Enones formation

Enone Formation from Ketones, and Oxidation of Alcohols... 

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. 

Enone formation-aromatization has been used for the synthesis of 7-hydro-xyalkavinone (716)[456]. The isotlavone 717 was prepared by the elimina-tion[457]. The unsaturated 5-keto allyl esters 718 and 719, obtained in two steps from myreene. were subjected to enone formation. The reaction can be carried out even at room temperature using dinitriles such as adiponitrile (720) or 1,6-dicyanohexane as a solvent and a weak ligand to give the pseudo-ionone isomers 721 and 722 without giving an allylated product(458]. 

Similarly, alkenylzirconium species prepared by the hydrozirconation of alkynes add in a conjugated fashion to enones. Formation of an intermediate zincate prior to transmetalation to the copper species facilitates the Michael addition (Scheme 2.62) [135]. This methodology has been applied to the preparation of protected misoprostol 129 (Scheme 2.63) [136, 137]. 

The last three substrates give rise to epoxyketone and enone formation. Nickon has studied the variation of the product ratio 315 314a as a function of the sensitizer used.227 He found that an increase of this ratio is paralleled by an increase of the energy of the excited singlet sensitizer. It was suggested that both products arise from the same intermediate hydroperoxide 313a by either elimination of water or... 

That enone formation accompanies allylic alcohol can be explained by the known oxidizability of alcohols on irradiated semiconductor surfaces (288) or by dehydration of an intermediate allylic hydroperoxide. 

Exclusive enone formation could be achieved by electrocatalytic oxygenation of 2-cyclopentene-l-acetic acid in the presence of a water-soluble iron(III) porphyrin (2-TMPyP)Fe [2-TMPyP =tetrakis(N-methyl-2-pyridyl)porphyrin]. Unfortunately, neither yields nor TONs are given [116]. 

The strong preference towards enone formation, which was realized by Gonzalez et al. employing iron(III) tetrasulfophthalocyanine and tBuOOH (Scheme 3.28, method B) [120], could be further improved by immobilization of the phthalocyanine complex on silica (method C). Under these conditions, p.-oxo dimeric species are suggested to be the active catalysts. 

For acyclic allylic alcohols, very little a,p-unsaturated enone formation was observed besides epoxidation. Chemoselectivity was much less for cyclic allylic alcohols, for which oxidation of fhe allylic alcohol group competed significantly with epoxidation. In the case of 2-cyclohexenol as the substrate, the enone was even found to be the main product. A comparative sandwich POM-catalyzed epoxidation study of various (subsfifufed) cycloalkenols revealed that the enone versus epoxide chemoselectivity is controlled by the C=C-C-OH dihedral angle Ma in the allylic alcohol substrate. The more this dihedral angle deviates from fhe optimum C=C-C-OW dihedral angle otw for allylic acohol epoxidation, the more enone is formed (Fig. 16.5). 

Introduction and stereochemical control syn,anti and E,Z Relationship between enolate geometry and aldol stereochemistry The Zimmerman-Traxler transition state Anti-selective aldols of lithium enolates of hindered aryl esters Syn-selective aldols of boron enolates of PhS-esters Stereochemistry of aldols from enols and enolates of ketones Silyl enol ethers and the open transition state Syn selective aldols with zirconium enolates The synthesis of enones E,Z selectivity in enone formation from aldols Recent developments in stereoselective aldol reactions Stereoselectivity outside the Aldol Relationship A Synthesis ofJuvabione A Note on Stereochemical Nomenclature... 

The aldol reaction is often used to make enones by dehydration of the aldol itself, a reaction which often occurs under equilibrating aldol conditions, but has to be induced in a separate step when lithium enolates or silyl enol ethers are used. In general one has to accept whatever enone geometry results from the dehydration, and this is usually controlled by thermodynamics, particularly if enone formation is reversible. Simple enones such as 46 normally form as the E isomer but the Z isomer is difficult to prepare. When the double bond is exo to a ring, e.g. 47, the E isomer is again favoured, but other trisubstituted double bonds have less certain configurations. 

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... 

The oldest but still occasionally useful method for enone formation from saturated ketones involves bromination and elimination of HBr from the bromoketone 133. The problem here is that the proton to be removed (Hb in 133) in the elimination is not the most acidic proton in the molecule Ha is much more acidic. 

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