Enol ethers acyl anion equivalent

The preparation of a-hydroxy carbonyl compounds has been accomplished by the oxidation of enolates using both oxygen6 and MoC PyHMPA-(MoOPh).7 Acyl anion equivalents offer another route to this useful class of compounds. The procedure presented here for the synthesis of 6-hydroxy-3,5,5-tr1methyl-2-cyclohexen-l-one illustrates the use of MCPBA oxidation of an enol silyl ether as a method for obtaining an a-hydroxy enone. The procedure is a scaleup of a published synthesis. ... 

When the ylid derived from the oxide 7 was treated with benzaldehyde, a 2-methoxy-l,3-diene was formed. This led us to attempt a synthesis of (i) ar-turmerone by a sequence (Scheme 3) in which 7 effectively acts as an acyl anion equivalent. The required aldehyde 8 was synthesized in good yield using initially diphenyl(methoxymethyl)phosphine oxide (3), and then chlorotri-methylsilane-sodium iodide (12) to cleave the enol ether. 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves9 and by the addition of hydrogen cyanide to silyl enol ethers.10 Sllylated cyanohydrins have proved to be quite useful 1n a variety of synthetic transformations, including the regiospecific protection of p-quinones,11 as Intermediates in an efficient synthesis of a-aminomethyl alcohols,6 and for the preparation of ketone cyanohydrins themselves.1 The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as acyl anion equivalents, providing general syntheses of ketones13 and acyloins.1 ... 

Aldehydes and ketones RCOR react with a-methoxyvinyllithium, CH2=C(Li)OMe, to give hydroxy enol ethers, RR C(OH)C(OMe)=CH2, which are easily hydrolyzed to acyloins, RR C(OH)COMe. ° In this reaction, the CH2=C(Li)OMe is a synthon for the unavailable H3C—C=0, °" and is termed an acyl anion equivalent. The reagent also reacts with esters RCOOR to give RC(OH)(COMe=CH2)2. A synthon for the Ph—C=0 ion is PhC(CN)OSiMe3, which adds to aldehydes and ketones RCOR to give, after hydrolysis, the a-hydroxy ketones, RR C(OH) C OH)COPh. ... 

Amino nitriles are useful for conjugate addition Acyl anion equivalents of the ester d1 synthon - C02R Methods Based on Vinyl (Enol) Ethers and Enamines Lithium derivatives of cyclic vinyl ethers The synthesis of pederin and related anti-tumour agents Lithium derivatives ofallenyl ethers Oxidative Cleavage of Allenes... 

Just as anions of allyl derivatives can be homoenolate equivalents (chapter 13) so anions of vinyl derivatives can be acyl anion equivalents. Vinyl (or enol) ethers can be lithiated reasonably easily, especially when there is no possibility of forming an allyl derivative, as with the simplest compound 81. The most acidic proton is the one marked and the vinyl-lithium derivative 82 reacts with electrophiles to give the enol ether of the product17 84. However, tertiary butyl lithium is needed and compounds with y-CHs usually end up as the chelated allyl-lithium 85. These vinyl-lithium compounds add directly to conjugated systems but the cuprates will do conjugate addition.18... 

A second major class of acyl anion equivalents are the enol ethers such as methyl 1-propenyl ether (359). When 359 was treated with tert-butyllithium (note the need for a stronger base with the less acidic vinyl hydrogen) and then condensed with benzaldehyde, the product was 260. Lithiation of vinyl derivatives was described in Section 8.5. Facile hydrolysis with aqueous acid liberated the corresponding ketone (361), completing the acyl anion equivalency. Schlosser co-workers found that a mixture of 5ec-butyllithium and potassium tert-butoxide could be used to generate the lithium anion of O-tetrahydropyranyl enol ethers.360 This modification generates a product that is more easily hydrolyzed to the ketone. 

Addition reactions of (l-methoxyalkyl)triphenylphosphonium ylides, derived from the corresponding phosphonium salts (82) and n-BuLi, to aldehydes at — 78 °C followed by quenching the reaction mixture with aqueous NH4CI at the same temperature alforded a-hydroxyketones instead of the expected enol ethers.This is the first example of phosphonium ylides acting as an acyl anion equivalent. Flash vacuum pyrolysis (FVP) in a conventional flow system at 10 (84), prepared in a few steps... 

Dithioacetal, Trithioorthoester, and Thioglycoside Activation. DMTSF provides a chemoselective reagent for dithioacetal activation in the presence of electron-rich alkenes. This bond-forming procedure complements the TiCLj mediated reaction between acetals and sUyl enol ethers demonstrated hy Mukaiyama. The generation of ketone precursors through dithioacetal carban-ion (acyl anion equivalents) chemistry further amplifies the significance of DMTSF activation. 

Potassium enolates derived from acylfulvalenes were trapped with TBDMSCl but not TMSCl or diphenylmethylsilyl chloride. Interestingly, TBDMSCl was found to be compatible with CpK anion at —78 °C. TBDMS enol ethers have also been used as /3-acyl anion equivalents. The TBDMS-silyl enol ethers of diketones (eq 7) and /3-keto esters (eq 8) may be prepared by mixing them with TBDMSCl in THF with imidazole. Alcohols may be protected under acidic conditions as their TBDMS ethers by treatment with /3-silyl enol ethers in polar sovents. 

Reductive nucleophilic acylation. The reagent 1 condenses with aldehydes and ketones to give products (2) of carbonyl addition, which do not undergo syn-elimination of —OSi(CH3)3 in situ. However, treatment of 2 with KH in THF affords enol ethers (3) in excellent yields. The latter products are readily converted into aldehydes (4) on hydrol) is with 90% aqueous formic acid ( 90% yield, equation I). The adducts (2) are desilylated to 5 with CsF in DMSO (equation II). In this case, 1 functions as an equivalent of the —CH2OCH3 anion. 

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