Benzo thiophene, Diels-Alder reactions

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

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). 

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>. 

Pyrroles, indoles and benzo[ft]thiophene act as good dienophiles in inverse electron demand Diels-Alder reactions with 1,2-diazines, 1,2,4-triazines and sy/n/n-tetrazines. This is examplified by the formation of compounds (189) in excellent yields on interaction of indoles and benzo[c]thiophene with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate (87JOC4610 90JOC3257). There are also many examples of such intramolecular reactions, e.g. (190 — 191). 

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). 

Vinylbenzo[6]thiophene undergoes Diels-Alder reactions with benzyne,468 maleic anhydride,469 benzo[6]thiophene-1,1-dioxide,469 p-benzoquinone, and various 1,4-naphthaquinones.469,470 With quinones, the product depends on the reaction conditions. For... 

Vinylbenzo[6]thiophene 90 reacted with benzoquinone to give a fully aromatized 1 1 cycloadduct 151 as result of a Diels-Alder reaction followed by dehydrogenation by excess quinone. Isolation of a dihydro derivative 152 was possible using a weaker solution of 3-vinylbenzo[b] thiophene, whereas a further excess of the vinyl compound and a very short reaction time afforded the terahydro derivative 153 (79AJC145). On the other hand, primary Diels-Alder adducts are isolated from 1-(3-benzo[6]thiophene)cyclohex-1 -ene and 1 -(3-benzo[fc]thiophene)-3,4-dihydronaphthalene on reaction with MA (50JA571). 

Diels-Alder reactivity of thiophene and benzothiophene remains poorly understood. AMI semiempirical studies examining the activation of thiophene for this thermally allowed [4+2] cycloaddition process have shown that the usual synthesis approaches (use of highly reactive dienophiles, substitution on thiophene, increased reaction pressures) have only small effects on rate enhancement. However, use of the corresponding S-methylthiophenium salts, which have little aromaticity, should provide excellent activation for Diels-Alder reactions of thiophenes even with poor dienophiles such as ethylene <95JHC483>. This AMI approach has been applied to examine Diels-Alder reactions of benzo[6] and benzo[c]thiophenes the theoretical data agree with experimental results <95JCS(P1)1217>. 

Thieno[2,3-c]furan behaves as a thiophene-2,3-quinodimethane equivalent. Diels-Alder reaction of furan 775 with +-phenylmaleimide or maleic anhydride followed by acid-catalyzed dehydration affords benzo [ Jthiophenes 776 (Scheme 123) <1996JOC6166>. 

Diels-Alder reaction of vinylthiophenes 853 with acetylenes having electron-withdrawing group(s) affords benzo-[/)]thiophenes 855 by loss of ethylene from the intermediates 854 (Scheme 131) <1998SC2531>. 

Benzyne (from pyrolysis of phthalic anhydride) reacts with thiophen at 690°C to give mainly naphthalene, benzo [b] thiophen (54), 2- and 3-phenyl-thiophens, and bithienyl.57 The bithienyl (probably the 2,2 -isomer) is also formed from thiophen alone under the same conditions. The phenylthiophens arise by insertion of benzyne into C—H bonds of thiophen. The source of naphthalene is most likely to be via a Diels-Alder reaction (Scheme 7, X = H), and Fields and Meyerson assume a mechanism involving initially 1,2-cyclo-addition of benzyne to a C—S bond of thiophen to account for the formation of 54 (Scheme 8).2,57,58 However, there is no evidence to support such a route, which seems unconvincing, not least because benzo [b]thiepin (53)... 

Benzo[6]thiophene, 3-pyrrolidino-cycloaddition reactions, 4, 789 Benzo[6]thiophene, 4,5,6,7-tetrafluoro-electrophilic substitution, 4, 797 synthesis, 4, 895, 932 Benzothiophene, tetrahydro-synthesis, 4, 908 Benzo[6]thiophene, vinyl-cycloaddition reactions, 4, 794 Diels-Alder reactions, 4, 908 Benzo[e]thiophene, 1 -alkenyl- 1,3-dihydro-... 

This bond order deviation from an ideal transition state structure to an example of cyclopropene added to a benzo-fused heterocycle may now be applied. Before we exEunine bond order deviation from an ideal transition state, we can take a look at the sums of rings bond order in the transition state structures. To simplify this picture, we will focus only on exo transition state structures between cyclopropene and benzo[c]heterocycles. Previously, we mentioned that the Diels-Alder reaction with benzo[c]heterocycles as dienes is a HOMO controlled diene reaction, therefore, an electron rich (higher sum of bond order) transition state structure should be energetically preferred. If this is the case, the order of reactivity should be benzo[c]furan, benzo[c]thiophene, and then benzo[c]pyrrole, which is exactly the same as determined on the basis FMO energy change (Table 23). 

The [4 + 2]cycloaddition reactions of benzo[c]thiophenes have been further exploited. 4,5,6,7-Tetrafluorobenzo[c]thiophene undergoes cycloaddition to DMAD and tetrafluorobenzyne this is followed by sulfur extrusion, yielding a naphthalene and an anthracene, respectively <90JCS(P1)1919>. The Diels-Alder reaction of l,3-bis(4-methoxyphenyl)benzo[c]thiophene, with iV-phenylmaleimide proceeds normally. However, with a sterically hindered substrate like l,3-bismesitylbenzo[c]-... 

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