Diels-Alder dienes, stereoselection

Lopez J. C., Lukacs G. Pyranose-Derived Dienes and Conjugated Enals. Preparation and Diels-Alder Cycloaddition Reactions ACS Symp. Ser. 1992 494 33-49 Keywords carbohydrate, befera-Diels-Alder reactions, stereoselectivity... 

As can be seen from some of the examples cited above, a single or predominant sulfur stereoisomer often results from the cycloaddition process, but sometimes mixtures of sulfur epimers are produced. In many of these cycloadducts the configuration at sulfur has not been determined, and thus not enough data are currently available to clarify what factors control the configuration established at sulfur. These cycloadditions do show the usual Diels-Alder syn stereoselectivity with respect to the 1,3-diene component. 

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 ... 

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

Based on the facile formation and reactivity of323, and the retro Diels-Alder reaction of 325306,310, a simple procedure has been developed for the stereoselective synthesis of functionalized conjugated dienes as well as vinylallenes311 (see equation 119). 

Carbene complexes which have an all-carbon tether between the diene and the dienophile react via intramolecular Diels-Alder reaction to give the corresponding bicyclic compound. The stereoselectivities of these reactions are comparable to those observed for the Lewis acid-catalysed reactions of the corresponding methyl esters and much higher than those of the thermal reactions of the methyl esters which are completely unselective. Moreover, the ris-sub-stituted complexes undergo endo-selective reactions where the corresponding reaction of the ester fails [109] (Scheme 61). 

The discovery that Lewis acids can promote Diels-Alder reactions has become a powerful tool in synthetic organic chemistry. Yates and Eaton [4] first reported the remarkable acceleration of the reactions of anthracene with maleic anhydride, 1,4-benzoquinone and dimethyl fumarate catalyzed by aluminum chloride. The presence of the Lewis-acid catalyst allows the cycloadditions to be carried out under mild conditions, reactions with low reactive dienes and dienophiles are made possible, and the stereoselectivity, regioselectivity and site selectivity of the cycloaddition reaction can be modified [5]. Consequently, increasing attention has been given to these catalysts in order to develop new regio- and stereoselective synthetic routes based on the Diels-Alder reaction. 

Dimethoxyethylacrylate (94) may be readily converted into the cationic species 95 by the action of Lewis acids [92] (Equation 3.32) the cationic species then undergoes Diels Alder reaction with a variety of dienes. The type of catalyst markedly affects the reaction yield, stereoselectivity and regioselectivity as shown in Scheme 3.19 and Equation 3.33. 

Aqueous cycloaddition using glyco-organic substrates. Facial stereoselectivity in Diels-Alder reactions of a chiral diene derived from D-glyceraldehyde [102]... 

Various 1,4-oxathiins have been converted to the sulfoxides in a highly stereoselective reaction. The sulfoxides undergo a thermal retro-Diels-Alder reaction to ot,a -dioxosulrines which can behave both as electron deficient dienes and as dienophiles, affording different oxathiins and dihydrothiopyran 1-oxides, respectively <96T12233>. In like manner, o-thioquinone 5-oxides have been generated and they too exhibit diene and dienophile behaviour <96T12247>. 

Lewis acids such as zinc chloride, boron trifluoride, tin tetrachloride, aluminum chloride, methylaluminum dichloride, and diethylaluminum chloride catalyze Diels-Alder reactions.22 The catalytic effect is the result of coordination of the Lewis acid with the dienophile. The complexed dienophile is more electrophilic and more reactive toward electron-rich dienes. The mechanism of the addition is believed to be concerted and enhanced regio- and stereoselectivity is often observed.23... 

A new noncarbohydrate-based enantioselective approach to (—)-swainsonine was developed in which the key step was an aqueous intramolecular asymmetric hetero-Diels-Alder reaction of an acylni-troso diene (Eq. 12.57).128 Under aqueous conditions there was significant enhancement of the trans stereoselectivity relative to the reaction under conventional nonaqueous conditions. 

It is of interest to investigate the usefulness of this theory to the chemical change involving the interaction between the conjugated systems 56,62,145). Such a-n interactions are frequently stereoselective. The addition to olefinic double bonds and the a, -elimination are liable to take place with the fraMS-mode 146h The Diels-Alder reaction occurs with the cis-fashion with respect to both diene and dienophile. 

Diels-Alder reactions are found to be little influenced by the introduction of radicals (cf. p. 300), or by changes in the polarity of the solvent they are thus unlikely to involve either radical or ion pair intermediates. They are found to proceed stereoselectively SYN with respect both to the diene and to the dienophile, and are believed to take place via a concerted pathway in which bond-formation and bond-breaking occur more or less simultaneously, though not necessarily to the same extent, in the transition state. This cyclic transition state is a planar, aromatic type, with consequent stabilisation because of the cyclic overlap that can occur between the six p orbitals of the constituent diene and dienophile. Such pericyclic reactions are considered further below (p. 341). 

Enantiomerically pure 1-sulfinyl-l,3-butadienes 577 are efficient chiral dienes providing the corresponding Diels-Alder products with high stereoselectivity. However, their use in asymmetric synthesis is limited to highly reactive... 

Note Added in Proof. The stereochemistry of the Diels-Alder addition reactions shown in Scheme 1 to give products 20-22 has been examined by 400 MHz lH-NMR. These data indicate that the cycloadditions occur with a high degree of stereoselectivity (having diastereoselectivities of greater than 94 6). The chiral Fe environment of the dienophile 17 strongly influences the direction of the facial attack of the diene reactants. 

Mg11 is often employed in stereoselective reactions. In hetero Diels-Alder reactions of aldehydes with Danishefsky s diene, Mg11 results in good acceleration and stereoselection, and 2,3-coproducts are obtained exclusively (Scheme 6).26 Milder Lewis acidity is necessary for obtaining higher yield and higher stereoselectivity in this reaction, which occurs through a cyclic transition state. 

In stereoselective reactions, Zn11 Lewis acids work well to achieve high selectivities (Scheme 54). Chiral complexes of Zn11 with chiral bis(oxazoline) ligands act as effective catalysts in Diels-Alder reactions of reactive dienes with dienophiles having bidentate chelating moieties such as... 

The reactions of 4-nitrobenzodifuroxan 242 with a series of common dienes, such as cyclopentadiene, cyclohexa-diene, isoprene, 2,3-dimethylbutadiene, and 1-acetoxybutadiene, with ethoxymethyleneacetylacetone were found to proceed very readily to afford stable cycloadducts, which are the result of highly stereoselective normal electron-demand (NED) Diels-Alder reactions. Due to the additional activation provided by the two adjacent furoxan rings, the nitroalkene double bond of compound 242 is also prone to undergo NED reactions with less reactive dienic structures, such as the enol form of ethoxymethyleneacetylacetone and the in situ generated 2-ethoxy-4-(2-furfur-yl)buta-l,3-diene <2004TL1037, 2005T8167>. 

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