And the Shapiro reaction

The Bamford-Stevens reaction and the Shapiro reaction share a similar mechanistic pathway. The former uses a base such as Na, NaOMe, LiH, NaH, NaNHa, heat, etc., whereas the latter employs bases such as alkyllithiums and Grignard reagents. As a result, the Bamford-Stevens reaction furnishes more-substituted olefins as the thermodynamic products, while the Shapiro reaction generally affords less-substituted olefins as the kinetic products. 

The first enantioselective total synthesis of (-)-myltaylenol was achieved in the laboratory of E. Winterfeldt. The authors used an intramolecular Diels-Alder cycloaddition and the Shapiro reaction as key transformations to construct the unusual carbon framework of this sesquiterpenoid alcohol natural product, which contains three consecutive quaternary carbon atoms. 

A.8 IMINES AND RELATED FUNCTIONAL GROUPS THE WOLFF-KISHNER REDUCTION AND THE SHAPIRO REACTION... 

With regard to the reaction above (5A.42), recall the abbreviation Ts = tosyl or p-toluenesulfonyl (i.e., P-CH3-C6H4-SO2-). The hydrazones (as the products with hydrazine are called) lend themselves to a number of unique transformations, of which we will discuss the Wolff-Kishner reduction and the Shapiro reaction. 

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. 

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. 

Liebeskind and associates converted 3,4-diisopropyl squarate (97) to stannylcyclobutenedione 98 via a 1,4-addition-elimination sequence. 98 was then coupled with 2-iodothiophene to afford substituted cyclobutenedione 99 [85]. In another case, 3-lithioquinuclidin-2-ene, generated from the Shapiro reaction of 3-quinuclidinone (100), was quenched with Bu3SnCl to afford a unique enamine stannane 101. The Stille reaction of stannane 101 and 5-bromo-2-formyl-thiophene then furnished 3-thienylquinuclidine 102 [86]. 

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 . 

The Shapiro reaction has been particularly useful for cyclic ketones, but the scope of the reaction also includes acyclic systems. In the case of unsymmetrical acyclic ketones, questions of both regiochemistry and stereochemistry arise. 1-Octene is the exclusive product from 2-octanone.207... 

The advantage of the Shapiro over Bamford-Stevens Reaction is, that the resulting dianion does not tend to rearrange, which can occur with intermediate carbenes and carbenium ions. However, the Shapiro reaction does not lead to high stereoselectivity between the -/Z-isomers. 

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... 

Usable vinyllithiums are obtained if (a) ortholithiation-resistant hydrazones derived from triisopropylphenylsulfonylhydrazine 15 are used,9 and (b) if the Shapiro reaction is carried out in a TMEDA-hexane mixture, which avoids protonation of the vinyllithium.10 For example, 16 forms stereoselectively from 15, with steric hindrance directing formation of the E hydrazone. The dianion of 16 decomposes at 0 °C to yield the vinyllithium 17 which reacts with electrophiles to yield products such as 18.11... 

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