Thiophenes Diels—Alder reaction

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). 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Benzo[b]thiophene, vinyl-cycloaddition reactions, 4, 794 Diels-Alder reactions, 4, 908... 

Strained pertrifluoromethyl-substituted valence tautomers of aromatic systems, such as tetrakis(trifiuoromethyl)Dewar thiophene [87] and hexalas(tnfluorQ-methyl)benzvalene [Diels-Alder reactions with various cyclic and acyclic dienes (equations 76 and 77). 

Melles and Backer " found, from a study of the oxidation of substituted thiophenes with perbenzoic or peracetic acid, that sulfones could be obtained from polysubstituted methyl- and phenyl-thiophenes and that the presence of electron-attracting groups, such as nitro, hindered the oxidation. Oxidation of thiophene - led to a product which was formed through a Diels-Alder reaction between the intermediate thiophene sulfoxide (211) and thiophene sulfone (212) and for which two alternative structures, (213) or (214), were suggested. Similar sesquioxides were also obtained from 2- and 3-methylthiophene and 3-phenylthiophene. The structures were not proved. Bailey and Cummins synthesized thiophene-1,1-dioxide... 

Thiophene 1,1-dioxide (61) is too unstable to isolate and dimerizes with loss of S02 to give 3a, 7a-dihydrobenzothiophene 1,1-dioxide (172) in 34%113. However, alkyl-substituted thiophene 1,1-dioxides can serve as dienes in the Diels-Alder reaction, since the aromatic properties of the thiophene nucleus are lost completely and the n-electrons of the sulfur atom are used for forming the bond with oxygen. The sulfones 173-178 are found to react with two moles of maleic anhydride at elevated temperature to give bicyclic anhydrides114. Thus, at high reaction temperature, S02 is split off to give cyclohexadiene... 

As vinylbenzofurans allow a large variety of substituted dibenzofurans to be synthesized, 2- and 3-vinylbenzo[b]thiophenes allow an easy entry, by Diels Alder reaction with the appropriate dienophiles, to substituted dibenzo-thiophenes which are not easily accessible by other methods. Vinylbenzo-[bjthiophenes are less reactive than the corresponding vinylbenzo[b]furans. Some cycloaddition reactions of 2-vinylbenzo[b]thiophene (82) with various dienophiles are reported [83] in Scheme 2.34. 

TT-Facial selectivity in the Diels-Alder reactions of thiophen 1-oxides has recently attracted keen attention (Scheme 49). Fallis and coworkers reported in situ generated 2,5-dimethylthiophene 1-oxide 98 reacted with various electron-deficient dienophiles exclusively at the syn face with respect to sulfoxide oxygen [57],... 

Furukawa and coworkers reported preparation and isolation of thiophene 1-oxides 111-113. Diels-Alder reaction of 111 with maleic anhydride, benzoquinone, and cw-l,2-dibenzoylethylene gave the corresponding syn adducts exclusively [61] (Scheme 50). 

Scheme 50 Diels-Alder reactions of thiophen 1-oxide 111 with dienophiles...

The oxidation of benzo[( ]thiophene by strains of pseudomonads produces the sulfoxide that undergoes an intramolecular Diels-Alder reaction followed by further transformation to benzo[fc]naphtho[l,2- (]thiophene (Figure 2.2b) (Kropp et al. 1994). 

Dichloro thiophene 1,1-dioxide (168) is stable and of particular interest in the Diels-Alder reactions . Thus, when 168 is treated with cyclopentadiene in acetone, adducts... 

Scheme 5.12 Pd-catalysed Diels-Alder reaction with thiophene-containing ligand.

The reaction of tetrafluorobenzyne with iV-methylpyrrole leads to a good yield of the adduct (106), and with thiophen to tetrafluoro-naphtha-ene 56>. That this latter reaction was the first example of a Diels-Alder reaction of thiophen was shown by following the reaction by XH n.m.r. spectroscopy. Evidence for the intermediacy of the episulphide (107) was obtained. 

It has been known that aromatic heterocycles such as furan, thiophene, and pyrrole undergo Diels-Alder reactions despite their aromaticity and hence expected inertness. Furans have been especially used efficiently as dienes due to their electron-rich properties. Thiophenes and pyrroles are less reactive as dienes than furans. But pyrroles with A-elecIron-withdrawing substituents are efficient dienes. There exists a limited number of examples of five-membered, aromatic heterocycles acting as dienophiles in Diels-Alder reactions. Some nitro heteroaromatics serve as dienophiles in the Diels-Alder reactions. Heating a mixture of l-(phenylsulfonyl)-3-nitropyrrole and isoprene at 175 °C followed by oxidation results in the formation of indoles (see Eq. 8.22).35a A-Tosyl-3-nitroindole undergoes high-yielding Diels-Alder reactions with... 

Propanophthalazine 200 was synthesized by a novel cycloaddition pathway. This synthesis was thought to proceed by a Diels-Alder reaction of the thiophene subunit of 197 to form intermediates 198 and 199, with the loss of ammonia, and not hydrogen sulfide elimination. Unfortunately, no yields were given <00JCR(S)20>. 

Dibenzothiophene is among the sulfides oxidized, and its monoxide was obtained in 89% yield albeit in a longer (6h) time. Thiophene itself was also oxidized, but its monoxide is known to be too labile for isolation (44-46). Instead, it was trapped by a Diels-Alder reaction, as shown in Scheme 8. 

Figure 8. Catalytic cycles for the Diels-Alder reactions of benzoquinone 47 with cyclohexadiene 48 (top) and tetramethyl thiophene dioxide 51. While the reaction of 47 with 48 suffers from product inhibition, adduct 52 is easily replaced by new reactants inside the capsule.

The unstable l,3-bis(methoxycarbonyl)selenolo- 190 and l,3-bis(methoxycarbonyl)tellurolo[3,4-f]thiophene 191 underwent Diels-Alder reaction with DMAD to produce cycloadducts, which lost selenium or tellurium and collapsed to tertracarbomethoxybenzo[f]thiophene 192 in low yields <20020L1193>. 

Substituted benzo[ ]thiophene derivatives have been prepared in excellent yields by a tandem Pummer rearrange-ment/Diels-Alder reaction of the intermediate furan with maleic anhydride or A -phenylmaleimide (Equation 87) <1996JOC6166>. 

The maleimide group can undergo a variety of chemical reactions. The reactivity of the double bond is a consequence of the electron withdrawing nature of the two adjacent carbonyl groups which create a very electron-deficient double bond, and therefore is susceptible to homo- and copolymerizations. Such polymerizations may be induced by free radicals or anions. Nucleophiles such as primary and secondary amines, phenates, thiophenates, carboxylates, etc. may react via the classical Michael addition mechanism. The maleimide group furthermore is a very reactive dienophile and can therefore be employed in a variety of Diels Alder reactions. Bisdienes such as divinylbenzene, bis(vinylbenzyl) compounds, bis(propenylphenoxy) compounds and bis(benzocyclobutenes) are very attractive Diels Alder comonomers and therefore some are used as constituents for BMI resin formulations. An important chemical reaction of the maleimide group is the ENE reaction with allylphenyl compounds. The most attractive comonomer of this family is DABA particularly when tough bismaleimide resins are desired. 

Tetrazines react with alkenes to give bicycles (403) which lose nitrogen to give the 4,5-dihydropyridazine (404). This can either tautomerize to a 1,4-dihydropyridazine, be oxidized to the aromatic pyridazine, or undergo a second Diels-Alder reaction to give (405). Many heterocycles can act as the dienophiles in such reactions for example thiophene gives (406). The reaction is also used to trap unstable compounds, for example, 2-phenylbenzazete (407) as compound (408). 

---