Shapiro reaction
Shapiro reaction | |
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Named after | Robert H. Shapiro |
Reaction type | Coupling reaction |
Identifiers | |
Organic Chemistry Portal | shapiro-reaction |
RSC ontology ID | RXNO:0000125 |
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 organolithium reagent.[1][2][3] The reaction was discovered by Robert H. Shapiro in 1967.[4] The Shapiro reaction was used in the Nicolaou Taxol total synthesis.[5] This reaction is very similar to the Bamford–Stevens reaction, which also involves the basic decomposition of tosyl hydrazones.
Reaction mechanism
In a prelude to the actual Shapiro reaction, a
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
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.[9]
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.[10]
A one pot in situ combined Shapiro-Suzuki reaction
The Shapiro reaction can also be combined with the 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 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.[11]
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
See also
References
- .
- ISBN 978-0471264187.
- .
- .
- ISBN 9783527292318.
- ^ Friedman, Lester; Litle, Robert L.; Reichle, Walter R. (1960). "p-Toluenesulfonylhydrazide". Organic Syntheses. 40: 93; Collected Volumes, vol. 5, p. 1055.
- ; Collected Volumes, vol. 6.
- ; Collected Volumes, vol. 7, p. 77.
- .
- .
- .
- .