Ketones Shapiro reaction

Ketone p-toluenesulfonylhydrazones are converted to alkenes on treatment with strong bases such as an alkyllithium or lithium dialkylamide.286 Known as the Shapiro reaction,2 7 this proceeds through the anion of a vinyldiimide, which decomposes to a vinyllithium reagent. Treatment of this intermediate with a proton source gives the alkene. 

The Shapiro reaction has been particularly useful for cyclic ketones, but its scope includes acyclic systems as well. In the case of unsymmetrical acyclic ketones,... 

The Shapiro reaction converts the p-lolucncsulfonylhydrazoncs of a, (3-unsaturated ketones to dienes (see Entries 3 to 5 in Scheme 5.14).289... 

Scheme 5.15 shows some examples of the Shapiro reaction. Entry 1 is an example of the standard procedure, as documented in Organic Syntheses. Entry 2 illustrates the preference for the formation of the less-substituted double bond. Entries 3, 4, and 5 involve tosylhydrazone of a, (3-unsaturated ketones. The reactions proceed by a -deprotonation. Entry 6 illustrates the applicability of the reaction to a highly strained system. 

Alkenyllithium compounds are intermediates in the Shapiro reaction, which is discussed in Section 5.7.2. The reaction can be run in such a way that the organolithium compound is generated in high yield and subsequently allowed to react with a variety of electrophiles.64 This method provides a route to vinyllithium compounds starting from a ketone. 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

Ketone p-toluenesulphonyl hydrazones can be converted to alkenes on treatment with strong bases such as alkyl lithium or lithium dialkylamides. This reaction is known as the Shapiro reaction68. When w./i-LinsaUi rated ketones are the substrates, the products are dienes. This reaction is generally applied to the generation of dienes in cyclic systems where stereochemistry of the double bond is fixed. A few examples where dienes have been generated by the Shapiro reaction have been gathered in Table 669. 

Conjugated dienes can be prepared from certain ketones via their trisylhydrazones (386) by the Shapiro reaction (equation 102). This involves a reductive metallation to a vinyllithium intermediate, transmetallation, for example, with Cu(I) iodide, and oxidative coupling. ... 

The Shapiro reaction occurs when a tosylhydrazone 86, easily prepared from a ketone and tosylhydrazine, is treated with 2 equivalents of an ethereal solution of n-butyllithium 87, resulting first in the removal of the N—H proton to give the anion 88 and then of a one proton from the less-substituted a position to give the dianion 89. Elimination of lithium p-toluenesulfinate in the rate-limiting step gives the lithium aUtenyldiazenide 90, which suffers loss of nitrogen to afford the alkenyllithium 91 (equation 31) ° . ... 

As described previously, the Shapiro reaction requires stoichiometric amounts of base to generate the alkyllithium reagents. An efficient catalytic method of the Shapiro reaction, which showed excellent regio- and stereo-selectivity, has also been reported. Indeed, the combination of ketone phenyl aziridinylhydrazones 116 and a catalytic amount of hthium amides leads to the corresponding alkene 117 in good overall yield (equation... 

The Shapiro reaction provides a convenient, easy and straightforward method to convert ketones into a plethora of olefinic substances in high yields. Many of these vinyllithium derivatives are useful for further synthetic manipulations. No attempt is made in this chapter to cover all the applications of the Shapiro reaction and only few representative examples will be described. A variety of polyolefins such as 119, used for cation olefin cyclization, can be stereospecifically formed in a concise and modular approach in a single step from the components shown in equation 42 via the Shapiro reaction . 

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. 

Reductive lithiation of the vinylsulfide 67 derived from a cyclic ketone provides a valuable alternative to the Shapiro reaction (section 8.1),84 and the sequence of events leading to 68 or 69 determines the regioselectivity. 

The decomposition of the dianions of arenesulfonylhydrazones, known as the Shapiro reaction,4 is one of the most reliable ways of making vinyllithium reagents. In the earliest, and still widely used, version of the reaction,1 a ketone is condensed with p-toluenesulfonylhydrazine 1 to yield a crystalline hydrazone such as 2. Deprotonation of 2 with base (usually BuLi) gives a monoanion 3, which, if heated, decomposes to a carbene 4 in... 

Geometrical stereoselectivity can often be achieved in the condensation of unsymmetrical ketones 8 with tosylhydrazine l,2 and this feature means Shapiro reactions direct from an unsymmetrical ketone 8 via E-9 lead to the less substituted vinyllithium 11. On the other hand, a sequential alkylation-Shapiro sequence from a starting symmetrical hydrazone 12 will reliably form the more substituted vinyllithium 14 via Z-9 Retention of Z stereochemistry in Z-9 is dependent on its re-use almost immediately on standing, for example, Z-9 (R = vinyl) equilibrates to an 85 15 ratio E Z-9J ... 

Vinyl silanes can be prepared directly from ketones using the Shapiro reaction... 

Conversion of ketones into arylsulfbnylhydrazones allows preparation of the corresponding vinyl lithiums by base-promoted decomposition ofthe hydrazone. This is known as the Shapiro reaction. 

Vinylsilanes may be prepared from the corresponding ketones by formation of the hydrazone followed by Shapiro reaction, quenching the vinylic anion with chlorosilanes. An equally effective process derives the vinylsilane from the vinyl chloride, in turn prepared simply from the ketone. The crucial oxidative transformation may be achieved in two ways. Firstly, ozonolysis in dichloromethane/methanol at approximately 0 C followed by reductive work-up affords the a-hy xy ketone, e.g. (96) to (97), via the intermediates (98) and (99). The outcome of the reaction varies with the solvent and work-up conditions, but using the combination indicated, good yields of the desired products are available. 

TransposMon of a carbonyl group. Two groups have used the Shapiro reaction to transpose a carbonyl group. Thus treatment of the tosylhydrazone of an o-sulfenylated ketone (1) with n-butyllithium and DABCO at -78 - 20° gives 2, which is hydrolyzed to the ketone 3 by mercuric chloride. ... 

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). "... 

A complementary approach, developed by Paquette, - uses substituted acryloyl chlorides as addends in reaction with structii ly embellished vinylsilanes. A general route to the vinylsilanes (87) was found in the silylation of vinyllithiums generated by the Shapiro reaction.The acylation with acryloyl chlorides takes place readily with aluminum trichloride to afford the divinyl ketones which are subsequently cyclized with tin tetrachloride. The Nazarov cyclization products were formed as a mixture of double tend isomers (equation 47). The best results were obtained with p,p-dimethylacryloyl chloride. Crotonyl chloride could be employed, but acryloyl chloride proved impractical. This metl owes much of its utility to the regiocontroUed synthesis of Ae vinylsilmes, thereby clearly establishing the loci of cyclopentannulation. 

As mentioned, LiAlH4 in refluxing THF was the initial system introduced to reduce preformed tosyl-hydrazones to hydrocarbons and a number of successful conversions have been reported, representative examples of which are presented in Table 5. Alkene side products often accompany the hydrocarbon products,a result attributed to proton abstraction from the a-carbon of intermediate (59), leading to a vinyldiimide anion (64), followed by N2 expulsion and protonation during work-up (Scheme 3). With certain ketones, including 17-keto steroids, alkenes are the major s or sole product (entries 7-9, Table 5). This side reaction mimics the elimination obtained upon treatment of to-sylhydrazones with other strong bases (i.e. alkyllithiums, the Shapiro reaction 29). Note that use of LiAlD4 introduces one deuterium (with H2O work-up) or two deuteriums (with D2O work-up entries 5 and 6, Table 5, respectively). 

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 title reaction represents the decomposition of arenesulfonylhydrazones with alkyllithium reagents to furnish unrearranged, less-substituted alkenes almost exclusively. The in situ generated alkenyllithium reagents can be further elaborated by reaction with an electrophile. Since the electrophile can be easily varied, the Shapiro reaction p>ermits the convenient transformation of a ketone into a single substituted alkene in a synthetically useful way. This section will highlight the versatility of this reaction in selective organic synthesis. 

The original Shapiro reaction involves the preparation of unfiinctionalized alkenes from ketone tosyl-hydrazones by quenching of the in situ generated alkenyllithium reagents with water. Recent applications of this reaction in natural product synthesis include the synthesis of 9(0)-methanoprostacyclin (Scheme 12), the in vitro conversion of humulene to A ( -capnellene (Scheme 13), the synthesis of die basic skeleton of isoadsirene (equation S2) ° and the total synthesis of the eudesmanolides rothin A and rothin B (equation 53). ... 

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