Stereochemistry in Diels-Alder reaction

Chiral sulfinyldicncs have also been used in Diels-Alder reactions [88] interest in the synthesis of 1- and 2-sulfinyldienes in enantiopure form [531] and in their use to control the stereochemistry in Diels-Alder reactions is growing fast (see [532] and references therein). 

Cycloadditions. In fact, cycloadditions like the Diels-Alder reaction are syn additions wherein the maximum overlap of the interacting n bonds eventually further governs the stereochemistry. In Diels-Alder reaction the 1, 4-addition of the double bond of a dienophile I i.e., 2, 4-cyclo hexene-1, 4-dione) to a conjugated diene II to generate a 6-membered ring, such that up to four new stereocenteres (i.e., chiral centres) may be created simultaneously at one go, as depicted below ... 

Maintaining an eye for ciarity With every edition we improve the presentation of topics, reactions, and diagrams where the opportunity arises. In this edition some examples include improved discussion and diagrams regarding endo and exo Diels-Alder transition states, the effect of diene stereochemistry in Diels-Alder reactions (Section 13.1 OB), and improved mechanism depictions for aromatic sulfonation and thionyl chloride substitution. 

Recent advances in the control of absolute stereochemistry in Diels-Alder reactions of 2-pyrones with dienophiles have been reviewed. The position of the electron-withdrawing group on simple y-pyrones is a decisive factor in the 4 - - 2-cycloaddition of y-pyrones with Danishefsky s diene and with azomethine ylides. The solid-state photo-4 -I- 2-cycloadditions of 2-pyrone-5-carboxylates with maleimides give only the... 

Although pyrroles do not generally participate in Diels-Alder reactions with olefinic dienophiles, the very reactive hexafluoro-Dewar benzene with pyrrole gives the 1 1 and 1 2 adducts, 27 and 28, both of which probably have all-ea o stereochemistry. Some other 7-azabicyclo-heptene derivatives have been obtained via cycloaddition reactions of 7-azaquadricyclanes (see Section II, F). 

Since both the diene and the dienophile in Diels-Alder reactions 2.84 react suprafacially, there are synthetically useful structural consequences, which incidentally prove that the stereochemistry of approach is suprafacial. Thus a diene with substituents at each end forming new bonds to one surface will create an adduct in which the stereochemical relationships are preserved. The trans,trans-diene 2.86 and diethyl acetylenedicarboxylate 2.87 give the... 

Fig. 6. Controlling stereochemistry and regiochemistry in Diels-Alder reactions by the application of very high pressure. The potential for using elevated pressures to obtain asymmetric induction is based upon exploiting the different volumes of activation between the competing diastereoisomeric transition states [48, 54]. In the first example, a AAV of 0.9 cm3 mol-1 favors the formation of diastereoisomer 15 over diastereoisomer 16 as the pressure is increased. In the second example, the increased ratio of 18 relative to 17 illustrates the importance of pressure variations in the control of regiochemistry...

We now turn to the stereochemistry governed by a ring system, and we shall look at both nucleophilic and electrophilic attack, since usually they have similar stereochemical preferences rather than contrasting preferences. In addition to several reactions that are straightforwardly electrophilic attack, we shall see several which can be described as electrophilic in nature, like the reactions of alkenes with osmium tetroxide, with peracids, with some 1,3-dipoles, and with boranes, and of dienes with dienophiles in Diels-Alder reactions. Some of these reactions are pericyclic, the pericyclic nature of which we shall meet in Chapter 6. For now, it is only their diastereoselectivity that will concern us. 

Secondary orbital interactions have also been invoked to explain regiochemistry as well as stereochemistry. Whereas 1 -substituted dienes sometimes have only a small difference between the coefficients on C-l and C-4 in the HOMO, they can have a relatively large difference between the coefficients on C-2 and C-3. Noticing this pattern, Alston suggested that the regioselectivity in Diels-Alder reactions may be better attributed, not to the primary interactions of the frontier orbitals on C-l and C-4 that we have been using so far, but to a... 

EtAlCk.catalyzed Diels-Alder reactions between alkyl-substituted 1,3-butadienes and (r -acrylol) (r -cyclopentadienyl) diacarbonyliron(II) complexes have been found, where the observed regio- and stereochemistry were consistent with that generally observed in Diels-Alder reactions [55]. Conventional Lewis acids such as BF -OEt. and TiCl4 were not effective in promoting the desired cycloaddition. 

The rates, regiochemistry, and stereochemistry of Diels-Alder reactions are affected by the solvent, and are often correlated to solvent polarity scales. In Chapter 15, we will cover orbital interactions that dictate the dominant regio-isomers of Diels-Alder reactions similar to that given below. The diene A is considered to be a nucleophile and... 

Casetta, M. Colona, S. Manfredi, A., Hydrophobic control of organic stereochemistry. Changes of regioselectivity in Diels-Alder reactions by salt effects, Gazz. Chim. Ital, 1989, 119,533-5. 

Endo-Exo Stereochemistry Sometimes Diels-Alder reactions give two types of products, viz, endo and exo isomers. The product in which substituent on dienophiie are cis to double bond formed in diene after Diels-Alder reaction is known as endo-isomer and the other product in which substituent on dienophiie are trans-to double bond is known as exo-isomer. Alteranatively, the product in which substituent is on the side away from bridge is known as endo-isomer and the product having substituent on the same side of the bridge is known as exo-isomer. 

Lewis acid catalysis increases the reactivity of dienophiles in Diels-Alder reactions by complexing to basic sites on the dienophile. In aldehydes, complexation takes place via the lone pair on the carbonyl oxygen. The stereochemistry is strongly influenced by the Lewis acids. Under chelating conditions, when ct-alkoxy aldehydes are used, the prevalent products from TiCU catalysis have cis configuration (eqs 27 and 28). Stereochemical aspects of pericyclic pathways or passage through aldol type intermediates have been summarized and discussed. ... 

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 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-... 

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