Thiophene 1-oxides, Diels-Alder

Scheme 27 Oxidative Diels-Alder cycloaddition of thiophene with Af-phenylmaleimide using H2O2/CF3CO2H as oxidant [41]...

Scheme 29 Oxidative Diels-Alder cycloaddition of 2,5-di- and tetrasubstituted thiophenes with iV-phenylmaleimide using m-CPBA/BFs EtaO complex as oxidant [13]...

A comparison of the wt-CPBA oxidized Diels-Alder reaction of thiophene derivatives with A -phenylmaleimide, with or without Lewis acid, showed that the overall yields of Diels-Alder products in the presence of /n-CPB A are much lower than those using /M-CPBA/BF3 Et20 complex, suggesting that the Lewis acid catalyst enhances the yield of the oxidative cycloaddition of thiophenes considerably [13],... 

The oxidative Diels-Alder cycloaddition of a variety of intriguing thiophene derivatives such as thiophenophanes and thiopheno crown ethers with... 

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). 

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... 

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). 

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... 

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. 

The reaction of butadiene with the sulfone of 3-benzo[6]thiophene-carboxylic acid under Diels-Alder conditions gives the adduct (32). Catalytic reduction over platinum oxide removes the 2,3-double bond. 

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). 

Proton abstraction from the pentamethylthiophenium ion (13) gave the ylide (141) reaction of this with p-nitrobenzaldehyde gave the epoxide (142) (74TL75). Thiophenium salts, in contrast to thiophene 1-oxides (Section 3.14.4.1), do not seem to undergo Diels-Alder additions (74TL75). 

Polysubstituted methyl- and phenyl-thiophenes could be oxidized with perbenzoic acid or peracetic acid to the corresponding sulfones electron-withdrawing groups like NO2 hindered the oxidation (63AHC(l)l). Yields of such dioxides have been improved by the use of three equivalents of MCPBA (76SC583). However, with thiophene and 2-methylthiophene as substrates, only the Diels-Alder adducts (145) between the intermediate sulfoxide and the final sulfone could be isolated. 

Finally, a Diels-Alder reaction with inverse electron demand, in which the thiophene acts as the 27r-component, has been reported (78AP728). Tetrazinedicarboxylic ester adds to thiophenes to give the adduct (290) loss of nitrogen from this is followed by oxidation, yielding the thieno[2,3-rf]pyridazines (291) in 10-15% yield. With 2,5-dimethyl-thiophene as the substrate, aromatization is blocked, and the product (292) is obtained in 57% yield. 

Oxidation of thiophene with perbenzoic acid,373,376 or peracetic acid,377, 378 affords the adduct (111), or its isomer (112) (the available evidence supports structure ni 377-378), by a Diels-Alder reaction between the intermediates thiophene-1,1-dioxide and thiophene-1-oxide. Similar reactions have been observed with substituted thiophenes.376 When a solution of thiophene-1,1-dioxide is allowed to stand, the adduct (113), or its isomer (114), is formed.373 378... 

Furan is readily hydrogenated, hence it is a source of commercial tetrahydrofuran (THF). Reaction with hydrogen sulfide over alumina produces thiophene. A recent patent describes a catalyst based on cobalt and molybdenum oxides supported on alumina for this reaction (105). Furan undergoes the Diels-Alder reaction with strong dienophiles. Hydrogenation of the product resulting from reaction with maleic anhydride, followed by hydrolysis and neutralization gives a herbicide, Endothall. 

Sulfur oxidation of the thiophene ring leading to thiophene-1-oxides or thiophene-1,1-oxides is useful for modifying the chemistry of the thiophene ring and this subject has been reviewed <02CHC632>. The structure and physical properties of quinquethiophene-1,1-dioxides have been studied in detail <02T10151>. The mechanism for the oxidation of thiophene to a mixture of thiophene-l-oxide (trapped as a Diels-Alder adduct) and thiophen-2-one was studied using... 

Aromaticity prevents thiophene taking part in Diels-Alder reactions, but oxidation to the sulfone destroys the aromaticity because both lone pairs become involved in bonds to oxygen. The sulfone is unstable and reacts with itself but will also do Diels-Alder reactions with dienophiles. If the dienophile is an alkyne, loss of SO2 gives a substituted benzene derivative. 

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