Diels-Alder adducts formation

A formally antiaromatic 1,4-dihydropyrazinothiadiazole has been prepared and characterized by single crystal X-ray spectroscopy. The antiaromatic character of which has been supported computationally using NICS measurements <20070L1073>. CHIH-DFT computational studies on acenaphtho[l,2-f]-l,2,5-thiadiazole 1,1-dioxide led to simulations of its infrared (IR) and ultraviolate (LJV) spectra, the dipole moment and polarizability <2007JMT373>. 4,6-Dinitrobenzothiadiazole was determined to have an electrophilic reactivity of —8.40 which corresponds to a pK z° of 7.86 for Meisenheimer complexation with water and is close to the demarcation boundary (E = —8.5) between super-and normal-electrophiles and between reactive dienophiles and inert partners in Diels-Alder adduct formation <20070BC1744>. 

A unique class of structures referred to as iptycenes has recently been reported by Hart et al. [129-131]. These architectures represent the first examples of all-hydrocarbon dendrimer prototypes. Starting with either benzene or triptycene as the initiator core, branch junctures were constructed in situ by Diels-Alder adduct formation to give the heptaiptycene (A) and the nonaiptycene (tri-... 

Other 1,4-Eliminations Fluoride ion induced desilylation is a very mild method that allows generation of heterocyclic o-quinodimethanes at ambient temperature and is suitable for inter- and intramolecular Diels-Alder adduct formation (Scheme 17). However, the presence of F can be a problem, leading to epimerisation of optically active centres <85CJC3526>. Long routes required for the synthesis of the silylated precursors and purification problems detract somewhat from this otherwise excellent method. 

Bauld has carried out a large number of mechanistic studies of radical cation mediated Diels—Alder and cyclobutanation reactions, as discussed in detail in two recent reviews. Much of the above discussion concerning the concerted vs. stepwise nature of the dimerization reactions also applies to the addition of an alkene radical cation to a different alkene. Although the addition of alkene radical cations to dienes can lead to both cyclobutane and Diels-Alder products, the latter usually predominate for dienes with at least modest s-cis conformer populations. It is clear that in some cases the Diels-Alder adducts arise via rearrangement of initial divinylcyclobutane products. However, cyclobutanation and Diels-Alder adduct formation have been demonstrated to occur by independent pathways in other systems. There is also considerable experimental and theoretical data in support of a concerted but nonsynchronous mechanism for these reactions. 

Helium. He NMR spectroscopy has been used to study the reversible Diels-Alder adduct formation between 9,10-dimethylanthracene and [ He C6o] or... 

Diels-Alder adduct formation between MA and anthracene, which is light catalyzed,and that of the photodienes are discussed elsewhere. 

The same researchers found that lanthanide triflates could catalyze aldol reactions and allylations in aqueous media [10]. However, Wang et al. exploited the potential of lanthanide triflates to act as stable Lewis-acid catalysts in the aqueous imino Diels-Alder reaction [11]. This variant of the aqueous heterocycloaddition protocol also expands the scope of such reactions. The use of higher aldehydes in such reactions generally met with limited success under the conventional protocol. For example, under the standard conditions, the reaction of hexanal and benzylamine hydrochloride with cyclopentadiene in water is sluggish and affords only 4% of the Diels-Alder adducts 26 and 27 in a 2.7/1 ratio. In sharp contrast, the addition of various lanthanide(lll) triflates (0.25 M) to this reaction results in substantial increases in both the rate and yield of Diels-Alder adduct formation. In particular, use of praseodymium(iii) triflate results in a 68% yield of adducts 26 and 27 ... 

The reactions of pyrroles with dimethyl acetylenedicarboxylate (DMAD) have been extensively investigated. In the presence of a proton donor the Michael adducts (125) and (126) are formed. However, under aprotic conditions the reversible formation of the 1 1 Diels-Alder adduct (127) is an important reaction. In the case of the adduct from 1-methylpyrrole, reaction with a further molecule of DMAD can occur to give a dihydroindole (Scheme 48) (82H(19)1915). 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

Suggest a reasonable pathway for the formation of each of the photoproducts formed on irradiation of the Diels-Alder adduct of 2,3-dimethylbutadiene and quinone ... 

Fluorinaied dienophiles. Although ethylene reacts with butadiene to give a 99 98% yield of a Diels-Alder adduct [63], tetrattuoroethylene and 1,1-dichloro-2,2-difluoroethylene prefer to react with 1,3-butadiene via a [2+2] pathway to form almost exclusively cyclobutane adducts [61, 64] (equation 61). This obvious difference in the behavior of hydrocarbon ethylenes and fluorocarbon ethylenes is believed to result not from a lack of reactivity of the latter species toward [2+4] cycloadditions but rather from the fact that the rate of nonconcerted cyclobutane formation is greatly enhanced [65]... 

Benz[/]isoindole 10 exists, on the basis of spectroscopic examination, predominantly in the benzenoid tautomeric form 10b, although the formation of the Diels-Alder adduct with N-phenylmaleimide suggests the presence of a small amount of the o-quinoid tautomer 10a (78JOC4469). 

Fig. 8.6 The calculated transition-state structure for the reaction of acrolein with butadiene leading to formation of vinyldihydropyran by a hetero-Diels-Alder adduct catalyzed by BH3 using a RHF/3-21G basis set [6]...

The reaction was studied in the absence, and presence, of (MeO)2AlMe as a model catalyst for the BINOL-AlMe system. The change in relative energy for the concerted hetero-Diels-Alder reaction, and formation of the hetero-Diels-Alder adduct 11 via a Mukaiyama aldol reaction, is shown in Fig. 8.13. The conclusion of the study was that in the absence of a catalyst the concerted reaction is the most... 

The structures along the reaction path in Fig. 8.13 are outlined in Fig. 8.14 starting with benzaldehyde activated by (MeO)2AlMe in the reaction with Danishefsky s diene 10 leading to the transition-state structure for the formation of the al-dol-like intermediate, and finally the formation of the hetero-Diels-Alder adduct. 

Despite the body of evidence in favor of the Mayo mechanism, the formation of diphenylcyclobutanes (90, 91) must still be accounted for. It is possible that they arise via the 1,4-diradical 94 and it is also conceivable that this diradical is an intermediate in the formation of the Diels-Alder adduct 95 (Scheme 3.64) and could provide a second (minor) source of initiation. Direct initiation by diradicals is suggested in the thermal polymerization of 2,3,4,5,6-pentafluorostyrene where transfer of a fluorine atom from Diels-Alder dimer to monomer seems highly unlikely (high C-F bond strength) and for derivatives which cannot form a Diels-Alder adduct. 

Various mechanisms have been proposed to explain the initiation processes. The self-initiated copolymerizations of the monomer pairs S-MMA and S-AN proceed at substantially faster rates than pure S polymerization. For S-AN333 and S-MAHJJ the mechanism of initiation was proposed to be analogous to that of S homopolymerization (Scheme 3.62) but with acrylonitrile acting as the dicnophile in the formation of the Diels-Alder adduct (Scheme 3.66). 

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. 

Actually, the reactions led to the formation of the corresponding acyclic Mannich-type addition products, which were further transformed into their corresponding Diels-Alder adducts by treatment with TFA (Scheme 5.18). The 5, P-bidentate character of the ligands was proven by isolation of one complex and its X-ray analysis. Complexes prepared with CuCl afforded the expected product in up to 80% ee, whereas the use of CuBr as the catalytic precursor allowed an enantioselectivity of 97% ee to be obtained with the similar ligand. 

Optically active Diels-Alder adducts were also prepared by using a one-pot preparative method and enantioselective formation of inclusion complex with optically active hosts in a water suspension medium.68 For example, A-ethylmaleimide reacts with 2-methyl-1,3-butadiene in water to give the racemic adduct 1. Racemic 1 and the optically active host 2 form enantioselectively a 1 1 inclusion complex of 2 with (+)-l in a water suspension. The inclusion complex can be filtered and heated to release (+)-l with 94% ee (Eq. 12.23). 

ILLUSTRATION 8.1 DETERMINATION OF HOLDING TIME REQUIREMENTS FOR THE FORMATION OF A DIELS-ALDER ADDUCT... 

Similar alkene formations via dealkoxycarbonylation and denitration have been reported for the synthesis of novel heterocycles. Heterocyclic nitro compounds such as 4-nitroisoxazole undergo the Diels-Alder reaction subsequent dealkoxycarbonylation and denitration give the products, which are regarded as the Diels-Alder adducts of five-membered heterocyclic arynes (Eq. 7.142).121... 

The critical role of the ion-radical pair in the cycloaddition reactions in equation (75) is demonstrated by a careful measurement of the quantum yields as a function of the dienophile concentration and by a study of the effect of solvent and salt on the dynamics of the ion pair ANT+ , MA-. 212 However, in the reported cases, back electron transfer effectively competes with the coupling within the ion-radical pair and thus limits the quantum yields for the formation of the Diels-Alder adduct.212... 

As mentioned above, the electrochemical oxidation of a diene yields 1,2- and 1,4-addition products when the reaction is carried out in the presence of a nucleophile such as methanol or acetic acid. When the oxidation is carried out in the absence of the nucleophile it usually yields a polymeric compound as the major product. The formation of a small amount of the Diels-Alder adduct is, however, observed when the reaction is carried out in CH2CI2 with graphite anode. One of the proposed reaction pathways is shown in equation 68, though it is not clear whether the cyclohexadienyl radical serves as a diene (as shown in equation 6) or a dienophile in the Diels-Alder reaction. 

Hetero Diels-Alder reactions are very useful for constructing heterocyclic compounds, and many important chiral molecules have thus been synthesized. Although the retro Diels-Alder reaction does not itself involve the asymmetric formation of chiral centers, this reaction can still be used as an important tool in organic synthesis, especially in the synthesis of some thermodynamically less stable compounds. The temporarily formed Diels-Alder adduct can be considered as a protected active olefin moiety. Cyclopentadiene dimer was initially used, but it proved difficult to carry out the pyrrolytic process. Pentamethyl cyclopentadiene was then used, and it was found that a retro Diels-Alder reaction could easily be carried out under mild conditions. 

The formation of Diels-Alder adducts is now used in the determination of the position of double bonds in polycyclic hydrocarbons. 

The Pd °-catalyzed dimerization of 2 leads to the Diels-Alder adduct 314 as the main product (81%), for whose formation only one allene group has participated in the dimerization process, in addition to the dimer 315 (14%), in which no allene group has survived in addition, several other dimers are produced in trace amounts [131]. 

Ohfune and coworkers78 used Diels-Alder reactions between 2-trimethylsilyloxy-l,3-butadiene (63) and acrylate esters 64 to synthesize constrained L-glutamates which they intended to use for the determination of the conformational requirements of glutamate receptors. The reactions between 63 and acrylate esters 64a and 64b did not proceed. Changing the ethyl and methyl ester moieties into more electron-deficient ester moieties, however, led to formation of Diels-Alder adducts, the yields being moderate to good. In nearly all cases, the cycloadducts were obtained as single diastereomers, which is indicative of a complete facial selectivity (equation 22, Table 1). Other dienes, e.g. cyclopentadiene and isoprene, also showed a markedly enhanced reactivity toward acrylate 64g in comparison with acrylate 64a. 

Niggli and Neuenschwander294 studied the reaction of fulvene (461) with cyclopen-tadiene. The main product fraction consisted of three 1 1 adducts, as illustrated in equation 138. Diels-Alder Adducts 462 and 463 resulted from attack of cyclopentadiene at the endocyclic and exocyclic double bonds of fulvene, respectively. The formation of 464 was rationalized by a [6 + 4] cycloaddition reaction followed by two [1,5] hydrogen shifts. It was stated that due to the absence of electron-donating and electron-withdrawing groups on both triene and diene, fulvene may have reacted via its HOMO as well as its LUMO. 

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