Aldehydes Shapiro reaction

Removal of the carbonate ring from 7 (Scheme 1) and further functional group manipulations lead to allylic alcohol 8 which can be dissected, as shown, via a retro-Shapiro reaction to give vinyl-lithium 9 and aldehyde 10 as precursors. Vinyllithium 9 can be derived from sulfonyl hydrazone 11, which in turn can be traced back to unsaturated compounds 13 and 14 via a retro-Diels-Alder reaction. In keeping with the Diels-Alder theme, the cyclohexene aldehyde 10 can be traced to compounds 16 and 17 via sequential retrosynthetic manipulations which defined compounds 12 and 15 as possible key intermediates. In both Diels-Alder reactions, the regiochemical outcome is important, and special considerations had to be taken into account for the desired outcome to. prevail. These and other regio- and stereochemical issues will be discussed in more detail in the following section. 

Shapiro Reaction Treatment of the tosylhydrazone of an aldehyde or a ketone with a strong base leads to the formation of an olefin, the reaction being formally an elimination accompanied by a hydrogen shift. This reaction is called Shapiro reaction. 

Direct transition from level 2 to level 0 can be achieved by way of the Wolff-Kishner reaction (treatment of the respective hydrazones with alkali), a classical pathway for the reduction of carbonyl compounds. At the same time, a direct conversion of aldehydes and ketones into alkenes is also feasible via reductive cleavage of their tosylhydrazones under the action of MeLi, the Shapiro reaction (Scheme 2.63). "... 

The Bamford-Stevens reaction is the base-catalyzed decomposition of arenesulfonylhydrazones of aldehydes and ketones, leading to the formation of alkenes an or cyclopropanes. There are several important general reviews in this area of organic synthesis. Since the reactions are mostly carried out either in protic or in aprotic solvents, the reaction types are divided into the protic and aprotic Bamford-Stevens processes. This section reviews recent examples in the synthesis of alkenes and cyclopropanes from arenesulfonylhydrazones, which is closely related to the following Shapiro reaction. 

The base catalyzed decomposition of arylsulfonylhydrazones of aldehydes and ketones to provide alkenes is called the Bamford-Stevens reaction. When an organolithium compound is used as the base, the reaction is termed the Shapiro reaction. The most synthetically useful protocol involves treatment of the substrate with at least two equivalents of an organolithium compound (usually MeLi or BuLi) in ether, hexane, or tetramethylenediamine. The in s/ft formed alkenyllithium is then protonated to give the alkene. The above procedure provides good yields of alkenes without side reactions and where there is a choice, the less highly substituted alkene is predominantly formed. Under these reaction conditions tosylhydrazones of a,(3-unsaturated ketones give rise to conjugated dienes. It is also possible to trap the alkenyllithium with electrophiles other than a proton. 

A novel class of chiral indenes (verbindenes) was prepared from enantiopure verbenone by K.C. Rupert and coworkers who utilized the Shapiro reaction and the Nazarov cyciization as the key transformations. The bicyclic ketone substrate was treated with triisopropylbenzenesulfonyl hydrazide to prepare the trisyl hydrazone that was then exposed to n-BuLi. The resulting vinyllithium intermediate was reacted with various aromatic aldehydes to afford the corresponding allylic alcohols. 

Addition of vinyl metals to aldehydes and ketones (chapter 16) also allows control over stereochemistry. The stereospecific vinyl anion equivalent 24 is one we made in chapter 16 by the Shapiro reaction. We repeat this scheme because it uses prenylation of a hydrazone aza-enolate to make the starting material for the vinyl-tin compound 25. 

The Bamford-Stevens synthesis is related to the Shapiro reaction (Shapiro and Heath, 1967 reviews Shapiro, 1976 Adlington and Barrett, 1983), in which a 4-toluenesulfonyl hydrazone of an aldehyde or a ketone is treated with at least two equivalents of a very strong base, usually, methyllithium (see Organic Syntheses examples of Chamberlin et al., 1983, and Shapiro et al., 1988). The Shapiro reaction leads to an olefin by a hydrogen shift. The mechanism has been proposed by Casanova and Waegell (1975) as given in (2-34). This mechanism involves a diazenide anion 2.81 as intermediate. 

As an example of the Shapiro reaction, the 2,4,6-triisopropylphenylsulphonylhydrazone of (-)-(3/ )-3-hydroxy-P-ionone (34) is treated with an excess of -BuLi in hexane in the presence of TMEDA to give the vinyllithium reagent 35 which, on condensation with the C27-aldehyde 36, furnishes the C4o-allylic alcohol 37 in 75% yield, en route to (3/ ,6 / )-P,E-carotene-3,19-diol [20] (Scheme 9). 

This reaction is closely related to the Shapiro Reaction developed 15 years later. The Shapiro Reaction is also the decomposition of p-toluenesulfonylhydrazones of ketones and aldehydes and is carried out under mild conditions to form less-substituted alkenes. 

This reaction was initially reported by Shapiro in 1967. It is a synthesis of olefins by means of a base-promoted decomposition of p-toluenesulfonylhydrazones of the corresponding ketones or aldehydes. Therefore, it is generally known as the Shapiro reaction, or Shapiro elimination." Occasionally, it is also referred to as the Shapiro olefination, Shapiro lithiation reaction, Shapiro fragmentation, or Shapiro degradation." ... 

Bamford-Stevens and Shapiro Reactions. The Bamford-Stevens reaction is used to obtain unsaturated compounds from tosylhydrazones. A base is required to generate its monoanion, which thermally decomposes to yield the corresponding di-azo derivatives. These reactive species evolve to give an aUcene through carbenium ions in protic solvents or carbenes in aprotic solvents. The thermal decomposition of the monoanions of trisyl-hydrazones is commonly used to obtain diazoalkanes for different applications such as functionalization of solid supports, epox-idation and alkenylation of aldehydes, or the study of radicals and carbenes The functionalization of a Merrifield resin with... 

Similarly, when an aldehyde or ketone is treated with p-toluenesulfonylhydrazine (P-CH3C6H4NHNH2), a p-toluenesulfonylhydrazone (tosylhydrazone) (Scheme 9.69) is formed. Now, when this stable, easily purified carbonyl derivative is treated with at least two equivalents of a strong base (such as methyllithium, CH3Li),proton loss on the carbon adjacent to the xp -hybridized center (i.e., the a-carbon) occurs and an organolithiated alkene results. Hydrolysis of the latter results in alkene formation and the consummation of the Shapiro reaction. ... 

Barrett and Adlington have shown that allenic dianions (96), prepared from a-keto-amides via the Shapiro reaction, react at C-2 with aldehydes, acetone, and deuterium oxide to form a variety of substituted acrylamide derivatives. ... 

Methyl vinyl ketone, when converted into the sulphonylhydrazone (189), undergoes the Shapiro reaction to generate 2-lithiobuta-l,3-diene (190), which then reacts with aldehydes to give 2-substituted dienes (191) in moderate yield. ... 

The Shapiro reaction of tosylhydrazones with base has now been extended as a route to a wider variety of functionalized olefins. Thus, treatment of tosylhydrazones, which contain only a tertiary a-hydrogen, with lithium iso-propylamide, can now yield trisubstituted olefins. The yields are only moderate, but the procedure is convenient. Regiospecifically generated tosyl-hydrazone dianions may be trapped with aldehydes and ketones to give, on neutralization, /3-hydroxytosylhydrazones further treatment with alkyl-lithium reagents yields allylic and homoallylic alcohols. These procedures are exemplified in Scheme 21. 

As with resin beads, gel-phase HR-MAS NMR spectroscopy can be used to analyze systems where the resin is grafted onto the base polymer units, known as crowns. The first example of HR-MAS NMR on crowns was demonstrated by Shapiro et al. The spectrum of a crown with the aldehyde 13 attached to the graft polymer has the characteristic peak at 10.2 ppm (Scheme 4.6). A Wittig reaction was performed on this substrate, and its... 

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