Meyer–Schuster rearrangement
The Meyer–Schuster rearrangement is the chemical reaction described as an acid-catalyzed rearrangement of secondary and tertiary propargyl alcohols to α,β-unsaturated ketones if the alkyne group is internal and α,β-unsaturated aldehydes if the alkyne group is terminal.[1] Reviews have been published by Swaminathan and Narayan,[2] Vartanyan and Banbanyan,[3] and Engel and Dudley,[4] the last of which describes ways to promote the Meyer–Schuster rearrangement over other reactions available to propargyl alcohols.
Mechanism
The
Edens et al. have investigated the reaction mechanism.
In a study of the rate-limiting step of the Meyer–Schuster reaction, Andres et al. showed that the driving force of the reaction is the irreversible formation of unsaturated carbonyl compounds through
Rupe rearrangement
The reaction of tertiary alcohols containing an α-
This alternate reaction is called the Rupe reaction, and competes with the Meyer–Schuster rearrangement in the case of tertiary alcohols.Use of catalysts
While the traditional Meyer–Schuster rearrangement uses harsh conditions with a strong acid as the catalyst, this introduces competition with the Rupe reaction if the alcohol is tertiary.
Applications
The Meyer–Schuster rearrangement has been used in a variety of applications, from the conversion of ω-alkynyl-ω-carbinol lactams into enamides using catalytic PTSA[14] to the synthesis of α,β-unsaturated thioesters from γ-sulfur substituted propargyl alcohols[15] to the rearrangement of 3-alkynyl-3-hydroxyl-1H-isoindoles in mildly acidic conditions to give the α,β-unsaturated carbonyl compounds.[16] One of the most interesting applications, however, is the synthesis of a part of paclitaxel in a diastereomerically-selective way that leads only to the E-alkene.[17]
The step shown above had a 70% yield (91% when the byproduct was converted to the Meyer-Schuster product in another step). The authors used the Meyer–Schuster rearrangement because they wanted to convert a hindered ketone to an alkene without destroying the rest of their molecule.