Meyer-Schuster rearrangements

The Meyer-Schuster rearrangement is the isomerization of secondary and tertiary a-acetylenic alcohols to a,P-imsaturated carbonyl compounds.  

Although a variety of acid catalysts are employed in the Meyer-Schuster and Rupe rearrangements, formic acid is commonly used to effect the respective transformations.  

Meyer and Schuster discovered the rearrangement that carries their names in an attempt to convert a-acetylenic alcohols such as 1 to the respective tertiary chloride in the presence of an acetyl chloride catalyst. Rather than the expected chloride products, a,p-imsaturated ketone 2 was obtained via a previously unknown acid-catalyzed rearrangement. Further research demonstrated the ability of a variety of acid catalysts (i.e., acetic acid, concentrated sulfuric acid, ether saturated with dry hydrogen chloride, and acetic anhydride) to induce the observed transformation.  

In contrast, tertiary propargylic alcohols with an expellable proton such as 3 will instead proceed via the Rupe rearrangement. Following dehydration to propargylic cation 10, elimination occurs to give enyne 11. Subsequent hychation of the alkyne gives 13, which tautomerizes to the a,P-unsaturated ketone 4. 

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When X=OH, this conversion of acetylenic alcohols to unsaturated aldehydes or ketones is called the Meyer-Schuster rearrangement The propargyl rearrangement can also go the other way that is, 1-haloalkenes, treated with organocopper compounds, give alkynes. ... 

When 2-ethynyl-2-hydroxyadamantane (31) was treated with 95% formic acid or dilute sulfuric acid only a Meyer-Schuster rearrangement took place to give 95% of 2-(formylmethylene)adamantane (32) (equation 10). No Rupe rearrangement took place29. 

Meyer-Overton hypothesis, 17 376-377 Meyer-Schuster rearrangement,... 

Acid-catalyzed rearrangement of tertiary a-acetylenic (terminal) alcohols, leading to the formation of a,(3-unsaturated ketones rather than the corresponding a,(3-unsaturated aldehydes. Cf. Meyer-Schuster rearrangement. 

Scheme 43 Ru-catalyzed Meyer-Schuster rearrangement of terminal alkynols...

It is noteworthy that the indenyl complex RuCl(ri -C9H7)(PPh3)2l4 provides an efficient catalyst precursor for the anti-Markovnikov hydration of terminal alkynes in aqueous media, especially in micellar solutions with either anionic (sodium dode-cylsulfate (SDS)) or cationic (hexadecyltrimethylammonium bromide (CTAB)) surfactants [38]. This system can be applied to the hydration of propargylic alcohols to selectively produce P-hydroxyaldehydes, whereas RuCl(Cp)(PMe3)2 gives a,P-unsat-urated aldehydes (the Meyer Schuster rearrangement products)(Scheme 10.8) [39]. 

The Welch group tackles stereoselective synthesis of LL-Z1271a using Wieland-Miescher diketone 144 [82] (3% overall yield) (Scheme 4). This synthesis includes, as key steps, the stereoselective introduction of the methyl on carbon 4 in an equatorial position, the formation of the y-lactone via bromolactonization and the construction of the 5-lactone C ring through a Meyer-Schuster rearrangement. 

Finally, the synthesis is completed by using the Meyer-Schuster rearrangement of the Aren-van Dorp synthesis on enone acetal 152. Treatment of 152 with lithium etoxyacetilide in THF gives an unstable tertiary allylic-propargylic alcohol that, when dissolved in methanol with a catalytic quantity of sulphuric acid produces 63 and its epimer 98 in a proportion of 7 3, respectively, in 42% yield. 

The Meyer-Schuster Rearrangement is similar to the Rape Rearrangement. 

Meyer-Schuster rearrangement Lithium methoxyacetylide, 166 Michael reaction (see Conjugate addition reactions)... 

Keywords propargyl alcohol, TsOH, Meyer-Schuster rearrangement, cinnamic aldehyde... 

A perusal of the literature discloses that ketones and aldehydes have rarely been reacted with 44. In view of the tendency of ynamines to add water and alkohols, it is obvious that ynamines 56 undergo intramolecular addition of water (Meyer-Schuster rearrangement) quite readily (96). This process is provoked already by silicagel, alumina or it even occurs spontaneously 146). 

H. Stark and co-workers prepared novel histamine Hs-receptor antagonists with carbonyl-substituted 4-[(3-phenoxy)propyl]-1/-/-imidazole structures. The Meyer-Schuster rearrangement was used for the synthesis of one of the compounds. The p-hydroxybenzaldehyde derivative was reacted with ethynylmagnesium bromide to afford a secondary propargylic alcohol. Upon hydrolysis with 2N HCI in a refluxing ethanol/acetone mixture, the corresponding p-hydroxy cinnamaldehyde was obtained. 

In the laboratory of S.C. Welch, the Meyer-Schuster rearrangement was the key step in the stereoselective total synthesis of the antifungal mold metabolite (+)-LL-Z1271a. A tricyclic enone acetal was treated with lithium ethoxyacetylide, and the crude product was exposed to H2SO4 in anhydrous methanol, which brought about the rearrangement and afforded the desired product in 30% yield along with 12% of an epimer. 

Swamlnathan, S., Narayanan, K. V. Rupe and Meyer-Schuster rearrangements. Cherm. Rev. 1971, 71,429-438. 

Erman, M. B., Gulyl, S. E., Aulchenko, I. S. A new efficient catalytic system for the Meyer-Schuster rearrangement. Mendeleev Common. 1994, 89. 

Yoshimatsu, M., Naito, M., Kawahigashi, M., Shimizu, H., Kataoka, T. Meyer-Schuster Rearrangement of y-Sulfur-Substituted Propargyl Alcohols A Convenient Synthesis of a,P-Unsaturated Thioesters. J. Org. Chem. 1995, 60,4798-4802. 

Lorber, C. Y., Osborn, J. A. Cis-dioxomolybdenum(VI) complexes as new catalysts for the Meyer-Schuster rearrangement. Tetrahedron Lett. 1996, 37, 853-856. 

Andres, J., Silla, E., Tapia, O. A quantum chemical study of protonated intermediates in Rupe and Meyer-Schuster rearrangement mechanisms. THEOCHEM 1983,14, 307-314. 

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