Alder endo rule

Alder Endo Rule In order to maximize secondary orbital interactions, the endo TS is favored in the D-A rxn. Tetrahedron 1983, 3,9, 2095... 

Although IMDA reactions are entropically less disfavored than the intermolecular versions, they are nonetheless not as simple as might at first appear. The well-known Alder endo rule and its frontier molecular orbital theoretical interpretation involving secondary orbital interactions, together with steric considerations, serve to explain the kinetic preference for the endo-product and the thermodynamic preference for the < o-product in IMDAs. For the IMDA reaction, an additional parameter, the effect of the tether that connects the diene to the dienophile to control the conformation available to a transition state has to be considered. 

The Alder endo rule is explained by FMO theory, invoking secondary orbital interactions, as mentioned in Section 11.4.C.92 A comparison of the endo transition state (81) with the exo transition state (82) for the reaction of cyclopentadiene and acrolein shows the orbitals of the carbonyl are properly aligned in 81 and of the correct symmetry for stabilization by the orbitals of the HOMOdiene- This interaction is absent in the exo transition state (82). This secondary orbital interaction stabilizes 81 and lowers the energy of that transition state relative to 82. Maleic anhydride reacts with cyclopentadiene, for example, to give only the endo product,93 and in like manner c/s-methacrylic acid reacts to give a 90 10 mixture of endo/exo cycloadducts.94... 

Interestingly, the cycloaddition of 10 and methyl vinyl ketone is also highly stereoselective with respect to the acetyl side chain in 59. Analogous double diastereoselectivity (endo face attack, Alder endo rule [139,202-204]) is observed for the cycloaddition of 10 to methyl acrylate (Scheme 7). As expected [179-184,205], the Diels-Alder additions of 10 are ortho regio-selective. 

Kurt Alder initially observed this preference for the endo product and it has come to be known as the Alder endo rule. Close scrutiny using modern mechanistic tools gives an understanding of this phenomenon as being driven by secondary orbital interactions. This preference for the endo product is also seen in reactions of acyclic dienes, but it is difficult to label the product unless there is a stereochemical marker (see Section 24.3.3). 

Section 24.3.1 noted that the Alder endo rule is applied to acyclic dienes as well as cyclic dienes, but it is more difficult to see the product in the former case. In order to form 21, an endo approach (22) of acrylonitrile to the diene is required. An exo approach used transition state 23, which leads to the other diastereomer, 20. There is disrotatory motion for both endo and exo approaches. When the alkene has a substituent containing a n-bond—particularly, a C=0 unit—endo approach is usually favored. An endo approach of the alkene combined with a disrotatory motion of the groups on the diene leads to formation of one diastereomer as the major product. The Diels-Alder reaction is diastereose-lective. Because the alkene may approach from either the bottom (see Figure 24.4) or the top, the product will he racemic. 

The Alder endo rule predicts an endo cycloadduct as the major product. 

In 1936, Alder left the University of Kiel to pursue research efforts in industry. He continued to study the diene reaction, focusing on the stereochemical course of the transformation. Consequently, the preference for endo products in the reaction is generally referred to as the Alder Endo Rule. Diels and Alder s achievements in advancing the utility of this powerful reaction were recognized with the Nobel Prize in chemistry in 1950. ... 

The Alder endo rule enables predictions of product structures that combine stereocenters generated from both the diene and dienophile. Based on Alder s pioneering studies, he demonstrated that endo products are... 

Figure 4.51. A cartoon representation of the Diels-Alder reaction between two cyclopenta-diene equivalents one of which acts as a diene and the other as a dienophile. Dicyclopentadiene (3a, 4,7,7a-tetrahydro-4,7-methano-lH-indene, tricyclo[5.2.1.0 ]deca-3,8-diene) is commercially available and is thermally decomposed ( cracked ) at its boiling point (170°C) to produce cyclopentadiene (bp 46°C). The latter slowly dimerizes at room temperature. Dicyclopentadiene exists almost completely as the endo isomer, which, it is argued, forms as result of maximum overlap of n orbitals during the reaction (the Alder Endo rule). The other potential isomer (the exo isomer) is not observed.

In concert with the general observation that electron withdrawing groups in the dienophilic portion of the Diels-Alder electrocyclic Jt4s-Fjt2s addition reaction facilitate the process (raising both the HOMO and LUMO of the alkene), haloal-kenes can serve in this capacity. As shown in Equation 7.69,1-bromoethene (ethylene bromide, H2C=CHBr) serves as a dienophile in the reaction with cyclopentadiene to provide both endo-2-bromobicyclo[2.2.1]heptane and the corresponding exo-isomer. As expected on the basis of the Alder Endo rule (Chapter 4), the former predominates in the uncatalyzed reaction. 

The first examples of hetero-Diels-Alder additions of SO2 involved highly reactive dienes 139 and 140. In 1992, Deguin et al. reported that simple 1,3-dienes undergo het-ero-Diels-Alder addition below 60°C in the presence of a large excess of SO2 and of a protic or Lewis acid promoter (Scheme 22.40). For instance, in the presence of CF3COOH, ( , )-deuteriopiperylene 141 equilibrates with sultine 142 at — 80°C. At —60°C, 142 is converted into the more stable isomeric sultine 143, thus, demonstrating the suprafaciality of the cycloadditions that obey the Alder endo) rule. ... 

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