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.Swaminathan, S.; Narayan, K. V. "The Rupe and Meyer-Schuster Rearrangements" Chem. Rev. 1971, 71, 429–438. (Review)Vartanyan, S. A.; Banbanyan, S. O. Russ. Chem. Rev. 1967, 36, 670. (Review)Engel, D.A.; Dudley, G.B. Organic and Biomolecular Chemistry 2009, 7, 4149–4158. (Review)Li, J.J. In Meyer-Schuster rearrangement; Name Reactions: A Collection of Detailed Reaction Mechanisms; Springer: Berlin, 2006; pp 380–381.()
Mechanism
The reaction proceeds by three major steps: (1) the rapid protonation of oxygen, (2) the slow, rate-determining step comprising the 1,3-shift of the protonated hydroxy group, and (3) the keto-enol tautomerism followed by rapid deprotonation.Edens, M.; Boerner, D.; Chase, C. R.; Nass, D.; Schiavelli, M. D. J. Org. Chem. 1977, 42, 3403–3408. () Formation of the unsaturated carbonyl compound is irreversible.Andres, J.; Cardenas, R.; Silla, E.; Tapia, O. J. Am. Chem. Soc. 1988, 110, 666–674. () Solvent is important and solvent caging is proposed to stabilize the transition state.Tapia, O.; Lluch, J.M.; Cardena, R.; Andres, J. J. Am. Chem. Soc. 1989, 111, 829–835. ()
Rupe rearrangement The reaction of tertiary alcohols containing an α-acetylenic group does not produce the expected aldehydes, but rather α,β-unsaturated methyl ketones via an enyne intermediate.Rupe, H.; Kambli, E. Helv. Chim. Acta 1926, 9, 672. ()Li, J.J. In Rupe rearrangement; Name Reactions: A Collection of Detailed Reaction Mechanisms; Springer: Berlin, 2006; pp 513–514.() This alternate reaction is called the Rupe reaction, and competes with the Meyer–Schuster rearrangement in the case of tertiary alcohols.
Use of catalysts The traditional Meyer–Schuster rearrangement is induced by strong acids, which introduces competition with the Rupe reaction if the alcohol is tertiary. Milder conditions are possible with transition metal-based and Lewis acid catalysts (for example, Ru-Cadierno, V.; Crochet, P.; Gimeno, J. Synlett 2008, 1105–1124. () and Ag-basedSugawara, Y.; Yamada, W.; Yoshida, S.; Ikeno, T.; Yamada, T. J. Am. Chem. Soc. 2007, 129, 12902-12903. () catalysts). Microwave-radiation with catalyst to give excellent yields with short reaction times and good stereoselectivity.Cadierno, V.; Francos, J.; Gimeno, J. Tetrahedron Lett. 2009, 50, 4773–4776.()
Use in organic synthesis The Meyer–Schuster rearrangement has been used in several syntheses. ω-Alkynyl-ω-carbinol lactams convert into enamides using catalytic PTSA) α,β-Uunsaturated thioesters have been prepared from γ-sulfur substituted propargyl alcohols.) 3-Alkynyl-3-hydroxyl-1H-isoindoles rearrange under mildly acidic conditions to the α,β-unsaturated carbonyl compounds.) The synthesis of a part of paclitaxel exploits this rearrangement for a diastereomerically-selective route to the E-alkene.)
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.
History The reaction is named after Kurt Meyer and Kurt Schuster.) Reviews have been published by Swaminathan and Narayan, Applications Used in Butaclamol synthesis. References