1970 s potent acaricidal activity in 3-aryl-4-hy-droxy-coumarins. III, and 2-aryl-l,3-indanediones, IV, and their enol esters was discovered at Union Carbide (1,2). Extensive synthesis and screening of analogs in the dione and enol ester series led to the field test candidates Va and Vb, active against both motile forms (mite) and eggs. Va and Vb embodied certain structural and physicochemical features shown by published QSAR studies (2,3) to be important in determining the level of activity in the 1,3-indanedione series (1) the dimension D2 across the aryl ring must be near 7A and symmetry is preferred (2) the... 

Addition of Carboxylic Acids Synthesis of Enol Esters... 

Silyl enol ethers, enol esters and alkyl enol ethers of ketones and aldehydes can be C-alkylated with reactive alkylating agents in the presence of Lewis acids86-90. However, information regarding the use of these reactions for diastereoselcctive or asymmetric synthesis is still limited. 

Carboxylic acids can be alkylated in the a position by conversion of their salts to dianions [which actually have the enolate structures RCH=C(0 )21497] by treatment with a strong base such as lithium diisopropylamide.1498 The use of Li as the counterion is important, because it increases the solubility of the dianionic salt. The reaction has been applied1499 to primary alkyl, allylic, and benzylic halides, and to carboxylic acids of the form RCHjCOOH and RR"CHCOOH.1454 This method, which is an example of the alkylation of a dianion at its more nucleophilic position (see p. 368), is an alternative to the malonic ester synthesis (0-94) as a means of preparing carboxylic acids and has the advantage that acids of the form RR R"CCOOH can also be prepared. In a related reaction, methylated aromatic acids can be alkylated at the methyl group by a similar procedure.1500... 

Chain extension.1 An alternative lo the malonic ester synthesis involves ttlkylnliim of r-bmyl lithioacetate, Yields arc improved by preparation of the enolate With l.il( A (4, 306) ui 78. Alkylaliun proceeds in highesl yields at -78 to -35"... 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

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