Chemical Sciences: A Manual for CSIR-UGC National Eligibility Test for Lectureship and JRF/Named Reactions/Shapiro Reaction

The Shapiro reaction or tosylhydrazone decomposition is an organic reaction in which a ketone or aldehyde is converted to an alkene through an intermediate hydrazone in the presence of 2 equivalents of strong base.Robert H. Shapiro ; Lipton, M.F.; Kolonko, K.J.; Buswell, R.L.; Capuano, L.A. Tetrahedron Lett., 1975, 1811. doi:10.1016/S0040-4039(00)75263-4Shapiro, R. H. Org. React., 1976, 23, 405. (Review)Adlington, R.M.; Barret, A.G.M. Acc. Chem. Res., 1983, 16, 55. (Review) The reaction was discovered by Robert H. Shapiro in 1975. The Shapiro reaction was used in the Nicolaou Taxol total synthesis. center|500px|The Shapiro reaction Reaction mechanism In a prelude to the actual Shapiro reaction a ketone or an aldehyde is reacted with p-toluenesulfonylhydrazideOrganic Syntheses Coll. Vol. 5, p.1055 (1973); Vol. 40, p.93 (1960) (Article) to a p-toluenesulfonylhydrazone (or tosyl hydrazone) which is an imine or hydrazone. Two equivalents of a strong base such as n-butyllithium then abstract first the hydrazone proton and then the less acidic α carbonyl proton leaving a carbanion. The carbanion proceeds in an elimination reaction creating the carbon to carbon double bond and converting the hydrazone group into a lithium diazonium group. This group expels nitrogen leaving a vinyllithium compound. center|Shapiro reaction mechanism Scope Although many secondary reactions exist for this functional group, in the Shapiro reaction in particular water is added resulting in hydrolysis to the alkene.Shapiro, R. H.; Duncan, J. H. Organic Syntheses Coll. Vol. 6, p.172 (1988); Vol. 51, p.66 (1971). (Article) Other reactions of vinyllithium compounds include alkylation reactions with for instance alkyl halides.Organic Syntheses Coll. Vol. 7, p.77 (1990); Vol. 61, p.141 (1983). (Article) In general the least substituted alkene is the preferred reaction product. frame|center|Shapiro reactions starting from 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 The Bamford-Stevens reaction is also a tosylhydrazone decomposition but in this reaction a much weaker base can only abstract the hydrazone proton and not the α carbonyl proton and the reaction mechanism now involves a carbene or in a protic solvent a carbocation. References