Diene and Dienophile

Open chain Outer ring Inner-outer ring Across ring 

---

Another form of selectivity can arise when substitirted dienes and dienophiles are employed in the Diels-Alder reaction. Two different cycloadducts denoted as endo and exo can then be formed (Figure 1.2). 

In 1961 Berson et al. were the first to study systematically the effect of the solvent on the endo-exo selectivity of the Diels-Alder reaction . They interpreted the solvent dependence of the endo-exo ratio by consideririg the different polarities of the individual activated complexes involved. The endo activated complex is of higher polarity than the exo activated complex, because in the former the dipole moments of diene and dienophile are aligned, whereas in the latter they are pointing in... 

Another consequence of the above analysis is, that the surprising inefficiency of micellar aggregates to catalyse Diels-Alder reactions can now be rationalised. Obviously, micelles are able to bind diene and dienophile efficiently but in different parts of the micelle. The reactions seems to take place at the surface of the micelle in a rather aqueous environment, where the concentration of diene is low. 

Chapter 5, may provide a rationale. Conclusions derived from a number of H-MVIR measurements indicate that cyclopentadiene has a high affinity for the interior of the micelles that were investigated, whereas the dienophile prefers the outer regions. In view of the structures of most dienes and dienophiles such a spatial separation can be expected for the majority of Diels-Alder reactions. This arrangement accounts for the unexpectedly small influence of micelles on the rates of Diels-Alder reactions as reported in the literature. 

This thesis has been completely devoted to catalysis by relatively hard catalysts. When aiming at the catalysis of Diels-Alder reactions, soft catalysts are not an option. Soft catalysts tend to coordinate directly to the carbon - carbon double bonds of diene and dienophile, leading to an activation towards nucleophilic attack rather than to a Diels-Alder reaction . This is unfortunate, since in water, catalysis by hard catalysts suffers from a number of intrinsic disadvantages, which are absent for soft catalysts. 

What combination of diene and dienophile would you choose in order to prepare each of the following compounds ... 

To deduce the identity of the diene and dienophile that lead to a particular Diels-Alder adduct we use curved arrows in the reverse fashion to undo the cyclohexene derivative Start with the tt component of the double bond in the SIX membered ring and move electrons in pairs... 

A very large number of Diels-Alder reactions are recorded in the chemical literature many of which involve relatively complicated dienes dienophiles or both On the basis of your knowl edge of Diels-Alder reactions predict the constitution of the Diels-Alder adduct that you would expect to be formed from the following combinations of dienes and dienophiles... 

It is also possible for a single monomer to behave as both diene and dienophile. Heating diacetylene [XXII] produces an infusible material which may be rationalized as follows ... 

Maleic anhydride has been used in many Diels-Alder reactions (29), and the kinetics of its reaction with isoprene have been taken as proof of the essentially transoid stmcture of isoprene monomer (30). The Diels-Alder reaction of isoprene with chloromaleic anhydride has been analy2ed using gas chromatography (31). Reactions with other reactive hydrocarbons have been studied, eg, the reaction with cyclopentadiene yields 2-isopropenylbicyclo[2.2.1]hept-5-ene (32). Isoprene may function both as diene and dienophile in Diels-Alder reactions to form dimers. 

Extrapolation from the known reactivity of cyclobutadiene would suggest that azetes should be highly reactive towards dimerization and as dienes and dienophiles in cycloaddition reactions and the presence of a polar C=N should impart additional reactivity towards attack by nucleophiles. Isolation of formal dimers of azetes has been claimed as evidence for the intermediacy of such species, but no clear reports of their interception in inter-molecular cycloaddition reactions or by nucleophiles have yet appeared. 

Also the mirror image of the strueture I, eorreetly denoted as exo-3,10-dihydroxy-3,5,8,10-tetra-methyltrieyelo[6.2.2.0 ]dodeea-5,l 1-diene-4,9-dione, would be possible sinee enantiomers are not differentiated by NMR. A retro-Diels-Alder fragmentation of I to CsH/oO explains why the moleeular ion eorresponding to the moleeular formula C16//20O4 is not deteeted in the mass spee-trum. The metabolite I eould be formed by Diels-Alder dimerisation of 1,5-dimethyleyelohexa-l,3-dien-5-ol-6-one J as the primary metabolite which acts as diene and dienophile as well... 

In general, stereochemical predictions based on the Alder rule can be made by aligning the diene and dienophile in such a way that the unsaturated substituent on the dienophile overlaps the diene n system. The stereoselectivity predicted by the Alder rule is independent of the requirement for suprafacial-suprafacial cycloaddition, since both the endo and exo transition states meet this requirement. 

How do orbital symmetry requirements relate to [4tc - - 2tc] and other cycloaddition reactions Let us constmct a correlation diagram for the addition of butadiene and ethylene to give cyclohexene. For concerted addition to occur, the diene must adopt an s-cis conformation. Because the electrons that are involved are the n electrons in both the diene and dienophile, it is expected that the reaction must occur via a face-to-face rather than edge-to-edge orientation. When this orientation of the reacting complex and transition state is adopted, it can be seen that a plane of symmetry perpendicular to the planes of the... 

More complete interpretations of Diels-Alder regioselectivity have been developed. MO results can be analyzed from an electrostatic perspective by calculating potentials at the various atoms in the diene and dienophile. These results give a more quantitatively accurate estimate of the substituent effects. Diels-Alder regioselectivity can also be accounted for in terms of HSAB theory (see Section 1.2.3). The expectation would be that the most polarizable (softest) atoms would lead to bond formation and that regioselectivity would reflect the best mateh between the diene and dienophile termini. These ideas have been applied using 3-2IG computations. The results are in agreement with the ortho rule for normal-electron-demand Diels-Alder reactions. ... 

Cycloadditions are not restricted to the reactions of combinations of neutral dienes and dienophiles. There are examples of corresponding reactions involving ionic intermediates. The addition of 2-methylallyl cation to cyclopentadiene is an example ... 

Compare electrostatic potential maps for the following Diels-Alder transition states cyclopentadiene+ethene, cyclopentadiene+acrylonitrile and cyclopentadiene+ tetracyanoethylene, with those of reactants cyclopentadiene, ethene, acrylonitrile and tetracyanoethylene. Are electrons transferred from diene to dienophile in the transition states (relative to reactants) or vice versa For which reaction is the transfer the greatest The least Quantify your conclusion by measuring the total charge on the diene and dienophile components in the three transition states. 

Is there a correlation between activation energy and the magnitude of charge transfer between diene and dienophile components in the transition state Explain. 

Lewis acids catalyze Diels-Alder reactions. Do they enhance overlap between diene and dienophile orbitals and/ or do they reduce the HOMO/LUMO energy difference ... 

Another stereochemical feature of the Diels-Alder reaction is that the diene and dienophile partners orient so that the endo product, rather than the alternative exo product, is formed. The words endo and exo are used to indicate relative stereochemistry when referring to bicyclic structures like substituted norbornanes (Section 4.9). A substituent on one bridge is said to be exo if it is anti (trans) to the larger of the other two bridges and is said to be endo if it is syn (cis) to the larger of the other two bridges. 

Endo products result from Diels-Alder reactions because the amount of orbital overlap between diene and dienophile is greater when the reactants lie directly on top of one another so that the electron-withdratving substituent on the dienophile is underneath the diene. In the reaction of 1,3-cyclopentadiene with maleic anhydride, for instance, the following result is obtained ... 

How could you use Diels-Alder reactions to prepare the following products Show the starting diene and dienophile in each case. 

Surprisingly, 2,5-dimethyl-3,4-diphenylcyclopentadienone (17) with ethyl l//-azepine-l-carb-oxylate (1) behaves as both diene and dienophile to give a separable mixture of the [4 + 2] 18 and [2 + 4] 19 7t-ewfo-cycloadducts,251 259 the latter being incorrectly formulated in the original paper251 as the opposite regioisomer. l-Mesyl-1//-azepine under similar conditions yields only the [2 + 4] cycloadduct [42% mp 158°C (dec.)],157 251 whereas with tetraphenylcyclopen-tadienone low yields of the [4 + 2] (9.7%) and [6 + 4] (1.7%) rc-adducts are reported.157... 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

---