Stereochemistry Diels—Alder reaction and

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... 

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. 

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. 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted important interest thanks to there various applications in different synthetic transformations. These simple structures, directly related to the well-documented Evans oxazolidinones, have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations (7V-enoyl derivatives), but mainly in condensation of their 7V-acyl derivatives on aldehydes. Those have shown interesting characteristics in anti-selective aldol reactions or combined asymmetric addition. Normally, the use of chiral auxiliaries which can accomplish chirality transfer with a predictable stereochemistry on new generated stereogenic centers, are indispensable in asymmetric synthesis. The use of OZTs as chiral copula has proven efficient and especially useful for a large number of stereoselective reactions. In addition, OZT heterocycles are helpful synthons that can be specifically functionalized. 

Intermolecular [4 + 2] cycloadditions exhibit strongly negative activation volumes and reaction volumes. High pressure, therefore, can be applied to accelerate Diels-Alder reactions and to shift the reaction equilibrium towards the cycloadducts. These effects are of particular advantage to (1) promote odierwise slow [4 + 2] cycloadditions involving heat or Lewis acid sensitive educts or products (2) suppress cycloreversion processes which are eidier thermodynamically favored or would interfere with a kinetically controlled stereochemistry. In view of a recent review (1985) only a few examples are presented here. 

Problem 16.22 Draw the products of each Diels-Alder reaction, and indicate the stereochemistry. 

The catalyst clearly makes methyl acrylate more electrophilic, however not much more electrophilic than maleic anhydride. This fact, together with the A5 value in the range typical of common Diels-Alder reactions, and with the stereochemical and orientational features mentioned, suggests that the catalysed reaction is similar in mechanism to the uncatalysed one . The electronic interactions that govern the course of the addition seem to be only strengthened. The stereochemistry of the AICI3 catalysed reaction of butadiene with 2-phenyl-2-cyclohexen-1-one favours, however, the existence of a dipolar intermediate. 

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 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 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-... 

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. 

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 ... 

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. 

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