Meyer–Schuster rearrangement

The Meyer- Schuster rearrangement is a chemical reaction in which an acid-catalyzed secondary and tertiary propargyl alcohols (R1 = H or Organylgruppe, R2 = H or Organylgruppe, R3 = H or Organylgruppe ) rearrange to α, β - unsaturated ketones. When a terminal alkyne to form α, β -unsaturated aldehydes. The names of reaction was discovered and published by Kurt H. Meyer and Kurt Schuster, 1922.

Reviews were posted by Swaminathan and Narayan, Vartanyan and Banbanyan and angels and Dudley, the latter describes ways to prefer the Meyer- Schuster rearrangement over other reactions of propargylic alcohols.

The base-catalyzed variant of the rearrangement is known as Faworski reaction.

Mechanism

The reaction mechanism starts with the protonation of the alcohol with water being eliminated in an E1 reaction and Allen from the alkyne is formed. Upon attack of the water molecule on the carbocation and subsequent deprotonation followed by tautomerism to a α, β -unsaturated carbonyl compound forms.

The reaction mechanism was suggested by Edens et al. examined. They found three characteristic steps of: ( 1 ) the rapid protonation of the oxygen, (2) the slow, rate-determining step of sigmatropic 1,3- rearrangement of the protonated hydroxy and keto -enol tautomerism, followed by the rapid deprotonation.

In a study of the rate-determining step of the Meyer- Schuster rearrangement Andres et al. Showed that the driving force of the reaction is the irreversible formation of the unsaturated carbonyl compound via the carbonium ion. They also showed that the reaction is supported by the solvent used. This has been further by Tapi et al. investigated, which showed that stabilizes the formation of solvent cages to the transition state.

Rupe rearrangement

The reaction of tertiary alcohols (R4, R5 = Organylgruppe ) contained in α - position, an alkyne group, does not lead to the expected alcohols, but to α, β -unsaturated ketones through an enyne intermediate. This reaction is carried out for tertiary alcohols in competition with the Meyer- Schuster rearrangement and is called Rupe rearrangement. The first step is protonation of the alcohol takes place, with water being split off. The result is a Propagylkation, which is deprotonated and reacts to an enyne. After protonation of this intermediate and the reaction with water is formed under Tautomerisation the α, β -unsaturated ketone.

Catalysts

The terms of the traditional Meyer- Schuster rearrangement using strong acids as catalyst results in the case of tertiary alcohols to side reactions such as the Rupe rearrangement. Through the use of transition metals and Lewis acids as catalysts, the reaction can be carried out under milder conditions, for example, ruthenium and silver - bearing catalysts. Carieno et al. reported the use of microwave irradiation InCl3 catalyst, leading to excellent yields and short reaction times, and remarkable stereoselectivity. An example from the publication is as follows:

Applications

The Meyer- Schuster rearrangement can find a number of applications, from the conversion of ω -alkyne - ω -carbinol lactams in enamides with PTSA as a catalyst on the synthesis of α, β -unsaturated thioesters from γ - sulfur substituted Propargylalcoholen to the rearrangement of 3 -alkyne -3 -hydroxy -1H- isoindoles under mildly acidic conditions to α, β -unsaturated carbonyl compounds. One of the most interesting applications is the synthesis of a partial structure of paclitaxel in a diasteroselektiven synthesis, which leads only to the E- alkene.

The synthesis step shown above is carried out in 70 % yield, and even in 91 % yield when the by-product is converted to a different step in the Meyer-Schuster product.