Diels-Alder reaction reversibility

Very recently, Cook and Danishefsky [24] reported an interesting regioselectivity of intramolecular Diels-Alder reactions reversed by the change in the dienophihc moieties from vinyl to allenyl group (Scheme 19). For R = 2-propenyl group, C is bonded to the methyl substituted carbon Cj of the cyclohexadienone ring. For R = 2,3-butadienyl, C is bonded to Cy... 

Because cyclopentadiene is fixed in the. v-cis conformation, it is highly reactive in the Diels-Alder reaction. It is so reactive, in fact, that at room temperature, cyclopentadiene slowly reacts with itself to form dicyclopentadiene. Cyclopentadiene is regenerated by heating the dimer above 200 °C. At this temperature, the Diels-Alder reaction reverses, and the more volatile cyclopentadiene monomer distills over into a cold flask. The monomer can be stored indefinitely at dry-ice temperatures. 

ANSWER At 165 °C, the Diels-Alder reaction reverses, and the low-boiling cyclopentadiene can be collected and kept at low temperature. If it is allowed to warm up, it again forms the Diels-Alder dimer. 

The Diels-Alder reaction, reverse electronic demand Diels-Alder reaction, as well as the hetero-Diels-Alder reaction, belong to the category of [4 2]-cycloaddition reactions, which are concerted processes. The arrow-pushing here is merely illustrative. 

The mechanism by which Lewis-acids can be expected to affect the rate of the Diels-Alder reaction in water is depicted in Scheme 2.6. The first step in the cycle comprises rapid and reversible coordination of the Lewis-acid to the dienophile, leading to a complex in which the dienophile is activated for reaction with the diene. After the irreversible Diels-Alder reaction, the product has to dissociate from the Lewis-acid in order to make the catalyst available for another cycle. The overall... 

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

The observation that in the activated complex the reaction centre has lost its hydrophobic character, can have important consequences. The retro Diels-Alder reaction, for instance, will also benefit from the breakdown of the hydrophobic hydration shell during the activation process. The initial state of this reaction has a nonpolar character. Due to the principle of microscopic reversibility, the activated complex of the retro Diels-Alder reaction is identical to that of the bimoleciilar Diels-Alder reaction which means this complex has a negligible nonpolar character near the reaction centre. O nsequently, also in the activation process of the retro Diels-Alder reaction a significant breakdown of hydrophobic hydration takes placed Note that for this process the volume of activation is small, which implies that the number of water molecules involved in hydration of the reacting system does not change significantly in the activation process. 

Another class of reaction where you can see at once that the disconnection is the reverse of the reaction is Pericychc Reactions. An example would be the Diels-Alder reaction between butadiene and maleic anhydride. Draw the mechanism and the product. 

In antithetical analyses of carbon skeletons the synthon approach described in chapter I is used in the reverse order, e.g. 1,3-difunctional target molecules are "transformed" by imaginary retro-aldol type reactions, cyclohexene derivatives by imaginary relro-Diels-Alder reactions. 

Diels-Alder reactions with butadiene are generally thermally reversible and can proceed in both gas and Hquid phases. The reactions are exothermic and foUow second-order kinetics first-order with respect to each reactant. 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

When both the 1,3-dipoIe and the dipolarophile are unsymmetrical, there are two possible orientations for addition. Both steric and electronic factors play a role in determining the regioselectivity of the addition. The most generally satisfactory interpretation of the regiochemistry of dipolar cycloadditions is based on frontier orbital concepts. As with the Diels-Alder reaction, the most favorable orientation is that which involves complementary interaction between the frontier orbitals of the 1,3-dipole and the dipolarophile. Although most dipolar cycloadditions are of the type in which the LUMO of the dipolarophile interacts with the HOMO of the 1,3-dipole, there are a significant number of systems in which the relationship is reversed. There are also some in which the two possible HOMO-LUMO interactions are of comparable magnitude. 

BMI also reacts with dienes to form Diels-Alder adducts [12]. When BMI reacts with a a,(n-biscyclopentadienyl compound or other bis-diene resin, the bis-maleimide chain is extended by the Diels-Alder reaction. Bis-maleimide, chain extended with bis-diene, is not used in adhesives. However, as the Diels-Alder reaction is reversible, there may be a possibility of recyclability of the cured resin by depolymerization of the backbone (Fig. 6). 

Literature articles, which report the formation and evaluation of difunctional cyanoacrylate monomers, have been published. The preparation of the difunctional monomers required an alternative synthetic method than the standard Knoevenagel reaction for the monofunctional monomers, because the crosslinked polymer thermally decomposes before it can revert back to the free monomer. The earliest report for the preparation of a difunctional cyanoacrylate monomer involved a reverse Diels-Alder reaction of a dicyanoacrylate precursor [16,17]. Later reports described a transesterification with a dicyanoacrylic acid [18] or their formation from the oxidation of a diphenylselenide precursor, seen in Eq. 3 for the dicyanoacrylate ester of butanediol, 7 [6]. 

It should be noted that the experimental activation enthalpy for the Diels-Alder reaction is 33 kcal/mol (estimated from the reverse reaction and the experimental reaction energy i.e. the MP2/6-31G(d) value is 14kcal/mol too low. Similarly, the calculated reaction energy of —47 kcal/mol is in rather poor agreement with the... 

R,R-DBFOX/Ph 250 reaction course 303 regioselectivity 216 retro-Diels-Alder reaction 29 reversal of enantioselectivity 224 rhodium... 

The Diels-Alder reaction is of wide scope. Not all the atoms involved in ring formation have to be carbon atoms the hetero-Diels-Alder reaction involving one or more heteroatom centers can be used for the synthesis of six-membered heterocycles. The reverse of the Diels-Alder reaction—the retro-Diels-Alder reaction —also is of interest as a synthetic method. Moreover and most importantly the usefulness of the Diels-Alder reaction is based on its 5y -stereospecifi-city, with respect to the dienophile as well as the diene, and its predictable regio-and c ifo-selectivities. °... 

There are Diels-Alder reactions known where the electronic conditions outlined above are just reversed. Such reactions are called Diels-Alder reactions with inverse electron demand For example the electron-poor diene hexachlorocy-clopentadiene 21 reacts with the electron-rich styrene 22 ... 

The Diels Alder reaction is reversible and the direction of cycloaddition is favored because two n bonds are replaced by two cr-bonds. The cycloreversion occurs when the diene and/or dienophile are particularly stable molecules (i.e. 

The photo-induced exo selectivity was observed in other classic Diels-Alder reactions. Data relating to some exo adducts obtained by reacting cyclopentadiene or cyclohexadiene with 2-methyl-1,4-benzoquinone, 5-hydroxynaphtho-quinone, 4-cyclopentene-l,3-dione and maleic anhydride are given in Scheme 4.13. The presence and amount of EtsN plays a decisive role in reversing the endo selectivity. The possibility that the prevalence of exo adduct is due to isomerization of endo adduct under photolytic conditions was rejected by control experiments, at least for less reactive dienophiles. 

Diels-Alder reactions of furans are markedly reversible because of the aromatic character of the furan nucleus [la]. The lability of the cycloadducts, even at relatively low temperatures, as well as the sensitivity to acidic conditions of both furans and cycloadducts, preclude the use of strong Lewis acids and have therefore given importance to the high pressure technique. 

Lubineau and coworkers [18] have shown that glyoxal 8 (Ri = R2 = H), glyoxylic acid 8 (Ri = H, R2 = OH), pyruvic acid 8 (Ri = Me, R2 = OH) and pyruvaldehyde 8 (Ri = H, R2 = Me) give Diels-Alder reactions in water with poor reactive dienes, although these dienophiles are, for the most part, in the hydrated form. Scheme 6.6 illustrates the reactions with (E)-1,3-dimethyl-butadiene. The reaction yields are generally good and the ratio of adducts 9 and 10 reflects the thermodynamic control of the reaction. In organic solvent, the reaction is kinetically controlled and the diastereoselectivity is reversed. 

The Diels-Alder reaction is usually reversible and has been used to protect double bonds. A convenient substitute for butadiene in the Diels-Alder reaction is the compound 3-sulfolene since the latter is a solid that is easy to handle while the former is gas. " Butadiene is generated in situ by a reverse Diels-Alder reaction (see 17-20). 

In another aspect of the mechanism, the effects of electron-donating and electron-withdrawing substituents (p. 1065) indicate that the diene is behaving as a nucleophile and the dienophile as an electrophile. However, this can be reversed. Perchlorocyclopentadiene reacts better with cyclopentene than with maleic anhydride and not at all with tetracyanoethylene, though the latter is normally the most reactive dienophile known. It is apparent, then, that this diene is the electrophile in its Diels-Alder reactions. Reactions of this type are said to proceed with inverse electron demand ... 

On heating, bicyclo[2.2.1]hept-2,3-en-7-ones (48) usually lose CO to give cyclohexadienes, in a type of reverse Diels-Alder reaction. Bicyclo[2.2.1]hepta-dienones (49) undergo the reaction so readily (because of the stability of the benzene... 

Reversal of the Diels-Alder reaction may be considered a fragmentation. See... 

They reported that the DFT calculations of 114 at the B3LYP/6-31G level showed that the ji-HOMO lobes at the a-position are slightly greater for the syn-n-face than for the anti face. The deformation is well consistent with the prediction by the orbital mixing rule. However, the situation becomes the reverse for the Jt-LUMO lobes, which are slightly greater at the anti than the syn-n-face. They concluded that the iyn-Jt-facial selectivity of the normal-electron-demand Diels-Alder reactions... 

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