By the Shapiro reaction

A more promising procedure for the formation of alkenes from tosylhydrazones is represented by the Shapiro reaction It differs from the Bamford-Stevens reaction by the use of an organolithium compound (e.g. methyl lithium) as a strongly basic reagent ... 

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. ... 

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. 

Reactive alkenyl anions prepared by the Shapiro reaction from trisylhydrazones of polyenones and their smooth 1,2-addition to polyenals provides a new route to the versatile synthesis of hydroxymethyl-... 

The synthon of the a-acrylate anion is available from a secondary a-keto carboxamide by the Shapiro reaction. The secondary a-ketoamide trisylhydrazones ate ptepar in a one-pot synthesis by reaction of the isocyanides with acid chloride, water and trisylhydrazine in sequence. In DME solvent, the hydra-zone (103) is smoothly metallated with BuLi to give Ae trianion (KH). Allylation of the trianion (104) gives the hydrazone (105). Alternatively, warming (104) up to room temperature yields the dianion (106) which can be intercepted with several electrophiles (Scheme 23). The adduct (107) is readily transformed into the rran -iodo lactone (108) stereospecifically (equation 56). This chemistry also has been applied to a new synthesis of -lactams (Scheme 24). ... 

P. Quayle and co-workers utilized the Dotz benzannulation reaction for the synthesis of diterpenoid quinones." The authors developed a novel synthetic approach to 12-O-methyl royleanone using a simple vinyl chromium carbene complex along with a disubstituted oxygenated acetylene. The bicyclic hydrazone was converted to the corresponding vinyllithium derivative by the Shapiro reaction and then functionalized to give the desired crude Fischer chromium carbene complex. The benzannulation took place in refluxing THF with excellent regioselectivity, and the natural product was obtained in 37% overall yield from the hydrazone. 

It appears that the lithiation site is determined by the geometry of the C=N bond. When a second (third ) lithiation is induced, it occurs on the same side as the first - and this is now the more crowded side 46. The regiochemistry is determined by the C=N bond but the stereochemistry remains as before. When the Shapiro reaction is allowed to go to completion, by warming to 0 °C, the unsymmetrical Z-vinyl lithium Z-47 is produced. This is the isomer that cannot be made by the Shapiro reaction from the methyl ketone 48. 

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 reaction mechanism has been confirmed by trapping of intermediates 13, 14 and 15. Because of the fact that neither a carbene nor a carbenium ion species is involved, generally good yields of non-rearranged alkenes 2 are obtained. Together with the easy preparation and use of tosylhydrazones, this explains well the importance of the Shapiro reaction as a synthetic method. 

The vinyl lithium reagents generated in the Shapiro reaction can be used in tandem reactions. In the reaction shown below, a hydroxymethyl group was added by formylation followed by reduction. 

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. 

Making the vinyllithium by a Shapiro reaction (section 8.1) from 164 bypasses the chemoselectivity problem altogether, and provides a useful cyclisation route to exo-methylene derivatives of five-, six- and seven-membered rings 165.78 The main by-products 166 are the result of protonating the vinyllithium. 

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. 

The reduction of a carbonyl group to an olefin has been accomplished by the Shapiro modification5 of the Bamford-Stevens reaction and by the hydride reduction of the corresponding enol ether,6 enol acetate,7 or en-amine.8 The nickel reduction of the thioketal has also been used successfully.9... 

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). "... 

Preparation. Both the title zirconium catalyst (1), and the corresponding hafnium derivative (2) have been synthesized according to Scheme 1. Addition of 2 equiv of 2-bomen-2-yllithium (4) (generated via the Shapiro reaction from (-b)-camphor (3)) to ethyl formate gives bis(2-bomen-2-yl)methanol (5). Cycliza-tion of alcohol (5) is carried out with Potassium Hydrogen Sulfate at 100-150 °C to afford dibornacyclopentadiene (6). Deprotonation of (6) with n-Butyllithium followed by reaction with Zir-conium(IV) Chloride affords (1). Reaction with HfCl4 affords (2). 

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). 

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