Enols conversion to ketones

E2, 192-196, 201, 323-325 enamine formation, 674 enol conversion to ketone, 355 enolization, 706, 709 epoxidation, 240 epoxide ring opening, 634, 636 esterification, 756—757 ether cleavage, 629 ether formation, 592... 

Structural effects on the rates of deprotonation of ketones have also been studied using veiy strong bases under conditions where complete conversion to the enolate occurs. In solvents such as THF or DME, bases such as lithium di-/-propylamide (LDA) and potassium hexamethyldisilylamide (KHMDS) give solutions of the enolates in relative proportions that reflect the relative rates of removal of the different protons in the carbonyl compound (kinetic control). The least hindered proton is removed most rapidly under these... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Concealed within spirocyclic intermediate 16 are rings B and F of ginkgolide B. Intermediate 16 is readily formed in two steps from a readily available starting material and it contains a strategically placed ketone carbonyl group which provides several options for further advance. A particularly straightforward route to 15 includes the conversion of ketone 16 into enol triflate 21 by means of McMurry s protocol.16 Thus, enolization of 16 with LDA in dimethoxyethane at -78 °C followed by triflation of the enolate oxygen atom with /V-phenyltrifluoromethanesulfonimide furnishes enol triflate 21 in a yield of 80%. 

A different method for the conversion of ketones to a-hydroxy ketones consists of treating the enolate with a 2-sulfonyloxaziridine (such as 15). This is not a free-radical process the following mechanism is likely ... 

For conversion of ketones to either (Z) or ( ) enol borinates, see, for example, Evans,... 

Longifolene has also been synthesized from ( ) Wieland-Miescher ketone by a series of reactions that feature an intramolecular enolate alkylation and ring expansion, as shown in Scheme 13.26. The starting material was converted to a dibromo ketone via the Mr-silyl enol ether in the first sequence of reactions. This intermediate underwent an intramolecular enolate alkylation to form the C(7)—C(10) bond. The ring expansion was then done by conversion of the ketone to a silyl enol ether, cyclopropanation, and treatment of the siloxycyclopropane with FeCl3. 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Conversion of ketone 80 to the enol silane followed by addition of lithium aluminum hydride to the reaction mixture directly provides the allylic alcohol 81 [70]. Treatment of crude allylic alcohol 81 with tert-butyldimethylsilyl chloride followed by N-b ro m o s u cc i n i m i de furnishes the a-bromoketone 82 in 84 % yield over the two-step sequence from a.p-unsaturated ester 80. Finally, a one-pot Komblum oxidation [71] of a-bromoketone 82 is achieved by way of the nitrate ester to deliver the glyoxal 71. It is worth noting that the sequence to glyoxal 71 requires only a single chromatographic purification at the second to last step (Scheme 5.10). 

In a separate, dry, 1-L, two-necked, round-bottomed flask fitted to a nitrogen bubbler and equipped with a magnetic stirring bar and a septum inlet is added a solution of 12.6 g (60.0 mmol) of 2-(hydroxymethylene)cyclododecanone (Note 4) in 500 mL of anhydrous ether. The stirred ethereal solution of the hydroxymethylene ketone is treated at 22°C with 33 mL of a freshly prepared mixture (1/1, v/v) of chlorotrimethylsilane and triethylamine (Note 5). An immediate reaction takes place with deposition of a white precipitate. The mixture is stirred thoroughly at 22°C for 15 min to insure complete conversion to the silyl enol ether. 

Acylbenzotriazoles 162 are efficient C-acylation reagents for the regioselective conversion of ketone enolates into P-diketones . Diethyl(l-benzotriazolmethyl)phosphinate (163) was found to be a convenient reagent for the stereoselective preparation of (E)-l-(l-alkenyl)benzotriazoles <00SC1413>. The novel three-carbon synthon 1-(1//-133-... 

To obtain complete conversion of ketones to enolates, it is necessary to use aprotic solvents so that solvent deprotonation does not compete with enolate formation. Stronger bases, such as amide anion ( NH2), the conjugate base of DMSO (sometimes referred to as the dimsyl anion),2 and triphenylmethyl anion, are capable of effecting essentially complete conversion of a ketone to its enolate. Lithium diisopropylamide (LDA), which is generated by addition of w-butyllithium to diisopropylamine, is widely used as a strong... 

Determined by NMR after conversion to the corresponding enol acetates. b Isolated yields of recovered ketone unless otherwise indicated. c Isolated yields unless otherwise indicated. d Not isolated. Determined by GC. 

The superfluous bromine is then removed by reduction with zinc in acetic acid (26-1). The 20 ketone is next protected against the strongly reducing conditions in the subsequent step by conversion to the ethylene glycol acetal (26-2). Birch reduction with lithium in liquid ammonia in the presence of ethanol proceeds as usual to the dihydrobenzene (26-3). Treatment of this last product with mineral acid serves to hydrolyze both the enol ether at the 3 position and the acetal at the... 

Chlorodifluoromethylketones underwent aldol reactions (Eq. 124) via zinc enolates, to afford good yields of a,a-difluoro-/ -hydroxy ketones, in a study by the Kyoto group [327]. Copper(I) or silver salt catalysis was essential and boron-trifluoride additive appeared to exert a key role in the conversion to the enolate. Earlier [328], chlorodifluoromethyl ketones had been converted to the di-fluoroenoxy silanes by the action of zinc in the presence of chlorotrimethyl silane. A difluoroenoxy silane was used by McCarthy and co-workers [329] to synthesise a kynureninase inhibitor (Eq. 125) Lewis acid-mediated reaction with a chloroglycinate installed the key carbon-carbon bond. 

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