Ethers, enol from esters

Template reactions between malonaldehydes and diamines in the presence of copper(II), nickel(II) or cobalt(II) salts yield neutral macrocyclic complexes (equation 15).99-102 Both aliphatic102 and aromatic101 diamines can be used. In certain cases, non-macrocyclic intermediates can be isolated and subsequently converted into unsymmetrical macrocyclic complexes by reaction with a different diamine (Scheme ll).101 These methods are more versatile and more convenient than an earlier template reaction in which propynal replaces the malonaldehyde (equation 16).103 This latter method can also be used for the non-template synthesis of the macrocyclic ligand in relatively poor yield. A further variation on this reaction type allows the use of an enol ether (vinylogous ester), which provides more flexibility with respect to substituents (equation 17).104 The approach illustrated in equation (15), and Scheme 11 can be extended to include reactions of (3-diketones. The benzodiazepines, which result from reaction between 1,2-diaminobenzenes and (3-diketones, can also serve as precursors in the metal template reaction (Scheme 12).101 105 106 The macrocyclic complex product (46) in this sequence, being unsubstituted on the meso carbon atom, has been shown to undergo an electrochemical oxidative dimerization (equation 18).107... 

If silylation alone (0.2 ml of BSTFA + 0.05 ml of TMCS) without the preceding methoximation is carried out, TMS enol ether—TMS esters are produced from keto acids. Using the procedure described, methoxime-TMS esters of keto acids and TMS ether—TMS esters of hydroxy acids are produced. Unsubstituted acids give TMS esters. The procedure eliminates possible losses of the derivatives, which can be caused by, e.g., evaporation of the solvent between the esterification and the silylation steps, and is quantitative. SE-30, OV-17 and OV-22 can be used and retention data on these stationary phases have been reported for 15 acids [159]. An example of the separation of the derivatives of some acids prepared by this procedure is illustrated in Fig. 5.12. 

B. Synthesis of Enolates from Enol Ethers and Esters. 542... 

Silyl enol ethers from aldehydes 54 and esters 57 are reagents that give clean reaction at the y-position with a variety of electrophiles 58. Acylation occurs under Friedel-Crafts conditions, and the crowded esterifying group (i-Pr)2CH in 59 ensures that reaction occurs entirely at the y-position. The product is a mixture of double bond positional isomers 61 as both are conjugated with one of the carbonyl groups. 

I, 5-dicarbonyl compounds and their interesting and varied chemistry, e.g., the formation of cyclohexenones from aldol condensation of the products. As an extension of the de Mayo reaction (the photocycloaddition of enolated /i-diketones to double bonds) enol esters, enol ethers, vinylogous esters and amides, and dioxinone have been employed as the enone components. Some intermolecular examples have already been discussed in Section 1.6.1.4.2.1.6. (cf. Table 4, entries 2 and 3) and some intramolecular systems are collected in Table 5, entries 10,... 

Alkoxycarbonylmethyl enol ethers. A convenient preparation of these enol ethers from carbonyl compounds is by a Rh2(OCOCF3)4-catalyzed reaction of a diazoacetic ester. The enol etherification is applicable to a-pyridone. 

A "salt-free" method for obtaining enol ethers from 3-keto-esters consists of heating the latter with the readily prepared silyl ester... 

An efficient method for the synthesis of 5- and 6-membered cyclic enol ethers from unsaturated esters is first to convert the esters into acyclic olefinic enol ethers, which are then transformed to the desired products by RCM, catalyzed by 8 (Fujimura 1994). Further examples will be found in Table 8.5. 

Preferential formation s. 17, 701 a-Oxomonoorganomercury compounds from enol-ethers and -esters s. 17, 702... 

Both enol esters and enol ethers (vinylogous esters) undergo similar intramolecular photocycloaddtions, but enol esters have advantage over enol ethers in terms of fragmentation process. Fragmentation of the cyclobutane photoadducts from enol esters is conveniently carried out under basic conditions, whereas that from enol ethers often requires additional operation to convert ether to ester or lactone (vide infra). For this reason, enol esters are more widely used than enol ethers. 

Full details have appeared of application of the C-silylated ester Me3 iCH2C02Et to silylations of alcohols mediated by fluoride ion (cf. 1,170)." In an extension of earlier work with the TMS enol ethers of esters (4,154), ketene methyl TBDMS acetal (50) has been advocated as a stable readily available reagent for conversion of alcohols to TBDMS ethers under mild conditions." In a related approach the O-silylated derivatives (51) and (52), readily formed from acetylacetone (R = Me) or methyl acetoacetate (R = OMe), have been found to be effective reagents for the transformation of alcohols to their TBDMSand TMS ethers," respectively reagents (51) require acid catalysis whereas (52) react without catalyst. Some further details have appeared... 

Redox glycosylation via thionoester intermediates. Barrett [112, 113] introduced the concept of redox glycosylation , where the usual glycosylation reaction is replaced by the esterification of an aldonic acid 164, followed by reduction to a reactive intermediate (enol ether from an ester or 0,S-ace al 166 from the thionoester... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Catalytic hydrogenation of the 14—15 double bond from the face opposite to the C18 substituent yields (196). Compound (196) contains the natural steroid stereochemistry around the D-ring. A metal-ammonia reduction of (196) forms the most stable product (197) thermodynamically. When R is equal to methyl, this process comprises an efficient total synthesis of estradiol methyl ester. Birch reduction of the A-ring of (197) followed by acid hydrolysis of the resultant enol ether allows access into the 19-norsteroids (198) (204). 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

The 1,3-dicarbonyl components can be replaced by an enol ether, which can be prepared by Claisen condensation from an ortho ester and a reactive methylene compound. ... 

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