Meyer-Schuster reaction

Regarding the first problem, the most elemental treatment consists of focusing on a few points on the gas-phase potential energy hypersurface, namely, the reactants, transition state structures and products. As an example, we will mention the work [35,36] that was done on the Meyer-Schuster reaction, an acid catalyzed rearrangement of a-acetylenic secondary and tertiary alcohols to a.p-unsaturatcd carbonyl compounds, in which the solvent plays an active role. This reaction comprises four steps. In the first, a rapid protonation takes place at the hydroxyl group. The second, which is the rate limiting step, is an apparent 1, 3-shift of the protonated hydroxyl group from carbon Ci to carbon C3. The third step is presumably a rapid allenol deprotonation, followed by a keto-enol equilibrium that leads to the final product. 

Andres, J., Cardenas, R., Silla, E. and Tapia, 0. A theoretical study of the Meyer-Schuster reaction mechanism minimum-energy profile and properties of transition-state structures,. /. Am. Chem. Soc., 110 (1988), 666-672... 

Tapia, O. and Andres, J. A simple protocol to help calculate saddle points. Transition state structures for the Meyer-Schuster reaction in non-aqueous media an ab initio MO study., Chem. Phys. Letters, 109 (1984), 471-477... 

Tapia, O., Lluch, J. M., Cardenas, R. and Andres, J. Theoretical study of solvation effects in chemical reactions. A combined quantum chemical/Monte Carlo study ofthe Meyer-Schuster reaction mechanism in water, J. Am. Chem.Soc., Ill (1989), 829-835... 

Andres, J., Arnau, A., Silla, E., Bertran, J., Tapia, O. Atheoretical study of the intramolecular solvolytic mechanism of the Meyer-Schuster reaction. MINDO/3 and CNDO/2 calculations of minimum energy paths. THEOCHEM1983, 14,49-54. 

The analysis of the first two mechanisms showed the solvolytic mechanism as the most favorable localizing itself during the reaction path to an alquinylic carbocation interacting electrostatically with a molecule of water. This fact has been supported by the experimental detection of alquinylic carbocations in solvolytic conditions. Things being like that, two alternatives remain for the slow stage of the Meyer-Schuster reaction, the solvolytic and the intermolecular mechanism, and it seems that the solvent has a lot to say in this. 

On comparing the solvolytic and intermolecular processes a smaller potential barrier is observed for the latter, thus the solvent plays an active part in the Meyer-Schuster reaction, being capable of changing radically the mechanism through which this takes place. It seems clear that in die presence of aqueous solvents the nucleophilic attack on the C3 precedes the loss of the water (solvolysis) a lesser activation energy corresponds to the intermolecular process than to the solvolytic. Moreover, if we analyze the intermolecular mechanism we can verify that the solvent stabilizes bofli die reactants as well as the products by the formation of hydrogen bridges. 

The synthetic practicality of the Meyer-Schuster rearrangement was demonstrated in the synthesis of ( )-virantmycin, a metabolite of Streptomyces nitrosporeus, which has been shown to possess antiviral activity. When the attempted conversion of 17 to 19 via a hydrogenation/cyclization sequence was unsuccessful, an alternate pathway utilizing the Meyer-Schuster reaction was explored. Treatment of 17 with acid was presumed to give the a,P-unsaturated ketone which underwent a spontaneous Michael reaction to give 18. Reduction of the resulting ketone 18 was followed by dehydration to provide 19. 

Deshong and Sandlier found that nitrochalcones, such as 26, were resistant to the Meyer-Schuster reaction under a variety of conditions. Fortunately reduction of the nitro group prior to the rearrangement proved to be a more effective strategy. Enhanced reactivity, due to the more electron rich aniline, allowed for Meyer-Schuster rearrangement which was immediately followed by cyclization to 27. While tertiary alcohols react more efficiently, this one-pot preparation of quinolines has proven general for a variety of nitroarenes. 

Specifically, the synthesis of the cyclohexyl components of the boll weevil sex pheromone featured the Meyer-Schuster reaction of 40, prepared via acetylide addition and acetylation of the resulting tertiary alcohol. Treatment of 40 with silver(I) carbonate in acetic acid resulted in smooth formation of aldehyde isomers 41 and 42 (47 53) in excellent yield. 

While these reactions can be thought of as Meyer-Schuster reactions, as a result of the products formed, it is likely their mechanism is somewhat different. Dudley and coworkers have proposed a hypothetical mechanism for this variant of the reaction. The gold catalyst is presumed to coordinate... 

Two alternatives remain for the slow stage of the Meyer-Schuster reaction, the solvolytic and the intermolecular mechanisms, and it seems that the solvent has strong influence. 

---