View source for Chemistry:Shapiro reaction

{{short description|Organic reaction}}
{{Reactionbox
| Name = Shapiro reaction
| Type = Coupling reaction
| NamedAfter = Robert H. Shapiro
| Section3 = {{Reactionbox Identifiers
   | OrganicChemistryNamed = shapiro-reaction
   | RSC_ontology_id = 0000125
 }}
}}
The '''Shapiro reaction''' or '''tosylhydrazone decomposition''' is an [[Chemistry:Organic reaction|organic reaction]] in which a [[Chemistry:Ketone|ketone]] or [[Chemistry:Aldehyde|aldehyde]] is converted to an [[Chemistry:Alkene|alkene]] through an intermediate [[Chemistry:Hydrazone|hydrazone]] in the presence of 2 equivalents of [[Chemistry:Organolithium reagent|organolithium reagent]].<ref>{{cite journal|last1 = Shapiro|first1 = R. H.|last2 = Lipton|first2 = M. F.|last3 = Kolonko|first3 = K. J.|last4 = Buswell|first4 = R. L.|last5 = Capuano|first5 = L. A.|title = Tosylhydrazones and alkyllithium reagents: More on the regiospecificity of the reaction and the trapping of three intermediates|journal = Tetrahedron Lett.|year = 1975|volume = 16|issue = 22–23|pages = 1811–1814|doi = 10.1016/S0040-4039(00)75263-4}}</ref><ref>{{cite journal|last = Shapiro|first = Robert H.|authorlink = Robert H. Shapiro|title = Alkenes from Tosylhydrazones|journal = Org. React.|year = 1976|volume = 23|issue = 3|pages = 405–507|doi = 10.1002/0471264180.or023.03|isbn = 978-0471264187}}</ref><ref>{{cite journal|last1 = Adlington|first1 = Robert M.|last2 = Barret|first2 = Anthony G. M.|title = Recent applications of the Shapiro reaction|journal = Acc. Chem. Res.|year = 1983|volume = 16|issue = 2|pages = 55–59|doi = 10.1021/ar00086a004}}</ref> The reaction was discovered by Robert H. Shapiro in 1967.<ref>{{cite journal|last1 = Shapiro|first1 = Robert H.|authorlink1 = Robert H. Shapiro|last2 = Heath|first2 = Marsha J.|title = Tosylhydrazones. V. Reaction of Tosylhydrazones with Alkyllithium Reagents. A New Olefin Synthesis.|journal = J. Am. Chem. Soc.|year = 1967|volume = 89|issue = 22|pages = 5734–5735|doi = 10.1021/ja00998a601}}</ref> The Shapiro reaction was used in the [[Chemistry:Nicolaou Taxol total synthesis|Nicolaou Taxol total synthesis]].<ref>{{cite book|title = Classics in Total Synthesis: Targets, Strategies, Methods|first1 = Kyriacos C.|last1 = Nicolaou|authorlink1 = K. C. Nicolaou|first2 = Erik J.|last2 = Sorensen|publisher = {{wipe|John Wiley & Sons}}|year = 1996|isbn = 9783527292318}}</ref> This reaction is very similar to the [[Chemistry:Bamford–Stevens reaction|Bamford–Stevens reaction]], which also involves the basic decomposition of tosyl hydrazones.

[[File:Shapiro reaction.svg|center|500px|The Shapiro reaction]]

==Reaction mechanism==
In a prelude to the actual Shapiro reaction, a [[Chemistry:Ketone|ketone]] or an [[Chemistry:Aldehyde|aldehyde]] '''(1)'''  is reacted with ''p''-toluenesulfonylhydrazide<ref>{{OrgSynth|first1 = Lester|last1 = Friedman|first2 = Robert L.|last2 = Litle|first3 = Walter R.|last3 = Reichle|year = 1960|title = ''p''-Toluenesulfonylhydrazide|volume = 40|pages = 93|collvol = 5|collvolpages = 1055|prep = cv5p1055}}</ref>'''(2)''' to form a ''p''-toluenesulfonylhydrazone (or [[Chemistry:Tosylhydrazone|tosylhydrazone]]) which is a [[Chemistry:Hydrazone|hydrazone]] '''(3)'''. Two equivalents of strong [[Chemistry:Base|base]] such as [[Chemistry:N-Butyllithium|''n''-butyllithium]] abstract the [[Chemistry:Hydron|proton]] from the hydrazone '''(4)''' followed by the less acidic proton α to the hydrazone carbon '''(5)''', forming a [[Chemistry:Carbanion|carbanion]]. The carbanion then undergoes an [[Chemistry:Elimination reaction|elimination reaction]] producing a carbon–carbon [[Chemistry:Double bond|double bond]] and ejecting the [[Chemistry:Tosyl|tosyl]] anion, forming a [[Chemistry:Diazonium compound|diazonium]] anion '''(6)'''. This diazonium anion is then lost as molecular nitrogen resulting in a vinyllithium species '''(7)''', which can then be reacted with various [[Chemistry:Electrophile|electrophiles]], including simple neutralization with water or an acid '''(8)'''.

:[[File:Shapiro Reaction.png|500px|Reaction diagram for Shapiro reaction]]

==Scope==
The position of the alkene in the product is controlled by the site of deprotonation by the organolithium base. In general, the kinetically favored, less substituted site of differentially substituted tosylhydrazones is deprotonated selectively, leading to the less substituted [[Chemistry:Vinyllithium|vinyllithium]] intermediate. Although many secondary reactions exist for the vinyllithium [[Chemistry:Functional group|functional group]], in the Shapiro reaction in particular [[Chemistry:Water|water]] is added, resulting in protonation to the [[Chemistry:Alkene|alkene]].<ref>{{OrgSynth|last1 = Shapiro|first1 = R. H.|last2 = Duncan|first2 = J. H.|title = 2-Bornene (1,7,7-Trimethylbicyclo[2.2.1]hept-2-ene)|collvol = 6|vollcolpages = 172|volume = 51|pages = 66|year = 1971|prep = cv6p0172|doi = 10.15227/orgsyn.051.0066}}</ref> Other reactions of vinyllithium compounds include alkylation reactions with for instance alkyl halides.<ref>{{OrgSynth|title = Generation and Reactions of Alkenyllithium Reagents: 2-Butylbornene|first1 = A. Richard|last1 = Chamberlin|first2 = Ellen L.|last2 = Liotta|first3 = F. Thomas |last3 = Bond|collvol = 7|collvolpages = 77|year = 1983|volume = 61|pages = 141|prep = cv7p0077|doi = 10.15227/orgsyn.061.0141}}</ref>
[[File:ShapiroReaction borneneSynthesis.svg|frame|center|Shapiro reactions starting from [[Chemistry:Camphor|camphor]] (1) through the intermediate hydrazone (2) to the vinyllithium (3). Addition of water (c) results in 2-bornene (4) and addition of an alkyl bromide (d) gives 5]]
Importantly, the Shapiro reaction cannot be used to synthesize 1-lithioalkenes (and the resulting functionalized derivatives), as sulfonylhydrazones derived from aldehydes undergo exclusive addition of the organolithium base to the carbon of the C–N double bond.<ref>{{cite journal|last1 = Chamberlin|first1 = A. Richard|last2 = Bloom|first2 = Steven H.|journal = Org. React.|year = 1990|volume = 39|issue = 1|pages = 1–83|title = Lithioalkenes from Arenesulfonylhydrazones|doi = 10.1002/0471264180.or039.01}}</ref>

==Catalytic Shapiro reaction==
Traditional Shapiro reactions require stoichiometric (sometimes excess) amounts of base to generate the alkenyllithium reagents. To combat this problem, Yamamoto and coworkers developed an efficient stereoselective and regioselective route to alkenes using a combination of ketone phenylaziridinylhydrazones as arenesulfonylhydrazone equivalents with a catalytic amount of lithium amides.
The required phenylaziridinylhydrazone was prepared from the condensation of undecan-6-one with 1-amino-2-phenylaziridine. Treatment of the phenylaziridinylhydrazone with 0.3 equivalents of LDA in ether resulted in the alkene shown below with a ''cis'':''trans'' ratio of 99.4:0.6. The ratio was determined by capillary GLC analysis after conversion to the corresponding epoxides with mCPBA. The catalyst loading can be reduced to 0.05 equivalents in the case of a 30mmol scale reaction.

The high stereoselectivity is obtained by the preferential abstraction of the α-methylene hydrogen syn to the phenylaziridine, and is also accounted for by the internal chelation of the lithiated intermediated.<ref>{{cite journal|title = The Catalytic Shapiro Reaction|first1 = Keiji|last1 = Maruoka|first2 = Masataka|last2 = Oishi|first3 = Hisashi|last3 = Yamamoto|journal = J. Am. Chem. Soc.|year = 1991|volume = 118|issue = 9|pages = 2289–2290|doi =10.1021/ja951422p}}</ref>

[[File:Catalytic Shapiro reaction.jpg|400px|The Shapiro reaction with ''N''-aziridinylhydrazones produces the alkene product, as well as stryrene and gaseous nitrogen as byproducts. The cycle of the catalytic Shapiro reaction is also shown.|center]]

==A one pot in situ combined Shapiro-Suzuki reaction==
The Shapiro reaction can also be combined with the [[Chemistry:Suzuki reaction|Suzuki reaction]] to produce a variety of olefin products. Keay and coworkers have developed methodology that combines these reactions in a one pot process that does not require the isolation of the [[Chemistry:Boronic acid|boronic acid]], a setback of the traditional Suzuki coupling. This reaction has a wide scope, tolerating a slew of trisylhydrazones and aryl halides, as well as several solvents and Pd sources.<ref>{{cite journal|first1 = Marco S.|last1 = Passafaro|first2 = Brian A.|last2 = Keay|title = A one pot ''in situ'' combined Shapiro-Suzuki reaction|journal = Tetrahedron Lett.|year = 1996|volume = 37|issue = 4|pages = 429–432|doi = 10.1016/0040-4039(95)02210-4}}</ref>
[[File:Shapiro-Suzuki reaction.jpg|300px|The Shapiro and Suzuki reactions are combined to yield a variety of alkene products.|center]]

==An application of the Shapiro reaction in total synthesis==
The Shapiro reaction has been used to generate olefins towards to complex natural products. K. Mori and coworkers wanted to determine the absolute configuration of the phytocassane group of a class of natural products called [[Chemistry:Phytoalexin|phytoalexin]]s. This was accomplished by preparing the naturally occurring (–)-phytocassane D from (''R'')-Wieland-Miescher ketone. On the way to (–)-phytocassane D, a tricyclic ketone was subjected to Shapiro reaction conditions to yield the cyclic alkene product.
<ref>{{cite journal|last1 = Yajima|first1 = Arata|first2 = Kenji|last2 = Mori|title = Synthesis and absolute configuration of (–)-phytocassane D, a diterpene phytoalexin isolated from the rice plant, ''Oryza sativa''|journal = Eur. J. Org. Chem.|year = 2000|volume = 2000|issue = 24|pages = 4079–4091|doi = 10.1002/1099-0690(200012)2000:24<4079::AID-EJOC4079>3.0.CO;2-R}}</ref>
[[File:Application in total synthesis.jpg|650px|Use of the Shapiro reaction in the synthesis of (–)-phytocassane D|center]]

==See also==
*[[Chemistry:Hydrazone iodination|Hydrazone iodination]]
*[[Chemistry:Wolff–Kishner reduction|Wolff–Kishner reduction]]

==References==
{{reflist}}
{{Alkenes}}
[[Category:Carbon-carbon bond forming reactions]]
[[Category:Olefination reactions]]
[[Category:Organic redox reactions]]
[[Category:Name reactions]]

{{Sourceattribution|Shapiro reaction}}