Thiophenes intramolecular cycloaddition

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... 

The thiophene ring system can be utilized as a synthetic scaffold for the preparation of nonthiophene materials as the sulfur moiety can be removed by reduction (desulfurization) or extrusion (loss of SO2). The extrusion of sulfur dioxide from 3-sulfolenes (2,5-dihydrothiophene 1,1-dioxides) give dienes (butadienes or o-quinodimethanes) that can be utilized to prepare six-membered rings by cycloaddition chemistry. For example, thermolysis of 3-sulfolene 120 provided tricyclic pyrazole 122 via an intramolecular cycloaddition of the o-quinodimethane 121 that results by extrusion of sulfur dioxide <00JOC5760>. Syntheses of 3-sulfolenes 123 and 124 <00S507> have recently been reported. 

The analogue 269 reacted via a remarkable intramolecular cycloaddition to the thiophene ring to give 270 as the primary product, which was then partially consumed by intermolecular cycloadditions of 269 to both the pyrazole C=N and the residual thiophene C=C to give 271 and 272, respectively (166,167). 

If a diene unit is located at an appropriate distance from the developing zwitterionic intermediate in such reactions (especially in good ionizing solvents), an intramolecular cycloaddition may intervene. This is what happens with the tetrahydrobenzo[c]thiophene 2,2-dioxide derivative (588), which leads to the bis-homobenzene (589) rapid valence isomerization of this gives the product (590) (770R(25)i). This process has been termed bis-homoconjugative rearrangement (Scheme 251). 

An interesting example of an intramolecular cycloaddition reaction has been observed in the case of the mesoionic 1,3-dithiolone (97) which contains a non-activated alkyne in the same molecule. Thus, on heating (97) at 40-45 or 100 °C, the tricyclic thiophene derivative (99) is obtained via the non-isolable primary adduct (98) (81LA347). 

Pericyclic reactions involving thiophenes have been utilized to prepare a variety of complex heterocycles. The intramolecular Diels-Alder reaction of 2-vinylbenzo[i]thiophene 92 produced a pair of tetracyclic adducts 93 and 94 <02TL3963>. Coupling of Fischer carbene 96 with 3-alkynylthiophene 95 led to the formation of thieno[2,3-c]pyran-3-one 97 in one step <02JOC4177>. An intramolecular cycloaddition of 97 then afforded tetracyclic adduct 98. A ruthenium-catalyzed cyclodimerization reaction involving bis-thienyl acetylene derivatives was... 

The observed regioselectivities during these cycloadditions have been explained in terms of qualitative frontier molecular orbital perturbation theory <78CB2028>. An intramolecular cycloaddition has been observed for the 1,3-dithiolone (111) to afford the tricyclic thiophene derivative (112) (Equation (13)) <81LA347>. 

Intramolecular azide cycloaddition to a thiophene double bond leads to 4/f-thieno[3,2- >]pyrrole derivatives <89TL1655>. 1,3-Dipolar intramolecular cycloaddition of a nitrile oxide on to the thiophene moiety gives (138) <88S342>. In a similar fashion, one double bond of thiophene acts as a dipolarophile to produce derivative (139) <89JOC5277>. 

Nakayama J, Sugihara Y (1999) Chemistry of Thiophene 1,1-Dioxides. 205 131-195 Namboothiri INN, Hassner A (2001) Stereoselective Intramolecular 1,3-Dipolar Cycloadditions. 216 1-49... 

The reaction of the a-bromo aldoxime 52e (R = R = Me) with unsaturated alcohols has been extended to the heterocyclic systems furfuryl alcohols and 2-thiophene methanol [29b]. The furanyl and thiophenyl oximes 63a-c were treated with NaOCl and the resulting heterocyclic nitrile oxides were found to undergo spontaneous intramolecular dipolar cycloaddition to produce the unsaturated tricyclic isoxazolines 64a-c in high yield (Eq. 5). In these cases, the heterocyclic ring acts as the dipolarophile with one of the double bonds adding to the nitrile oxide [30]. 

An attractive approach toward the preparation of polycyclic systems containing a thiophene ring involves the intramolecular [3 - - 2] cycloaddition of thiocarbonyl ylides. A number of representative examples were reported using mesoionic compounds. Gotthardt et al. (151) used l,3-dithiolium-4-olates such as 89 bearing an olefinic side chain. Upon heating to 120 °C in xylene, the polycyclic tetrahy-drothiophene 90 was formed (Scheme 5.33). 

Thiophenes can function either as a diene or as a dienophile in an intramolecular Diels-Alder reaction (90CC405). The 7V-(2-thienyl)allene carboxamide (182) on heating at 130°C leads to (183) by a [4 + 2] cycloaddition in which the thiophene functions as a 4ir component, followed by the usual extrusion of sulfur. 

A number of examples of photoaddition to alkynes has been described. Dimethyl acetylenedicarboxylate has been found to add to methyl-substituted 3-benzoylthiophens301 and to thiophen and 2,5-dimethylthiophen302 on irradiation. Benzo[f>]thiophen also undergoes cycloaddition reactions with alkynes,303 and in the case of dimethylacetylene dicarboxylate, product formation has been shown to be wavelength dependent.304 Intramolecular [ 2 -(- 2] cycloaddition has been observed on both direct and triplet-sensitized irradiation of the alkyne (353) and gives the cyclobutene (354)305 the isomer (355) is formed on prolonged irradiation. 

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