Tosylhydrazones, Shapiro reaction

Regioselectivity in the context of substituted alkenyl anion has also been addressed. It is known that the base-induced fragmentation of tosylhydrazones (Shapiro reaction) derived from a-substituted ketones leads predominantly to the "kinetic" (cf. ketone enolates)... 

Butyllithium/N, N, N, N -tetramethylenediamine Synthesis of ethylene derivs. from tosylhydrazones Shapiro reaction [Pg.488]

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 ... 

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. 

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) ° . ... 

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. 

The Shapiro Reaction, a variation on the Bamford-Stevens Reaction, is the base-induced reaction of tosylhydrazones to afford alkenes. This reaction is carried out with two equivalents of an organolithium compound. 

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). "... 

The reaction of alkyllithium reagents with acyclic and cyclic tosylhydrazones can lead to mixtures of elimination (route A) and addition (route B) products (Scheme 22). The predominant formation of the less-substituted alkene product in the former reaction (Shapiro Reaction) is a result of the strong preference for deprotonation syn to the N-tosyl group. Nucleophilic addition to the carbon-nitrogen tosyl-hydrazone double bond competes effectively wiA a-deprotonation (and alkene formation) if abstraction of the a-hydrogens is slow and excess organolithium reagent is employed. Nucleophilic substitution is consistent with an Su2 addition of alkyllithium followed by electrophilic capture of the resultant carbanion. 

In addition to carbon-carbon bond forming reactions of derived anions, hydrazones and oximes are important derivatives of carbonyl groups for the Beckmann rearrangement (of oximes to amides, equation 55)203.204 jmd the Shapiro reaction (tosylhydrazones to alkenes, equation 56). ° Of historical... 

The reaction of a tosylhydrazone with at least 2 equiv. of an alkyllithium reagent in ether or hexane generates the dianion (Shapiro reaction) this gives, after loss of Ts" and N2, the vinyllithium compound, which can be trapped by a variety of electrophiles, e.g. H", CO2, DMF (Scheme 27). The less-substituted alkene is formed predominantly under these conditions. 

The reaction of tosylhydrazones with sodium in ethylene glycol to give alkenes had been observed before (Bamford-Stevens reaction) other bases, e.g. NaOMe, alkali metal hydrides and NaNH2 were also used. However, in these cases side reactions occur and, in contrast to the Shapiro reaction, the more highly substituted alkene is predominantly formed. Two mechanisms are discussed for these reactions a mechanism via a carbenium ion, which usually takes place in protic solvents, and a carbene mechanism in aprotic solvents (Scheme 28). In both cases diazo compounds are intermediates, which can sometimes be isolated. ... 

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. 

The Shapiro reaction is the conversion of ketone to an alkene via a tosylhydrazone. The tosylhydrazone is treated with two equivalents of strong base, typically n-BuLi or MeLi, to afford an alkenyllithium species which is quenched with an electrophile to form an alkene (see also chapter 5, 5.1.25 Shapiro reaction). Reviews (a) Chamberlin, A. R. Bloom, S. H. Org. React. 1990, 39,1-83. (b) Shapiro, R.H. Org. React. 1976,23,405. 

The reaction of tosylhydrazones with ArX under the influence of (dba)3Pd2-X-Phos performs the equivalent of an arylative Shapiro reaction/ A mixture of carbonyl compounds and TSNHNH2 can be employed in lieu of the tosyhydrazones/ ... 

The mechanism of the Shapiro reaction is believed to involve initial deprotonation of the NH proton from tosylhydrazone 5 to generate 6, which undergoes a second deprotonation adjacent to the hydrazone group to afford dianion 7. Elimination of lithium p-toluene-... 

In most cases the regiochemistry of the Shapiro reaction is controlled by steric factors, with the second metalation occurring at the less-substituted a-carbon atom of the hydrazone.2 For example, a-methyl ketone 10 was transformed to disubstituted alkene 11 in 69% yield as a single regioisomer via conversion to a tosylhydrazone followed by treatment with -BuLi. However, the regiochemical outcome of Shapiro reactions involving a,p-unsaturated hydrazones is difficult to predict in the absence of data obtained from reactions of structurally related substrates, as the second metalation can occur at either the a - or y-position. 

As mentioned above, one significant problem with the use of phenyl- or tosylhydrazones in the Shapiro reaction is competing deprotonation of an orfAo-position on the aromatic ring. This side reaction often leads to diminished yields and/or the requirement for >3 equivalents of the alkyllithium base. This problem has been addressed through the use of trisylhydrazones (trisyl = 2,4,6-triisopropylphenyl), which do not contain aromatic protons that are easily metalated.11 For example, trisylhydrazone 15c... 

The two modifications described above have allowed for the efficient capture of vinyllithium intermediates generated in Shapiro reactions with a wide variety of electrophiles. For example, the alkyllithium reagent 20 prepared from treatment of trisylhydrazone 18 with n-BuLi was effectively trapped with benzaldehyde (62% yield, 21), 1 -bromobutane (58% yield, 22), and bromine from 1,2-dibromoethane (43% yield, 23)." Similarly, formation of 20 from tosylhydrazone 19 followed by trapping with CO2 afforded 24 (52% yield). The reaction of intermediate 20 (generated from 19) with cyclohexenone provided 25, the product of 1,2-addition, in 61% yield.13... 

The a-alkylation of sulfonylhydrazone dianions with disulfides followed by Shapiro reaction has been used to effect the 1,2-transposition of carbonyl groups.19,20 As shown below, treatment of tosylhydrazone 31 with n-BuLi/TMEDA followed by addition of dimethyl disulfide and deprotonation with an additional equivalent of w-BuLi provided vinylsulfide 32.19 Exposure of this compound to mercuric chloride in hot aqueous acetonitrile provided ketone 33 in 75% overall yield. 

The conversion of ketone 38 to alkene 40 in the context of Winterfeldt s synthesis of (-)-myltaylenol was accomplished in two steps using classical conditions for the Shapiro reaction.22 The tosylhydrazone 39 was generated cleanly from 38 in near quantitative (98%) yield. Treatment of 39 with excess n-BuLi provided 40 in 90% yield. 

Several approaches to the synthesis of taxol and the taxane skeleton have employed Shapiro reactions.25 An interesting route to the taxol A-ring that illustrates the utility of dianion functionalization prior to alkene generation was recently described by Koskinen.256 As shown below, treatment of tosylhydrazone 48 with 2.2 equiv of n-BuLi... 

The Shapiro reaction appeared to offer a reasonable alternative protocol. To this end, ketone 146 was converted to the corresponding tosylhydrazone 149 in reasonable yield (70%, in addition to recovered starting material). Both diastereomers of 149 were then subjected to a variety of standard, literature procedures [56]. In no case was product observed, only recovered starting material. Careful examination of the... 

Shapiro reaction. (2, 418-419 6, 598-600). Several laboratories have used EDA instead of an alkyllithium for decomposition of tosylhydrazones of ketones to olefins. Trisubstituted alkenes can be prepared by this modification in moderate yields from tosylhydrazones that contain only tertiary a-hydrogens. This modification also favors formation of the (Z)-disubstituted olefin. ... 

Conversion of Ketones to Vinylsilanes. Ketones can be transformed into vinylsilanes via intermediate trapping of the vinyl anion from a Shapiro reaction with TMSCl. Formation of either the tosylhydrazone or benzenesulfonylhydrazone (eq 26) followed by reaction with n-butyUithium in TMEDA and TMSCl gives the desired product. 

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