Carbonyl compounds fragmentation synthesis

A 2-cyclohexenone derivative can be transformed into the corresponding epoxy tosyl-hydrazone by sequential treatment with peracid and tosylhydrazine. The elimination of nitrogen and p-toluenesulfinate and fragmentation after rearrangement to the 3-tosylazo allylic alcohol may occur under mild conditions. Carbonyl compounds with 5,6-triple bonds are formed in high yields (J. Schreiber, 1967 M. Tanabe, 1967). If one applies this reaction to a 9,10-epoxy-1-decalone, a ten-membered 5-cyclodecyn-l-one ring is formed (D. Felix, 1971). This product is an important intermediate in the perfume industry and has been used on a large scale. For this purpose Eschenmoser developed a synthesis in which the readily removed styrene was split off instead of a sulfmic acid. Thus a l-amino-2-phenylaziridine hydrazone was used instead of a tosylhydrazone (D. Felix, 1968). ... 

The epoxide can be prepared from an alkene and the amide from a carboxylic acid. The new target. 2-ethyl-2-hexenoic acid, has a CC double bond in conjugation with the carbonyl group of the carboxylic acid. Whenever a compound with an ,/3-unsaturated carbonyl group is encountered, it is worthwhile to consider the possibility of using an aldol condensation (see Section 20.5) or a related reaction to prepare it. To examine this possibility, the aldehyde that will provide the carboxylic acid upon oxidation is disconnected at the double bond. Because both fragments produced by this disconnection are the same, it is apparent that an aldol condensation of butanal can be employed to prepare this compound. The synthesis was accomplished as shown in Figure 23.5. 

Another synthesis based on the combination of these fragments is the 1,3-dipolar cycloaddition of carbonyl compounds to nitrile ylides. The latter are generated by photolysis of 1-azirines when the irradiation is carried out in the presence of an acyl chloride and triethylamine, oxazoles are formed in moderate yields (equation 121). 

Two different approaches are commonly used for the synthesis of alkynes. In the first, an appropriate electrophile undergoes nucleophilic attack by an acetylide ion. The electrophile may be an unhindered primary alkyl halide (undergoes Sn2), or it may be a carbonyl compound (undergoes addition to give an alcohol). Either reaction joins two fragments and gives a product with a lengthened carbon skeleton. This approach is used in many laboratory syntheses of alkynes. 

Sulfoxides fragment on heating to form alkenes and sulfenic acids. This reaction, known for over a century, has been developed into a useful alkene synthesis, - particularly for the synthesis of a,p-un-saturated carbonyl compounds as illustrated in equations (16)-(18). ... 

Selenoxide elimination is now widely used for the synthesis of a,p-unsaturated carbonyl compounds, allyl alcohols and terminal alkenes since it proceeds under milder conditions than those required for sulfoxide or any of the other eliminations discussed in this chapter. The selenoxides are usually generated by oxidation of the parent selenide using hydrogen peroxide, sodium periodide, a peroxy acid or ozone, and are not usually isolated, the selenoxide fragmenting in situ. The other product of the elimination, the selenenic acid, needs to be removed from the reaction mixture as efficiently as possible. It can disproportionate with any remaining selenoxide to form the conesponding selenide and seleninic acid, or undergo electrophilic addition to the alkene to form a -hydroxy selenide, as shown in... 

Schreiber, J., et al. Synthesis of acetylenic carbonyl compounds by fragmentation of a,P-epoxy ketones with p-tolylsulfonylhydrazine. Helv. Chim. Acta 1967, 50, 2101-2108. 

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