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. The reaction was discovered by Robert H. Shapiro in 1967. The Shapiro reaction was used in the Nicolaou Taxol total synthesis.
In a prelude to the actual Shapiro reaction a ketone or an aldehyde is reacted with p-toluenesulfonylhydrazide to a p-toluenesulfonylhydrazone (or tosylhydrazone) which is an imine or hydrazone. Two equivalents of a strong base, such as n-butyllithium, then abstract first the proton from the hydrazone and then the less acidic proton α to the hydrazone carbon, leaving a carbanion. The carbanion proceeds in an elimination reaction to create the carbon–carbon double bond. This step results in expulsion of the tosyl group and formation of a diazonium anion. The anion then collapses, falling off as a neutral nitrogen molecule. The result is a vinyllithium at the position where the nitrogen had been attached. This organolithium carbon is both nucleophilic and basic. It can be reacted with various electrophiles or simply neutralized with water or an acid.
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 vinyllithium intermediate. Although many secondary reactions exist for the vinyllithium functional group, in the Shapiro reaction in particular water is added, resulting in protonation to the alkene. Other reactions of vinyllithium compounds include alkylation reactions with for instance alkyl halides.
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.
- Shapiro, R. H.; Lipton, M.F.; Kolonko, K.J.; Buswell, R.L.; Capuano, L.A. Tetrahedron Lett., 1975, 1811. doi:10.1016/S0040-4039(00)75263-4
- Shapiro, R. H. Org. React., 1976, 23, 405. (Review)
- Adlington, R.M.; Barret, A.G.M. Acc. Chem. Res., 1983, 16, 55. (Review)
- Shapiro, Robert H.; Heath, Marsha J. J. Am. Chem. Soc., 1967, 87, 5734–5735. doi:10.1021/ja00998a601
- Organic Syntheses Coll. Vol. 5, p.1055 (1973); Vol. 40, p.93 (1960) (Article)
- Shapiro, R. H.; Duncan, J. H. Organic Syntheses Coll. Vol. 6, p.172 (1988); Vol. 51, p.66 (1971). (Article)
- Organic Syntheses Coll. Vol. 7, p.77 (1990); Vol. 61, p.141 (1983). (Article)
- Chamberlin, A. R.; Bloom, S. H. Org. React. 1990, 39, 1. doi:10.1002/0471264180.or039.01