Enolate Enone

C>2 is known to react with olefins to form allylic hydroperoxides via the Schenck reaction. Even if cyclohexene has a rather low reactivity towards 02 [19], it is likely that at least part of the allylic oxidation products (enylOOH, enol, enone) arise from a 02 reaction, rather than from a free radical chain process. 

Reaction conditions 120 mmol cyclohexene, 60 mmol H2O2 (35 % in water), 30 ml isopropanol, 333 K, 0.36 mmol Mo or 0.09 mmol Mo (for Mo blue on DS-Zn,Al-LDH). X = conversion. EnylOOH = cyclohex-2-enyl hydroperoxide, enol = cyclohex-2-enol, enone = cyclohex-2-enone. 

Nazarov processes have allowed access to intermediate cyclic enolates . Enone 134 undergoes a Nazarov cyclization catalysed by a Lewis acid [e.g. Cu(OTf)2] to give the intermediate enol complex 135, which undergoes tautomerization to the diastereoiso-merically pure cyclic enone trans-136 in almost quatitative yield (equation 35)445,446... 

Epoxide, diol, benzaldehyde, enol, enone, ketone... 

Co4P2W180 6810-, CoPWu0395 , MnIIIPW110394, MnIIPW110395, FemPW110394, NiPW110395 Cyclohexene Epoxide, enol, enone CDMANOb MeCN Mechanism study 459,460... 

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. 

Avoidance by choice of oxygenated starting materials Oxidation through Lithiation and Ort/ro-Lithiation Hydroxylation of Pyridines by ortho-Lithiation Synthesis of Atpenin B Introducing OH by Nucleophilic Substitution Part II - Oxidation of Enols and Enolates Direct Oxidation without Formation of a Specific Enol Selenium dioxide Nitrosation with nitrites Nitrosation with stable nitroso compounds Indirect Oxidation with Formation of a Specific Enol Enone Formation Pd(II) oxidation ofsilyl enol ethers Bromination of enols in enone formation Sulfur and selenium compounds in enone formation Asymmetric Synthesis of Cannabispirenones... 

Indirect Oxidation with Formation of a Specific Enol Enone Formation... 

Oxidation of silylenol ethers and enol carbonates to enones... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

The decarboxylation-allylation of allyl enol carbonates proceeds smoothly[450]. The isomeric enol carbonates 699 and 701 of the enone 698 undergo regiospecific allylation, giving the regioisomers 700 and 702 selectively. 

Ailyl enol carbonates derived from ketones and aldehydes undergo Pd-cat-alyzed decarboxylation-elimination, and are used for the preparation of a, /3-unsaturated ketones and aldehydes. The reaction is regiospecific. The regio-isomenc enol carbonates 724 and 726, prepared from 723, are converted into two isomeric enones, 725 and 727. selectively. The saturated aldehyde 728 can be converted into the a,/3-unsaturated aldehyde 730 via the enol carbonate 729[459]. 

The Pd enolates also undergo intramolecular Michael addition when an enone of suitable size is present in the allyl d-keto ester 744[465]. The main product is the saturated ketone 745, hut the unsaturated ketone 746 and ally-lated product 747 are also obtained as byproducts. The Pd-catalyzed Michael... 

Conversion of PGA2 to the highly sensitive PGC2 was accomplished by deconjugation of the enone system by formation of the y-extended enolate using rm-alkoxide as base and a-protonation by pH 4 buffer. 

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. 

Reduction of a conjugated enone to a saturated ketone requires the addition of two electrons and two protons. As in the case of the Birch reduction of aromatic compounds, the exact order of these additions has been the subject of study and speculation. Barton proposed that two electrons add initially giving a dicarbanion of the structure (49) which then is protonated rapidly at the / -position by ammonia, forming the enolate salt (50) of the saturated ketone. Stork later suggested that the radical-anion (51), a one electron... 

Reversible electron addition to the enone forms the radical anion. Rate determining protonation of the radical anion occurs on oxygen to afford an allylic free radical [Eq. (4b) which undergoes rapid reduction to an allylic carbanion [Eq. (4c)]. Rapid protonation of this ion is followed by proton removal from the oxygen of the neutral enol to afford the enolate ion [Eq. (4c)]. 

Protonation of the a-carbanion (50), which is formed both in the reduction of enones and ketol acetates, probably first affords the neutral enol and is followed by its ketonization. Zimmerman has discussed the stereochemistry of the ketonization of enols and has shown that in eertain cases steric factors may lead to kinetically controlled formation of the thermodynamically less stable ketone isomer. Steroidal unsaturated ketones and ketol acetates that could form epimeric products at the a-carbon atom appear to yield the thermodynamically stable isomers. In most of the cases reported, however, equilibration might have occurred during isolation of the products so that definitive conclusions are not possible. 

If the equilibrium were established rapidly, reduction of the free ketone as it formed would result in a substantial loss of product. Lithium enolates are more covalent in character than are those of sodium and potassium and consequently are the least basic of the group. This lower thermodynamic basicity appears to be paralleled by a lower kinetic basicity several workers have shown that lithium enolates are weaker bases in the kinetic sense than are those of sodium and potassium." As noted earlier, conjugated enones... 

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-... 

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