Diels-Alder reactions defined

The reactivity of the thiocarbonyl group of 1,2-dithiocarbonyl compounds is well suited for 2n participation in Diels-Alder reactions with typical dienes (Chapter 5). In addition, frequent and well-defined Diels-Alder reactions with 4tt participation of symmetrical 1,2-dithiocarbonyl compounds with olefinic and acetylenic dienophiles have been detailed.36-39... 

Alternatively, authors have repeatedly invoked the internal pressure of water as an explanation of the rate enhancements of Diels-Alder reactions in this solvent ". They were probably inspired by the well known large effects of the external pressure " on rates of cycloadditions. However, the internal pressure of water is very low and offers no valid explanation for its effect on the Diels-Alder reaction. The internal pressure is defined as the energy required to bring about an infinitesimal change in the volume of the solvents at constant temperature pi = (r)E / Due to the open and... 

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. 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

Removal of the carbonate ring from 7 (Scheme 1) and further functional group manipulations lead to allylic alcohol 8 which can be dissected, as shown, via a retro-Shapiro reaction to give vinyl-lithium 9 and aldehyde 10 as precursors. Vinyllithium 9 can be derived from sulfonyl hydrazone 11, which in turn can be traced back to unsaturated compounds 13 and 14 via a retro-Diels-Alder reaction. In keeping with the Diels-Alder theme, the cyclohexene aldehyde 10 can be traced to compounds 16 and 17 via sequential retrosynthetic manipulations which defined compounds 12 and 15 as possible key intermediates. In both Diels-Alder reactions, the regiochemical outcome is important, and special considerations had to be taken into account for the desired outcome to. prevail. These and other regio- and stereochemical issues will be discussed in more detail in the following section. 

Jorgensen et al. [84] studied how solvent effects could influence the course of Diels-Alder reactions catalyzed by copper(II)-bisoxazoline. They assumed that the use of polar solvents (generally nitroalkanes) improved the activity and selectivity of the cationic copper-Lewis acid used in the hetero Diels-Alder reaction of alkylglyoxylates with dienes (Scheme 31, reaction 1). The explanation, close to that given by Evans regarding the crucial role of the counterion, is a stabilization of the dissociated ion, leading to a more defined complex conformation. They also used this reaction for the synthesis of a precursor for highly valuable sesquiterpene lactones with an enantiomeric excess superior to 99%. 

In 1994, Kiindig et al. described a related catalyst, in which both CO ligands have been replaced by a chiral F,f -chelate ligand providing evidence that structurally defined cationic Fe sandwich complexes are indeed efficient catalysts for Diels-Alder reactions [33]. 

An interesting mechanistic issue was raised by Firestone on the aqueous Diels-Alder reaction between 2-methylfuran and maleic acid in water, which is found to be 99.9% stereospecific.80 By adding heavy atom (defined as any below the first complete row of the periodic table) salts to the aqueous media, it was found that addition of heavy but not light atom salts reduced the degree of stereospecificity significantly in the retrodiene reaction. The results suggest that a large portion of the Diels-Alder reaction occurs via diradical intermediates (Scheme 12.2). 

Concerted cycloaddition reactions provide the most powerful way to stereospecific creations of new chiral centers in organic molecules. In a manner similar to the Diels-Alder reaction, a pair of diastereoisomers, the endo and exo isomers, can be formed (Eq. 8.45). The endo selectivity in the Diels-Alder arises from secondary 7I-orbital interactions, but this interaction is small in 1,3-dipolar cycloaddition. If alkenes, or 1,3-dipoles, contain a chiral center(s), the approach toward one of the faces of the alkene or the 1,3-dipole can be discriminated. Such selectivity is defined as diastereomeric excess (de). 

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

The synthesis of the macrocycles 43 (Scheme 9) is an example of repetitive, highly stereoselective Diels-Alder reaction between bis-dienes 41 and bis-dienophiles 42, containing all oxo or methano bridges syn to one another. The consecutive inter- and intramolecular Diels-Alder reactions only succeed at high pressure. Obviously, both reactions are accelerated by pressure. The macrocycles are of interest in supramolecular chemistry (host-guest chemistry) because of their well-defined cavities with different sizes depending on the arene spacer-units. 

Cycloadditions of reactants with opposite electronic properties are defined as Diels-Alder reactions with inverse electron demand or inverse Diels-Alder reactions. 

Due to the formal analogy to the classical Diels-Alder reaction, the mechanism of cyclic peroxide formation through cycloadditions of 1,3-dienes with O2 was considered for a long time to involve a concerted suprafacial [4 4- 2]-cycloaddition of a super-dienophile, namely a singlet oxygen to 1,3-dienic system In such a case, the concerted or almost concerted cycloaddition must be c -stereospecific and the stereochemical properties of the diene must be reflected in the three-dimensional structure of cyclic peroxide according to well-defined rules. Indeed, it was found in early stereochemical... 

An interpretation of the results and a hypothesis on potential intermediates was difficult at this stage, since no defined complexes could be obtained. The first identification of species present in solution during the catalysis of the Diels-Alder reaction was achieved in a collaboration between our group and three physical chemists, Bertagnolli, Gescheidt, and Schweiger [64]. Using various techniques... 

Diels-Alder reaction, for example, is much better suited as a unimolecular reaction than the bimolecular cycloaddition because the former allows better control of precursors, in which the structural properties are well defined (96JA8755). Fragmentation of a molecule may be initiated by various methods depending on how the required energy is supplied. 

Recently, Fukuzumi et al. reported the photochemical Diels-Alder reaction with Danishefsky s diene [252], A mixture of C6o and the stereochemically defined (lii,3Z)-l,4 disubstituted Danishefsky s diene 77 was irradiated for 9h at -30°C to avoid the thermal reaction (Scheme 30). A high pressure mercury lamp... 

This three-component reaction as the key step of this synthesis is called a domino-Knoevenagel-hetero-Diels-Alder reaction. Domino reactions are defined as processes of two or more bond forming reactions in which a subsequent transformation takes place by virtue of the functionalities introduced in a former transformation.2,16 The tetrahydrocarbolinaldehyde 11 first reacts in a Knoevenagel type condensation with Meldrum s acid 14 and ethyleneammonium diacetate 41 as the catalyst to oxabutadiene 44 which then undergoes a Diels-Alder reaction with enol ether 13. 

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