Alder’s endo-rule

As expected from Alder s endo rule, and justified by consideration of maximum accumulation of unsaturation in the transition state, secondary orbital interactions and dispersion forces, furan reacts with maleic anhydride in acetonitrile at 40 °C (78JOC518) to give initially... 

Alder s endo rule applies not only to cyclic dienes like cyclopentadiene and to disubstituted dienophiles like maleic anhydride, but also to open chain dienes and to mo no-substituted dienophiles diphenylbutadiene and acrylic acid, for example, react by way of an endo transition structure 2.113 to give largely (9 1) the adduct 2,114 with all the substituents on the cyclohexene ring cis, and equilibration again leads to the minor isomer 2.115 with the carboxyl group trans to the two phenyl groups. 

Alder s endo rule leads substituents in open-chain trans dienes to be alias on the cyclohexene ring. 

The Stereoselectivity of Diels-Alder Reactions. One of the most challenging stereochemical findings is Alder s endo rule for Diels-Alder reactions. The favoured transition structure 6.180 has the electron-withdrawing substituents in the more hindered environment, under the diene unit, giving the kinetically more favourable but thermodynamically less favourable adduct 6.181. Heating eventually equilibrates the adducts in favour of the exo adduct 6.182, by a retro-cycloaddition re-addition pathway. 

Endo versus exo geometry in the Diels-Alder reaction When the Diels-Alder reaction forms bridged bicyclic adducts and an unsaturated constituent is located on this bicyclic structure, the chief product is normally the kinetically favoured endo-isomer, Alder s endo rule. 

Alder s endo rule specifies a preference for endo (C) over exo (D) addition. However, this rule appears to be strictly applicable only to the addition of cyclic dienophiles (e.g. maleic anhydride, p-qui-nones) to cyclic dienes (e.g. cyclopentadienes). 

Acrylates. Cyclopentadiene is often used to evaluate selectivity in asymmetric Diels-Alder reactions. Table 6.4 lists the selectivities found for acrylate cycloadditions using the auxilieuies shown in Figure 6.13 under conditions that are optimized for each auxiliary. Note that there are four possible norbomene stereoisomers, two endo and two exo. In accord with Alder s endo rule, the endo is heavily favored in all these examples. Although several authors report selectivities in these reactions in terms of selectivity for one endo adduct over the other, the selectivities indicated in the table reflect the total diastereoselectivity of the major adduct over the other three, if this information could be deduced from the information provided in the paper. 

The relative orientations of the diene and dienophile in a favorable TS for a Diels-Alder reaction is predicted by Alder s endo-rule [33]. The Alder s endo-rule states that for Diels-Alder reactions of substituted butadiene derivatives with dienophiles having an electron-withdrawing substituent, kinetically controlled endo-TS will be preferred over exo-TS because of secondary orbital interactions of the electron-withdrawing substituent with the butadiene n system. The endo-TS has lower activation energy than that of exo-TS. The product derived from endo-TS is called kinetically controlled product and the product derived from exo-TS is called thermodynamically controlled product. Frequently a mixture of both stereoisomers is formed and sometimes the thermodynamically controlled cxo-product predominates. It has been observed that reaction of butadiene with maleic anhydride using deuterium-labeled butadiene gives 85 % of the endo-pioduct 50 from endo-TS [33]. The reaction of cyclopentadiene with maleic anhydride also gives 97.5 % cnJo-product 51. The secondary orbital interactions in preferred endo-TS are shown in Fig. 3.8. 

As with butadiene, a Diels-Alder reaction with normal electron demand occurs, that is, the HOMO of furan (see Figure 5.2c) interacts with the LUMO of maleic anhydride. The reaction is diastereoselective. Alder s endo-rule applies to the stereochemistry of the cycloadducts 21/22 thus, in acetonitrile at 40°C, the mdo-adduct 21 is formed 500 times faster than the evo-adduct 22 owing to kinetic control. However, with a sufficiently long reaction time, product formation becomes subject to thermodynamic control the initially formed mdo-compound is completely converted via the educts to the exo-compound, which is more stable by 8 kj mol. ... 

According to Alder s Endo rule (1930) Endo isomers are major products in Diels-Alder reactions. These results look surprising on the grounds that Endo-isomers are less stable for steric reasons. But, Endo-rule can be rationalized on the basis of frontier orbital theory. Endo-transition state is stablized by secondary interactions in comparison to exo-isomers in which secondary interactions are absent. This facts makes endo-isomers more stable, i.e.,why they are major-products in Diels-Alder reactions. 

The thermal Diels-AIder reactions of perfluorocyclopentadiene with diethyl maleate and diethyl fumarate have been shown to proceed in accordance with the cis principle enunciated by Alder and Stein. Further evidence for the normal behaviour of perfluorocyclopentadiene in such 1,4-additions is provided by the observation that hydrolysis of the amide produced by treatment of the diene with A-allyltrifluoroacetamide at 50 °C yields the azatri-cyclononane (19) (see Scheme 4) obviously, Alder s endo rule applies to this cycloaddition. The same technique has been used to show that the Diels-AIder adduct obtained from perfluorocyclohexa-1,3-diene and A-allyltri-fluoroacetamide at 110°C is predominantly or even exclusively the endo-isomer. ... 

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