Ketone arylation intermediate

Reactivity factors in additions to carbon-hetero multiple bonds are similar to those for the tetrahedral mechanism of nucleophilic substitution. If A and/or B are electron-donating groups, rates are decreased. Electron-attracting substituents increase rates. This means that aldehydes are more reactive than ketones. Aryl groups are somewhat deactivating compared to alkyl, because of resonance that stabilizes the substrate molecule but is lost on going to the intermediate ... 

Unlike triarylmethane dyes, comparatively little work has been done with diaryl heteryl-, and aryl diheteryl methane compounds. Analogous to triarylmethanes, triheterylmethane dyes are also prepared using POCl3 and a ketone. The intermediate leuco compounds (similar to 65, see Scheme 8) are not isolated40 in the case of triheterylmethane leuco dyes. 

Vinyl-l//-isochromenes can be prepared in moderate yield by a palladium-catalyzed coupling of ( )-(3-(2-bromo-phenyl)allyloxy)tenM)i i r l)si Iyl derivatives 157 with ketones. The reaction proceeds via initial ketone arylation to furnish the intermediate 158 followed by intramolecular cyclization of the ketone enolate onto the tethered allylic system (Scheme 50) <2000CG1675>. 

Instead of amino-ketones, compounds may be used which are capable of forming amino-ketones as intermediates. Thus, if phenols and phenol ethers are acylated with y- or 8-amino acids in the presence of polyphosphoric acid, the intermediate amino-ketones cyclize to 2-aryl-z31-pyrrolines or 2-aryl-J -piperideines95 (Scheme 1). 

The abihty to perform oxidations without generating species harmful for potential intermediates of further transformations is important to perform multistep synthesis, such as the domino reactions described below (Section 5). In this respect, the use of aryl hahdes as readily available, stable and cheap oxidants (hydride acceptors) is a powerful option due to the production of inert, dehalogenated aryl by-products in anaerobic conditions. Commercially available Pd and Ni complexes with NHC ligands were found to be active in a temperature-controlled domino oxidation/R-ketone arylation with aryl halide. ... 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

Aryl or alkenyl halides attack the central carbon of the allene system in the 2,3-butadien-l-ol 120 to form the 7r-allyl intermediate 121, which undergoes elimination reaction to afford the o,/3-unsaturated ketone 122 or aldehyde. The reaction proceeds smoothly in DMSO using dppe as a ligandflOl]. 

The aryl- and heteroarylfluorosilanes 541 can be used for the preparation of the unsymmetrical ketones 542[400], Carbonylation of aryl triflate with the siloxycyclopropane 543 affords the 7-keto ester 545. In this reaction, transme-tallation of the siloxycyclopropane 543 with acylpalladium and ring opening generate Pd homoenolate as an intermediate 544 without undergoing elimination of/3-hydrogen[401],... 

You learned in Section 17 8 of the relationship among hemiacetals ketones and alcohols the for mation of phenol and acetone is simply an example of hemiacetal hydrolysis The formation of the hemiacetal intermediate is a key step in the synthetic procedure it is the step in which the aryl—oxygen bond is generated Can you suggest a reasonable mechanism for this step" ... 

When aiomatics aie present, they can capture the intermediate vinyl cation to give P-aryl-a,P-unsatutated ketones (182). Thus acylation of alkyl or aryl acetylenes with acyhum salts in the presence of aromatics gives a,P-unsaturated ketones with a trisubstituted double bond. The mild reaction conditions employed do not cause direct acylation of aromatics. 

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

Depending on the specific reaction conditions, complex 4 as well as acylium ion 5 have been identified as intermediates with a sterically demanding substituent R, and in polar solvents the acylium ion species 5 is formed preferentially. The electrophilic agent 5 reacts with the aromatic substrate, e.g. benzene 1, to give an intermediate cr-complex—the cyclohexadienyl cation 6. By loss of a proton from intermediate 6 the aromatic system is restored, and an arylketone is formed that is coordinated with the carbonyl oxygen to the Lewis acid. Since a Lewis-acid molecule that is coordinated to a product molecule is no longer available to catalyze the acylation reaction, the catalyst has to be employed in equimolar quantity. The product-Lewis acid complex 7 has to be cleaved by a hydrolytic workup in order to isolate the pure aryl ketone 3. 

In this example, the /3-diketone 2-methyJ-l,3-cyclopentanedione is used to generate the enolate ion required for Michael reaction and an aryl-substituted a,/3-unsaturated ketone is used as the acceptor. Base-catalyzed Michael reaction between the two partners yields an intermediate triketone, which then cyclizes in an intramolecular aldol condensation to give a Robinson annulation product. Several further transformations are required to complete the synthesis of estrone. 

The principles outlined above are, of course, important in electro-synthetic reactions. The pH of the electrolysis medium, however, also affects the occurrence and rate of proton transfers which follow the primary electron transfer and hence determine the stability of electrode intermediates to chemical reactions of further oxidation or reduction. These factors are well illustrated by the reduction at a mercury cathode of aryl alkyl ketones (Zuman et al., 1968). In acidic solution the ketone is protonated and reduces readily to a radical which may be reduced further only at more negative potentials. 

Ordinary ketones are generally much more difficult to cleave than trihalo ketones or p-diketones, because the carbanion intermediates in these cases are more stable than simple carbanions. However, nonenolizable ketones can be cleaved by treatment with a 10 3 mixture of t-BuOK—H2O in an aprotic solvent such as ether, dimethyl sulfoxide, 1,2-dimethoxyethane (glyme), and so on, or with sohd t-BuOK in the absence of a solvent. When the reaction is applied to monosubstituted diaryl ketones, that aryl group preferentially cleaves that comes off as the more stable carbanion, except that aryl groups substituted in the ortho position are more readily cleaved than otherwise because of the steric effect (relief of stain). In certain cases, cyclic ketones can be cleaved by base treatment, even if they are enolizable. " OS VI, 625. See also OS VH, 297. 

Despite the great success of the transmetalation process in the enantiose-lective arylation of ketones, its extension to allylation or alkynylation reactions failed, providing the corresponding tertiary alcohols with enantiomeric excesses never higher than 50% ee. On the other hand, more success has been found in the alkenylation of ketones. The process started with the hydrozirconation of terminal alkynes to give the corresponding alkenylzirconium intermediates, which were transmetalated by reaction, in this case, with various ketones in the presence of the HOCSAC ligand. This protocol tolerated the presence of other carbon-carbon multiple bonds on the alkyne, as well as different functionalities and achieved excellent results for alkyl ketones, a,(3-unsaturated ketones and even dialkylketones, as shown in Scheme 4.22. 

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