Tricyclic thiophene

Scheme 1.18. Cationic domino rearrangement for the synthesis of tricyclic thiophenes.

Similarly, the adducts of A -allylthiophenamines with DMAD lead to the formation of various tricyclic thiophene derivatives through hetero-Cope rearrangements. An analogous reaction of N-propynylaniline, on the other hand, leads to the formation of a pyrrole derivative (71) (Scheme 10). ... 

Other troponoids, such as tricyclic thiophenes 473 and 398b, are synthetic precursors of potential drugs (66HCA214 90HCA1197). With regard to... 

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). 

O-Acyl derivatives of thiohydroxamic esters (Barton esters) react with benzynes to afford a tricyclic thiophene ring system thus the pyridine derivative 30 gives benzo[4,5]thieno[2,3-A pyridines 31 (Scheme 14) <2002JOC3409, CHEC-III(3.11.3.3)900>. 

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>. 

A route " in which the 3,4-bond is made by an intramolecular pinacol reaction is nicely illustrated by the formation of a tricyclic thiophene with two cyclobutane fused rings. In this example, it was necessary to force the double dehydration required for aromatisation, because of the strain in the system. Starting materials for this route are easily obtained from sodium sulfide and two mole equivalents of a 2-bromo-ketone. 

Thiols and thioethers are the most commonly encountered sulphur derivatives which can be directly reduced to alkanes. For this purpose, Raney Ni has been traditionally used. An example of its use is the synthesis of let- and 7j5-eremophilanes from a tricyclic thiophene precursor (equation 29) However, more recently nickel complex reducing agents ( NiCRA ) have been profitably and effectively used for this purpose, as indicated by the reduction of dodecanethiol to dodecane (equation 30)". Similarly, nickelocene in the presence of LAH has been used to effect desulphurization of thiols . A combination of NaEtaBH and FeCl2 also achieves the thiol-to-alkane transformation quite satisfactorily The increasing utility of nickel boride has also been exploited for the transformation of sulphides to alkanes as indicated in equation 31. ... 

S. M. H. Kabir, M. Miura, S. Sasaki, G. Harada, Y. Kuwatani, M. Yoshida and M. lyoda. New S5mtheses of tricyclic thiophenes and cychc tetrathiophenes using transition-metal-catalyzed cychzation. Heterocycles, 52, 761-774 (2000). 

Scheme 12.46 Au-catalyzed synthesis of tricyclic thiophene/furan or thiophene/pyrrole.

Aminothiophenes and 3-aminobenzo[Z)]thiophene undergo thermal [2 + 2] cycloaddi-tion reactions with activated alkynes. The reactions are solvent dependent thus in non-polar solvents at -30 °C, 3-pyrrolidinothiophene adds to DMAD to give a [2 + 2] cycloadduct which is ultimately converted into a phthalic ester. In methanol, however, a tricyclic product is formed (Scheme 54) (81JOC424. ... 

Denitrocyclization strategy is potentially useful for the synthesis of a wide range of tricyclic compounds. The approach was found useful for the synthesis of thienobenzothiazole 339 and 343 starting from the corresponding bromonitro-thiophenes 336 and 340, respectively (Scheme 52) (68MI2, 72IJS(B)109). 

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]. 

In this chapter we describe a novel, safe and efficient large-scale synthetic approach to tricycle thienobenzazepines. The key steps in the synthesis include a chemoselective hydrogenation of an aryl-nitro functionality in the presence of a 3-bromo thiophene and a subsequent palladium-catalyzed intramolecular aminocarbonylation telescoped sequentially after simple catalyst and solvent exchange. 

A New Improved Synthesis of Tricycle Thienobenzazepines Apphcation of chemistry recently developed by Knochel" combined with the well-described halogen dance (HD) reaction, allowed preparation of our key intermediate A in only three synthetic transformations (Scheme 6.4). In this respect, treatment of 2-bromo-5-methylthiophene with hthium diisopropylamide followed by dimethylformamide afforded aldehyde 11 in good yield, lodo-magnesium exchange with conunercial 4-iodo-3-nitro anisole followed by reaction with 11 afforded the thiophene catbinol 12. Dehydroxylation of 12 provided our key intermediate A which presented the requisite functionality to examine our approach to the construction of the seven-member ring system. 

A general synthesis of dibenzo-annelated dithieno[3,Z-b Z, 3 - thiophene 18 has been reported from bis(o-hydro-xyl)diacetylenes. This cyclization constructs a fused tricyclic skeleton in one pot. The subsequent dechalconization with copper powder produces a series of thiophene and selenophene-based heterocenes (Scheme 64) <20050L5301>. 

Reaction of the 2-amino-substituted thiophene 244 with pyrrolidinone in the presence of phosphorus oxychloride led to efficient formation of the central six-membered ring of tricycle 245 in 57% yield (Equation 67)... 

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. 

Similar to the Pd-catalyzed pyrrole and thiophene annulations, an intramolecular Heck reaction of substrate 91 resulted in benzofuran 92 [80], Such an approach has become a popular means of synthesizing fused furans. Muratake et al. exploited the intramolecular Heck cyclization to establish the tricyclic core structure en route to the synthesis of a furan analog of duocarmycin SA, a potent cytotoxic antibiotic [81]. Under Jeffery s phase-transfer catalysis conditions, substrate 93 was converted to tricyclic derivatives 94 and 95 as an inseparable mixture (ca. 4 1) of two double bond isomers. 

More activated substrates such as thiophene, produce a mixture of a,a -dithiophene mono-, di-, tri-, tetra-, and polysulfides. When both a-positions of thiophene are taken by methyl groups, a and a fused tricyclic product... 

While ring annulation is not uncommon, the formation of a five-membered ring onto an existing pytazine is somewhat unique. Thus, 25 reacts with malononitrile and then with an amine to form the tricyclic product 26 (Equation 9) <2001MC152>. Thiophene and pyrrole analogs of 25 react similarly. Note that 26 is suitably substituted to add yet another ring. 

Ring closure of certain thiophene diesters 74a or cyanoesters 74b under Dieckmann conditions (EtOH/EtONa) has recently been shown to give thieno[2,3-6]pyrroles (75a, b) in high yield (65-90%).72 A thieno-[2,3-6]pyrrole diester (75 R5 = OCH2COzEt) prepared in this way failed to undergo further cyclization to the tricyclic system 76 under the same conditions.7215... 

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