Styrenes Diels-Alder reactions

As we saw in the Diels-Alder reaction, styrene derivatives could potentially undergo that reaction to yield 52. The latter could enter into an ene reaction, a DA reaction, or aromatization. This has been a matter of controversy in the past which may be dispensed with here, since in specific cases as will be seen all possible alternatives are known. Given rearrangement. 

The second mechanism, proposed by Mayo (116), involves the Diels-Alder reaction of two styrene molecules to form a reactive dimer (DH) followed by a molecular assisted homolysis between DH and another styrene molecule. 

Bis(trifluoromethyl)-l,l-dicyanoethylene is a very reactive dienophile. It undergoes facile and high-yield [2+4] cycloadditions with 1,3-dienes, cyclopen-tadiene, and anthracene [707] (equation 86). It is reactive enough in a Diels-Alder reaction with styrene [702] (equation 86). 

Reaction of 2-(arylmethyleneamino)pyridines 335 and styrenes in the presence of hydroquinone afforded 2,4-diaryl-3,4-dihydro-2/f-pyrido[l,2-n]pyrimidines 336 by means of an inverse electron demand Diels-Alder reaction (95MI10). Reaction of 2-(benzylideneamino)pyridines 337 and chloroacetyl chloride gave 2-aryl-4//-pyrido[l,2-n]pyrimidin-4-ones 338 (97JMC2266). 

Reaction of 2-aminopyridines with formaldehyde and electron rich styrenes 383 permitted the synthesis of 3,4-dihydro-2//-pyrido[l,2-n]pyr-imidines 384 (96TL2615). First imines 382 formed they are involved in a formal aza-Diels-Alder reaction to give compounds 384. 

When Diels and Alder published their famous paper in 1928, Diels had been working with related reactions for several years [6]. In 1925, Diels reported the reaction of azodicarboxylic ester (Et0C(0)2CN=NCC(0)0Et) with compounds containing a conjugated diene system. He found that addition of the azodicarboxylic ester occurs at the 1,4-position of the conjugated system as with cyclopentadiene and with butadiene. This work probably led to the famous Diels-Alder reaction. In 1927, Diels and his student Alder published a paper on the reaction of azodicarboxylic ester with styrene. 

There are Diels-Alder reactions known where the electronic conditions outlined above are just reversed. Such reactions are called Diels-Alder reactions with inverse electron demand For example the electron-poor diene hexachlorocy-clopentadiene 21 reacts with the electron-rich styrene 22 ... 

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]. 

Vinylnaphthalenes give Diels-Alder reactions more easily than styrenes and have been used to synthesize steroid-like compounds. 2-Vinylnaphthalene (61) is less reactive than 1-vinylnaphthalene (62) (Figure 2.7) it requires drastic conditions to undergo Diels-Alder reaction and the yields are low. Better results can be obtained by carrying out the reaction under high pressure (Chapter 5). Some Diels-Alder reactions of 1-vinylnaphthalene (62) are summarized in Scheme 2.23. 

Harano and colleagues [48] found that the reactivity of the Diels-Alder reaction of cyclopentadienones with unactivated olefins is enhanced in phenolic solvents. Scheme 6.28 gives some examples of the cycloadditions of 2,5-bis-(methoxycar-bonyl)-3,4-diphenylcyclopentadienone 45 with styrene and cyclohexene in p-chlorophenol (PCP). Notice the result of the cycloaddition of cyclohexene which is known to be a very unreactive dienophile in PCP at 80 °C the reaction works, while no Diels-Alder adduct was obtained in benzene. PCP also favors the decarbonylation of the adduct, generating a new conjugated dienic system, and therefore a subsequent Diels-Alder reaction is possible. Thus, the thermolysis at 170 °C for 10 h of Diels-Alder adduct 47, which comes from the cycloaddition of 45 with 1,5-octadiene 46 (Scheme 6.29), gives the multiple Diels-Alder adduct 49 via decarbonylated adduct 48. In PCP, the reaction occurs at a temperature about 50 °C lower than when performed without solvent, and product 49 is obtained by a one-pot procedure in good yield. 

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. 

An interesting parallel was found while the microwave-enhanced Heck reaction was explored on the C-3 position of the pyrazinone system [29]. The additional problem here was caused by the capability of the alkene to undergo Diels-Alder reaction with the 2-azadiene system of the pyrazinone. An interesting competition between the Heck reaction and the Diels-Alder reaction has been noticed, while the outcome solely depended on the substrates and the catalyst system. Microwave irradiation of a mixture of pyrazinone (Re = H), ethyl acrylate (Y = COOEt) and Pd(dppf)Cl2 resulted in the formation of a mixture of the starting material together with the cycloaddition product in a 3 1 ratio (Scheme 15). On the contrary, when Pd(OAc)2 was used in combination with the bulky phosphine ligand 2-(di-t-butylphosphino)biphenyl [41-44], the Heck reaction product was obtained as the sole product. When a mixture of the pyrazinone (Re = Ar) with ethyl acrylate or styrene and Pd(dppf)Cl2 was irradiated at 150 °C for 15 min, both catalytic systems favored the Heck reaction product with no trace of Diels-Alder adduct. 

Show how styrene can be prepared using the following reactions somewhere in your synthetic procedure, (a) Hofmann elimination, (b) Grignard reaction, (c) Diels-Alder reaction. Compare the atom economies of each process. Identify any issues raised by using this approach to determine the most efficient synthetic route. 

A recent patent describes the synthesis and catalytic use of Al-containing TUD-1 materials. Some of the reactions demonstrated inclnde hydrogenation of mesitylene (Pt as active metal) and dehydration of 1-phenyl-ethanol to styrene. Several other conceptnal reactions were also described, amongst others the Diels-Alder reaction of crotonaldehyde and dicyclopentadiene and the amination of phenol with ammonia. 

TABLE 2.4 Activation Enthalpies AW (kcal/mol) for the Ortho I Meta and Endo/Exo Pathways for the Diels-Alder Reactions Between o-QM and MVE, Styrene, and MVK in the Gas Phase"... 

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... 

A combination of a metathesis and a Diels-Alder reaction was published by North and coworkers [263]. However, this is not a true domino reaction, as the dienophile (e. g., maleic anhydride) was added after the in situ formation of the his-butadiene 6/3-89 from the fois-alkyne 6/3-88 and ethylene. The final product is the fois-cycloadduct 6/3-90, which was obtained in 34% yield. Using styrene as an un-symmetrical alkene instead of ethylene, the mono-cycloadduct 6/3-91 was formed as a mixture of double-bond isomers, in 38% yield (Scheme 6/3.26). 

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... 

Diels-Alder catalysis.1 This radical cation can increase the endo-selectivity of Diels-Alder reactions when the dienophile is a styrene or electron-rich alkene. This endo-selectivity obtains even in intramolecular Diels-Alder reactions. Thus the triene 2, a mixture of (Z)- and (E)-isomers, cyclizes in the presence of 1 to 0° to the hydroindanes 3 and 4 in the ratio 97 3. Similar cyclization of (E)-2 results in 3 and 4 in the ratio 98 2 therefore, the catalyst can effect isomerization of (Z)-2 to (E)-2. Even higher stereoselectivity is observed when the styrene group of 2 is replaced by a vinyl sulfide group (SC6H5 in place of QHtOCT ). 

Uses Synthetic rubbers and elastomers (styrene-butadiene, polybutadiene, neoprene) organic synthesis (Diels-Alder reactions) latex paints resins chemical intermediate. 

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>. 

Since the seminal work of Bartlett [363] there have been relatively few reports of useful cycloadditions of fluoroalkenes. Recent work by Haufe showed that fluorine atom substituents depress the reactivity of styrene derivatives in the Diels-Alder reaction with 1,3-diphenylisobenzofuran. A single fluorine atom in the /1-position lowered the rate of the [4 + 2] reaction by a factor of ten when the fluorine atom occupied the -position (Eq. 142), the reaction was over 30 times slower than that of the unsubstituted styrene. 

Styrene, leads to [4 + 2]-adducts exclusively (251-258) 242 is also isolated in varying amounts, With methyl sorbate both [4 + 2]- and [4 + 4]-adducts (259-262) are obtained. 1,4-Dicarbomethoxybutadiene does not add to 138 242 is obtained in 90% yield. All photoadducts (251-262) are photolabile on irradiation (z — 253.7 nm) they are reconverted to 138 and the alkene. Significantly for preparative purposes, the product distributions (stereo-, regio-, and peri-selectivity) differ considerably from those obtained in the thermal Diels-Alder reactions (Section IV,B) mechanistic details are given in the original papers. 

In an ingenious application of the extrusion reaction, 1-alkenyl-1,3-dihydro-benzo[c]thiophene 2,2-dioxides have been thermolyzed the diene system so generated undergoes an intramolecular Diels-Alder reaction with the isolated double bond in the side chain (79HCA2017). An (E) configuration of the diene is necessary for this purpose (Scheme 233). The by-products are styrenes arising from the (Z)-isomer. The same approach has also been used to prepare a steroid derivative (Scheme 233) (80JOC1463). 

Diels-Alder reactions have been conducted on solid phase, with either the dieno-phile or the diene linked to the support [156]. The reaction conditions and the regio-and stereoselectivities observed are similar to those in solution [58,157,158]. Illustrative examples of Diels-Alder reactions leading to support-bound cyclohexenes are listed in Table 5.10. Further examples include the cycloaddition of polystyrene-bound 2-sulfonyl-l,3-butadiene and V-phenylmaIcimidc [51], the high-pressure cycloaddition of 1,3-butadienes to resin-bound 1 -nitroacrylates [95], and the intramolecular Diels-Alder reaction of styrenes with acrylates [159]. 

BUTADIENE. [CAS 106-90-0]. CHrCH C CH3, 1,3-butadiene (methyl-allene), formula weight 54.09. bp —4.41cC, sp gr 0.6272, insoluble in H2 O. soluble in alcohol and edier in all proportions, Butadiene is a very reactive compound, arising from its conjugated double-bond structure. Most butadiene production goes into die manufacture of polymers, notably SBR (styrene-butadiene rubber) and ABS (acryloiiitrile-buladiene-slyrene) plastics. Several organic syntheses, such as Diels-Alder reaction, commence with the double-bond system provided by this compound. 

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