From allylic vinylic ethers

The enthalpy change in the formation of 5-hexenal from allyl vinyl ether amounts to -17 kcal moL S. W. Benson and H. E. O Neal, in Kinetic Data on Gas Phase Unimolecular Reactions , U. S. Department of Commerce, Washington, DC, 1970, p. 363. 

Eilbracht et al. have developed rhodium- or ruthenium-catalyzed one-pot synthesis of cyclopentanones from allyl vinyl ether via tandem Claisen rearrangement and hydroacylation [109-111]. This protocol requires elevated temperature (140-220°C) and also requires alkyl or aryl substituents at the terminal position of the allylic double bond to prevent undesirable double bond migration in the intermediary formed, unsaturated aldehyde. 

Analysis of the MEP from allyl vinyl ether to 4-pentenal derived from individual IRC calculations led the authors to dissect the reaction path into three segments. The first segment (3 kcal mol energy increase) is characterized by conformational reorganization around the three tr-bonds in the allyl vinyl ether. Within the... 

Allyl vinyl ethers have been prepared using the ylide (101) but only from non-enolizable carbonyl compounds. The ethers rearrange on heating to give a-allyl aldehydes, e.g. (102). 

The reactants can be made from allylic alcohols by mercuric ion-catalyzed exchange with ethyl vinyl ether.220 The allyl vinyl ether need not be isolated and is often prepared under conditions that lead to its rearrangement. The simplest of all Claisen rearrangements, the conversion of allyl vinyl ether to 4-pentenal, typifies this process. 

The corresponding methyl ester similarly underwent the facile rearrangement. A solvent polarity study on the rearrangement rate of the allyl vinyl ether was conducted in solvent systems ranging from pure methanol to water at 60°C.156 The first-order rate constant for the rearrangement of the allyl vinyl ether in water was 18 x 10-5 s 1, compared with 0.79 x 10-5 s 1 in pure methanol. 

As shown earlier in many examples, the Claisen rearrangement of allyl vinyl ethers also provides a very powerful method for carbon-carbon bond formation in domino processes. Usually, the necessary ethers are formed in a separate step. However, both steps can be combined in a novel domino reaction developed by Buchwald and Nordmann [306]. This starts from an allylic alcohol 6/4-102 and a vinyl iodide 6/4-103, using copper iodide in the presence of the ligand 6/4-104 at 120 °C to give 6/4-105 (Scheme 6/4.25). The reaction even allows the stereoselective formation of two adjacent quaternary stereogenic centers in high yield. 

Severance, D. L. and Jorgensen, W. L. Effects of hydration on the Claisen rearrangement of allyl vinyl ether from computer simulations, JAm.Chem.Soc., 114(1992), 10966-10968... 

The procedure described illustrates a new general synthetic method for the preparation of (E)-3-allyloxyacrylic acids and their conversion to a-unsubstituted y,6-unsaturated aldehydes by subsequent Claisen rearrangement-decarboxylation. Such aldehydes are traditionally prepared by Claisen rearrangements of allyl vinyl ethers. Allyl vinyl ethers are typically prepared by either mercury-catalyzed vinyl ether exchange with allylic alcohols or acid-catalyzed vinylation of allylic alcohols with acetals. The basic conditions required for alkoxide addition to the betaine to produce carboxyvinyl allyl ethers, as described in this report, nicely complements these two methods. In addition, this Claisen rearrangement is an experimentally very simple procedure, since sealed tube and other high pressure vessels are not required. The allyloxyacrylic acids are heated neat (in most cases a small amount of hydroquinone is added) and, by adjusting the pressure at which the reaction is performed, the aldehyde products distill from the reaction mixture in analytically pure form. 

Of course, the rich information available from a QM/MM simulation does not come without cost. The QM/MM Claisen simulation required several million AMI calculations to be carried out while AMI is a very efficient level of QM theory for a molecule as small as allyl vinyl ether, that still represents an enormous investment of computational resources. As a result, the application of QM/MM methodologies based on the formalism of Eqs. (13.4) and (13.5) has tended not to be especially systematic, i.e., choices of QM and MM models and necessary coupling parameters have tended to be made on an ad hoc basis, without regarding parameter transferability as being an issue of paramount concern. 

The transition metal complex-catalyzed formation of 1,3-dioxepanes from vinyl ethers has also been described. For example, reaction of allyl vinyl ether 157 with a nonhydridic ruthenium complex at higher temperatures and without any solvent produced 1,3-dioxepane 159 whereas, the use of a hydridic ruthenium complex resulted in the formation of vinyl ether 158 by double-bond isomerization (Scheme 43). It was suggested that cyclic acetal formation proceeds via a 7i-allyl-hydrido transient complex, which undergoes nucleophilic attack of the OH group at the coordinated Jt-allyl <2004SL1203>. 

PdCl2(PhCN)2-catalysed Claisen rearrangement of the allyl vinyl ether 474 derived from cyclic ketone at room temperature affords the syn product 475 with high diastereoselectivity [203]. In contrast to thermal Claisen rearrangement, the Pd(II)-catalysed Claisen rearrangement is always stereoselective, irrespective of the geometry of allylic alkenes. The anti product is obtained by the thermal rearrangement in the presence of 2,6-dimethylphenol at 100 °C for lOh. 

Fig. 14.47. Preparation of an allyl vinyl ether, D, from allyl alcohol and a large excess of ethyl vinyl ether. Subsequent Claisen rearrangement D C...

The effects of solvation have been studied by an implementation of an ellipsoid cavity model into Kohn-Sham theory [94]. The lowering of the activation energy by water solvation of the allyl vinyl ether has been calculated to be 0.3 kcal/mol by this method. This value is considerably lower than the results from other calculations on the same system using cavity models [95], free energy perturbation [96], or QM/MM calculations [97] as well as the values... 

The allyl vinyl ether needed for the Claisen rearrangement is an enol ether of an unsaturated aldehyde with an unsaturated alcohol. The two starting materials are themselves derived from a common precursor, making this a most efficient process Heating the enol ether promotes [3,3]-sigmatropic rearrangement propelled by the formation of a carbonyl group. 

It can be seen from the examples displayed above that the Claisen rearrangement of allyl vinyl ethers with an amino substituent at C(n and C(2) proceeds much faster than that of allyl vinyl ether itself. Several models98- 00 have been proposed in order to interpret the substituent effect on the rate of Claisen rearrangement. Both the acceleration of the rearrangements of / -allyloxyenamine and 0-allylketene TV, 0-acetals and deceleration of the reaction of enamine 120 are in agreement with the prediction of the models. 

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