The Modified Wittig–Claisen tandem reaction is a cascade reaction that combines the Wittig reaction and the Claisen rearrangement in a single sequence. In this process, the Wittig reaction first generates an allyl vinyl ether intermediate, which then undergoes a [3,3]-sigmatropic Claisen rearrangement to produce a γ,δ-unsaturated ketone or aldehyde as the final product.
The reaction has been employed as a useful retrosynthetic strategy in organic synthesis, particularly for the construction of cyclic ketones bearing a double bond at the γ,δ-position. It has been applied to the synthesis of various complex natural products and other molecules.
One notable application was reported by Paquette and co-workers, who used a tandem process combining Tebbe olefination (a reaction similar to the Wittig reaction) with a Claisen rearrangement to construct the 4-cyclooctenone structure by expanding the six-membered ring of a 2-cyclohexanone derivative.
The tandem Wittig–Claisen reaction has also been applied to the construction of the spiro[pyrrolidin-3,3′-oxindole] ring system found in natural products such as horsfiline. In that synthesis, starting from o-nitrobenzaldehyde, a Wittig–Claisen reaction sequence produced a 4-pentenal derivative that served as a versatile intermediate, ultimately leading to the total synthesis of horsfiline, an active ingredient in traditional herbal medicine with analgesic effects.
