Benzo thiophenes cycloadditions

Thermal and photochemical cycloaddition reactions undergone by thiophene and its derivatives are discussed in this section. The first number within parentheses refers to the number of 7r-electrons of the thiophene ring taking part in the cycloaddition, and the second number the contribution of the addend. Thermal and photochemical [2 + 2] cycloaddition reactions of thiophenes and benzo[ ]thiophenes form part of an extensive review on [2 + 2] cycloaddition reactions of heterocyclic compounds (77AHQ2l)253). 

Incidentally, a 1,3-cycloaddition of benzyne to thiophene has been postulated (81CC124) to account for the small, but reproducible amount of benzo[ >]thiophene formed in this reaction (Scheme 79). Reactive alkynes have been successfully used as dienophiles to cycloadd with thiophenes benzene derivatives are obtained after extrusion of sulfur from the adduct (Scheme 80) (72TL605, 72TL1909, 73CB674). 

The cycloaddition of a variety of sulfur heterocycles to alkenes has also been reported. Dibromomaleic anhydride undergoes [ 2 + 2] cycloaddition to thiophen295 and to benzo[b]thiophen.296 The photoaddition of benzo-[(>]thiophen 1,1-dioxides to alkenes also affords cyclobutane derivatives.297 Of particular interest is the addition of 3-acetoxybenzo[6]thiophen (350) to cyclohexene to give the adduct (351), which on treatment with base, undergoes a retro-aldol ring opening to benzo[6]thiepinone (352).298 A mixture of stereoisomeric cyclobutane derivatives were obtained on irradiation of 2,6-diphenyl-4//-thiopyran-4-one 1,1-dioxide in cyclohexene.299 The [ 2 + 2] cycloaddition of sulfolen to maleic anhydride and to maleimide has been reported.300... 

Such [2 + 2] cycloadditions have also been observed when the alkyne is electron-rich and the benzo[ ]thiophene electron-poor. Thus 3-nitrobenzo[6]thiophene reacts with ynamines to form the cycloadduct (285) the addition is regioselective and the product shows no tendency to isomerize to the corresponding benzothiepin (74TL2503). 

The benzo[ ]-fused systems participate in a number of [2 + 2] cycloaddition reactions. The photocycloaddition products of benzo ] thiophenes and DMAD are dependent on the irradiation wavelength at 330 nm 240 is formed, while at 360 nm the rearranged product 241 is produced. 

Benzo[ ]thiophene participates in intramolecular dipolar cycloaddition with an in situ generated carbonyl ylide the reaction fails with the corresponding thiophene <2006JA10589>. 

Diels-Alder cycloadditions of thiophene-1,1-dioxides with cyclopentadiene can take place either in the (2-1-4) or (4-1-2) mode depending on whether the thiophene dioxide has two or one electron-withdrawing substituents <2006T4139>. 1,3-Dipolar cycloaddition of benzo[/)]thiophene 1,1-dioxide with azomethine ylides has been reported <2006TL5139>. 

Vinyl- and 3-vinyl-thiophenes behave as a diene on reaction with dienophiles to give six-membered ring-fused thiophenes. Cycloaddition of the cyclobutene 842 with 841 or with 844 followed by aromatization gives benzo[/ ]thio-phene-fused benzocyclobutenedione 843 or 845, respectively (Scheme 129) <1996J(P1)497>. Heterohelicene 847 is synthesized by the reaction of 846 with 1,4-benzoquinone <2001JA11899>. 

As a typical cyclic a,/ -unsaturated sulfone, benzo[ ]thiophene 1,1-dioxide 38 participates in [2+4] cycloadditions (Scheme 31) [135]. 

Benzo[ ]thiophenes undergo photochemical [2+2] cycloaddition, for instance with 1,2-dichloro-ethene in the presence of benzophenone as sensitizer ... 

Thiophene is generally considered the most aromatic of the five-membered heterocycles, hence its reluctance to function as a diene in cycloadditions. A detailed study of the reaction of thiophene with six common benzyne precursors showed that side reactions with intermediates en route to benzyne often dominate the reaction course. Best results were obtained with diphenyliodonium-2-carboxylate 294, which gave up to 30% yields of naphthalene, presumably mainly through intermediate 295. Other benzyne-derived products [benzo( )thiophene, 0.5% 2-phenylthiophene, trace diphenyl sulfide, trace 1- and 2-naphthyl phenyl sulfides, 9 and 6%, respectively o-(2-thienyl)biphenyl, 4%] bring the... 

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). 

Benzo[6]thiophene, 2-acetyl-3-hydroxy-synthesis, 4, 892 Benzo[6]thiophene, 2-acyl-synthesis, 4, 918 Benzo[6]thiophene, 3-acyl-synthesis, 4, 918- 19 Benzo[6]thiophene, acylamino-synthesis, 4, 815 Benzo[6]thiophene, alkenyl-synthesis, 4, 917 Benzo[6]thiophene, 2-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 3-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 4-alkoxy-synthesis, 4, 930 Benzo[6]thiophene, 2-alkyl-synthesis, 4, 877-878 Benzo[6]thiophene, 2-alkylthio-synthesis, 4, 931 Benzo[6]thiophene, 2-amino-diazotization, 4, 810 reactivity, 4, 797 stability, 4, 810 synthesis, 4, 869, 924-925 tautomerism, 4, 38 Benzo[6]thiophene, 3-amino-cycloaddition reactions, 4, 68 synthesis, 4, 109, 881, 925 Benzo[6]thiophene, 4-amino-synthesis, 4, 925 Benzo[6]thiophene, 5-amino-synthesis, 4, 925 Benzo[6]thiophene, 7-amino-synthesis, 4, 925 Benzo[6]thiophene, 3-t-amyl-synthesis, 4, 915 Benzo[6]thiophene, 2-aryl-synthesis, 4, 881... 

Benzo[6]thiophene, 1,2-dimethyl-cycloaddition reactions with dichloroethene, 4, 793 Benzo[6]thiophene, 2,3-dimethyl-nitration, 4, 763... 

Benzo[6]thiophene, methoxynitro-Meisenheimer complexes, 4, 816 Benzo[6]thiophene, 2-methyl-cycloaddition reactions, 4, 793 protonation, 4, 47 sulfonation, 4, 764 synthesis, 4, 879, 915 Benzo[6]thiophene, 3-methyl-cycloaddition reactions, 4, 793 1-oxide... 

Benzo[6]thiophene, 4-N-methylcarbamoyl-biological activity, 4, 913 Benzo[6]thiophene, 2-methyl-3-vinyl-cycloaddition reactions, 4, 795 Benzo[fc]thiophene, 2-( 1 -naphthyl)-synthesis, 4, 915 Benzo[6]thiophene, 2-nitro-reduction, 4, 815 synthesis, 4, 923 Benzo[6]thiophene, 3-nitro-cycloaddition reactions, 4, 789 Benzo[6]thiophene, 4-nitro-synthesis, 4, 923 Benzo[6]thiophene, 5-nitro-synthesis, 4, 923... 

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

The 1,3-dipolar cycloaddition of mesitonitrile oxide 575 to benzo[h]thiophene S-oxides 576 in non-stereoselective and both syn and anti adducts 577 are obtained674,675 (equation 366). 

The synthetic utility of o-quinodimethane generated by cheletropic elimination of S02 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide122. When 1,3-dihydro-l-(4-pentenyl)benzo[c]thiophene 2,2-dioxide (201) prepared from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide and 4-pentenyl bromide is heated in di-n-butyl... 

Finally, many [4+2] cycloaddition strategies utilizing various substituted thiophenes as dienes have been reported. The reaction between 2-(prop-l-enyl)-l-benzo[fo]thiophene and 3-chlorocyclobut-3-ene-l,2-dione followed by bromination and loss of HBr gives a... 

Dipolar cycloaddition reaction of benzo(A)thiophene-l,1-dioxide 282 with nonstabilized azomethine ylides gave high overall yield of new pyrrolo derivatives 5 and 6 with low stereoselectivity (Scheme 50) <2006TL5139>. 

Benzo[Z>]thiophene reacts with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate in a cycloaddition-fragmentation reaction to yield (143), whereas benzo[6]furan and N- methylindole yield products (144) arising from ring opening and recyclization (76AP679). 

In more esoteric compounds like (50) (78JA4326) and (51) (78CB1330) there is no reported tendency for cycloadditions to occur. A doubly protonated cation of undetermined structure reportedly forms on protonation of (50), however. Benzo[6 ]thiophenes can be annelated in a similar manner as occurs with (52) (79JOC2491). The question of the localization of double bonds in benzo[c] fused heterocycles continues to attract theoretical interest (77JA8248). 

Although thermally allowed, the [2 + 4] cycloaddition of thiophene with nitrile oxides leads to low yields of products, even when thiophene itself is used as solvent (77JCS(P2)706, 78T3545). The yield is improved if the dimerization of the nitrile oxide is retarded. Both mono- and bis-adducts have been isolated. The most important feature of the cycloaddition, however, is the regiospecificity (Scheme 77). In contrast, benzo[6]thiophene gave a mixture of both possible regioisomers, although not in equal amounts. 

The only other dipolar species that has been added to thiophene is the carbonyl ylide (287). Thus tetracyanoethylene oxide, as the carbonyl ylide, reacts with thiophene to form the adduct (288) in 70% yield (65JA3657, 68T2551). Several monosubstituted thiophenes have been used in this reaction. From competitive experiments it has been shown that the rate of cycloaddition to furan and benzo[6]furan is greater than that to thiophene and benzo[6]thiophene respectively (75ACS(B)441). 

---