The Meyer-Schuster Rearrangement of Ethoxyalkynyl Carbinols

Abstract

The combination of electron-rich alkoxyacetylenes and cationic gold catalysts provides excellent reactivity for the Meyer-Schuster rearrangement under mild conditions. Optimization of the reaction conditions with respect to stereoselectivity and investigations into the scope and mechanism of the rearrangement of secondary ethoxyalkynyl carbinols (γ-ethoxy-substituted propargyl alcohols) to α,β-unsaturated esters are described.

Meyer-Schuster - gold - alkoxyacetylene - propargyl alcohol - rearrangement

References and Notes

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<A NAME="RS00207ST-8">8</A>

Ethoxyacetylene was purchased from Sigma-Aldrich as a 40% solution in hexane and used as received.

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Protic acids in the absence of gold are significantly less effective (ref. 2). Examples of the protic-acid-catalyzed Meyer-Schuster rearrangement of ethoxyalkynyl carbinols:

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<A NAME="RS00207ST-12">12</A>

Satisfactory characterization data (¹H NMR, ¹³C NMR, IR, HRMS) were obtained for all compounds. Yields refer to at least 50 mg of material isolated in >95% purity.

<A NAME="RS00207ST-13">13</A>

An insoluble residue, which has no apparent impact on the course of the reaction, was observed in the solutions of AuCl (Aldrich, 99.9%) in 1:1 THF-CH₂Cl₂. Identical results were obtained when this catalyst solution was filtered, decanted, or used with the unknown residue in place.

<A NAME="RS00207ST-14">14</A>

2-Butanone is the recommended solvent in a forthcoming study on the transpositional hydrolysis of propargylic acetates (Prof. Liming Zhang, University of Nevada, Reno, private communication; Yu, M.; Li, G.; Wang, S.; Zhang, L. Adv. Synth Catal. 2007, in press, DOI: 10.1002/adsc.200600579).

<A NAME="RS00207ST-15">15</A>

In fact, simultaneous addition of the solutions of the gold and silver salts to the reaction mixture provided the enoate products with slightly better selectivity, but we consider the sequential addition protocol to be more easily duplicated and thus preferable.

<A NAME="RS00207ST-16">16</A>

Isomerization of the Z-enoates to the E-enoates does not occur under the reaction conditions: extending the reaction time does not have a significant effect on the product ratio, and resubjecting the enoate mixtures to the rearrangement conditions does not change the ratio of stereoisomers. Therefore, we assume that the nonthermodynamic product distribution is purely the result of kinetic control.

<A NAME="RS00207ST-17">17</A>

To the extent that the additive is incorporated into the product, the Meyer-Schuster reaction is not a true ‘rearrangement’, although it is generally referred to as such in a formal sense for the sake of simplicity.

<A NAME="RS00207ST-18">18</A>

Control experiments confirmed that the rearrangement conditions do not promote transesterification between the ethyl and propyl esters, so the incorporation of the propanol additive is most likely occurring during the course of the rearrangement.

<A NAME="RS00207ST-19">19</A> For a previous report on the combined use of oxygen-activated alkynes and cationic gold catalysts, see: Zhang L. Kozmin SA. J. Am. Chem. Soc.  2004,  126:  11806