Diels-Alder reactions of dienes

The Diels-Alder reactions of dienes 11 and 12 with many dienophiles allowed other fluorinated aromatics to be synthesized [12,13]. For example, diene 11 reacted with dimethylacetylenedicarboxylate and ethylpropiolate (Scheme 2.8) to give trifluoromethyl diethylphthalate and trifluoromethylethylbenzoate, and diene 12 with/ -benzoquinone affords 5-fluoronaphthoquinone (Equation 2.5). 

Table 5.2 High pressure Diels-Alder reactions of diene 77 with dienophiles 78...

Indium trichloride [30] and methylrhenium trioxide [31] catalyze the aqueous Diels-Alder reaction of acrolein and acrylates with cyclic and open-chain dienes. Some examples of the cycloaddition of methyl vinyl ketone with 1,3-cyclohexadiene are reported in Scheme 6.18. MeReOs does not give satisfactory yields for acroleins and methyl vinyl ketones with substituents at the jS-position and favors the self-Diels-Alder reaction of diene. 

Anti TT-facial selectivity with respect to the sterically demanded substituent in the Diels-Alder reactions of dienes having unsymmetrical tt-plane has been straightforwardly explained and predicted on the basis of the repulsive interaction between the substituent and a dienophile. However, there have been many counter examples, which have prompted many chemists to develop new theories on the origin of 7t-facial selectivity. We have reviewed some theories in this chapter. Most of them successfully explained the stereochemical feature of particular reactions. We believe that the orbital theory will give us a powerful way of understanding and designing of organic reactions. 

Diels-Alder reactions in supercritical water have also been investigated.57 Kolis has shown that Diels-Alder reactions of dienes with various electron-poor dienophiles can be performed in supercritical water with high yields of the desired product without the addition of... 

The aqueous Diels-Alder reaction has also been used for bioconjugate studies. A Diels-Alder reaction of diene oligonucleotides with maleimide dieneophiles was used to prepare oligonucleotide conjugates in aqueous media under mild conditions (Eq. 12.39).102 A Diels-Alder-type cycloaddition of an electronically matched pair of saccharide-linked conjugated dienes and a dienophile-equipped protein was the... 

Tab. 7.1 Diels-Alder reactions of dienes 1-3 using the GS/MW process [15, 16]. 

Diels-Alder reactions of dienes/dienophiles with cumulated... 

The most important development within the field of Diels-Alder chemistry during the past two decades must be considered to be the design and application of chiral Lewis acid catalysts. From the mid 80s on, the number of literature reports about the design and application of chiral Lewis acids in the synthesis of chiral Diels-Alder adducts from achiral precursors grew exponentially, but it started to level off and decrease again in the mid 90s. Several excellent reviews about the application of chiral Lewis acids in Diels-Alder reactions have been published41,43 44. In this section, the recent literature about the chiral Lewis acid catalyzed all-carbon Diels-Alder reactions of dienes with dienophiles is reviewed, which, as such, has not been reviewed before. 

The formation of heterocycles by cycloaddition reactions of conjugated dienes is the subject of this chapter. Almost the entire account is devoted to the Diels-Alder reaction of dienes with heterodienophiles to yield six-membered ring compounds (equation 1). Many such reactions have been reported and there is a plethora of reviews. Somela p are general others are cited at appropriate places in the text. This account is highly selective, concentrating on recent work with particular regard to the stereochemistry of these processes. 

In this chapter we wish to review the collected evidence for the astonishing effects of water on reactivities and selectivities as exemplified by the Diels-Alder reactions of dienes. Examples of Lewis acid and micellar catalysis in aqueous media are also presented. Finally, the newest computational investigations including solvent effects on Diels-Alder reactions are put forward in order to rationalize some of the remarkable observations. 

The syntheses described in this subsection rely upon the availability of o-diaroylbenzenes. A few methods seem to be of broader applicability. As Adams and co-workers have shown, the Diels-Alder reaction of dienes and diaroylethylenes gives 4,5-diaroylcyclohexenes, which on subsequent treatment with catalytic amounts of acid (sulfuric or phosphoric) form 4,7-dihydrobenzo[c]furans. Subjecting these compounds to the action of 2 moles of bromine in acetic acid in the presence of sodium acetate resulted in diaroylbenzenes (Eq. fi). - - ... 

J. C. Lopez, E. Lameignere, and G. Lukacs, Stereospecificity in Diels-Alder reactions of dienes and dienophiles derived from methyl 4,6-O-benzyIidene-a-D-glucopyranoside, J. Chem. Soc. Chem. Commun. p. 706 (1988). 

The asymmetric Diels-Alder reaction of diene and cyclopentenone derivatives can be promoted by a chiral titanium catalyst prepared in situ from (Pr 0)2TiCl2 and a tartrate-derived o.,a,a, a -tetraalkyl-l,3-dioxolane-4,5-dimethanol [54] (Eq. 8A.31). The resulting adducts can easily be tranformed to estrogens and progestogens. 

The use of isopropylidine acetals (112) as tethers in the intramolecular Diels-Alder reactions of dienes with alkenes facilitates the formation of civ-fused cycloadducts (113) from an endo transition state (Scheme 41).218 The intramolecular Diels-Alder reaction of 4-[tris-(2-mcthylcthyl)silyl]oxy-2//-thiopyran derivatives with potential dienophiles tethered at C(2), C(3), C(5), and C(6) positions yielded cycloadducts when the dienophiles were activated with a carbomethoxy group.219 By the substitution of a phenylsulfonyl group on the dienophile of 2-benzopyran-3-ones, it is possible to enhance exo addition during intramolecular Diels-Alder cyclizations to yield a predominance of trans-fused hexaphenanthrenes related to natural products.220 The intramolecular Diels-Alder reaction of 2-furfuryl fumarates has been investigated by molecular mechanics (SIBFA)/continuum reaction field computations.221 The intramolecular 4 + 2-photo-cycloaddition of A-benzylcinnamamides (114) in the presence of C(,H6 gives 3-azatricyclo[5.2.2.01,5]undeca-8,10-dien-4-ones (115) with high stereoselectivity (Scheme 42).222... 

Saigo and co-workers reasoned that, by analogy, high levels of diastereofacial discrimination could be achieved in the Lewis acid-mediated Diels-Alder reaction of dienes with oxazolidinone 108-derived dienophiles. Indeed, excellent regioselectivities (endo. exo) and diastereoselectivities were reached in the Diels-Alder reaction of 109 with cyclic and acyclic dienes using Et2AlCl as the activator (Scheme 24.28).107 The selectivities obtained actually surpassed those reported with cis-1 -amino-2-indanol 1 as the chiral auxiliary (93% de) (see Scheme 24.16).82 The additional bulk... 

Diels-Alder reactions. The laboratories of Breslow and of Grieco have reported that water can enhance the rate of Diels-Alder reactions of dienes that possess carboxylic acid or similar hydrophilic groups (12, 314). Liotta et al. have examined solvent effects on cycloaddition reactions of benzoquinones with dienes substituted with a relatively hydrophobic group, and report significant rate enhancement in ethylene glycol relative to benzene (26 1) or even to reactions in the absence of a solvent. They attribute the solvent effect to aggregation of the diene and the quinone. 

The moderate Lewis acidity of ruthenium complexes was used to promote catalytic Diels-Alder reaction of dienes and acrolein derivatives [21-23]. The enantioselective Diels-Alder reaction of methacrolein with dienes was catalyzed with cationic ruthenium complexes containing an arene or cyclo-pentadienyl (Cp) ligand and a chiral ligand such as phosphinooxazoline, pyridyl-oxazoline, monoxidized 2,2 -bis(diphenylphosphino)-1, T-binaphthyl (BINPO)or l,2-bis[bis(pentafluorophenyl)phosphanyloxy]-l,2-diphenylethane (BIPHOP-F). The reaction gave the cycloadduct in high yields with excellent... 

More recently, a fluorous organocatalyst has been used to perform selective Diels-Alder reactions of dienes with oc,(3-unsaturated aldehydes in acetonitrile-water. The chiral fluorous imidazolidinone catalyst can be recovered using fluorous silica (80-90% recovery efficiency) and reused. Figure 7.10. Further organocatalytic reactions are presented later in this chapter. 

Nevertheless, because of its weak influence, the silyl substituent hardly interferes with more potent re-giochemical control elements, as demonstrated by the acetoxy-directed Diels-Alder reaction of diene (166) with methyl acrylate (Scheme 40). The major endo product (168) was then converted to ( )-shi-kimic acid (171). 

Table 25 Lewis Acid Catalyzed Diels-Alder Reactions of Dienes to N-Acryloyl-(S)-proline Benzyl Ester (391)...

Asymmetric Diels-Alder reactions of dienes substituted widi a removable chiral moiety with prochiral dienophiles have been much less extensively studied. Hie few successful examples involve ester or ether derivatives of 1,3-dienols. 

Table 2. Enantioselective Diels-Alder reaction of dienes and acetylenic dienophiles catalyzed by 2, 4, and 6."...

Chiral alkyldihaloboranes are among the most powerful chiral Lewis acids. In general, however, because alkyldihaloboranes readily decompose to alkanes or alkenes as a result of protonolysis or /3-hydride elimination, it is difficult to recover them quantitatively as alkylboronic acids. Aryldichloroborane is relatively more stable and can be reused as the corresponding boronic acid. We have developed chiral aryldichlorobor-anes 23 bearing binaphthyl skeletons with axial chirality as asymmetric catalysts for the Diels-Alder reaction of dienes and a,/3-unsaturated esters (see, e.g., Eq. 37) [36]. 

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