Ketones production from enols

Lead tetraacetate can effect oxidation of carbonyl groups, leading to formation of a-acetoxy ketones,215 but the yields are seldom high. Boron trifluoride can be used to catalyze these oxidations. It is presumed to function by catalyzing the formation of the enol, which is thought to be the reactive species.216 With unsymmetrical ketones, products from oxidation at both a-methylene groups are found.217... 

The hydroboration of disubstituted (internal) alkynes leads to a mixture of two ketones. When 2-pentyne reacts with borane, two vinylboranes are formed in virtually equal amounts 120 and 121. There is no significant difference in steric hindrance to make one transition state favored over the other, so both vinylboranes are formed. Subsequent oxidation leads to the isomeric ketone products (from their respective enols) 2-pentanone (122) and 3-pentanone H23). To conclude, hydroboration of a terminal alkyne leads to an aldehyde as the major product, whereas hydroboration of an internal alkyne gives a mixture of two isomeric ketones. 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol (ene + ol), but is instead a ketone. Although the enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerisni. The individual keto and enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost never isolated. We ll look more closely... 

Further insight into the P-borylation reaction of a,P-enones (Scheme 2.32) showed that the reaction can be carried out in THF, and the catalyst generated in situ from CuCl (5 mol%), the imidazolium salt (5 mol%), and NaO Bu (10 mol%), to form the [Cu(O Bu) (NHC)] as the catalysis initiating species. In this case, stable boron enolate products are formed which need to be hydrolysed by methanol to the ketone products [114]. 

Ketone-aldehyde additions have been effected using TiCl4 in toluene.24 These reactions exhibit the same stereoselectivity trends as other titanium-mediated additions. With unsymmetrical ketones, this procedure gives the product from the more-substituted enolate.25... 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

Scheme 2.11 shows some examples of Robinson annulation reactions. Entries 1 and 2 show annulation reactions of relatively acidic dicarbonyl compounds. Entry 3 is an example of use of 4-(trimethylammonio)-2-butanone as a precursor of methyl vinyl ketone. This compound generates methyl vinyl ketone in situ by (3-eliminalion. The original conditions developed for the Robinson annulation reaction are such that the ketone enolate composition is under thermodynamic control. This usually results in the formation of product from the more stable enolate, as in Entry 3. The C(l) enolate is preferred because of the conjugation with the aromatic ring. For monosubstituted cyclohexanones, the cyclization usually occurs at the more-substituted position in hydroxylic solvents. The alternative regiochemistry can be achieved by using an enamine. Entry 4 is an example. As discussed in Section 1.9, the less-substituted enamine is favored, so addition occurs at the less-substituted position. 

A lower molecular weight methyl ketone and an olefin are isolated as products of this reaction. That the enol is formed as a primary product which rearranges to the ketone follows from its detection in the IR spectrum of gaseous 2-pentanone upon photolysis. 3 In addition to the ketone and olefinic products, one usually obtains varying amounts of cyclobutanols. 

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... 

Despite the fact that the electrochemical oxidation of most of the nonconjugated dienes generally does not give products which result from interaction of the double bonds with one another, the anodic oxidation l-acetoxy-l,6-heptadienes gives intramolecularly cyclized products, that is, the cyclohexenyl ketones (equation 15)13. The cyclization takes place through the electrophilic attack of the cation generated from enol ester moiety to the double bond. 

Trost s group reported direct catalytic enantioselective aldol reaction of unmodified ketones using dinuclear Zn complex 21 [Eq. (13.10)]. This reaction is noteworthy because products from linear aliphatic aldehydes were also obtained in reasonable chemical yields and enantioselectivity, in addition to secondary and tertiary alkyl-substituted aldehydes. Primary alkyl-substituted aldehydes are normally problematic substrates for direct aldol reaction because self-aldol condensation of the aldehydes complicates the reaction. Bifunctional Zn catalysis 22 was proposed, in which one Zn atom acts as a Lewis acid to activate an aldehyde and the other Zn-alkoxide acts as a Bronsted base to generate a Zn-enolate. The... 

Because the aldol reaction is reversible, it is possible to adjust reaction conditions so that the two stereoisomeric aldol products equilibrate. This can be done in the case of lithium enolates by keeping the reaction mixture at room temperature until the product composition reaches equilibrium. This has been done, for example, for the product from the reaction of the enolate of ethyl /-butyl ketone and benzaldehyde. 

Regioisomer 49a was obtained in the form of its ring tautomer 3-hydroxy-3,5,5-trimethyl-l,2-dioxolan, produced by ketonization of the initial enol and cyclization. b No products from 49a and 49b could be detected. r 8% of i S.S), (S,/ )-54J was formed as side products in a 23 77 ratio. d Only ( )-configured hydroperoxides 44g were detected. 

Recently it has been reported that the catalytic isomerization of allylic alcohols is promoted by [Rh(diphosphine)(solvent)2]+ at 25°C yields synthetically useful quantities of the corresponding simple enols and that the transformation of allylic alcohols to enols and thereby to ketonic products proceeds catalytically via hydrido-7t-allylic and hydrido-7t-oxy-allylic intermediates, respectively [20]. Consistently observed, enantioselection has been in the process of conversion of a prochiral enol to a chiral aldehyde. Thus, the prochiral substrate 32 is transformed to the optically active aldehyde 34 with 18% ee by using [Rh(BINAP)]+ catalyst (eq 3.13). Accordingly, this isomerization proceeds via a different mechanism from that of the isomerization of allylamine. For the reaction mechanism of the... 

It was reported that the structure of the product obtained (68% yield) by acid-catalysed (8% HC1, reflux, 18 hr) hydrolysis and decarboxylation of the (3-keto ester 1 was not the expected diketone, but the stable enol 2 (mp 128-130°C), and that the equilibrium could not be reversed from enol to ketone, even on treatment of 2 with dilute alkali for 10 days. The evidence cited in support of 2 was entirely spectroscopic, as follows "C14H16O3 (232) M+ 232, Xmax (ethanol) 266 nm (log e, 4.09). The IR spectrum of 7 (= 2) showed a broad band between 3000-3500 cm 1 (enolic OH) and a sharp peak at 1705 cm-1 (ring -C=0) in the NMR spectrum (CDCI3) of 7 (s 2) a broad peak was present at 85.95 (1H, olefmic) and a downfield signal (exchangeable with D2O) at 811.1 (1H) indicating the presence of an enolic OH group."... 

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