Metal enolates acetals

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

As first demonstrated by Stork,the metal enolate formed by metal-ammoni reduction of a conjugated enone or a ketol acetate can be alkylated in liquic ammonia. The reductive alkylation reaction is synthetically useful since ii permits alkylation of a ketone at the a-position other than the one at whicf thermodynamically controlled enolate salt formation occurs. Direct methyl-ation of 5a-androstan-17-ol-3-one occurs at C-2 whereas reductive methyl-... 

In spite of their intrinsic synthetic potential, addition reactions of metal enolates of non-stabilized esters, amides, and ketones to epoxides are not widely used in the synthesis of complex molecules. Following the seminal work of Danishefsky [64], who introduced the use of Et2AlCl as an efficient catalyst for the reaction, Taylor obtained valuable spiro lactones through the addition reaction of the lithium eno-late of tert-butyl acetate to spiro-epoxides, upon treatment of the corresponding y-... 

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

For the synthesis of 2-519, the amines 2-516 were first treated with AlMe3 in benzene at r.t. and after addition of the enol acetates 2-515, easily accessible from 2-513 and 2-514, heated under reflux. Mechanistic investigations using on-line NMR spectroscopy, reveal that a metalated amide 2-517 is formed first. This then leads to a N-acyliminium ion 2-518 which undergoes an electrophilic substitution. Overall, three new bonds are formed selectively in the domino process, and the alkaloid scaffolds 2-519 are provided in very good yields of 79-89%. Interestingly, use of the keto esters 2-513 instead of 2-515 did not lead to the desired products 2-519. 

Whereas metal-catalyzed decomposition of simple diazoketones in the presence of ketene acetals yields dihydrofurans 121,124,134), cyclopropanes usually result from reaction with enol ethers, enol acetates and silyl enol ethers, just as with unactivated alkenes 13). l-Acyl-2-alkoxycyclopropanes were thus obtained by copper-catalyzed reactions between diazoacetone and enol ethers 79 105,135), enol acetates 79,135 and... 

TiCl, on the silyl ketene acetal however, other data suggest that metal enolates may not be involved (73b). In subsequent studies, this reaction has been extended to chiral imines (81,82). 

Extensive investigations have been directed toward the development of chiral ester enolates that might exhibit practical levels of aldol asymmetric induction. Much of the early work in this area has been reviewed (111). In general, metal enolates derived from chiral acetate and propionate esters exhibit low levels of aldol asymmetric induction that rarely exceed 50% enantiomeric excess. The added problems associated with the low levels of aldol diastereoselection found with most substituted ester enolates (cf. Table 11) further detract from their utility as effective chiral enolates for the aldol process. Recent studies have examined the potential applications of the chiral propionates 121 to 125 in the aldol condensation (eq. [94]), and the observed erythro-threo diastereoselection and diastere-oface selection for these enolates are summarized in Table 31. For the six lithium enolates the threo diastereoselection was found to be... 

It is important that the indicator color, showing a small excess of strong base, not be discharged completely since the presence of any excess enol acetate or ketone will permit equilibration of the isomeric metal enolates. Consequently, the addition of this reactant is complete if further additions will discharge completely the color of the indicator. 

The present preparation illustrates a general and convenient method for a two-step deoxygenation of carbonyl compounds to olefins. Related procedures comprise the basic decomposition of p-toluenesulfonylhydrazones, the hydride reduction of enol ethers, enol acetates, enamines, the reduction of enol phosphates (and/or enol phosphorodiamidates) by lithium metal in ethylamine (or liquid ammonia),the reduction of enol phosphates by titanium metal... 

The present procedures illustrate general methods for the use of preformed lithium enolates5 as reactants in the aldol condensation6 and for the quenching of alkali metal enolates in acetic anhydride to form enol acetates with the same structure and stereochemistry as the starting metal enolate.7 The aldol product, [Pg.55]

Aldol reactions of both (E)- and (Z)-ketene acetals are highly susceptible to KOBuc catalysis. In the presence of 5 mol% of KOBuc, aldol reactions proceeded to completion within minutes at -78 °C < 1994JA7026>. A double-label crossover experiment, devised to probe the nature of the silicon group transfer in the alkoxide-catalyzed aldol reaction, suggested that free metal enolates are the true reactive species adding to the aldehydes. 

Steroidal enol acetates were similarly epoxidized. This method has undoubted advantages over the tradional epoxidation by peracids. Metal-catalyzed epoxidation of 1-acetoxycyclohexene is a key step in a novel synthesis of catechol from cyclohexanone via the sequence465... 

Dichloroketene is convenient to use, blit the two chlorine atoms are not usually needed in the product. Fortunately, these can be removed by zinc metal in acetic acid solution. Zinc forms a zinc enolate, which is converted... 

Rate constants and activation energies for liquid- and gas-phase isomerization of a-pinene have been determined.310 The activity of metal sulphate monohydrates in isomerizing a-pinene is correlated with the strength of co-ordination of the water of crystallization to the metal ion.3" Pyrolysis of chrysanthanol acetate (217 R = Ac) gives citronellal and the (E)- and (Z)-3,7-dimethylocta-l, 6-dien-l -ol acetates in 20, 28, and 3% yields respectively formation of the enol acetates is consistent with a biradical or a concerted pathway.312 Further work directed towards C-l—C-7 bond pyrolysis of pinane derivatives shows C-l—C-7 C-l—C-6 bond cleavage ratios of 4 51 for (217 R = Ac), 13 22 for (217 R = H), 6 7 for (218 R = H), and 43 35 for (218 R = Me) the expected acyclic and cyclic alcohol, aldehyde, and ketone pyrolysis products are obtained.313 The ene reaction between /3-pinene and methyl... 

Metal enolates can be fluorinated successfully with perchloryl fluoride, e. g. formation of 4,114 but due to the aggressive nature of perchloryl fluoride its applications are limited114 (caution see Vol.ElOa, p265ff). Alternatively, fluorination can be performed by acetyl hypofluorite generated from elemental fluorine and acetic acid/sodium acetate,95115 e.g. formation of 2-fluoro-l-phenylethanone (5).115... 

The (E)I(Z) notation is adopted for the definition of the geometries of silylketene acetals as well as metal enolates. As a consequence, silylation of ( )-lithium ester enolates leads to (Z)-silylketene acetals. 

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