Ketones, reaction with nitro enolates

In contrast, the tin(Il) enolates of cyclohexanone undergo addition to (2f)-(2-nitroethenyl)ben-zene to give 2-(2-nitro-l-phenylethyl)cyclohexanones with high anti diastereoselection5. The analogous reactions with cyclopentanone and 4-tert-butylcyclohexanone were less diastereose-lective with anti/syn ratios of 70 30 and 62 38. respectively. Modest to excellent diastereoselec-tivity was observed with acyclic ketones (d.r. 75 25 to 90 10) however the precise stereochemical details were not provided. 

Considerable use has also been made of allyl carbonates as substrates for the allylation of Pd enolates.9 The reaction of Pd° complexes with allyl enol carbonates119,120 proceeds by initial oxidative addition into the allylic C—O bond of the carbonate followed by decarboxylation, yielding an allylpalladium enolate, which subsequently produces Pd° and the allylated ketone (equation 22). In like fashion, except now in an intermolecular sense, allyl carbonates have been found to allylate enol silyl ethers (equation 23),121 enol acetates (with MeOSnBu3 as cocatalyst) (equation 24),122 ketene silyl acetals (equation 25)123 and anions a to nitro, cyano, sulfonyl and keto groups.115,124 In these cases, the alkoxy moiety liberated from the carbonate on decarboxylation serves as the key reagent in generating the Pd enolate. 

Various a-nitro ketones, widely used as synthetic intermediates, have been prepared by reaction of silyl enolates with tetranitromethane in the dark at room or low temperature or under photochemical conditions. The highly coloured solutions are due to intermolecular 1 1 electron donor-acceptor complexes formed between the enolate and tetranitromethane. The formation of similar vividly coloured complexes with electron acceptors such as chloranil, tetracyanobenzene and tetracyanoquinonedimethane readily establishes silyl enolates as electron donors. The formation of radical cations as reactive intermediates has been confirmed. 

The nitro group can be converted into other useful functional groups following conjugate addition. Reduction gives primary amines while hydrolysis reveals ketones. The hydrolysis is known as the Nef reaction and used to be achieved by formation of the nitro-stabilized anion with a base such as sodium hydroxide followed by hydrolysis with sulfuric acid. These conditions are rather unforgiving for many substrates (and products) so milder methods have been developed. One of these involves ozonolysis of the nitro enolate at low temperature rather than treatment with acid. 

Aromatic nitro-compounds can be made to condense with silyl-enol-ethers using tris(dimethylamino) sulfur (trimethylsilyl)difluoride (TASF) a non-aromatic nitronate intermediate is aromatised by reaction with bromine, without isolation, to provide a 2-(orf/to-nitroaryl)-ketone and thence an indole after nitro group reduction. ... 

Note that nitro enolates have other synthetic uses. When nitrobutane was treated with sodium hydroxide, nitro-enolate 205 was formed. Rather than addition of an aldehyde or a ketone, 205 was treated with concentrated sulfuric acid to form butanal, with loss of N2O, in what is known as the Nef reaction. 28 Modern versions of this reaction use bases such as LDA and less vigorous oxidizing agents such as MoOPh. 29 The Knoevenagel disconnection is ... 

Acid catalysis is preferable to base for the condensation of 5a-cholestan-3-one (341) with pentyl nitrite to form the hydroxyimino-ketone (342). The dioxime (343) afforded the [2,3-c]furazan 2-oxide (344) on oxidation with hypochlorite. Nitration of the 3-ketone (341) with ethyl nitrate and base gave the 2-nitro-enol (345) the derived 3-oxime (346) gave the furazan oxide (344) on reaction with acid. Nitration of 5a-cholestan-7-one gave the 6a- and 6)5-nitro-ketones (347), apparently the first epimeric pair of steroidal nitro-ketones to be... 

Use of oxygen, the most common oxidant, for oxidation of the a"-adducts is limited to the adducts of primaiy and secondary carbanions. Since the oxidation of these a"-adducts by oxygen proceeds efficiently only in the presence of an excess of base, we suppose that the dianions produced via further deprotonation of the a"-adducts are oxidized by oxygen [17]. This process is illustrated by direct ONSH in nitroarenes with enolates of ketones that proceeds selectively para to the nitro group [18, 19]. On the other hand, reaction of such enolates with m-nitroanilines—an efficient synthesis of nitroindoles proceeds mostly ortho to the amino and nitro groups [18]. Both of these reactions proceed in the presence of atmospheric oxygen and do not require another oxidant (Scheme 11.9). 

Enolates of aldehydes, ketones, and esters and the carbanions of nitriles and nitro compounds, as well as phosphorus- and sulfur-stabilized carbanions and ylides, undergo the reaction. The synthetic applications of this group of reactions will be discussed in detail in Chapter 2 of Part B. In this section, we will discuss the fundamental mechanistic aspects of the reaction of ketone enolates with aldehydes md ketones. 

Rawal and Kozmin have utilized a Reissert type reaction in the total synthesis of tabersonine. The requisite nitro ketone is prepared by SNAr reaction of o-nitrophenylphenyliodonium fluoride with ketone silyl enol ether (Scheme 10.10).96... 

The illustrative example is the synthesis of heptane-2,5-dione (Expt 5.105). A related reaction is the interaction of a silyl enol ether, derived from a ketone, with a nitro olefin in the presence of either titanium(iv) chloride or... 

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