Cross-conjugated enolate

Two consecutive enolate alkylations were utilized to generate the quaternary carbon atom (Scheme 38). Alcohol 238 was transformed into the protected hydroxy enone 244. Regioselective deprotonation at the a-position of the ketone 244 led to a cross-conjugated enolate that was alkylated with the allylic iodide 245. The vinyl silyl moiety in 245 represents a masked keto group [127]. The choice of the TBS protecting group for the hydroxyl group at of 244 was crucial in order to prevent the deprotonation at the y-posi-... 

The reagent is extremely useful for the preparation of cross-conjugated enolates of a,(5-un saturated systems ... 

Any equilibrium will produce the thermodynamically most stable enolate. The most stable enolate will have the greatest charge delocalization. In the above example, the thermodynamically favored enolate is conjugated the kinetically favored enolate is not. Common conditions for thermodynamic control are to use average bases (like sodium ethoxide or potassium tert-butoxide, p abH 16 to 19) in alcohol solvents. Proton transfer equilibria rapidly occur among base, solvent, ketone, and enolate. Sodium hydride or potassium hydride in an ether solvent are also thermodynamic reaction conditions that allow equilibration between the ketone and the enolate. Enones have two possible enolates weaker bases give the thermodynamically more stable extended enolate, whereas kinetic conditions produce the cross-conjugated enolate. 

The lithium enolates of 4-methoxybut-3-en-2-ones 10, when treated with acid chlorides, yield the cross-conjugated enol system 11 by C-acylation. As a masked triketone it cyclizes to form the 2,6-disubstituted 4i/-pyran-4-ones on addition of catalytic amounts of CF3COOH ... 

In a modification of this approach, the li enolates of 4-methoxybut-4-en-2-ones 12 were C-acylated with acid chlorides giving rise to the cross-conjugated enols 13. As a masked 1,3,5-tricarbonyl compound, 13 is transformed into 2,6-disubstituted 4-pyrones by acid-induced cyclization. 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

Photochemical oxacarbene formation, 307 Photochemical rearrangements of cross-conjugated cyclohexadienones, 330 Photochemical rearrangements of enol esters and enol lactones, 339... 

Reduction of the aromatic nucleus in AjjV-dimethylbenza-mide occurs by an initial single electron transfer to give a radical anion. Protonation of the radical anion generates a radical and a second electron transfer gives the amide enolate 1. Protonation of the cross-conjugated trienolate moiety in 1 occurs carbonyl group to give the cyclohexa-1,4-diene 2. ... 

Recently, Kochi et al. described a novel photochemical synthesis for a-nitration of ketones via enol silyl ethers. Despite the already well-known classical methods, this one uses the photochemical excitation of the intermolecular electron-donor-acceptor complexes between enol silyl ethers and tetranitrometh-ane. In addition to high yields of nitration products, the authors also provided new insights into the mechanism on this nitration reaction via time-resolved spectroscopy, thus providing, for instance, an explanation of the disparate behavior of a- and (3-tetralone enol silyl ethers [75], In contrast to the more reactive cross-conjugated a-isomer, the radical cation of (3-tetralone enol silyl ether is stabilized owing to extensive Tr-delocalization (Scheme 50). 

Enolates may be derived from a,/l-unsaturated ketones 16 by base-catalyzed proton abstraction. Under kinetic control the a -proton is abstracted and a cross-conjugated metal dienolate is formed, whereas under thermodynamic conditions the extended dienolate is the major product3,, l. Successful alkylations of dienolates derived from cyclic a,/l-unsaturated ketones have been performed (see Section 1.1.1.3.1.1.2.1.). The related a,/ -unsaturated ester systems have also been investigated22-24. Open-chain structures 16 pose a rather complicated... 

The thermal isomerization of a spirocyclic enol ether to the ketone [202] (Eq. 176) is probably a homolytic process. However, it is noted that part of the driving force for the reaction must be the bonding of the ethereal oxygen to a designated donor atom of the cross-conjugated cyclohexadienone moiety. 

Octalone dienamines, e.g. 152, have shown a remarkable solvent dependence in the reaction with methyl vinyl ketone (equation 31)86. In methanol, reaction occurs primarily at the less reactive -position of the dienamine and the mechanism probably involves a prototropic shift in the initially formed enolate anion to give 153, and subsequent cyclization onto C-8a of the enimmonium salt to give 154. In toluene, the change in regioselectivity is complete and the product obtained is 157, which must arise from 156, formed in turn from cycloaddition to cross-conjugated dienamine 155. 

Quinones have been extensively used for aromatization reactions in addition to the dehydrogenation of steroidal ketones and lactones. Interestingly, whereas chloranil (29) and a number of other quinones oxidize steroidal 4-ene-3-ones (32) selectively to 4,6>dienones (34),DDQ (28) results only in the formation of the 1,4-dienone (36 Scheme 21).This divergent b vior is best exfdained by the intermediacy of the kinetic enolate (35) in the case of the higher potential DDQ, but of the thermodynamic enolate (33) in the case of the less reactive quinones.Addic conditions need to be avoided if the cross-conjugated ketone (36) is the desired inoduct since under these conditions the 3,5-dienol (33) becomes both the kinetic and the thermodynamic enol, resulting only in the formation of the linear di-enone." ... 

Stork has demonstrated that, in analogy with enolate chemistry, deprotonation of a,3 unsaturated im-ines with butyllithium under kinetic control produces the cross-conjugated anion.Conversely, use of slightly less than 1 equiv. of lithium diisopropylamide leads ultimately (by equilibration) to the conjugated system (equation 47). 

In general, the thermodynamically stable extended dienolates (M) have been prepared by deprotonation of enones (62) with sodium or potassium alkoxides in protic solvents or with sodium or potassium hydride in aprotic solvents.Kinetically formed cross-conjugated lithium enolates may be converted into the corresponding extended systems in the presence of excess ketone but in certain cases equilibration is quite slow. Presumably, because the Tr-electron density is higher at the a-carbon than the y-carbon, extended dienolates normally react with alkylating agents to produce a-alkyl-f3,y-unsaturated ketones. 

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