4//-furo indoles

Furo[3.4-b]indoles are also potential indolequinodimetbane equival-ents[ll,12]. For example, 16.6A generates a furo[3,4-b]indole in situ which is trapped by dimethyl acetylenedicarboxylale generating the carbazole 16.6C[I2]. 

Bromination of 4//-furo[3,2-b]indole (50) occurred at the 2-position and was assisted by prior N-benzylation with the 4-benzoyl compound a 61% yield of the 2-bromo derivative was obtained. Thus, a-attack in the furan moiety predominates (78JHC123). When the pyrazolofuran (51) was treated with one molar equivalent of bromine, a mixture of the 2-bromo... 

Transition metal catalyzed decomposition of diazoester 64b, which is available from 64a with TsNj/base, results in the formation of furo[3,4-b]indole 65. This intermediate is trapped intramolecularly in situ to give 66. Furo[3,4-b]indoles of type 67 can be prepared similarly... 

Furthermore, the Wu group [141] has prepared isoquinolines and iso-indoles starting from 2-(2-phenylethynyl)-benzonitrile, while Yamamoto and coworkers [142] prepared benzopyrans from alkynylbenzaldehydes, the Cacchi group [143] synthesized benzofurans, and Balme and coworkers [144] furo[2,3-fo]pyridones. 

The pyrido[3, 4 4,5]furo[3,2-A]indole 24 can be prepared by Curtius rearrangement of 3-[5-(2-nitrophenyl)-2-furyl]-propenoic azide 25, followed by reduction of the nitrophenyl functionality of the product 26, chlorination of the tetracyclic product (PCI5), then reduction (Zn/AcOH) to give the parent compound 24 <1987CCC192> (Scheme 7). 

Internal nitrenes normally react at the adjacent position. Reduction of 2-(2-nitrophenyl)furan by ethyl phosphite yields furoindole derivatives in fair yield (34%) only, whereas much better results attend the pyrolysis of 2-(2-azidophenyl)furan.280 Furopyrazoles are obtained similarly.281 Azidofurans yield nitrenes that insert into adjacent CH links to form furo-pyrroles.282 Quite different results attend either the pyrolysis or the photolysis of azide 107a for the expected insertion into the side chain occurs giving the related indole but it is accompanied by the surprising replacement of furan oxygen by nitrogen producing 107b and similar products.283... 

Adapting Gribble s method for synthesizing indol-3-yl triflate [37], Mdrour et al converted 2-formyl- l-(phenylsulfonyl)- l//-indole (31) to indol-2-yl triflate 32 in two steps. 32 was subsequently coupled with benzofuryl-2-boronic acid to furnish 2-benzofurylindole 33 [38, 39]. In another case, 2-bromoacetaniline was coupled with 2-formyl-3-furylboronic acid 35 [40]. The resulting Suzuki coupling adduct underwent a spontaneous cyclization, forming tricyclic furo[2,3-c]quinoline 36. 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

The furo[3,4-3]indoles undergo cycloaddition reactions with NPMI, maleic anhydride, and DMAD in the presence of -TsOH to give the fused carbazoles 125-129, products of the subsequent in situ ring-opening of the oxobridge of the intermediary cycloadducts (Scheme 12) <1996JOC6166>. 

The regioselectivity of 2,4-cycloaddition of furo- and pyrrolo[3,4-, ]indoles with 3,4-didehydropyridines was studied <2001EJ04543>. The results of this key reaction step in the synthesis of ellipticines are summarized in Equation (1). 

The furo[3,4- ]pyrroles 132, 133 <2002TL6983>, thieno[2,3-f]furan 134, <1996JOC6166>, and furo[2,3-f]pyrrole 135 <1995T193>, which are mostly less stable than the benzo-fused analogues, were trapped by Diels-Alder reactions with dienophiles followed by elimination of water to give the corresponding indoles 136-139, 140, 141, and benzothiephenes 142, 143, and 144 with good to excellent yields (Scheme 13). 

The substituted furo[3,2-3]indole-2-carbonitrile 228 with a fluorous tin azide (C6F]3CH2CH2)3SnN3) gave the corresponding tetrazole derivative 229 (Equation 4) <1999T8997>. 

Generally, cycloadditions represent powerful reactions for construction of heterocycles. Tandem intramolecular Diels-Alder/retro-Diels-Alder reaction sequences were applied in the syntheses of many A,B-diheteropentalenes <1996GHEC-II(7)1>. Gribble and co-workers <1998SL1061> reported new syntheses of pyrrolo[3,4-, ]indoles 426, benzo[4,5]furo[2,3-f]pyrroles 429, and benzo[4,5]thieno[2,3-4pyrroles 430 using the 1,3-dipolar cycloaddition... 

A structurally novel series of substituted 10//-benzo[4,5]furo[3,2- ]indole-l-carboxylic acids 504-507 was prepared and shown to possess potent, bladder-selective smooth muscle relaxant properties and thus is potentially useful for the treatment of urge urinary incontinence. Electrophysiological studies using rat detrusor myocytes have demonstrated that prototype compound 8 produces a significant increase in hyperpolarizing current, which is iberiotoxin (IbTx)-reversed, thus consistent with activation of the large-conductance Ca -activated potassium channel (BKca) <2001BML2093>. 

Substituted furo[3,2- ]pyridines are under investigation for use as 5-HTip receptor agonists since indole analogues are known in this application. Compound 152 may have potential as a therapeutic agent for treating migraine <2004BML167>. 

Dimethyl-4-(phenylsulf-onyl)furo[3,4-b]indole Me02C=CC02Me ch3 qG PhS02 co2CH3 A/ co2ch3 100 [15]... 

Benzyl-1 -(tt rt-butyldimethyl-silyloxy)furo[3,4-b]indole (1) CH2--=CHCO,Me (2) BF,—OEt2 Methyl-9-benzyl-4-hydroxycarba7.ole-3- carboxylate 87 [16]... 

Furo[3,4-h]indoles have also been prepared as transients for inter- and intramolecular Diels-Alder reactions (96JOC6166) (see Section IV). 

Fischer indole synthesis, 157 fluorinated phosphine, 136 fuostifoline, 276 furo[2,3- ]pyridine, 281 furopyrimidine, 281, 393 furo[2,3-c]quinoline, 274 furylaniline, 272 furylboronic acid, 274 furylpyridine, 274 furylstannane, 277-9 2-furylzinc chloride, 271-4... 

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