Substituted styrenes, Diels-Alder reactions

Styrenes may act as 2n and 4n components of the Diels-Alder reaction depending on the substitution site and the electronic effects of the substituent. Electron-donating groups at the a-carbon of the olefinic double bond enhance the dienic reactivity of styrenes [30]. 

Chemoselective alkenylation in the C-3 position of N-substituted 3,5-dichloropyrazin-2(lH)-ones has been described by Van der Eycken et al. [27]. When a mixture of N-substituted 3,5-dichloropyrazin-2(lH)-one, ethyl acrylate, and NEts in DME, using Pd(OAc)2/DTPB [2-(di-f-butylphosphanyl)bi-phenyl] as a precatalyst, was irradiated for 15 min at 150 °C, the desired /1-fimctionabzed ethyl acrylates could be obtained in moderate yields (Scheme 81). When styrene was used as an alkene, a mixture of E and Z products was isolated. The type of catalyst used proved to be important to avoid competitive Diels-Alder reaction of ethyl acrylate with the hetero-diene system of 3,5-dichloro-l-benzylpyrazin-2(lH)-one. 

The hetero-Diels-Alder reaction can also employ dienes containing heteroatoms. Cycloaddition of substituted styrenes with di-(2-pyridyl)-1,2,4,5-tetrazine was investigated by Engberts (Eq. 12.56).127 Again, the rate of the reaction increased dramatically in water-rich media. Through kinetic studies, they showed that the solvent effects on the... 

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

Inverse type hetero-Diels-Alder reactions between p-acyloxy-a-phenylthio substituted a, p-unsaturated cabonyl compounds as 1-oxa-1,3-dienes, enol ethers, a-alkoxy acrylates, and styrenes, respectively, as hetero-dienophiles result in an efficient one step synthesis of highly functionalized 3,4-dihydro-2H-pyrans (hex-4-enopyranosides). These compounds are diastereospecifically transformed into deoxy and amino-deoxy sugars such as the antibiotic ramulosin, in pyridines having a variety of electron donating substituents, in the important 3-deoxy-2-gly-culosonates, in precursors for macrolide synthesis, and in C.-aryl-glucopyranosides. 

Novel 2-amino-substituted- 3-methylenedihydropyrans 2 have been obtained from inverse electron demand Diels-Alder reactions of allenamides with heterodienes <99TL6903> and the reaction of styrenes with a,p-unsaturated 2-oxonitriles yields predominantly the cis-2-aryldihydropyran-6-carbonitriles 3 <99HCA1122>. 

D. Seebach, Preparation of dendritic and non-dendritic styryl-substituted Salens for cross-linking suspension copolymerization with styrene and multiple use of the corresponding Mn and Cr complexes in enantioselective epoxidations and hetero-Diels-Alder reactions, Chem - Eur.J. 2001, 7, 2873-2887. 

Similar applications of chiral titanium Lewis acid catalysts to asymmetric [2 + 2] cycloadditions, with up to nearly quantitative asymmetric induction, have employed 4-benzoquinones as additions and substituted styrene-type substrates11. In all of these asymmetric [2 + 2]-cvcload-dition reactions, the Lewis acid catalyst presumably is attached to peripheral functional groups and thus, similar to Lewis acid catalyzed Diels Alder reactions (see Section 1.5.8.3.5.4.), is only indirectly involved in the reaction course7. 

BH3 Copolymerisation of the vinyl-substituted monomer with styrene and Promotor in Mukaiyama aldol reactions Scheme 1.6 JO). Yields are comparable but enantiomeric excesses are lower than those obtained with the soluble Ts-Val-OH.257 Catalyst for Diels-Alder reaction of cyclopentadiene and methacrolein (Scheme 1.6.30) P ... 

The hetero-Diels-Alder reaction can also employ dienes containing heteroatoms. Cycloaddition of substituted styrenes with di-(2-pyiidyl)-... 

The kinetics of the Diels-Alder reactions of di(2-pyridyl)-l,2,4,5-tetrazine with substituted styrenes have been investigated in aqueous media and in organic solvents. The second-order rate constants of this reaction increase dramatically in water-rich media. A decrease in pH accelerates the aqueous Diels-Alder reaction even more. The Hammer p-values and also the electronic demand 77-values of the reaction are solvent sensitive. In protic solvents, the dipolar character of the activated complex is increased but, simultaneously, hydrogen-bond interactions stabilize the activated complex. These effects are most pronounced in 2,2,2-trifluoroethanol, which shows that the aqueous accelerations cannot be attributed solely to solvent-induced changes of the reaction mechanism <1996JOC2001>. 

A concise synthesis of substituted stUbenes from propargylic phosphonium salts by a cobalt-catalyzed Diels-Alder/Wittig olefination reaction has been described (Figure 1.4) [37]. It was shown that the cobalt(I)Diels-Alder reaction of propargylic phosphonium salts and alkyne-fimctionalized phosphonium salts with 1,3-dienes led to dihydroaromatic phosphonium salt intermediates that were directly used in a one-pot Wittig-type olefination reaction with aldehydes. Subsequent oxidation led to styrene- and stUbene-type products with the formation of three new carbon-carbon bonds. The reaction gives predominantly the Econfigured products. 

Danishefsky s interest in the development of synthetically useful Diels-Alder reaction methodology has recently extended to two different dienophiles. First, he studied the reactivity of enyne dienophiles to show that ynones react preferentially to enones. Substituted styrene 78 is the exclusive product on intermolecular Diels-Alder reaction of diene 76 with dienophile 77 followed by a retro Diels-Alder reaction (to generate 2-methylpropene) and two desilylations. ... 

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