Aldehydes, reaction with nitro enolates

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. 

Mukaiyama aldol reaction of aliphatic trimethylsilyi enol ethers with aromatic aldehydes trimethylsilyi nafion nitro [131]... 

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 ... 

The two products arise from the fact that the enolate-aldehyde reaction generates both the R- and the S-alcohol units in the product. Compound 91 is 1-deoxy-l-nitro-d-arabinitol and 92 is 1-deoxy-l-nitro-d-xylitol. Deoxy indicates that an oxygen atom has been removed from Cl relative to 13. When 91 is treated with NaOH and then with sulfuric acid, the product is d-lyxose (17). Under the same conditions, 92 is converted to d-xylose, 16. In principle, this process can be repeated indefinitely to produce even longer chain aldose monosaccharides. 

Doubly deprotonated methyl 3-nitropropanoate (25) is a new reagent which is alkylated and hydroxyalkylated exclusively at the 2-position by alkyl halides and aldehydes respectively (Scheme 39) a double alkylation can also be performed. Elimination of HNOg with DBN, or better with DBU, in THE furnishes the corresponding a-methylenealkanoates. (3-Nitro-ketones also result from the reaction of 1,1-dinitrohalides with ketone enolates. ... 

The significant synthetic advantage of this approach is the isolation of regio-and stereo-defined enol silyl ethers of optically active y-nitro aldehydes (Table 4.2). For example, after the reaction of 16a with trans-cinnamaldehyde, the resulting mixture can be directly purified by silica gel column chromatography to produce the optically active enol silyl ether 20a in 90% yield (Table 4.2, entry 1). High... 

Aliphatic nitro compounds show a number of reactions which parallel those of carbonyl chemistry. Primary and secondary nitro compounds exhibit tautomerism paralleling keto-enol tautomerism (Scheme 3.94a). Aliphatic nitro compounds dissolve in aqueous sodium hydroxide with the formation of sodium salts. The resultant anions behave as carban-ions and will condense with aldehydes. An example involves the formation of m-nitrostyrene from nitromethane and benzaldehyde (Scheme 3.94b). 

In conclusion, C-C bond formation on carbohydrates has absorbed lots of widely used methods from general synthetic organic chemistry. Typical among these methods are intramolecular alkylation and intramolecular condensation of aldehyde with enolates, phosphonates, and nitro-stabilized anions. Metal-mediated radical reactions, cycloadditions, and rearrangements have also been applied frequently. 

The conjugate bases of carbonyl compounds, enolates, react with ketones and aldehydes in the aldol reaction. The reaction is usually executed in two stages. First, the enolate is generated, usually by deprotonation of the carbonyl compound at low temperature with a strong base such as LDA, KHMDS, or LiHMDS, but not always. Then the electrophilic carbonyl compound is added to the reaction mixture. Under these conditions, the reaction usually stops at the /3-hydroxycarbonyl stage. The nucleophilic component may be any carbonyl compound, or even a nitrile, a sulfonyl compound, or a nitro compound (honorary members of the carbonyl family). 

Selenenyl halides are relatively stable, though moisture sensitive, compounds that are generally prepared by the reactions shown in Scheme 7 and behave as electrophilic selenium species. They react with ketones and aldehydes via their enols or enolates to afford a-seleno derivatives (e.g. (17) in equation 11). Similar a-selenenylations of /3-dicarbonyl compounds, esters, and lactones can be performed, although the latter two types of compounds require prior formation of their enolates. Moreover, the a-selenenylation of anions stabilized by nitrile, nitro, sulfone, or various types of phosphorus substituents has also been reported (equation 12). In many such cases, the selenenylation step is followed by oxidation to the selenoxide and spontaneous syn elimination to provide a convenient method for the preparation of the corresponding Q ,/3-unsaturated compound (e.g. 18 in equation 11). Enones react with benzeneselenenyl chloride (PhSeCl) and pyridine to afford a-phenylselenoenones (equation 13). 

Michael Reaction (Section 19.8A) A Michael reaction involves the addition of a weakly basic nucleophile to a carbon-carbon double bond made electrophilic by conjugation with the carbonyl group of an aldehyde, a ketone, or an ester or with a nitro or cyano group. The mechanism of the Michael reaction involves initial formation of an enolate anion in base and attack of the enolate nucleophile at the )3-carbon of the Michael acceptor to create a new resonance-stabilized enolate anion intermediate that is protonated on oxygen to create an enol and regenerate the base then tautom-erization to the keto form completes the reaction. The base is catalytic in the Michael reaction. 

A new synthesis of aldehydes with 2-methyl-2-thiazoline has the advantage of releasing the aldehydes from the thiazolidine intermediate under neutral conditions . Acetylene derivatives can be obtained from aldehydes via dibromomethylene compounds Novel reactions of alkynes with cationoid electrophiles have been published. -Diketones and 2-ketoalkoximes can be obtained by this reaction from acid chlorides and aliphatic nitro compounds respectively Addition of aldehydes to activated carbon-carbon double bonds occurs smoothly in the presence of cyanide ions as catalysts . Poly- -carbonyl compounds have been prepared by condensation of two anions, whereby the enolate salt of a y8-keto ester condenses as an electrophilic anion with strong nucleophiles such as the dianion of benzoylacetone. ... 

---