Diels—Alder reaction stereochemistry

Note that the stereochemistry comes out right. H s a and b are cis because they were cis in the starting quinone and the Diels-Alder reaction is stereospecific in this respect. H is also cis to and H " because the Diels-Alder reaction is stereoselectively endo. These points are described in more detail in Norman p.284-6 and explained in Ian Fleming Frontier Orbitals and Organic Chemical Reactions, Wiley 1976, p. 106-109. How would you make diene A ... 

The stereochemistry of the 1,3-dipolar cycloaddition reaction is analogous to that of the Diels-Alder reaction and is a stereospecific syn addition. Diazomethane, for example, adds stereospecifically to the diesters 43 and 44 to yield the pyrazolines 45 and 46, respectively. 

Stereochemistry of Diels-Alder Reactions. Thermodynamic vs. Kinetic Control... 

Figure 15.6 FMO rationalizes the stereochemistry of substituted Diels-Alder reactions...

The Diels-Alder reactions of the methyl or ethyl ester of benzenesulfonylindole-2-acrylic acid with several l-alkoxycarbonyl-l,2-dihydropyridines are reported and only a single stereoisomer was obtained, as in the case of l-methoxy(ethoxy)-carbonyl-1,2-dihydropyridines. However, when the Diels-Alder reaction of 17 was carried out with 8g[R = (CHsjsC], a mixture of two stereoisomers 18gand25were obtained in a 1 1 ratio (65% total yield). The bulky rerr-butyl group creates sufficient steric interference with the indole ring to cause the loss of stereochemistry ... 

The Diels-Alder reaction is one of the most useful synthetic reactions for the construction of the cyclohexane framework. Four contiguous stereogenic centers are created in a single operation, with the relative stereochemistry being defined by the usually ewdo-favoring transition state. 

The classic method for controlling stereochemistry is to perform reactions on cyclic substrates. A rather lengthy but nonetheless efficient example in the prostaglandin field uses bicyclic structures for this purpose. Bisacetic acid derivative S is available in five steps from Diels-Alder reaction of trans-piperylene and maleic anhydride followed by side-chain homologation. Bromolactonization locks the molecule as bicyclic intermediate Esterification, reductive dehalogen-... 

One of the most useful features of the Diels-Alder reaction is that it isstaeo-specific, meaning that a single product stereoisomer is formed. Furthermore, the stereochemistry of the reactant is maintained. If we carry out the cycloaddition with a cis dienophile, such as methyl ds-2-butenoate, only the cis-substituted cyclohexene product is formed. With methyl tmtts-2-butenoate, only thetrans-substituted cyclohexene product is formed. 

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. 

Show the product of the Diels-Alder reaction of the following diene with 3-buten-2-one, H2C=CHCOCH3. Make sure you show the full stereochemistry of the reaction product. 

Show the structure, including stereochemistry, of the product from the following Diels-Alder reaction ... 

A Dimethyl butynedioate undergoes a Diels-Alder reaction with (2 ,4 )-hexadiene. Show the structure and stereochemistry of the product. 

What stereochemistry would you expect for the product of the Diels-Alder reaction between (2 ,4 )-2,4-hexadiene and ethylene What stereochemistry would you expect if (2 ,4Z)-2,4-hexadiene were used instead ... 

Diels-Alder reaction, 492 characteristics of, 492-497 dienes in, 496-497 dienophiles in. 493-494 electrostatic potential map of. 493 endo stereochemistry of, 495 HOMO in. 1188-1189 LUMO in. 1188-1189 mechanism of. 493 s-cis diene conformation in, 496-497... 

Enantiotopic (NMR), 455 Endergonic. 153 Endergonic reaction, Hammond postulate and, 197-198 Endo stereochemistry, Diels-Alder reaction and, 495 Endothermic, 154 -ene, alkene name ending, 176 Energy difference, equilibrium position and, 122... 

Exo stereochemistry, Diels-Alder reaction and, 495 Exon (DNA), 1108-1109 Exothermic, 154... 

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. 

Pericyclic Diels-Alder reactions are suprafacial reactions and this manner of bond formation preserves in the cycloadduct the relative stereochemistry of the substituents at Ci and C4 and at Ci and C2 of the parents diene and dienophile, respectively (Scheme 1.7). The relative stereochemistry of the substituents in the... 

According to frontier molecular orbital theory (FMO), the reactivity, regio-chemistry and stereochemistry of the Diels-Alder reaction are controlled by the suprafacial in phase interaction of the highest occupied molecular orbital (HOMO) of one component and the lowest unoccupied molecular orbital (LUMO) of the other. [17e, 41-43, 64] These orbitals are the closest in energy Scheme 1.14 illustrates the two dominant orbital interactions of a symmetry-allowed Diels-Alder cycloaddition. 

The more reactive furan (139a) undergoes thermal Diels-Alder reaction [52] with reactive dienophiles such as maleic anhydride and maleimide (Scheme 5.21). Whereas the cycloaddition with the maleic anhydride afforded the exoadduct at room temperature, the stereochemistry of the reaction of maleimide depends on the reaction temperature. 

The synthesis of chaparrinone and other quassinoids (naturally occurring substances with antileukemic activity) is another striking example [16a-c]. The key step of synthesis was the Diels-Alder reaction between the a,/l-unsaturated ketoaldehyde 1 (Scheme 6.1) with ethyl 4-methyl-3,5-hexadienoate 2 (R = Et). In benzene, the exo adduct is prevalent but it does not have the desired stereochemistry at C-14. In water, the reaction rate nearly doubles and both the reaction yield and the endo adduct increase considerably. By using the diene acid 2 (R = H) the reaction in water is 10 times faster than in organic solvent and the diastereoselectivity and the yield are satisfactory. The best result was obtained with diene sodium carboxylate 2 (R = Na) when the reaction is conducted 2m in diene the reaction is complete in 5h and the endo adduct is 75% of the diaster-eoisomeric reaction mixture. 

Keywords asymmetric synthesis, stereochemistry, inverse electron-demand Diels-Alder reaction, rare earth metals... 

The stereochemistry of the Diels-Alder reaction can be considered from several aspects ... 

Diels-Alder reaction is one of the most fundamental reactions for organic synthesis. Its synthetic utility is unquestioned. The stereochemistry of the reactions has attracted much attention. The retention of stereochemistry in the diene and the dienophile, the predominant formation of endo-attack products in the reactions of cyclic dienes, and highly controlled regioselectivity in the reactions of substimted dienes and... 

Aromatic thioureas were more active than alkyl (octyl, cyclohexyl) derivatives. Thioureas with trilluoromethyl substituents were even more effective. The same group also showed that these organocatalysts can act as weak Lewis acids and are thus able to alter the stereochemistry of the Diels-Alder reaction between cyclopentadiene and chiral acrylamide derivatives (Scheme 49) [167]. 

The enyne cross metathesis was first developed in 1997 [170,171]. Compared to CM it benefits from its inherent cross-selectivity and in theory it is atom economical, though in reality the aUcene cross-partner is usually added in excess. The inabihty to control product stereochemistry of ECM reactions is the main weakness of the method. ECM reactions are often directly combined with other transformations like cyclopropanation [172], Diels-Alder reactions [173], cychsations [174] or ring closing metathesis [175]. 

Diels-Alder reactions are attractive for synthetic application because of the predictable regio- and stereochemistry. There are, however, limitations on the types of compounds that can serve as dienophiles or dienes. As a result, the idea of synthetic equivalence has been exploited by development of dienophiles and dienes that meet the reactivity requirements of the Diels-Alder reaction and can then be converted to the desired structure. For each of the dienophiles and dienes given below, suggest a Diels-Alder reaction and subsequent transformation(s) that would give a product not directly attainable by a Diels-Alder reaction. Give the structure of the diene or dienophile synthetic equivalent and indicate why the direct Diels-Alder reaction is not possible. 

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