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. The reaction was discovered by Robert H. Shapiro in 1975. The Shapiro reaction was used in the Nicolaou Taxol total synthesis.

Reaction mechanism

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 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.

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 substiuted vinyllithium intermediate. Although many secondary reactions exist for the vinyllithium functional group, in the Shapiro reaction in particular water is added, resulting in hydrolysis to the alkene. Other reactions of vinyllithium compounds include alkylation reactions with for instance alkyl halides.

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

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.

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.

See also

• Hydrazone iodination