Allylic ketene acetal

To avoid the formation of ketenes by alkoxide elimination, ester enolates are often prepared at low temperatures. If unreactive alkyl halides are used, the addition of BU4NI to the reaction mixture can be beneficial [134]. Examples of the radical-mediated a-alkylation of support-bound a-haloesters are given in Table 5.4. Further methods for C-alkylating esters on insoluble supports include the Ireland-Claisen rearrangement of O-allyl ketene acetals (Entry 6, Table 13.16). Malonic esters and similar strongly C,H-acidic compounds have been C-alkylated with Merrifield resin [237,238]. 

The allyl ketene acetal Claisen rearrangement of uronic acid derivatives with furanoside structures has been studied. The Claisen rearrangement of alkenyl-substituted ketene acetals (84), produced in situ by selenoxide elimination from the corresponding phenylselenoacetaldehyde-derived acetals (83) of enantiomericaUy pure... 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

Conversion of allyl alcohol esters into their corresponding trimethylsilyl or t-butyldimethylsilyl ketene acetals, followed by mild thermolysis, results in... 

Silyl enol ethers and ketene acetals derived from ketones, aldehydes, esters and lactones are converted into the corresponding o/i-unsaturated derivatives on treatment with allyl carbonates in high yields in the catalytic presence of the palladium-bis(diphenylphosphino)ethane complex (32). A phosphinc-free catalyst gives higher selectivity in certain cases, such as those involving ketene acetals. Nitrile solvents, such as acetonitrile, are essential for success. 

A solution of Pd(OAc)2 (0.1 mmol), the ketene acetal (lmmol) and allyl methyl carbonate (2 mmol) in MeCN (5 ml) was heated under reflux for 2-6h, the course of reaction being monitored by t.l.c. or g.l.c. analysis. On completion, the cooled reaction solution was filtered through fluorosil. The... 

Ireland-Claisen rearrangement of O-allyl-O -trimethylsilyl ketene acetals... 

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

Entry 6 is an example of application of the chiral diazaborolidine enolate method (see p. 572). Entry 7 involves generation of the silyl ketene acetal by silylation after conjugate addition of the enolate of 3-methylbutanoyloxazolidinone to allyl 3,3,3-trifluoroprop-2-enoate. A palladium catalyst improved the yield in the rearrangement... 

Rearrangement of allyl trimethylsilyl ketene acetal, prepared by reaction of allylic ester enolates with trimethylsilyl chloride, to yield Y,5-unsaturated carboxylic a-cids. The Ireland-Claisen rearrangement seems to be advantageous to the other variants of the Claisen rearrangement in terms of E/Z geometry control and mild conditions. 

Heating of an allylic alcohol with an excess of trialkyl orthoacetate in the presence of trace amounts of a weak acid to give a mixed orthoester. The orthoester loses ethanol to generate the ketene acetal, which undergoes [3,3]-sigmatropic rearrangement to give a Y,5-unsaturated ester. 

Alkyl, aryl, allyl, benzyl, vinyl, ethynyl tellurides, tellurobutadienes, divinyltellurides, tellurobutenines, telluro(thio)- and telluro(seleno)ketene acetals and j3-(phosphorovinyl) tellurides are susceptible to such exchange, giving the corresponding lithium compounds trapped in sequence with selected electrophiles. ... 

The undefined mechanism of the aldol-type Mukaiyama and Sakurai allylation reactions arose the discussion and interest in mechanistic studies [143-145]. The proposed mechanism was proved to proceed through the catalytic activation of the aldehyde and its interaction with the silyl ketene acetal or allylsilane producing the intermediate. From that point the investigation is complicated with two possible pathways that lead either to the release of TMS triflate salt and its electrophihc attack on the trityl group in the intermediate or to the intramolecular transfer of the TMS group to the aldolate position resulting in the evolution of the trityl catalyst and the formation of the product (Scheme 51). On this divergence, series of experimental and spectroscopic studies were conducted. 

Among the most commonly applied chiral moiety for nitrones (2) is the N-a-methylbenzyl substituent (Scheme 12.6) (18-25). The nitrones 8 with this substituent are available from 1 -phenethylamine, and the substituent has the advantage that it can be removed from the resulting isoxazolidine products 9 by hydrogeno-lysis. This type of 1,3-dipole has been applied in numerous 1,3-dipolar cycloadditions with alkenes such as styrenes (21,23), allyl alcohol (24), vinyl acetate (20), crotonates (22,25), and in a recent report with ketene acetals (26) for the synthesis of natural products. Reviewing these reactions shows that the a-methylbenzyl group... 

Allylic esters of fluoroacetic acid were used in the Ireland silyl ketene acetal rearrangement procedures by the Welch group at Albany [164]. For example, Eq. (53) shows a highly diastereoselective rearrangement which formed an early stage in syntheses of 2,3-dideoxy-2-fluoro-3-C-methyl pentose nucleosides [165, 166]. If a stereoselective synthesis of a functionalised monofluorocompound is... 

This reaction, also, has been performed diastereoselectively.461 Allylic silanes R.2C=CHCH2SiMe3 can be used instead of silyl enol ethers (the Sakurai reaction). 462 Similarly, silyl ketene acetals, e.g., 56, give 8-keto esters, in MeN02 as solvent, for example,463... 

Reacting an allylic alcohol with an ynavnine to generate an 0-allyl ketene (EA -acetal results in the Ficini-Claiscn rearrangement.1-53 Reaction of (E)- or (Z)-3a with (V,/V-diethyl-2-(phcnyl-sulfanyl)cthynamine results in low diastcreoselectivity in the formation of 6-(benzyloxy)-A ,A-diethyl-2-(phenylsulfanyl)-3-(trifiuoromethyl)hex-4-enamide (5).34 As is the case for the results in Table 23, the stereoselectivity and chemical yield are better for (E)-3a than for (Z)-3a. 

Keywords Catalyst, Alkylation, Allylation, Arylation, Mannich reaction, Carbon-nitrogen double bond, Imine, Nitrone, Aldimine, Organozinc reagents, Silyl ketene acetal, Silyl enol ether, Amine, (3-Amino acid... 

Imines are, preferably, used in the N-Boc-protected form less electrophilic N-allyl and N-benzyl imines gave unsuccessful results [36], The tert-butyldimethyl-silyl ketene acetals are the most suitable silyl ketene acetal substrates. It should be added that a low temperature is required to suppress an undesired uncatalyzed reaction that leads to racemates. 

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