Styrenes hetero-Diels-Alder reactions

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... 

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. 

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. 

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

Wijnen, f.W., Zavarise, S., Engberts, J.B.F.N. and Charton, M., Substituent effects on an inverse electron demand hetero Diels Alder reaction in aqueous solution and organic solvents cycloaddition of substituted styrenes to di(2 pyridyl) 1,2,4,5 tetrazine, /. Org. Chem., 1996,61, 2001-2005. 

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. 

More recently, a catalyst-free aqueous version of this strategy was proposed with simple acyclic 1,3-dicarbonyls, formaldehyde, and styrene or anilines derivatives (Scheme 40) [131], In the first case (Scheme 40), the very reactive 2-methylene-1,3-dicarbonyl intermediate reacts smoothly at 80°C with a variety of substituted styrenes to give the corresponding dihydropyrans in moderate to good yields. Remarkably, when styrenes were replaced by A-ethylaniline, a novel five-component reaction involving twofold excess of both formaldehyde and 1,3-dicarbonyl selectively occurred (Scheme 41). The result is the formation of complex fused pyranoquinolines following a Friedel-Craft alkylation - dehydration sequence to furnish the quinoline nucleus, which suffers the Hetero-Diels-Alder cyclization in synthetically useful yields. 

The influence of a low pH on the rate of reaction was also observed in the hetero Diels-Alder of di(2-pyridyl)-l,2,4,5-tetrazine with substituted styrenes [49]. 

Schemes 58-62. A new non-rigid phosphine ligand was synthesized and reacted with Fe(CO)5 to form the mononuclear iron complex (Equation (81)). Phosphino-oxazoline ligands were used as assembling ligands for hetero-metallic complexes, where the phosphorus atom binds to iron and the nitrogen atoms act as donor atoms to copper, cobalt, or palladium (Scheme 58). The copper complex catalyzes cyclopropanation and Diels-Alder reactions. When 2-(A -diphenylphosphinomethyl-A -cyclohexyl)aminopyridine (NNP) reacts with Fe(CO)5 in ethanol, /ra .r-(OC)3Fe(NNP)2 is formed (Scheme 59). This monometallic complex can then be reacted with a copper salt in CH2GI2 to form a complex having an Fe-Cu dative bond. The complex was demonstrated to be an efficient catalyst for the cyclopropanation of styrene by ethyl diazoacetate and for the Diels-Alder reaction of cyclopentadiene and methacrolein. No other heterometallic complexes have been shown to have such reactivity. Previously known...

Af-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4+2] cycloaddition with alkenes and alkynes.15 The reaction has been utilized as a useftil method for the construction of heterocycles and acyclic amino alcohols. The reaction can be explained in terms of an inverse electron demand Diels-Alder type process that involves an electron-deficient hetero-diene with an electron-rich dienophile. Af-Acyliminium ions generated by the cation pool method were also found to undergo [4+2] cycloaddition reaction to give adduct 7 as shown in Scheme 7.16 The reaction with an aliphatic olefin seems to proceed by a concerted mechanism, whereas the reaction with styrene derivatives seems to proceed by a stepwise mechanism. In the latter case, significant amounts of polymeric products were obtained as byproducts. The formation of polymeric byproducts can be suppressed by micromixing. 

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